ROBERT C. RANDALL, Plaintiff, v. THE UNITED STATES OF AMERICA, et. al.,

What follows is the entire sworn testimony of Robert Randall, as transcribed by me, Ricardo Pereyda, from the original archived record. I have also included exhibits 1-28.

There are another set of “lettered” exhibits which will be dissected in another blog. This is not for the easily distracted, or busy professional. This document is meant for the reader, the ones who have time to jump into the deep end, swim around for awhile, and relax with their floaties. There are other blogs breaking this document down into easily digestible parts, which all are encouraged to at least skim through.

One thing I can state with confidence, because it happened to me when I got access to these archives after being in this movement for over a decade, you’ll learn something new about what you thought you knew.

With that said, have at it:

IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA 

ROBERT C. RANDALL, Plaintiff, v. THE UNITED STATES OF AMERICA, et. al., 

CIVIL ACTION NO. 

AFFIDAVITS AND EXHIBITS TO MEMORANDUM OF POINTS AND AUTHORITIES IN SUPPORT OF MOTION FOR A TEMPORARY RESTRAINING ORDER OR IN THE ALTERNATIVE OR A PRELIMINARY INJUNCTION

AFFIDAVIT OF ROBERT C. RANDALL:

I, Robert C. Randall, the plaintiff in this action, being duly sworn, hereby make oath that, to wit: 

1. I concluded my formal education in 1971 when I received a Master of Arts degree in speech. I have been employed since 1971 in the following jobs: cab driver, newspaper drama critic, and college and junior speech instructor. When it became necessary to devote my full energies to resolving my health situation, I declined an invitation to return to my position as an instructor at Prince George's Community College in the fall of 1976. Since that time I have been engaged in an attempt to stabilize my health care through the legalization of the medicine necessary to the maintenance of my sight, including the following activities: Speeches at numerous colleges, state legislatures and federal administrative hearings; correspondence with a variety of government officials, glaucoma patients and others who have a medical need for marijuana and authorship of an assortment of articles, including completion of the draft of a book. 

2. I began suffering from the problems diagnosed as eye strain in 1967. These problems were diagnosed as glaucoma by Dr. Ben S. Fine, a board-certified ophthalmologist, in September of 1972. At this time, visual acuity in my right eye was 20/400 and in my left eye was 20/40. I was placed on a routine of conventional antiglaucoma drugs to control my intraocular pressure (IOP). Elevated IOP is a symptom of glaucoma. It also causes nerve damage leading, eventually, to blindness. The first medication prescribed by Dr. Fine, Pilocarpine, caused severe myopia, but controlled my IOP. 

3. By early fall of 1973, I began developing a tolerance to Pilocarpine. In other words, the medication was not able to keep my intraocular pressure to within a safe range (10 to 20mm). The strength of the Pilocarpine was increased. 

  4. In the fall of 1973, I discovered that smoking marijuana reduced my IOP. As IOP increases, “halos” (multi-colored circles_ form around lights. Approximately one hour after smoking marijuana my halos disappeared. This discovery was not communicated to my doctor at this time. 

5. Throughout the fall of 1973 Dr. Fine continually adjusted my medication to compensate for developed tolerances. Pilocarpine had become ineffective. An Epinephrine compound, E-Pilo, was attempted several times but eliminated because of extreme stinging of the eyes. By January 1974, I was using Phospholine-Iodide (.03%). Within one month, I was forced to increase my use of this drug from one to two times a day in order to achieve adequate IOP control. 

6. By the early summer of 1974, however, my eye pressure was again escalating and I began serious self-medication with marijuana (I.e., adding it to my conventional medications). From that time until the present I have used marijuana on a regular basis as part of my medical regimen. The only exceptions have been during times when I was unable to locate or afford the drug or when my abstinence was required for a medical reason, such as a test. Until I received an authorized government supply of the drug, I often suffered periods when I could not purchase the drug from persons I knew and trusted. On such occasions, I purchased the drug from strangers. These arrangements made me extremely apprehensive concerning the safety of using marijuana which might have been adulterated with a dangerous substance. When I began my self-medication I used approximately 5 to 6 marijuana cigarettes per day to control my IOP and fault progressive nerve damage. Cost (approximately $125 per week on the street market) also interrupted my use of the drug on occasion. I attempted to grow marijuana plants but was sometimes unsuccessful. Although problems of locating and paying for marijuana constantly interrupted my steady use of the drug, I never allowed myself to be without the drug for more than a few days. The only other times during which I have been without marijuana as a medicine to control my OP have been when required for medical tests. Until I informed Dr. Fine of my use of marijuana in September of 1975, I would purposefully not smoke the day prior to visiting him in order that he could determine the IOP reducing effect of my conventional medications unaffected by marijuana. I also did not use marijuana for the first few days of Dr. Hepler’s tests, during my week of confinement for tests at Johns Hopkins, during a number of days (each separated by periods of marijuana use at the outset of Dr. Merritt’s treatment, nor during the period of Timolol tests conducted by Dr. Shields — each period of non-use was required in order to determine whether conventional medication alone controlled my IOP. Although I have used marijuana steadily for four years, neither I nor my doctors have noted any significant side effects of my marijuana usage. 

7. The two longest periods I have been without marijuana since the summer of 1974 were during the week of tests at Johns Hopkins and during the two and one half weeks of Timolol tests. During the Johns Hopkins test, I was under the constant observation of physicians. During the Timolol test, Timolol initially reduced my eye pressure into a safe range but this effect progressively deteriorated. On days when I have been unable to smoke marijuana as needed throughout the day (for example, while attending the March 15, 1978 meeting of the Controlled Substance Advisory Committee), my IOP can escalate dramatically causing a rapid onset, within two hours, of “halos” and blurred vision. Measurements indicate that my eye pressure in such instances rises to between 40 and 60 mm. Even one day at such levels could cause permanent loss of sight. 

8. During November and December of 1974 my conventional medications were again proving ineffective. Dr. Fine added Diamox at 125mg. Four times a day to my routine. This conventional routine, as supplemented with marijuana, continued to control my IOP throughout the next year, however, the Diamox was increased to 250mg. Four times a day. During this year I suffered from fatigue, listlessness, and loss of appetite, all side effects of this medication. These problems disappeared when Diamox was later discontinued. 

9. Also, during November and December of 1974, Dr. Fine first raised the possibility of surgery. At this time he recommended against surgery. During the course of our relationship we discussed surgery on several occasions. He has never recommended surgery. Instead, he has outlined the potential advantages and disadvantages of glaucoma surgery. He explained that unless my IOP could be controlled I would eventually be blind, that surgery was an alternative means of reducing IO, but that surgery was sufficiently risky that it should not be undertaken until all available medical therapies proved ineffective in reducing IOP. The surgical risks he outlined included the significant possibility that the surgery might be ineffective. In my case this possibility is increased by the extent to which my pressure fluctuates (from 15 to 40mm. In the course of one day) making it more difficult to judge the degree to which the “outlaw channel” should be enlarged. Of course, ineffective surgery would have to be repeated. Dr. Fine also explained that eye surgery is very delicate; side effects include blindness caused by ruptured vessels, infection, or mistake and subsequently developing cataracts which themselves may necessitate surgery. Repetitive surgery increases these risks because eye tissue has been thinned and scar tissue developed by original surgery. Even if surgery is successful and no side effects have developed, as one grows older surgery may again be necessary due to changes in IOP levels which commonly result as one ages. 

10. After Dr. Fine explained the surgical procedure and the attendant risks, I rejected surgery; I have continued to reject this alternative since my regimen of conventional medications and marijuana adequately controls my IOP with less risk. 

11. My attempt to grow marijuana plants led to my arrest on charges of possession of marijuana in August of 1975. In November of 1976 I was found not guilty by Judge Washington of the District of Columbia Superior Court. Judge Washington’s opinion held that my defense of medical necessity was valid. 

12. Prior to my arrest I had not informed Dr. Fine of my use of marijuana. I feared how Dr. Fine might react to the tension created by the drug’s illegality combined with its medical usefulness. Subsequent to my arrest, this was less of a deterrent, and I informed Dr. Fine of my self-medication with marijuana. Although he was interested in this fact, he did not express any medical opinion as to my discovery. He did, however, forward my medical history to Dr. Hepler of UCLA so that I could take part in Dr. Hepler’s marijuana research.From this time forward I used marijuana to treat my glaucoma with Dr. Fine’s knowledge, if not his acquiescence. 

13. I contacted Dr. Hepler in October of 1975. Dr. Hepler was conducting research at the Jules Stein Eye Institute at UCLA on marijuana’s effects on IOP in the glaucomatous eye. Arrangements were made for me to participate in this program in December of 1975. 

14. I was admitted to the hospital at UCLA on December 7, 1975. Prior to being accepted as a test subject, I was given a personality test and interviewed by a staff psychiatrist. For the next two days Dr. Hepler gave me an extensive eye examination and attempted, unsuccessfully, to control my IOP with conventional medications alone. Dr. Hepler discontinued my current conventional medications and substituted Pilocarpine, in Ocusert -40 (continuous delivery system) form, and Glaucon at 2% twice a day (an Epinephrine Compound which avoided the stinging previously caused by medications in this family). From December 9 through December 18 he tested marijuana’s effect on my IOP when used in combination with conventional drugs. 

15. Dr. Hepler informed me directly of his conclusions. I am legally blind in my right eye and have substantial damage to my left eye. Conventional medications alone do not control my IOP. Conventional medications used in combination with marijuana, do control my IOP. The failure to control my IOP will cause further damage to both eyes, leading to total blindness. Dr. Hepler advised against surgery so long as my IOP could be controlled by any medical therapy. 

16. Upon my return to Washington I continued my routine of marijuana and conventional drugs with Dr. Fine’s knowledge. However, he substituted Phospholine Iodide at .02% twice daily for the Ocusort Pilocarpine. The Glaucon was continued. In addition, I was self-medicating with 5 marijuana cigarettes per day. Although this regimen prevented substantial elevation in my IOP, it did not keep my pressures under control during the entire day. 

17. Upon the recommendation of Dr. Fine I was admitted in March of 1976 to Johns Hopkins Wilmer Eye Institute in order to determine whether any conventional medications could control my IOP. These tests were conducted for one week and included the use of all conventional medications at maximum strength in various combinations. Pilocarpine at 4% four time a day in combination with Glaucon 2% twice a day was the first routine attempted. Next, Diamox at 100mg. Per day was added to the above therapy. Pilocarpine was discontinued to test the effects of Glaucon and Diamox. Phospholine Iodide at .25% (first at once a day then twice) was net employed in combination with Diamox and Glaucon. The above described tests, therefore, included the maximum dosages of all three families of glaucoma medications. No conventional medications adequately controlled my IOP. See Ex. 24. These high dosages caused unpleasant side effects; including fatigue, gastric distress, lid spasms, and severe accommodative myopia. After these tests Dr. Fine returned me to my regular medical routine: Phospholine Iodide .03% two times a day and Glaucon 2% twice a day in combination with marijuana self-medication. Later in the summer the Phospholine Iodide was increased to .06%. Daranide (a carbonic anhydrase inhibitor) was added at 150mg. Per day. This was discontinued after one month because of extreme gastric distress, anorexia, back pain (kidney area), fatigue, intense depression, and disoriented and confused thinking. These effects ceased when I discontinued taking the Daranide.

18. On May 20, 1976 my prior attorneys formally requested that the DEA provide me with legal marijuana to treat my disease. DEA referred the request to FDA who referred it to NIDA in June. I was later informed that NIDA would make the drug available if I could locate an ophthalmologist willing to prepare and file a research protocol, an application for an IND and a request to be registered by DEA under the Controlled Substances Act. See Exs. 1, 2. 

19. Thus began the most frustrating and psychologically intense months of my life. Dr. Fine, who had been supervising my glaucoma treatment since 1972 (without knowledge that I was regularly using marijuana from the summer of 1974 until August of 1975, and, since August of 1975, with knowledge of my use of marijuana) refused to get involved because of the onerous bureaucratic requirements. I contacted a number of other doctors, many of whose names I cannot recall, but I personally spoke with Drs. Kupfer and Baldwin of the National Eye Institutes; a doctor recommended by Dr. Hepler, Dr. Kolsky; Dr. Schwartz at Georgetown University; and Dr. Armoly at George Washington University. Each doctor refused to get involved for a variety of reasons including the substantial red-tape involved, fear of publicity, and involvement in other research leaving no time. I also contacted a number of ophthalmologists and other doctors requesting recommendations of doctors who might be willing to get involved. I contacted residents who were willing to get involved in the research but did not believe that their respective universities would allow them to do so until they completed their residencies. One of the more frustrating aspects of this exercise was that some of the contacts did not involve a simple request and the negative response. Instead, Dr. Hepler’s test results, the Wilmer Eye Institute test results, an opportunity to examine my eyes, discussion with the agency officials and time for reflection prior to refusing my involvement. 

20. I kept NIDA informed of my lack of progress. The agency, particularly in the person of Phyllis Lessin, was sympathetic and by July had begun to assist in my search for a doctor. With no success, NIDA contacted a number of doctors. I was informed that doctors from as far away as Boston and North Carolina had been approached. Doctor Fine also attempted to find an ophthalmologist willing to do marijuana research.

21. Finally, even NIDA became frustrated with its inability to locate a doctor. A new approach was suggested by NIDA whereby they would inform me of the name of any doctor who might be willing to get involved and I would initiate the contact. The purpose of such an approach was to accentuate the person's needs and deemphasize the bureaucratic problems associated with such a program. The first doctor suggested by NIDA was out of town. His telephone answering service immediately transferred me to the office of another doctor who had previously refused to become involved. I believed at this point that we were close to having contacted every Washington area ophthalmologist. But, this process also proved unsuccessful. 

22. In August of 1976 NIDA suggested that I contact the Drug Abuse Council for assistance in locating an ophthalmologist willing to become involved in marijuana research. The Drug Abuse Council attempted unsuccessfully to locate an ophthalmologist, but did contact a psychiatrist willing to hold the research license if an ophthalmologist would serve as a co-investigator. This was the exact arrangement which had been used at UCLA. Also in August, NIDA suggested that it would actually hold the research license if an ophthalmologist would serve as a co-investigator. As a co-investigator, the ophthalmologist only would be responsible for monitoring my medical progress. Dr. Fine agreed to serve as a co-investigator under either procedure. NIDA, however, without explanation, rejected both alternatives even though one was identical to that used in the only other smoked-marijuana research program and the other suggestion had been originated by NIDA. The suggestion concerning NIDA’s holding of the license was referred to as a “Compassionate IND.”

23. On September 7, 1976, I was informed that Dr. Merritt of Howard University had applied for an IND for marijuana testing upon glaucoma patients. I am not aware whether the timing of his application was coincidental or was the result of NIDA’s efforts to locate an investigator. 

24. My original request to the DEA on May 20, 1976 was that I be given legal access to marijuana to treat  my disease. This request was denied on June 11, 1976. See Exs. 1, 2. During my attempt in June, July and August of 1976 to locate a doctor to apply for an IND, my discussions with NIDA usually concerned their suggestion of a “Compassionate IND”. I was told that such an IND would recognize my need to receive the drug for treatment in order to save my sight. I did not understand, nor am I certain the government understood, the degree to which they would treat me as a research subject until much later in the program. 

25. I first saw Dr. Merritt on September 9, 1976. He initially monitored my response to a number of conventional medications. His attempts to control my IOP by using only conventional medications failed, as had the attempts of Dr. Fine, Dr. Hepler and Dr. Diamond at the Wilmer Eye Institute of Johns Hopkins University. 

26. Approval of Dr. Merritt’s application by various government agencies and actual arrangements for the distribution of the drug delayed my receipt of marijuana from Dr. Merritt until November 12, 1976.

27. As NIDA was considering approval of Dr. Merritt’s license they also communicated to me the conditions of my involvement in the program. At the outset I was promised immunity, but I was informed that I would have to undergo complete hospitalization during any use of the drug. I objected and was then informed that, although I would not have to be hospitalized, I would have to be in the hospital each time I actually used the drug. I again objected, explaining that I needed 6 to 10 marijuana cigarettes a day which would require my effective complete hospitalization or repeated trips each day to a hospital. Next I was informed that I could have a take-home supply of marijuana, but only if I purchased and installed a 750 pound safe. Again I objected because of the expense. Finally, Phyllis Lessin explained on September 300, 1976 that I would be allowed a one-week take-home supply of marijuana through Dr. Merritt, but only if I remained silent about my involvement in the program. The imposition of the silence restriction was an emphatic condition on my participation. My objection to this condition was just as emphatic. On October 4, 1976 I was informed by Dr. Focus that the Drug Enforcement Administration had no objection to my weekly take-home supply of the drug and that FDA and NIDA had approved a weekly take-home supply. 

28. On October 7 and 8, 1976 I declined interview requests because I did not yet understand the exact nature of the program. I determined it would be wise to await an explanation from NIDA concerning the scope of Dr. Merritt’s program and the limitations which would be placed upon those involved in it. 

29. On October 7, 1976 the National Organization for the Reform of Marijuana Laws independently learned of the program and issued a press release discussing it. The description of the program in several respects was different from what had been explained to me. Therefore, I contacted Phyllis Lessin to request a clarification. Instead of clearing up the inconsistencies she only stressed that I not make any public statements concerning Dr. Merritt’s program. I again explained to Ms. Lessin that I would not comply with her request. 

30. On October 14, 1976 I granted a request for an interview with the Los Angeles Times. The article also contained information provided by persons at NIDA, FDA and DEA. 

31. Dr. Merritt requested that I undergo hospitalization for initial marijuana tests in November of 1976. He explained that the hospitalization was not necessary for my health care but would assist his research. I agreed to hospitalization as long as I would not be forced to pay the costs. Since no funds were available for this research program, I was never hospitalized. At a later time Dr. Merritt believed funding for his research would be made available. Therefore, I was processed for admission to the hospital. The funding did not materialize, however, and I was not actually hospitalized. Throughout the course of the research program I paid for weekly office visits ($20-35) which were necessitated only to monitor research. While I was being treated by Dr. Fine, office visits were required only on four to six week intervals. 

32. Beginning November 18, 1976 I accepted a number of speaking engagements and interview requests. These public appearances included testimony before 6 state legislatures and agencies and appearances before 3 schools and colleges. 

33. The information communicated in each public statement was essentially the same: marijuana is effective in treating glaucoma, it is a relatively safe drug, I am presently involved in a government licensed research program allowing me to smoke marijuana for my glaucoma, and without the use of marijuana I could be blind. The purpose of my public statements were threefold. First, to inform state legislatures of the therapeutic use of marijuana. Second, to create public pressure in order to ease the burdensome restrictions on marijuana’s therapeutic use and research. Third, to let other glaucoma victims know that they may wish to raise the possibility of using marijuana with their doctors prior to submitting to dangerous surgical procedures or resulting blindness. 

34. I accepted each public appearance with knowledge that NIDA had demanded that I make no public statements about the program. However, after due consideration I decided that my right to express myself, particularly when I believed my message to be so important, should not be subjugated to unreasonable administrative requests. 

35. Prior to my involvement in the research program, it had been explained to me by persons at NIDA that I would receive immunity for possession and use of marijuana supplied by the federal government. But, I began receiving marijuana without any statement of immunity on November 12, 1976. My written request for immunity was formally denied by DEA in a letter written March 4, 1977, two weeks after I spoke to the New Mexico legislature (which eventually passed therapeutic legislation). See Ex. 3. DEA stated that although immunity could be granted to “those engaged in research,” only doctors performing research work “engaged in it”. Therefore, research subjects were not immune. My request to the author of this letter, to the Attorney General, and to Peter Bourne of the White House that this policy be reconsidered, were unsuccessful. See Exs. 4-7. 

36. On May 9, 1977 I participated in a panel discussion with, among others, Dr. Robert Peterson of NIDA. During this panel discussion I advocated that the agencies were not only uncooperative in assisting therapeutic research on marijuana, but were a deterrent to the initiation of such research. Moreover, this deterrent effect was inhumane, since people were going blind whose sight could be saved by a sensitive response. On May 12, 1977 the Drug Abuse Research Advisory Committee (DARAC) met. This committee, as reflected in its minutes, questioned my public appearances and decided to limit my take-home supply of marijuana to a one day supply. See Exs. 8 at pp. 15-16, 9 at pp. 3-4. On May 13, 1977, upon instructions from DARAC, Dr. Merritt refused to give me any further marijuana. I contacted Dr. Tocus of FDA who stated he would inform Dr. Merritt that he could give me a one day supply. I responded that such an arrangement would make it impossible for me to travel away from the District of Columbia. He states that such was probably the motivation of some of the DARAC committee members. I learned later that Dr. Merritt informed Dr. Tocus that he would not dispense the drug daily as he was a doctor and not a pharmacist. Dr. Tocus allowed a weekly supply. On May 16, 1977 Dr. Tocus allowed resumption of a one week supply, but only pending the location of a pharmacy to dispense the drug on a daily basis. See Ex. 10.

37. On April 24, 1977 I wrote to Peter Bourne of the White House, emphasizing my therapeutic need for marijuana. In May, I again wrote to Peter Bourne, requesting that he assist me in resolving this supply problem. I informed him that the requirement that I visit a pharmacy each day would eliminate my freedom to travel. Dr. Bourne responded on June 6, 1977 that the agencies had power all along to limit my supply to a one day supply but had refrained from exercising that power in “compassion” for my case. However, the publicity had caused them to reconsider. See Ex. 11. I also requested assistance with the supply problem from Mr. Scigliaro of DARAC and Commissioner Kennedy of the FDA, to no avail. See Exs. 12-15. Although my week-long supply was never again cut off, two things were made clear: It could be cut off as soon as the pharmacy arrangements were concluded and those in power would ignore this situation in “compassion” for me as long as I toned down my public criticism of the agencies and my public discussion of marijuana’s therapeutic value. I knew the pharmacy had been identified and was operative. Therefore, it appeared that the only condition to the imposition of a daily supply requirement concerned my future public statements. 

38. The June 6 letter from Dr. Bourne which “explained” the government’s position vis-a-vis my supply and publicity, also affirmed the government’s denial of immunity. See Ex. 11. Since I was beginning to fear what I interpreted as government threats, I gave a copy of this letter to the National Organization for the Reform of Marijuana Laws requesting their advice. Without my permission they gave this letter to Jack Anderson who released it on Good Morning America (ABC morning news show), on June 15, 1977. On June 20, 1977, I was at a meeting of the Ohio Drug Studies Institute when I received a call from a friend, who explained that Dr. Merritt who informed me that unless I signed a “consent” form, marijuana could no longer be made available. I returned to Washington on June 21, 1977, and examined the consent form. To the best of my recollection, in addition to consenting to allowing the use of marijuana, to which I readily agreed, the form required my consent to treatment with a placebo without my knowledge. I refused to sign the form demanding to know why, ten months after the beginning of the research program, but only six days after an embarrassing letter by Dr. Bourne was made public, I was being required to sign a consent form. In particular, I objected to the placebo provision, since the absence of marijuana for an extended period might blind me. Dr. Tocus through Dr. Merritt, informed me that unless I signed the form, I would not receive another supply of marijuana. I signed the form but crossed through the placebo provision. In addition, I executed a Statement of Duress indicating that I was being coerced through threats concerning the loss of marijuana into the signing of the form. Dr. Tocus accepted the crossed-through consent form and the Statement of Duress thereby allowing continuation of my supply of marijuana upon the condition that I not publicly discuss the consent form. 

39. On August 11, 1977, I attended a Drug Abuse Research Advisory Committee meeting and requested reconsideration of the decision to limit my supply to once a day. My request was ignored. 

40. At the same meeting, I requested that marijuana be made available to me for treatment purposes instead of research. This request also was ignored. See Ex. 16 at p. 7. A similar request made on my behalf to Dr. Bourne on July 14, 1977 was unsuccessful. See Exs. 17, 18. 

41. On November 29, 1977,I learned from Dr. Merritt that he was concluding the program in Washington, D.C. because he had accepted an offer on the faculty of the University of North Carolina Medical School. Dr. Merritt was my personal physician for a total of 17 months. During 15 months he distributed marijuana to me and observed its effect on my glaucoma. My medical regimen over this period included Glaucon 2% and Phospholine Iodide .06% both twice daily and 6 to 10 marijuana cigarettes at .9 grams, 2% to 3% THC. For a few weeks Carbachol was substituted for the Phospholine Iodide to prevent the development of a tolerance to the Phospholine Iodide. During these 15 months, I personally observed that my eye pressures were under control and that my sight did not deteriorate. Dr. Merritt’s tests confirmed these personal observations. 

42. Subsequent to learning of Dr. Merritt’s planned departure, I personally requested Dr. Bourne’s assistance on December 1, 1977. I asked that he agree to talk with me so that a resolution of the problem concerning access to marijuana could be found. His only response to this oral request was that he would “consider it”. 

43. By letter of December 5, 1977, I requested that Dr. Bourne assist me in my efforts to retain my sight. See Ex. 19. He responded on December 19, 1977: “As for the cessation of your treatment by Dr. Merritt, that issue should be resolved between you and Dr. Merritt.” See Ex. 20. I understood his response to mean that he was unwilling to be of any assistance. 

44. On December 5, 1977, I also asked Phyllis Lessin at NIDA for assistance. She stated that NIDA was not willing to help find a solution. 

45. Dr. Merritt left the District of Columbia on January 20, 1978. His license to do marijuana research while he was associated with Howard University thus terminated. My final supply of government-issued marijuana expired on January 25, 1978. 

46. My first action following termination of this program was to make other arrangements for a limited supply of uncontrolled marijuana. Except for a two and a one half week test concerning Timolol, I have not been without marijuana since the day my government supply was terminated. Such marijuana, however, is not dose controlled and is much more difficult and dangerous to use for therapeutic purposes. I am aware of general news reports concerning recent poisoning of imported marijuana and thus fear that the use of street marijuana might result in side effects caused by chemical adulterants. Moreover, if forced to purchase marijuana on the street, the expense would be exorbitant.

47. Subsequent to the expiration of the supply of marijuana given to me by Dr. Merritt, and subsequent to my attempts at re-establishing legal access, I began to search for counsel to represent me in this matter. On or about February 20, 1978, my present counsel agreed to represent me. My attorneys informed me of their desire to seek an informal resolution of this matter prior to bringing it to the court’s attention. After a period of time during which all necessary facts were collected and reviewed, one of my attorneys, on MArch 3, 1978, called Phyllis Lessin of NIDA seeking assistance in effectuating an informal resolution. However, Ms. Lessin told him that NIDA was not willing to assist in the resolution of my problem. My attorney informed her that absent informal resolution, judicial action might be sought.

48. On March 15, 1978, I attended, along with counsel, a joint meeting of the Drug Abuse Research Advisory Committee and the Controlled Substance Advisory Committee, and made clear to these Committees my intent to seek other remedies if the agencies could or would not respond. With my approval, on March 20, 1978, my attorney wrote to Dr. DuPont, Commissioner Kennedy, The Honorable Peter Bensinger, Dr. Bourne and their legal advisors, informing them that we would be seeking  judicial action if we did not receive a response by March 31, 1978 indicating interest in the possibility of informally resolving the conflict created by my need to receive marijuana to treat my glaucoma. See Ex. 21. 

49. A response from Dr. DuPont, dated April 5, 1978, recognized that the only way to receive marijuana under present FDA statutes and regulations is to do so under an IND. See Ex. 22. From my previous experience I understand that this would require the near-impossible task of locating a researcher and again submitting myself to being a government research subject. The availability of marijuana under an IND, even if a practical reality, would not allow me to use marijuana for the purpose of treating my disease as I would once again be a research subject whose health care could be subject to the research motivated whims of the investigator or the various federal agencies involved. The response from Dr. DuPont was confirmed in a letter dated April 24, 1978 from Dr. Tocus on behalf of Commissioner Kennedy. See Ex. 25. 

50. Dr. DuPont’s letter also referred me to Dr. Gaasterland of the National Eye Institute who suggested that I consider the drug Timolol as an alternative to marijuana. By letter dated April 10, 1978 I requested, through counsel, that the government make this drug available to me. See Ex. 23. Although all research necessary for the filing of a New Drug Application has been completed, until that application is approved the drug is not available for commercial distribution. The letter on my behalf to the government requested that they inform me or my counsel by April 12, 1978 if there was a “substantial possibility” that Timolol could be made available to me. 

51. On April 11, 1978, my attorney was informed by FDA counsel that the availability of TImolol was within the discretion of the manufacturer of the drug, Merck, Sharpe & Dohme. Merck informed my counsel that Dr. Pollack at Johns Hopkins University in Baltimore was involved in a “maintenance” research programDr. Pollack, however, refused to consider admitting me to this program. Merck suggested a number of other doctors who were involved in Timolol maintenance research programs, and after various contacts, Dr. Bruce Shields at Duke University in North Carolina expressed a “moral” responsibility to determine whether Timolol would be effective on any patient whose only alternative to blindness was surgery. After an examination on April 18, 1978, Dr. Shields admitted me to his Timolol maintenance program. 

52. Dr. Shields explained that he was prescribing the highest allowable dosage of Timolol to be used twice a day. Timolol had a substantial initial impact and lowered my IOP to well within the safe range. However, this initial effectiveness soon began, and has continued, to deteriorate to the extent that on Friday, May 5, 1978, Dr. Shields determined that the drug would not be an effective treatment. See Exs. 26, 27. In order to determine whether Timolol would prove to be an effective alternative therapy, I did not use marijuana to treat my disease during this test period from April 18 to May 5. 

53. During an examination on April 25, 1978, Dr. Shields drew a sketch of what his direct examination of my optic disc revealed. He explained that healthy optic nerves are pink, while dead nerves show up as white. In the sketch below dead nerves are indicated by lines drawn through the portion of the disc which is dead; healthy nerves are indicated by the unlined area. The optic disc is a circle; live nerves toward the center of the circle are necessary for the central vision. The loss of central vision results in an inability to read or define small objects. The sketch was drawn to display graphically the delicate balance upon which my sight rests. The sketch below is my reproduction of Dr. Shields’ sketch. 

54. By the end of November, 1977, the government agencies involved in this action were aware thatDr. Merritt’s research program would be terminated. In addition, I made requests, as did my counsel, for assistance in saving my sight since my access to the only drug which had proven effective in preventing blindness had been terminated. Yet, I was not informed of Timolol’s possible availability until my lawyers formally informed the defendants of my intention to file a civil action demanding the relief necessary to save my sight. 

55. When Timolol was suggested by the defendants I was initially quite apprehensive. Determining the effectiveness of Timolol required terminating a medical regimen, the use of marijuana, which for four years had effectively halted the otherwise certain onset of blindness. Additionally, it was necessary that I undergo the substantial inconvenience of traveling to Durham, North Carolina, once a week. It was also necessary that I turnover my health care to a doctor with whom I was unfamiliar. Finally, I was forced to undergo “tests” with a drug not yet commercially available, and for which the FDA was unable to provide me with test results. All of these considerations were accentuated by my knowledge that the margin of error in the treatment of my eyes is slim – only a slight amount of additional nerve damage will result in my total blindness. However, the possibility that an “available” drug might prove effective in controlling my glaucoma led to my decision to determine Timolol’s effectiveness. 

56. On Wednesday, May 3, 1978, by hand delivered letter, my counsel informed Dr. Tocus and Mr. Bill Hill, Assistant General Counsel to FDA, that Timolol was having a decreasing effect and that absent a reversal of this trend, which we had no reason to expect would occur, my counsel would file the instant action. The letter also requested reconsideration of a prior refusal to make marijuana available for my therapeutic use. See Ex. 28. 

57. Since neither Timolol nor any conventional medication has proved effective in controlling my glaucoma, I am now faced with only three options: 

1. Continuing use of marijuana which for four years has proven effective in controlling my glaucoma and preventing the onset of blindness; 

2. Submitting to a substantially risky surgical procedure recommended only when all medications at their maximum tolerable dosage levels are unable to control glaucoma; 

3. Continuing a treatment program with commercially available, but now ineffective, drugs with the inevitable result: blindness. 

Obviously I have no desire to live the rest of my life in blindness, and I am unwilling to risk a surgical procedure which itself presents a substantial possibility of failure, and which could rob me of my remaining sight, when such risks are totally unnecessary. For four years marijuana has prevented me from going blind. My choice of medication, and that of my doctor, if we were free to choose unrestrained, is both obvious and sensible – the continued therapeutic use of marijuana. 

Exhibits 1-10 for Robert Randall Affidavit

Exhibit 1 - Letter from Robert J. Rosthal to John W. Karr, Esq. (6/11/1976)

United States Department of Justice

Drug Enforcement Administration

Washington, D.C. 20537

June 11, 1976

John W. Karr, Esq. 

Karr & Graves

625 Washington Building

Fifteenth Street and New York

Avenue, N.W.

Washington, D.C. 20005

Re: Robert C. Randall

Dear Mr. Karr: 

In telephone conversations with you and your associate, Paul R. Smollar, I stated that it was the opinion of DEA’s Office of Chief Counsel that 21 C.F.R. 1307.03 did not offer grounds for the exemption application of Robert C. Randall. We believe that our suggestion that you proceed in this matter through the Food and Drug Administration offers the best opportunity for resolution of the matter. Once again I assure you that if I can help in that regard you have only to call on me. 

Sincerely,

Robert J. Rosthal

Deputy Chief Counsel

Exhibit Number Two

May 20, 1976

The Administrator 

Drug Enforcement Administration

Department of Justice 

Washington, D.C. 20537

Re: Exemption Application of Robert C. Randall

Sir:

On the authority of 21 C.F.R. §1307.03 an exception is hereby requested for our client Robert C. Randall that will permit him to use marijuana for the prevention of blindness, in whatever dosage may be prescribed by his physician.

Mr. Randall suffers from glaucoma, a condition first diagnosed in the fall of 1972. Now 28, Mr. Randall has already lost all sight in his right eye and the sight through his left is seriously imperiled. Following extensive medical research (on Mr. Randall and other subjects) it has been established by Dr. Robert S. Hepler, a well-known researcher in the field, that marijuana taken in combination with conventional medications provides Mr. Randall “with control of intraocular pressure unobtainable utilizing other medications alone.” (Hepler affidavit) This conclusion is reinforced by further tests and studies conducted at the Johns Hopkins Hospital and by Mr. Randall’s attending physician in the Washington area, Dr. Ben S. Fine (affidavit attached).

The net of the medical evidence is that without marijuana Mr. Randall is sure to go blind; with it, there is some chance that his sight can be saved. Because this is a matter of the utmost urgency we request that you give this request expedited treatment. If you require additional information, please call at any time. 

I hope that your favorable disposition of this request will be forthcoming at the earliest practicable date. 

Sincerely,

John W. Karr

Exhibit Number 3

United States Department of Justice

Drug Enforcement Administration

Washington, D.C. 20537

March 4, 1977

Mr. Robert Randall

700-A 8th Street, S.E. 

Washington, D.C. 20003

Dear Mr. Randall:

This letter is being written in reply to the correspondence which you recently directed to Mr. Peter B. Bensinger, Administrator of the Drug Enforcement Administration, concerning your participation in a research project involving the use of marijuana in the treatment of glaucoma. 

With reference to the first matter which you have presented, we have explored the possibility of providing an exemption from prosecution for the subjects of such a research project and have determined, for the following reasons, that the statute does not give us the authority to grant such an exemption.

Section 872 ( c ) of Title 21 of the United States Code (copy enclosed) permits the Attorney General to authorize “persons who are engaged in research” to withhold the names and identifying characteristics of “persons who are the subjects of such research.” It is obvious from the wording of this section that Congress considered the persons engaged in research to be a separate and distinct group from those who are the subject of the research. 

Section 872 ( d ) of Title 21 of the United States Code authorizes the Attorney General to exempt “persons engaged in research” from prosecution for the possession, distribution and dispensing of controlled substances to the extent authorized by the Attorney General. This section does not speak of “persons who are the subjects of research.”

Since Congress recognized the subjects of research as a separate and distinct group from those engaged in research, we must conclude that it was the intent of Congress to exclude such individuals from the protection offered from this section. Therefore, we have no authority to grant exemption from prosecution for the subjects of a research project. 

With regard to your stated concern about the possible interruption of your supply of this research drug, I must say that I appreciate your position. If Dr. Merritt, as the principal investigator of this research project, has experienced problems in the system of delivery of medication which he has chosen to employ, he should contact Dr. Edward Tocus at the Food and Drug Administration in order to submit an acceptable amendment to the scientific protocol which he provided to that agency prior to the initiation of this research project. 

I trust that this information will be of some assistance to you in this matter. 

Sincerely,

Kenneth A. Durrin, Acting Director

Office of Compliance and Regulatory Affairs

Exhibit Number 4

April 24, 1977

709-A 8th Street S.E.

Washington, D.C. 20003

Mr. Kenneth A. Durrin

Acting Director

Office of Compliance and Regulatory Affairs

Drug Enforcement Administration

Washington, D.C. 20537

Dear. Mr. Durrin:

Enclosed is what seems to be the file copy of a letter you wrote me on March 4, 1977. I must admit extreme disappointment in DEA’s position on both the immunity requirements of those individuals provided with marijuana on an outpatient basis for therapeutic use, and the construction of a rational effective delivery system for making the drug available in situations where affirmative therapeutic benefits are demonstrable.

I would request that DEA re-examine its positions on both of these matters as the position now taken by the agency appear, on their face, to be absurd and incompatible with the cogent and aggressive research necessary in this area. Questions of the public health pre-dominate in this area and DEA’s actions would appear to do little to advance the interest of public health. 

Hopeful that DEA acts to end all confusion in this vitally important area, I remain,

Sincerely yours,

Robert Randall

Exhibit Number 5

709-A 8th Street S.E.

Washington, D.C. 20003

May 18, 1977

The Honorable Griffin Bell

Attorney General of the United States

Department of Justice

Washington, D.C. 

Dear Mr. Bell: 

On September 30, 1976, DEA, in a joint action with FDA and NIDA, licensed a marijuana/glaucoma investigation at Howard University here in Washington, D.C.. That program was the direct result of a petition I filed with the DEA on May 20, 1976.

In my petition I requested immediate access to federal stocks of marijuana for the treatment of glaucoma. I further requested immunity or the present Schedule 1 restrictions which surround the possession or use of marijuana. Additionally I requested that, as much as possible, my medical care be left in the hands of a medical doctor trained in ophthalmology. 

I accepted the research solution provided by the various research and enforcement bureaucracies because my needs were medical and my personal health considerations were dominant. I was assured, however, that DEA would provide immunity status to myself and others involved in out-patient use of cannabis. 

On November 12, 1976, Howard University Hospital began to provide me with, on average, a weekly supply of marijuana. At this time DEA had not made a certificate of immunity available to me. My physician at Howard, Dr. John Merritt, indicated that those individuals responsible within the DEA were on vacation. 

Over the next months I waited formalization of my immunity status by the DEA. Transitional problems were mentioned and I did not wish to put demands on the DEA during the shift in administrations. I now believe that DEA intended to delay provision of immunity until a shift in administration clouded the question and made resolution of the problem more difficult. 

Finally, I wrote Mr. Peter Bensinger, Director of DEA, and requested certification of my immunity. I also made requests for information on what was to be a joint DEA-NIDA plan for a delivery system for those placed on out-patient use of marijuana. The reply I received from the DEA is enclosed. 

It would appear that the DEA has suffered a lapse of memory. O am now told that providing immunity cannot be done. To support this claim DEA stretches Congressional intention to the very limits of reasonable comprehension. DEA’s position on Schedule I immunity, as defined in the letter sent to me, would effectively render ALL Schedule I research subjects criminal. Research subjects have enjoyed immunity status during the time they participated in research programs. After leaving these programs Congress has provided for confidentiality. DEA seeks to re-write the will of Congress by separating ‘research subjects’ from those ‘engaged in research’. This appears to be little more than an attempt on the part of DEA to cripple therapeutic, out-patient testing of marijuana. 

Over the past six months DEA has not arrested me, though I have been constantly in possession of a Schedule I substance for which, according to the DEA, I have no immunity status. The DEA has helped to make this drug available. 

Having read the Controlled Substance Act (1970) it is clear to me that you, as Attorney General, have power to provide immunity status. I request that you review the confused and convoluted position now being assumed by DEA and overrule the agency’s defective understanding of Congressional intent. 

In the past six months my use of marijuana has led to a stabilization of my eye condition and stopped the progression of blindness. I am very hopeful that this benefit, which I have already been forced to prove in court, will not again be questioned by federal agencies, especially agencies engaged in law enforcement, not medical research. I would further hope that you would not prohibit me from gaining immunity from marijuana’s Schedule I restrictions. I am certain that my biological interests are superior to, and more pressing than, any claim which DEA might make in denying me such immunity. To prevent another court battle against DEA’s inept treatment of marijuana related immunities for therapeutic use and investigation, I pray you will provide this matter with thought and concern. 

Until I hear from you I remain uncertain of my legal status beyond Washington, D.C.. In Washington, at least, I feel protected byJudge James Washington’s Common Law decision of ‘necessity’. 

Sincerely,

Robert Randall

Exhibit Number 6

709-A 8th Street S.E. 

Washington, D.C. 20003

May 20, 1977

Doctor Peter Bourne

Office of Drug Abuse Policy

The White house

Washington, D.C.

Dear Dr. Bourne:

It would appear that NIDA, FDA, and DEA are beginning to approach the therapeutic investigation of marijuana with increasing fragmentation and disorder. It would also appear that these agencies are engaged in a coordinated attempt to irrationally, and for purposes of policy maintenance, corrupt or erode basic elements required both in my own medical care and in therapeutic research in general.

DARAC (Drug Abuse Research Advisory Committee) of FDA voted on May 12th to restrict my access to marijuana to a daily supply. While I realize members of DARAC are doubtless experienced in abuse programs directed at addict treatment via methadone maintenance and other techniques, I sincerely doubt DARC possesses either the experience or expertise to involve itself in discussions of glaucoma therapy employing marijuana. 

The intent of DARAC’s decision is to ‘control’ marijuana access for ‘research’ purposes. It also has the effect of medically entrapping me in Washington, D.C., limiting my freedom of travel, and endangering my freedom of speech. DARAC and FDA seem to have made a mistake in assuming that a research subject has lost his status as a citizen. I would deeply appreciate any attempt on your part to render the DARAC recommendation inactive. I would also appreciate details on appeal procedures within FDA, HEW, and the Carter Administration via the Office of Drug Abuse Policy. 

Additionally, DEA has forgotten its obligation to provide immunity status. I have been informed that DEA will not offer immunity to ‘research subjects’ but only to those ‘engaged in research’. This rather strained attempt to eliminate the possibility of conducting out-patient tests of marijuana’s therapeutic effectiveness, say in glaucoma management, has been appealed by me to Attorney General Bell. I question the wisdom of DEA’s understanding of Congressional intent. Taken to its fullest the DEA rendering of the Controlled Substances Act would immediately criminalize ALL individuals who act as research subjects in Schedule I investigations. In short, DEA’s posture is absurd and without logical defense. 

I have no question that both the DARAC and DEA attempts to alter the structure of therapeutic marijuana research reflect bureaucratic displeasure with my conduct. My conduct, inclusive of free speech and travel, is, I think, defensible in a court of law. DEA’s attempt to refuse immunity directly confronts my need for the drug to maintain a central biological functionL sight. My biological interest in a sane, balanced program is extreme. Corruption of that program for ‘research purposes’, or for ‘security considerations’ cannot be tolerated if I expect to secure myself from further visual damage. They cannot be tolerated if we are going to aggressively pursue marijuana’s therapeutic potential. 

Since DARAC and DEA insist on disrupting, constricting, and altering the context of my own treatment, and by extension those who will follow, and because drug abuse considerations do not properly translate into the therapeutic area, I hope you will find some way to bring reason to the structure. As incoming Director of the Office of Drug Abuse Policy I would hope you have influence over DARAC and DEA, and can bring perspective and common sense to the chaos which apparently dominates current policy. 

Until I hear from you, I remain, 

Sincerely yours,

Robert Randall

RCR:aol

P.S. The DARAC recommendation was implemented as FDA policy immediately. It was then verbally rescinded so that a weekend supply could be made available to me, but re-imposed when that supply was provided through Dr. John Merritt at Howard University. On MoOnday, May 16th, FDA again rescinded the DARAC recommendations and ordered Dr. Merritt to provide me with my usual supply (one week) until the mechanics of establishing the DARAC policy can be worked through. This should illustrate the inconsistency and ineptness of the DARAC/FDA position. 

Exhibit Number 7

United States Department of Justice 

Drug Enforcement Administration

Washington, D.C. 20537

June 9, 1977

Mr. Robert Randall

709-A 8th Street, S.E.

Washington, D.C. 20003

Dear Mr. Randall:

Your letter of May 18, 1977, addressed to the Attorney General has been referred to this office for reply. The authority to grant exemption from prosecution to persons engaged in research has been delegated by the Attorney General to the Administrator of the Drug Enforcement Administration in Section 0.100 of Title 28 of the Code of Federal Regulations. 

The letter you received from Mr. Kenneth A. Durrin, Acting Director, of the Office of Compliance and Regulatory Affairs, dated March 4, 1977, contains a correct statement of the law. 

Section 872 ( d ) of Title 21 of the United States Code does not give DEA the authority to grant exemption to persons who are the subjects of research. Contrary to the statements in your letter, we are aware of no case where exemption from prosecution has been granted to the subjects of a research project.

Sincerely,

Robert J. Rosthal

Acting Chief Counsel

(Illegible handwritten note included to Robert at the end of letter)

Exhibit 8

Minutes

Drug Abuse Advisory Committee

FY 77-3 May 12, 1977

Parklawn Building, Conference room “M”

5600 Fishers Lane

Rockville, Maryland 20857

Attendees

Committee Members

Robert B. Forney, Ph.D., Chairman

Sidney Cohen, M.D. 

Loretta Finnegan, M.D.

Frank R. Freemon, M.D.

James W. Gibb, Ph.D.

Janice L. Stickney, Ph.D.

Coy W. Waller, Ph.D.

James H. Woods, Ph.D.

NIDA

Jack D. Blaine, M.D

M.C. Braude, Ph.D. 

Jackie Bryant

Dorynne Czechowicz, M.D.

Phyllis Lessin

R. Phillipson, M.D. 

Charles Sharp, Ph.D.

Richard Stillman, M.D.

Stephan Szara, D.Sc., M.D.

Robert Willette, Ph.D.

FDA Staff

Eileen Barker, M.D.

W. Danny Brown, Ph.D.

Glenna Fitzgerald, Ph.D.

Ferdinand Hui, Ph.D. (Lecturer)

Ronald Kartzinel, Ph.D., M.D. (Acting Director, DNDP)

D.J. McGrath, M.D.

Doris C. Morrow

J.A. Scigliano, Ph.D. (Executive Secretary)

E.C. Tocus, Ph.D. (Chief, Drug Abuse Staff)

Guests

Elmer J. Ballintine, M.D., NEI

Sharon Bell, Reporter, Bowers Reporting Company

Eric D. Caine, M.D., NIMH

Michael H. Ebert, M.D., NIMH

Howard A. Gross, M.D., NIMH

Ralph Helmsen, M.D. NEI

Jaime Manuel, Philippines, Intl. Visit. Prog., FDA

Mary Jane McErtel, SKF Labs. Philadelphia, PA>

Arthur A. Wykes, Ph.D., NLM

Lecturers

S.E. Sallan, M.D., Children's Cancer Hospital, Boston, Massachusetts

Richard M. Gottlieb, M.D., Montefiore Hospital. Bronx, New York

John C. Merritt, M.D., Howard University, Washington, D.C.

The third meeting in FY 77 of the Drug Abuse Research Advisory Committee (DARAC) was called to order at 8:30 a.m. by the Chairman, Dr. Robert B. Forney. The OPEN HEARING was announced and comments from the public were invited. There was no response, and therefore after a reasonable period of time the Open Hearing was declared closed. The balance of the time allocated was used to take care of some housekeeping items. 

Minutes

The following corrections to the February 10/11, 1977 minutes were recommended: 

Page 12, *redacted*, paragraph 2, line - add symptoms so that the corrected copy reads: The results of this study suggest withdrawal symptoms on high doses but not those symptoms associated with heroin withdrawal. 

Page 12, *redacted*, paragraph 1, lines 4 & 5 - strike “effect on the heart” and replace with: … but it is positive as it regards “highs” and the chronotropic effect of marihuana. The tachycardia does show tolerance effects. 

Page 12, last paragraph (the *redacted* material) - The “flying” studies brought out that THC has an addictive effect on alcohol but not dramatically so and there appears to be no synergism. This was observed in the “flying” not in the personal interactions study. 

Page 12, *redacted*, paragraph 1 strike intermediate. The sentence then reads: …marihuana has significant effects on social interactions and interpersonal effects. 

Page 13, a typo on line 10 - should be furnish and not frunish.

Page 2 - promptly appears twice in the first sentence, eliminate one of them. 

Page 5 - change were to was in the last paragraph so that it reads: REM sleep was not increased ….etc. 

With these corrections the minutes were approved, and the Chairman and Executive Secretary completed the signature page of minutes. 

Action Report

The report having been furnished to the committee membership prior to the meeting, the Chairman suspended the reading of the report and asked for comments. As there were none, he proceeded to the item on the Agenda. 

Review of INDs, Amendments and Progress Reports

The meeting being completely OPEN the reviews were presented and discussed; however, the protocols were identified only by title as represented in these minutes. 

The Progress Report “Marihuna Effects onLungs and EEG” and the amendment “Beta-Blocking effects of propranolol on the effects of marihuana smoking” were the first projects under consideration for review. The initial evaluation of the submission was accomplished through an August mail review by the committee. 

The present consideration reflects the review by the in-house Medical Officer of the amendment, the Principle Investigator’s reply to a deficiency letter, and the progress report, submitted in response to an annual request for a progress report. 

The medical evaluation of the amendment reflects that: practolol is not approved under an NDA or medical use in the United States; the FDA would not approve the use of two investigational new drugs simultaneously in human subjects for investigation; and the FSA has never approved an aerosol THC formulation or its administration in humans. It was recommended to advise the sponsor that: the THC/practolol proposed study should not be initiated, the FDA had not approved use of a THC aerosol formulation; and the sponsor should furnish the formulation of the THC aerosol solution in the THC/isoproterenol study.

With regard to the progress report, the medical officer points out that the results of exposing seven (7) male asthmatics to aerosol THC vs. dilation isoproterenol indicate that THC produced a long-lasting broncho-dilation without untoward tachycardia or a “high”, and that 120mg. Propranolol prevents most of the typical effects of one marijuana cigarette, but that a significant number of subjects developed nausea after receiving alcohol in orange juice followed in one hour by a THC cigarette. He recommended NAI. The committee concurred with the recommendations of the medical officer both for the amendment and the progress report. 

The next item for review, a progress report, is represented by copies of two (2) reprints from the scientific literature. The principle investigators submitted “Psychological Effects of Oral Delta-9-THC in Advanced Cancer Patients”, Comprehensive Psychiatry, 17 (5): 641-646 (Sept/Oct 1971), and “The Analgesic Properties of Delta-9-tetrahydrocannabinol (THC) and Codeine”, Clin. Pharmacol. And Therapeutics, 18 (1): 84-89 (July 1975). These were reviewed by members of DARAC.

The two (2) reports are of single experiments into the analgesic effects of THC in man. Of the experiments which show that THC is quite active in standard analgesic tests in rodents, there is considerable conjecture as to whether THC accomplishes its analgesic effect in doses that render the animal less than competent to perform other tasks. 

The study used 34 women and 12 men. All subjects were advanced cancer patients. The average age was 51 and the subjects reported continuous pain of moderate intensity. There were a variety of types of cancer among the patients and they were taking other analgesics but these were withheld for 41/2 hours prior to beginning the THC assessment. Oral doses of 10 mg. And 20 mg. of THC were compared to oral doses of 60 mg. And 120 mg. of codeine. Drug treatments were given to each patient on successive days in random sequence. The patients reported on: pain relief, side effects, and subjective effects. The subjective effects also were evaluated by a questionnaire. 

Other determinations on an hourly basis were: blood pressure, heart rate and respiratory rate. 

Neither the 60 mg. dose THC produced significantly higher numbers or reports of sleepiness, dizziness, ataxia and blurred vision. 

Questionnaires filled out by the subjects during time of drug action indicated a decrease in sociability. Five subjects, one after 10 mg. THC and our after 20 mg. THC had adverse effects. Two were discontinued because of these problems. 

The most common adverse reaction was a profound anxiety attack which included palpitations, shortness of breath, and chest or abdominal pain. Two reactions persisted beyond the normal period of drug action. Tachycardia was not observed. 

On the basis of the data presented in the two reports there appears to be little therapeutic value of THC as an analgesic. It was recommended that the report was acceptable but to look into the matter of the female subjects conforming to the FDA guidelines for marihuana in human research subjects. 

The amendment to the study “Comparative Evaluation of THC and Compazine for effect on nausea, vomiting, anorexia and dysphoria attributed to cancer chemotherapy” was reviewed in-house by the medical officer. The amendment proposed that half of the subjects will be assigned randomly to the schedule in the original report, the other half will receive the following dosage regimen: 

Capsules of THC will be given at 22 hr., 19 hr., and 16 hr. Prior to cancer chemotherapy in addition to the dosage administration similar to that received in the regular treatment schedule, e.g., 

Patient receives 10 mg. @ 3, 6, and 9 p.m. on Monday and a 15 mg. dose @ 7 a.m. on Tuesday, with another dose simultaneously with ca-chemotherapy @ 10 a.m. and the final THC dose at 1 p.m. on Tuesday. 

Intraocular pressure measurements will be taken on the patients prior to THC administration and again one hour before the cancer chemotherapy.

Medical evaluation presented no objection to the proposed procedures except to question the clinical value of the IOP readings. It was recommended that the study may proceed. 

The committee concurred with the recommendations. 

The study “To assess the clinical effects of THC on spasticity in patients with CNS Disease” was reviewed in-house by the medical officer and the pharmacologist. In their evaluation of the submission, it was found to lack preclinical data which would provide a basis for rational use of THC in the treatment of muscular hypertonicity. The only supporting evidence presented is anecdotal and based upon second-hand reports of casual marihuana use by the patients of the sponsor. 

In their recommendations, the reviewers stated that the animal data was insufficient to warrant studies in humans. In the disapproval letter, the principle investigator was requested to submit the results of studies in a suitable animal model for muscular hypertonicity or literature references to studies which would support the testing of THC in treatment of muscular hypertonicity. 

The committee agreed with the action taken by the staff. 

Next a new submission, a “double-blind crossover study to evaluate THC for effect on primary anorexia nervosa in young women was at first discussed by the assigned DARAC reviewers and then it was discussed by the entire committee. 

The estimated duration of the study is three years. The 20 patients to be used are females between the ages of 18 and 40. The basic justification or using females is extended by the sponsor, as follows: 

The mutagenic and teratogenic potential of cannabis as reviewed by the Committee on Drugs, American Academy of Pediatrics, is reported to have very little of such effects in humans. Evidence from animal studies was suggestive enough to warrant special precautions to avoid giving THC to women who might become pregnant in this study. 

The criteria for selecting research subjects, therefore, include:

1. Amenorrhea. Amenorrhea required for participation. If menses occur before or during the study, active medication will be discontinued immediately. 

There are no reported cases of pregnancy in patients with anorexia nervosa; the basic nature of this complex psychosomatic illness makes concomitant pregnancy extremely unlikely, since the delicate physiologic endocrine balance involved in ovulation is severely disturbed. 

Weight gain will be constantly monitored, and medication discontinued in any patient whose weight has returned from the decrement of 25% or original body weight or 15% of ideal weight. 

Previous investigation has shown that anorexia nervosa patients, whose weight corresponds to the research criteria of this study, have plasma estradiol levels of less than 10 picograms per ml. and that they are not ovulating. Plasma estradiol will be determined weekly, and any patient with levels greater than 50 picograms, which is indicative of follicular maturation, will be discontinued from the protocol. 

During the course of the medication trial the patient is restricted to the locked research unit and is closely observed by the staff. If the patient leaves the unit for special testing procedures, she is accompanied by staff at all times. 

Spontaneous ovulation has not been observed until body weights increased as previously described, at which time they would be excluded from the protocol. Since patients with anorexia nervosa are not usually sexually active, and no pregnancies have been reported in sexually active patients who meet the research criteria, these precautions should be adequate to exclude the possibility of pregnancy.

1. Age of onset prior to 30 years.

1. The anorexia accompanied by weight loss of at least 25% of original body weight or 15% of ideal weight from metropolitan Life Tables. 

1. A distorted, implacable attitude towards eating food or weight that overrides hunger, admonitions, reassurances and threats. 

1. No medical illness that could account for the anorexia and weight loss. 

1. No other primary psychiatric disorder, with particular reference to primary affective disorders with schizophrenia. 

1. At least two (2) of the following manifestations: lanugo, bradycardia, periods of overactivity, episodes of bulimia and vomiting.

This is a double-blind controlled trial to investigate efficacy of THC in enhancing weight gain in young women with primary anorexia nervosa. Patients will be randomly assigned to THC or diazepam (an active placebo) in a two-week crossover design with a total of 20-test-days used for the full study. All trials would be administered for five consecutive days, Monday through Friday. Medication will be given 90 minutes before meals with THC in increasing daily doses of 7.5 mg. to 30 mg. and diazepam in increasing daily doses of 3 mg. to 15 mg. Blood levels of THC and 11-Nor-9-Carboxy- 9THC be quantitatively assayed. Of the medication containing diazepam, desmethyldiazepam also will be monitored. 

Comments and Critique 

1. There is justification for this study: anorexia has a reported mortality rate of 15-21%; its incidence is increasing; there is little agreement on a treatment modality; and the anecdotal reports of marihuana stimulating appetite. 

2. The patients will receive medical, laboratory and psychiatric evaluations as well as from the approach of psychology, and occupational, recreational and art therapy. 

3. Extensive rating scales will be used, both of the self-administered and the blind-rater types. 

4. The investigators appear well aware of the hazards and precautions which must be considered with this study. 

5. The consent form is well elaborated. 

6. The Research Review Committee of the Institution has approved the study. 

Recommendation

Approval by unanimous acclaim. The proposal is well-organized, carefully designed and should provide scientifically valid, and clinically important information. The investigators are well qualified in both psychopharmacology and the management of anorexia nervosa. The potential risks have been extensively considered and the risk of pregnancy is nil in the proposed population. The potential benefit of THC may have been understated since the feeding disorder is the primary problem in these patients, and any modality which has the potential of correcting this problem would be a primary benefit to these patients. 

It is suggested that the period of amenorrhea be extended to six (6) months in part to insure that a uniform population is involved. 

Management plans, after the one-month study, for the successful patients is discussed in the informed consent document, i.e., a new protocol will be submitted (amend IND). 

A phase II study “to determine the effectiveness of THC as an antiemetic for the control of nausea and vomiting following antineoplastic chemotherapy” was presented by the reviewers and further discussed by the whole committee. This study comes from a cancer treatment center and the investigators have outstanding credentials in the field of cancer but very little experience with psychopharmacology. 

The study calls for 64 patients; all types of cancer will be considered as a qualifying factor for selection, except; subjects with brain metastases receiving brain or spinal radiation; currently using marihuana or other controlled substance; having angina pectoris or a history of allergy to marihuana/THC. Therefore a conglomerate of people of both sexes, of all ages, all with different kinds of chemotherapy and a variety of cancers. 

All patients must have received chemotherapy in the past, were nauseated following chemotherapy and did not improve from standard antiemetics. The dosage is 15 mg/M2 of body surface q 6 hr. for 4 doses which will be increased to 20 mg. if there is no response. Three courses will be considered an adequate trial. Data on nausea and vomiting will be gathered from patient interview, from nurse observation and from other health care team reports. 

The patients will be informed of side effects and toxicity. Upon the manifestation of toxicity the medication will be immediately discontinued. 

Nausea and vomiting will be graded on a scale of 1 to 6; from 1 = no nausea or vomiting to 6 = nausea with severe vomiting greater than 10 times in 24 hours. 

Somnolence will be graded on a scale of 1 to 4 where 1 = none and 4 = severe, bedridden with somnolence for 12 hours or more. 

Response will be graded: Complete = no nausea or vomiting; Partial = 2-4; No Response = 5-6.

Discussion and Critique 

In this study it is not absolutely clear how the nausea and vomiting observations from three possible reporters will be evaluated, i.e., the test subject, the nurse and other health care team member; the same lack of clarity applies to the “high”, side effects and somnolence. There is an inherent weakness in the protocol, when considering the objective of the study, due to the lack of a control drug. The investigators justify the absence of a control in that all the subjects have failed on the standard antiemetics. 

Recommendations

Approval with communication of deficiencies, and that the study may start when these have been corrected, i.e., 

1. Define patient group more closely (criteria for patient selection);

2. Define more clearly what constitutes one course cancer chemotherapy, type of chemotherapy and maximum duration of a course of treatment.

When communicating with the investigator(s) state that “we do not require but suggest the inclusion of an active placebo group, with the placebo administered concurrently in order to better define THC response.”

Preclinical Staff Actions (includes clinical and preclinical drug shipments).

There were 67 shipments to preclinical studies and 12 shipments to clinical studies. 

Discussion Topics

1. Conflict of Interest of Special Government Employees - John A. Scigliano, Ph.D. 

The Executive Secretary reviewed the material presented in the memo of the Associate Commissioner for Administration regarding this topic. The key points ventured around (1) documentation in the verbatim transcripts and the summary minutes of those instances in which a committee member withdrew from participation and (2) whether the member actually absented himself/herself from the room. 

The memo differentiates between absence from closed and open meetings. Policy would not mandate absence from OPEN meetings. During the discussion the committee generally felt that although withdrawing from participation, when discussing protocol of the colleague of a member or of an investigator from his institution, may satisfy the administrative policy, they would prefer to voluntarily absent themselves from the room as they always have in the past. 

The committee did, however, unanimously endorse the need to enter non-participation, and/or absence from room in the transcript and the minutes for documentation.

1. Open Agency Regulations - John A. Scigliano, Ph.D.

The Executive Secretary reviewed the material presented in the memo from the Acting Commissioner of Food and Drugs regarding this topic. The key points made were that the FDA, in its efforts to inform the public how decisions are reached and how the public may participate in the process, has taken three important actions. 

1. The Administrative Practices and Procedures Regulation; 

2. The Freedom of Information Regulations; and

3. The Conduct of Advisory Committee Meetings in Public.

These regulations support the premise that continued public confidence in the FDA, and continued credibility with the public, depend on how successful we all are in maintaining an agency that is responsive to the needs of the public. 

      C. Developing an FDA Position regarding the Decriminalization of Cannabis - 

Edward C. Tocus, Ph.D.

The Chief , Drug Abuse Staff, reviewed the FDA regulations with regard to what position would not be in conflict with the regulations. He stated, “The FDA is bound by the FD&C Regulation; it remains neutral to the discussion of “decriminalization”; the drug is made available as the “Regs” permit and as the FDA, DEA and NIDA presently are doing; availability of supplies is open to all applicants who meet the requirements of the “Regs”; and finally, to remove it (cannabis) or change (it) from schedules requires legislative action.

    D. A Congressional Inquiry regarding Supplies of Schedule I Substance - 

John A. Scigliano, Ph.D.

The Executive Secretary brought to the attention of the committee one specific example of the use of Congressional intercession to “bypass” established practices for reordering of supplies of Schedule I substances. The case in point was one in which the government had made an exception in favor of the investigator several times, yet the investigator continued to be dissatisfied and resorted to contacting his Congressman. A number of problems like this occur occasionally. 

This particular investigator was pursuing “blanket order” drug shipments without furnishing the basic requirements for reorders, i.e.,

1. An accounting of the previous shipment(s);

2. Presentation of a brief progress report reflecting drug used under (1); and 

3. Justify the quantities requested in the new order.

The committee encouraged the continued need for satisfying the basic requirements for reorders.

Lectures

S.E. Sallan, M.D. - “THC vs. nausea and vomiting associated with cancer chemotherapy” a long term study. 

Dr. Sallan reviewed the rationale for the studies, the previous data very briefly, and some insight into where they are at the present time and where they might go in the future. 

He reported that to those uninitiated in the area of cancer chemotherapy, the most important observation is that nausea and vomiting of CNS origin is one of the major morbidities of the treatment. Subjects who have received or are receiving cancer chemotherapy experience a nausea and vomiting which is not controlled by conventional antiemetics. This is a standard part of their life and becomes extraordinarily difficult to live with.

Using slides he presented the psychological mechanism of nausea and vomiting of CNS origin. One slide showed a cross-section of the medulla showing the chemo-receptor trigger zone (CTZ) to be in the mid-section and the VC (the true vomiting center) which is deep in the medulla. He stated that all vomiting is mediated through the vomiting center which can come directly through vagal, psychological or other stimuli to the VC or it can be transmitted through the CTZ. Cancer chemotherapeutic agents are thought, as are other emetic blood-borne drugs, to act through the CTZ which in turn stimulates the VC, which in fact induces the vomiting.

The antiemetics which are available today are essentially the phenothiazines, the barbiturates, the antihistamines and a miscellaneous group like Tigan; Haloperidol, etc. These drugs are used daily in a standard fashion and their efficacy in patients undergoing cancer chemotherapy has proven to be variable and usually ineffective. 

The phenothiazines are used to suppress the CTZ. The barbiturates are very likely used in high overdoses to suppress the brain in general – precipitating absence of vomiting on the basis of depression; the mechanism of toxic overdoses appears to apply to the antihistamines and the other miscellaneous drugs as well. One of the questions which these researchers have been trying to answer (not from brain physiology or pharmacology but from extrapolating from the clinical model) was whether in fact THC is acting as a primary central depressant in high doses or whether there is some specificity for the VC. 

The initial motivation to study THC to control vomiting came from anecdotal experiences related by the patients, who smoked marihuana to allay the anxiety preceding cancer chemotherapy. They found not only diminution of anxiety but also the control of nausea and vomiting. In some, the benefits were such that they were able to eat, as opposed to vomiting and experiencing anorexia. Thus the study was designed to attempt to verify the anecdotal reports. 

In the first study, the research design is a randomized double-blind study using each patient as his own control. Patients are selected if they were failures for control of nausea and vomiting by routine treatment. The responses that were elicited included: 

1. Complete response;

2. Partial response (50% reduction of vomiting);

3. Transient response (a delay in the onset of vomiting);

4. No response (50% reduction in vomiting in comparison to placebo).

The patients were asked to evaluate responses by a self-administered questionnaire. Twelve of fifteen patients responded to THC. Three of the fifteen had no response. Side effects encountered included: a “high”, somnolence and hallucinations .

In a second study Compazine, an active placebo, is compared to THC in the same research design of the first study. Fifty-two subjects were enrolled in this study. Eighteen received a single course; six received two courses; and twenty-eight received three courses. 

The conclusion of this study was that THC was an acceptable drug, such as Compazine, for the nausea and vomiting of cancer chemotherapeutic agents.  

Dr. Sallan felt that better results could be attained if a different route of administration other than oral route would be considered; schedules could probably be better adapted to the individual patients. The dose of 10 mg/M2 seemed to be the best. The speaker also felt that radio-immuno assays should be considered. 

Future studies should include the inhalation route of administration of THC since it is believed to be more readily absorbed across the lung membrane. Additionally, continuous low dose therapy may be efficacious, or perhaps a transdermal delivery system should be evaluated. 

The report was accepted and continuation was recommended. 

R.M. Gottlieb, M.D. - “THC vs. nausea and vomiting associated with cancer chemotherapy” a report on a short term study. 

This study has been underway for less than one year. The speaker was asked to discuss the design of the study (to compare it with that of the Boston group); bring up any problems encountered; present any preliminary data and respond to deficiencies communicated to him. 

The first patients were enrolled December 1976. There have been nine patients who have had ten drug (THC) trials. In addition, to determine whether or not THC has antiemetic activity in patients receiving cancer chemotherapy, these investigators plan to look at the following problems:

1. Whether the type of chemotherapy being used influences the effectiveness of the antiemetic agent; and

2. Whether or not certain subjective effects influence the response, as: setting in which drug is taken; personality of the patient; and influence of “learning to appreciate the ‘high’”.

The investigator feels that the personality of the patient is very important in determining the response which results from the administration of THC. He also feels that the plasma level of THC should be monitored and correlated to the response to the drug. 

Patients ranged from 22 - 60 years old (7 women, 2 men) and all but two received combined chemotherapeutic drugs. All but one vomited on the therapy. 

Dr. Gottlieb questioned whether a truly double-blind study was possible because of the side effects which are apparent when THC is administered. 

The report was accepted and the committee recommended continuation of the study. 

J.C. Merritt, M.D. - “THC Effects on the I.O.P. of Glaucoma”.

This investigator reviewed the definition of glaucoma in its broadest sense as well as to define primary and secondary glaucoma. In addition open-angle and closed-angle glaucoma were also described. Statistics were given as to the ratio distribution of blindness secondary to glaucoma. A discussion concerning the normal and abnormal pressures of the eye was included, as well as the various instruments which are used to evaluate eye pressures. He reflected that pressure never blinded anyone, optic nerve damage does. The concern is the effect of pressure on the optic nerve.

It was not clear as to when Dr. Merritt was able to begin the study. 

Influenced by a possibility that the condition of the patient would deteriorate if taken off standard medication and perhaps raise a legal question, it was therefore decided to measure an additive effect of marihuana and at a later date remove the standard medication.

Dr. Merritt assessed his patient’s condition by two methods: 

1. Tonometry - the measuring of IOP by standard means; and

2. Tonography (measures the functioning of the trabeculum) – whereby, outflow of fluid through the trabecular meshwork is “supposedly” measured. This method appears to introduce a lot of subjectivity. 

However, he reported on 13 patients in the study, most of whom had open-angle glaucoma. Initially the study group was of people with documented glaucoma. There were no controls. Each patient served as his own control in that each remained on his standard medication. 

There were five females and eight males. The diagnosis was:

10 patients open-angle glaucoma

2 patients closed-angle glaucoma 

1 patient miscellaneous 

Of the open-angle glaucoma patients, 7 of the 10 had a significant decrease in IOP after THC administration (additive effect with standard drug). Six of seven showed this effect after smoking marihuana yet only one of seven showed the effect after oral THC (only five were tried on oral THC). Because of the low effect on oral medication, the potency of the capsules were suspect and samples returned to supplier (NIDA) for analysis. These were found to be 60% of label. Therefore oral medication was discontinued and no results with any confidence can be applied to these very limited oral trials. 

The patient population used in this study generally may be likened to an abandoned group of patients. These were subjects who were treated for years, most time on various medications and taking all they could tolerate. It was not a good sampling of glaucoma patients - really a very heterogeneous group. 

The investigators criteria for allowing marihuana to be supplied on an out-patient basis (take-home) were those patients whose tonograms showed dramatic decreases in pressure after medication; also those people with chronic open-angle glaucoma in whom the risk-benefit was tipped in favor of the benefit. 

Future Plans: 

1. Tonograms to be prepared on all patients; 

2. Correlate IOP reduction and THC blood levels (this has not been done to date);

3. Stop the standard medication and administer only THC to in-hospital patients to measure true THC effect rather than an additive effect; and

4. Incorporate a control group and match by age, sex and possibly race. 

Problems:

1. Distribution of cigarettes to out-patients (take-home) and

2. Identification cards for out-patients carrying legal marihuana cigarettes.

These patients have take-home privileges of marihuana cigarettes. 

The matter of “Take-home” of Schedule I substances was brought up relative to the study of Dr. Merritt Reference was made to the recommendation of the Committee which allows one-day supply of marihuana, marihuana cigarettes or THC to accompany an out-patient to his home. How then was Mr. Randall able to be on hand in Washington, D.C. to pick up a daily supply? How many cigarettes and/or for how many days are supplies issued in the Merritt study? 

Dr. Merritt stated that a week’s supply was issued and he justified this on the basis that personally, as the Schedule I researcher licensed to do so, he could not handle daily issuances. He sees the patient weekly, checks progress and then issues a supply of cigarettes for the next week. 

An alternate plan to daily dispensing by Dr. Merritt was considered, that of establishing a stock of marihuana cigarettes in a government pharmacy convenient to Mr. Randall. 

Additionally DARAC discussed a further liberalization of the take-home “guideline” to include a sufficient supply to cover the weekend, i.e., pick up of Saturday and Sunday’s needs on Friday. This amendment to the dispensing guide for outpatients was recommended and unanimously approved by the committee. 

The staffs of FDA and NIDA were asked to work with DEA, contact the USPHS Outpatient Clinic at 4th and C, S.W., HEW South Building, and make the necessary arrangements for daily dispensing of marihuana cigarettes from that facility. 

Evaluation of preclinical data regarding the tetratology of cannabis (THC) was presented by Dr. Ferdinand Hui of the Drug Abuse Staff. His presentation covered the literature and material filed by NIDA in the master file for cannabis (DMF-1631). 

A “memorandum of summary” covering the “evaluation and recommendation for the safe use of Delta-9-THC in women of childbearing potential” was prepared by Dr. Hui and submitted to the Chief, Drug Abuse Staff. A copy of the memo, dated 13 May 1977, is enclosed in summary of his presentation. 

Unfinished Business and Adjournment 

As there was no other business to bring before the committee, the meeting was adjourned at 4:18 p.m. by the Acting Chairman*, Dr. Coy W. Waller. 

(*Due to a prior commitment the Chairman found it necessary to leave before the close of the meeting. Before his departure he asked Dr. Waller to chair the balance of the meeting.)

I certify that I attended the FY 77-3 meeting of the Drug Abuse Research Advisory Committee of the Food and Drug Administration and that these minutes accurately reflect what transpired. 

Signed August 11, 1977

Robert B. Forney, Ph.D. 

Chairman 

Drug Abuse Council

Advisory Committee

John A. Scigliano, Ph.D.

Executive Secretary

Drug Abuse Research

Advisory Committee

Coy W. Waller, Ph.D.

Acting Chairman

Drug Abuse Research

Advisory Committee

Exhibit Number 9

Minutes

Drug Abuse Research Advisory Committee

FY 77-2 Meeting

February 10-11, 1977

Neuropsychiatric Institute, Medical School, UCLA, Los Angeles, California

Attendees

Chairman: 

Robert B. Forney, Ph.D.

Members: 

Sidney Cohen, M.D.

Loretta P. Finnegan, M.D.

Frank R. Freeman, M.D. 

James W. Gibb, Ph.D. 

Marilyn E. Hess, Ph.D. 

Janice L. Stickney, Ph.D.

Coy W. Waller, Ph.D.

James H. Woods, Ph.D.

FDA

Denis J. McGrath, M.D., Medical Officer, Drug Abuse Staff

John A. Scigliano, Ph.D., Executive Secretary

David Blake, Ph.D., Consultant

Guests

Richard Bleich, R.Ph., UCLA

David Burman, M.D., USC

Paul Clopton, M.S., USC

Gordon Dow, Pharm.D., California Research Panel

Frank Dufour, M.D., UCLA

Lynn Fairbanks, Ph.D., UCLA

Mrs. R.B. Forney, Private Citizen 

Kay R. Jamison, Ph.D., UCLA

William G. Jochimsen, Abbott Laboratories 

Pat Lee, R.Ph., Southern California Cancer Center

Kari Loronzo, Bower Reporting (2/11)

George M. Milne, Pfizer Central Research

Robert Nowlan, M.S., UCLA MJ Research Project

P.B. Polatin, M.D., UCLA

Mary K. Rassekh, Bowers Reporting Company (2/10)

Bobbie Rosenblatt, UCLA

Gregory Sarina, M.D., UCLA

Sally Thomas, R.N., Ph.D., UCLA

Lecturers

Robert S. Hepler, M.D.

David Janowsky, M.D. 

Herbert Moskowitz, Ph.D.

J. Thomas Ungerleider, M.D. 

The FY 77-2 meeting of DARAC was called to order by Chairman Forney promptly at 0900, and began in CLOSED SESSION. 

The minutes of the November 11, 1976 meeting were considered. The following corrections were recommended:

1. Add David Blake, Ph.D., Consultant as attending, under the heading FDA:

2. Misprint on page 9, line 7, replace position with positive; and

3. Spelling corrections on page 14, 3rd paragraph, line 3 should be indices. 

With the incorporation of these corrections the minutes were approved unanimously. The signature page was signed by the Chairman and the Executive Secretary. 

Action Report

The Executive Secretary, DARAC, reported that within 48 hours a memorandum was sent to the Acting Commissioner, FDA, with highlights of the November 11th meeting. This covered: 

1. Statement of FDA Policy on Marihuana Studies: 

1. The Committee reiterated that studies involving females of childbearing potential will require special consideration. Particular attention will be given to the scientific merits of research proposals. 

2. The Committee generally would not allow naive subjects except as justified by the experimental design and considered on an individual basis. 

3. The Committee generally would allow take-home of one 15mg. dose of THC with exceptions to be considered on an individual basis. 

4. Protocols to elucidate possible therapeutic properties will be considered at this time in two categories: symptomatically for nausea and vomiting of cancer chemotherapy and for disease use for reducing I.O.P. of glaucoma. 

5. Committee recommended publication of the Guide in: The U.S. Journal of Drug and Alcohol Dependence and The Journal (Canada). This is in process. 

2. Advice on the INDs has been implemented. 

3. Schedule I Instruction Brochure – the 3 agencies are working toward the development of the format. This project has not been completed. 

4. Single Agency Committee – 

1. A memorandum of agreement has been drawn up. At present time the required signatures have not been affixed to the document. 

2. The document reads as follows: 

“Recent experience has shown that the Committee (DARAC) has become almost exclusively advisory to FDA with little NIDA involvement, that continued joint operation is no longer in the best interest of either agency, and that it would be appropriate to recharter it as a single agency committee. ‘The following points of agreement were established by representatives of the two agencies on October 20, 1976:

1. FDA will be sole sponsor of DARAC with total responsibility for administrative and fiscal support.

2.NIDA may propose agenda items which fall within the scope of the committee charter and for which NIDA requires action. 

3. NIDA may designate two, non-voting liaison representatives to attend and participate in meetings. FDA will provide these liaison representatives with agendas and all necessary working papers in advance of meetings, as well as summary minutes following meetings. 

4. NIDA may propose prospective members for the Committee and will provide biographical and related supportive materials. 

‘This memorandum, bearing the signature of both agency heads, will serve as the official memorandum understanding with regard to future operation of the Committee and the responsibilities of the signatory agencies.’” 

As the liaison representative, NIDA has named Dr. Szara (Dr. Sorer, Alternate) for the Biomedical Branch, and Dr. Willette (Jackie Bryant, Alternate) for the Technology Branch. 

THE MERRITT STUDY RE “effects of THC (Cannabis) on I.O.P. (glaucoma)” has received much publicity in the lay press because of patient Randall. He has been very visible and vocal at NORML and state legislature meetings: Indiana and Mississippi, where he spoke out in favor of the decriminalization of cannabis. Members of the Committee expressed great concern that a research subject could travel far from the research facility with supplies of cannabis cigarettes from government stocks when in fact the study was approved on an inpatient basis and present policy of FDA limits dispensing only one day’s supply of THC on an outpatient basis. FDA records show that the DARAC did not recommend nor did the FDA authorize any take home medication in the pilot phase of the study. There is no documentation of DEA authorizing it either. 

Some questioned whether the P.I. had adequate control of the supplies or was adhering to the approval protocol. 

The protocol was approved to study the dose effect of oral THCon IOP of the patient and if necessary to go to the smoking of cannabis. 

The committee suggested contacting the P.I. for clarification . Initial FDA approval was given to the study with an understanding that quarterly reports would be required in the early stages of the study. The first report is due. Therefore it was recommended that Dr. Merritt be invited to present the P/R at the next DARAC meeting on May 12, 1977. 

Next the Chairman advised the Committee to submit summary statements about the reports to be presented later in the day and the next day. These should include judgmental statements covering whether the study is well controlled, the value of the data, etc.

REVIEW OF INDs, AMENDMENTS, PROGRESS REPORTS

On the five lectures presented the Committee members will submit in writing evaluation and recommendations upon return to home. The conclusions and recommendations will be brought to the attention of the full committee at the May 12th meeting. 

Shipments and Preclinical Studies

Concurrence was reached with staff action and a motion for blanket approval was passed unanimously. 

A request was made for Nominations to fill Committee vacancies occurring at the end of June 30, 1977. Placed in nomination were:

Dr. Sidney Cohen – he has served 2 full terms, is not eligible to succeed himself until after 1 year break of serve. However he stated he would not accept another appointment but rather would prefer to serve as a consultant on a year to year basis. This latter will be communicated to the Committee Management Branch.

Reese T. Jones, M.D. – indicated to FDA on previous contact that he was too busy.

Michael Hart Ph.D., M.D. was nominated; he is interested; we will pursue his consideration.

Jack D. Blaine, M.D. – he is assigned to NIDA.

Leo Hollister, M.D. – a former member/chairman was proposed. 

Keith Greene, Ph.D. – of value for IOP research.

Jennifer James, Ph.D., Anthropologist, in the Seattle area is involved in addiction and women in crime. She will be contacted. 

Jorge Perez-Cruet, M.D. at the Missouri Institute of Psychiatry; is a Psychopharmacologist; has excellent credentials; we have his C.V.; has Spanish surname and is located in a desirable geographical location.

Pat Hughes, M.D. (Epidemiologist for Addiction).

C.R. Schuster, Ph.D., has been on committee in the past; committee has expertise like Schuster’s. 

Carl Chambers, Ph.D., Epidemiologist, Florida – Too busy. 

Questioned about Geographic area – a number of qualifying characteristics, in addition to expertise, are recommended by the guidelines of the Advisory Committee Act, as: equal opportunity for minorities, etc. At the present time we require 2 M.D’s and 1 female with place of origin being West or Southwest; Northwest; Southeast.

A request was made for Agenda Items for May 12 meeting: recommended were: 

1. Lectures from investigators in the Eastern part of the U.S. in the field of IOP reduction and against nausea and vomiting associated with cancer chemotherapy. The names of Dr. Merritt, Dr. Sallan and Dr. Gottlieb were recommended. 

2. To consider for discussion the “take-home” medication relative to the change in marihuana laws – decriminalization. 

3. To consider 2 subsections under Schedule I to controlled substances (currently there are 2 pharmacological sub-class).

1. For compounds with major degree of harmfulness or dependency producing potential; and

2. For compounds with moderate degree of harmfulness or dependency producing potential.

      4. Invite a local judge who hears marihuana cases to present his views on how he judges the criminal merits of a case. 

5. Where do we go with THC (cannabis) when data from research permits the conclusion of efficacy for a therapeutic condition? What about a sponsor and the filing of an NDA?How can removal from Schedule I of THC and/or cannabis be effected?

This latter would remove and permit, say THC, for a specific use for which it had proven therapeutically effective. Reclassification of that form of the drug which is shown to be effective. It appears that DEA, DARAC and FDA would be involved in such action.

Public Hearing

Time was allotted between 1:30 and 2:30 p.m. for comments or questions from the public. Since there was no one from the non-scientific public community the Chairman closed the Public Hearing portion of the meeting. The following topics were brought up during this time period.

1. Statement of the FDA Policy on Marihuana. It was accepted as presented in the BOOK. Recommendations were made for its publication. FDA staff will pursue this. The journals are named elsewhere in these minutes. See under “Action Report”(1)(e). The “Hospital Formulary” was also suggested as a journal which would serve a desired audience. Other suggestions were: the J.A.Ph.A; “Letter to the Editor” type of communication to such journals as “Science”, JPET; JAMA, etc. 

2. Fully OPEN meetings of Advisory Committees.

The Executive Secretary announced that after the 12th of March 1977 all advisory committees would be conducted on an OPEN basis since the justifications used in the past would not be acceptable. 

The review of IND material would be so arranged that confidential material would not be disclosed at anytime during the meeting. All material for a meeting would be presented as enclosures to an internal memorandum to the committee members from the FDA. Patient names, IND numbers, names of investigators and institutions not previously disclosed to the public would not be disclosable before the open public meetings. The title of the research may be stated and discussion, critique and recommendations may be stated. Names of reviewers will be disclosed by virtue of their presentations. The DARAC membership list is already made available to anyone requesting it. In an OPEN meeting the investigator himself may be in the audience.

1. Study Section review of grant applications and the “Sunshine Act.”

The Blue Sheet was quoted in this regard: “NIH Grant review under the “Sunshine Act” to start March 12th despite outcries. No chance Congress will intervene to exempt NIH from open meeting edict. 

“March 12th, the last day of the 180 day grace period provided by the Government in the ‘Sunshine Act’ is the last day NIH study groups and Advisory Council deliberations on grant applications can legally be closed to the public.”

1. Review of Contractor’s Annual Report on development of dosage forms of THC. 

1. Aerosolized THC – the contractor states that the aerosol batches are acceptable. However, small amounts of short, fibrous fibers were found in some of the aerosol containers upon inspection. Their evaluation of this product is reflected in 2 paragraphs lifted from the report:

“While clinical investigation is not within the scope of this contract, a large study showed that a THC aerosol did increase bronchial dilation with minimal systemic effects. The dosage form, however, caused bronchial irritation sufficient to negate the therapeutic effects.”

“It appears that an investigation of the formulation is needed before further clinical studies are done.”

We get the impression that this product may have been given to humans. The DARAC and FDA had not approved it. Safety in animals has not been reported to the FDA, in fact the FDA has questioned the use of the product, for the contract states that “if there is further interest in this dosage form, the formulation will have to be changed. The questions brought up by the FDA are logical ones which could be answered without too much effort. Again, if there is interest in the aerosol dosage form, the discussion with FDA will have to continue until they are satisfied.”

1. Topical Ophthalmic preparation:

Without having filed preclinical safety data on a new route of administration an ophthalmic solution has been sent to investigators to evaluate its effect on IOP. The contractor hoped that some interest could be generated in clinical ophthalmology groups to permit further evaluation of this dosage form. The FDA has no animal safety data on a topical ophthalmic solution. 

It was suggested that possibly D. Keith Greene has animal safety data which would support clinical testing. (Note: The FDA will contact Dr. Greene, request raw data and their evaluation.)

The consensus of the committee was to pursue the preparation of an Ophthalmic Solution of THC and test it for safety in animals. Also it was suggested that Dr. Hepler be queried about his interest in an ophthalmic preparation. 

It was emphasized that animal safety data is required for any New Drug/New Route formulation. SO that requirements for this Schedule I drug is no different.

5. Nomogram for calculating dose from the standpoint of body surface area. It was noted that one was included in the BOOK for information.

6. Effect of marihuana on diarrhea. By copy of a memorandum from Chief, DAS; the Exec. Secy., DARAC, the committee was appraised of another “therapeutic” property by anecdotal reference – an antidiarrhetic. The reference is to a male, high school teacher who had about 6ft. of his intestines removed because of ileocolitis. There followed lack of control of bowels even with high doses of Lomotil and no more success with questran. Later when smoking cannabis the teacher experienced no problem with regulation of bowels. To test the notion of marihuana effect he discontinued smoking several weeks and diarrhea returned even though he continued on the conventional therapy. Returning to smoking “pot” again the diarrhea was abated. This was reported to the federal government, the subject states, so that the information would benefit others. 

Lecture on “Tolerance, Withdrawal and Cannabis”

Tolerance and withdrawal of cannabis, was discussed at length by Dr. Sidney Cohen, UCLA. The data which were presented support tolerance, however, this characteristic does not occur in all bodily systems, i.e., it doesn’t occur with regard to its effect on I.O.P. but it is positive as it regards “highs” and the chronotropic effect of marihuana. The tachycardia does show tolerance effect. 

The result of this study suggest withdrawal symptoms on high doses but not those symptoms typically associated with opiate withdrawal. The full report will be filed in the official file of IND 11-235. The Committee will submit their evaluation of the report. 

Lecture on “Marihuana and Interpersonal Interactions” was reported on by Dr. David Janowsky of USC. He concluded that the results of his investigation suggest that marihuana has significant effects on social interactions and interpersonal effects. Such effects, may, in part determine why marihuana is a problem drug. 

The study involved mental health professionals serving as “helpers”. In this study the P.I. observed that THC has an additive effect on alcohol but not dramatically so and there appears to be no synergism. The full report will be filed in the official file of IND 11-499. The Committee will furnish to FDA an evaluation of the report. 

Lecture on the “Use of Cannabis for Glaucoma” was reported on by Dr. Robert S. Hepler.

I.O.P. reduction is due to a fluid deficit in the eye. 

It is hypothesized that this comes about by the reduction in blood flow through the anterior uvea. No tolerance was seen with regard to I.O.P. reduction. The traditional agent’s effect was enhanced by THC but not all subjects received benefit.

Cannabinol and delta-8-THC are also active in I.O.P. reducers but cannabidiol is not. 

The members of the committee will furnish the FDA an evaluation of the research findings. This review and a copy of the report will be filed in the official file of IND 11-235. 

Lecture on “Cannabis for nausea and vomiting” was discussed by Dr. J. Thomas Ungerleider, also of UCLA. 

He reviewed the literature and compared a number of characteristics of on-going studies with his proposed research. Following his discussion, which was enhanced by a slide presentation, he responded to various deficiencies of his proposed plan by acceding to the recommendations made by DARAC and conveyed to him by FDA letter.

He submitted an amendment to be placed in the official file of IND 12-585.

The Committee recommended that the proposed amendment be accepted. 

Lecture on “Effects of Marihuana on Driving'' was presented as a report of his progress by Herbert Moskowits, Ph.D. 

The results from the simulator, which permits repeatable conditions, seem to parallel those from the “real” situation. It was repeatedly emphasized that a person should not drive or operate machinery after smoking “pot” and still under the influence of the drug. The operator of a vehicle does not appear able to accommodate to errors of judgment, his peripheral vision is “wiped out”, his braking time is delayed; and there is competition for his attention to the “road”  with minor, attention holding matters. A copy of the presentation will be furnished as a Progress Report and filed in the official jacket of IND 12-805.

The formal part of the meeting at UCLA adjourned at 2:45 p.m. and the attendees proceeded to the simulator sites for the demonstrations until 5:00 p.m.

The next meeting was set for May 12. 1977 and will be held in the Parklawn Building, Rockville, Maryland. 

I have read and certify that these minutes are an accurate description of the business transacted on February 10-11, 1977 at the Drug Abuse Research Advisory Committee meeting held at the Neuropsychiatric Institute, UCLA, Los Angeles, California. 

Signed May 12, 1977

Robert B. Forney, Ph.D.

Chairman

John A. Scigliano, Ph.D.

Executive Secretary

Exhibit Number 10

May 25, 1977

709-A 8th St. SE

Washington, D.C.

Doctor Edward C. Tocus

Chief, Drug Abuse Staff

Food and Drug Administration

5600 Fishers La.

Rockville, Maryland 20857

Dear Doctor Tocus:

It is my understanding that on May 12th, DARAC, a drug abuse advisory group, made various recommendations to the Food and Drug Administration. It is also my understanding that the DARAC group will not approve of the minutes of the May 12th meeting until mid-August.

As FDA has attempted to implement the DARAC recommendations, only to find itself confronted with logistical problems, and as the DARAC group has not even had time to give such recommendations an internal review, I think it would be highly inappropriate for FDA, through your office or any other office, to impose those recommendations at this time. 

I am still shocked that neither FDA nor DARAC made any consideration for my medical well being in attempting immediate imposition of the May 12th recommendations. It is unsettling, to say the least, to return to Washington and find that the physician authorized to provide you with a critical medication has been abruptly dis-authorized by some almost unknown group expert in abuse, not therapy. To find any recommendation of any committee of any agency so rapidly transferred into concrete policy is, itself, a wonder. 

It was doubly dis-concerting to find that FDA-DARAC policy had not provided an alternate manner of supply. In effect, by policy decisions based on recommendations not more than hours old, FDA had disrupted my access to a medication which is critical to the maintenance of my sight. That Doctor Merritt has been verbally re-certified, dis-certified, and re-certified within a week only intensifies the impression that the DARAC recommendations are poorly considered, medically unsound, and serve little valid purpose. 

As the DARAC recommendations would appear to have profound impacts on various of my Constitutional rights as a citizen, and as DARAC has not even approved the minutes of the May 12th meeting, I trust there will be no further interference with my access to marijuana until DARAC finalizes its recommendations. If, at that time, the DARAC recommendations still constitute an infringement on my basic freedoms, then I will appeal the policy through available channels. 

It is impossible for me to bring further objections to the DARAC recommendations until they are made available to the public. From those bits and pieces of policy which I have gained in conversation it would seem some portions of the DARAC opinion may be worth consideration and review by FDA. These possibilities, of course, remain mysterious until the records are publicly available. 

I realize there are many difficulties surrounding the ‘bureaucratic solution’ to my Petition of May 20th, 1976. However, I cannot tolerate unwarranted and sudden interferences with my regimen of medical therapy and expect to retain my vision. The events surrounding May 12 thru 16 constitute a direct threat to the rational, stable, and medically valid treatment that I was led to expect. This letter is my attempt to stress paramount concern that my medical care be more fully considered and that my rights as a citizen be respected. 

As the DARAC group is one which exists unacknowledged by many I was shocked to find it capable of generating decisions concerning my physical health. It is possible, I imagine, that other, additional, as yet unknown committees, advisory groups, panels, commissions, and boards may also have, or believe to have, a voice in the conduct of my medical treatment. If possible, could you please provide me with a complete listing of those bodies with policy power over my situation, as viewed by FDA. 

Cc: Doctor Donald Kennedy, Administrator, FDA

Joseph Califano, Secretary, HEW

Doctor Peter Bourne, Office of Drug Abuse Policy

Exhibit 11

THE WHITE HOUSE

WASHINGTON

June 6, 1977

Dear Mr. Randall: 

Thank you for your letter of April 24 concerning the several issues surrounding the scheduling of marihuana and its therapeutic applications. 

As a physician, I understand and have great empathy with the issues you raised. I can assure you that my feelings are shared by hundreds, perhaps thousands, of physicians and researchers who have fought to bring relief and discover new treatments and cures. The responsible agency staffs and researchers involved in the marihuana and glaucoma issue all share with me a great feeling of compassion and are pledged to pursue the question. 

However, this compassion cannot be allowed to overshadow the basic questions. Although they are cumbersome and complex, the laws and agencies dealing with drug control and use were established to protect the public. It would not be responsible to permit desperate and unsuspecting victims of various diseases to be exposed to unproven and perhaps harmful drugs or “cures”. The fact that your eye pressures, as well as those of others, are lowered by smoking marihuana, or taking THC orally is certainly encouraging; but this in itself does not warrant distributing marihuana openly for possible glaucoma sufferers to treat themselves. 

As you well know, glaucoma is a complex disease resulting from a number of possible causes. Results to date, from the studies conducted by Dr. Hepler and Dr. Merritt, indicate that the cannabinoids only have effect on open angle glaucoma, which represents about 65 percent of the known cases. We don’t know yet if the cannabinoids have any adverse effects that may develop with time. They may, in fact, accelerate the degenerative processes. It is very necessary to learn these things under carefully controlled settings. 

I have also been informed that work is progressing on the development of a cannabinoid eye drop, which would circumvent the undesirable central effects associated with smoking marihuana. If the eye drops are effective, it will facilitate the research by other investigators who are seriously concerned about the effects of marihuana on the body.

It is partially true that research with Schedule I drugs is more difficult than non-scheduled drugs, but these difficulties are minor. Even if marihuana were not scheduled, an Investigational New Drug Authorization (IND) would still be required. This is the more difficult step as it is essential that the safety of the research subjects is assured and that the research design will produce results that can be interpreted. I understand that technical questions remain about your status under the law in that you are not really legally authorized to possess marihuana to treat your glaucoma. Under the law, the researcher (Dr. Merritt in your case) is authorized to possess and administer it. If you disregard some of the conditions of the study, it may be jeopardized. I understand that the agencies involved have not authorized your take-home supply but have chosen to overlook it in their compassion for your case. Publicity in the case has forced consideration of tightening up the dispensing of your supplies. I have been informed that efforts are being made to try to make this as convenient for you as possible. We do not want to interfere with your rights, but as a patient taking part in a research study, you have certain responsibilities to assure its success.

I am sorry that the important research issues involved here have been confused with the legal questions. As you are aware, I have long advocated a more sensible Federal penalty structure for possession of small amounts of marihuana. This so-called decriminalization is important for providing proper perspective of our Federal drug laws and society’s values. As you are probably aware, the U.S. Court of Appeals recently handed down an opinion on the NORML petition. It is not certain what will follow from this, but it is clear that the issue will continue to be reviewed and debated at all levels. The National Institute on Drug Abuse (NIDA) and others have pursued many medical issues with marihuana’s present scheduling. It has not impeded planned, serious, and careful research. This is what is needed. 

Sincerely yours,

Peter G. Bourne, M.D. 

Director

Office of Drug Abuse Policy

Mr. Robert C. Randall

709-A 8th Street, S.E.

Washington, D.C. 20003

Exhibit 12

709-A 8th Street S.E.

Washington, D.C. 20003

May 31, 1977

Mr. John Scigliano

Executive Secretary/DARAC

Food and Drug

Division of Drugs

5600 Fisher Lane

Rockville, Md.

Dear Mr. Scigliano:

I was greatly surprised on May 13th to find that DARAC, a drug abuse group, had made recommendations to the Food and Drug Administration which directly affects my health. It would appear that little consideration to the impact of these policies on my health was made. Further, it strikes me that the DARAC recommendations have almost no respect for basic Constitutional rights. I am not certain that therapeutic investigations and Constitutional freedoms are conflictive values. I cannot be certain of the impact of the DARAC recommendations until minutes of the May 12th meeting are made available to me. However, initial reports are, I think, cause for great concern. 

As I was unaware of the existence of DARAC, or of any power the DARAC group might have over my rational medical treatment, I would greatly appreciate information on the group’s relationship with FDA. I would also appreciate information on the nature of the group’s authority (created by law, regulation, etc.) and its mandate. I have searched for information on these areas but have not been able to locate any substantive data. A list of members, inclusive of their areas of expertise, would also be warmly appreciated. 

The DARAC-FDA policy has already seriously confused my access to a critical medication, and I hope no further, sudden, unwarranted action will be taken on the still unapproved recommendations made on May 12th. I would like to know the date and location of the next DARAC meeting. I would also appreciate a copy of the minutes from DARAC’s last two meetings which were held, I believe, in February, 1977, and November, 1976. 

I realize I have posed many questions. However, as the status and stability of my eyesight is involved I think you will understand my concern. I will greatly appreciate your help in this matter. Hopeful to hear from you shortly, I remain, 

Sincerely yours,

Robert Randall

Cc: Dr. Edward Tocus, Chief-Drug Abuse, FDA

Dr. Donald Kennedy, Administrator, FDA

Exhibit 13

709-A 8th Street S.E.

Washington, D.C. 20003

June 5, 1977

Doctor Donald Kennedy

Administrator, FDA

5600 Fisher Lane

Rockville,Md. 20857

Dear Dr. Kennedy:

For the past seven months I have been receiving, on average, a week’s supply of marijuana for the treatment of open angle glaucoma. This marijuana is authorized by several federal agencies and is provided to me as a ‘solution’ to a petition I filed with the DEA on May 20, 1976. Dr. John Merritt, of Howard University, supplies me with this drug and supervises my medical treatment. 

This program of marijuana therapy has succeeded in retarding the advance of my glaucoma, has led to visual field stability, and has generally improved my medical prognosis. 

I accepted the multi-bureaucratic ‘solution’ because it was alternative offered me by federal agencies. During this same period I was on trial in D.C. Superior Court for marijuana possession. The Court ruled my use of marijuana constituted a ‘medical necessity’. There is now seven months of research evaluation to support this decision. Additionally there have been tests at UCLA which verify my medical needs. It has become increasingly self-evident that the multi-bureaucratic solution is, in effect, a slap-dash agreement. Already tensions within the various agencies are placing a strain on the situation and, as a result, on the conduct of my medical care. 

I have been forced to appeal various DEA actions to the Attorney General. If accepted, DEA’s present interpretations would result in immediate criminalization of all research subjects engaged in Schedule I investigations. 

I was hopeful that FDA would not seek to interfere with my medical treatment and would allow me to reap the benefits available from marijuana in peace. That, however, does not seem to be the case. On May 13th I learned that DARAC (Drug Abuse Research Committee) had recommended fundamental alterations in my access to a critical medication. These recommendations were made at a May 12th meeting and FDA attempted to institute these changes immediately. 

While the DARAC recommendations are not and will not be public until August, it appears that DARAC intended to restrict the availability of marijuana to a daily supply. There are no valid medical reasons for such an alteration. Nor does the alteration impact on security concerns or other, more valid research areas. 

The most obvious, indeed the glaring, impact of the DARAC recommendations would be to deprive me of my freedom of movement. If the DARAC policies are implemented I would become a medical prisoner of Washington. 

I have tolerated a high level of absurdity, confusion, and politically motivated doubletalk in trying to gain a simple, direct, and biologically quantifiable medication which is generally available, albeit illegally, on street corners, high school parking lots, and fast food chain outlets. The process has been expensive in terms of my health and pocketbook. 

But I will not tolerate a functionary ‘advisory committee, expert in drug abuse, addict rehabilitation, and drug reform, to dictate my medical future. The DARAC policy recommendations are little less than interferences in my Constitutionally protected freedoms. 

It is my opinion that NIDA, DEA, and FDA have dismissed information important to the public health because it is ‘inconvenient’ to pursue. I understand that such an opinion may distress members of committees which are formulated on the premise that ALL marijuana users are drug abusers. I am not. I will not be treated as such. And I will not permit a group totally without expertise in ophthalmologic matters, or even in the therapeutic use of marijuana, to force me to choose between securing my eyesight and my basic civil right. 

In apparently chaotic, ill considered ways, FDA has attempted to implement the DARAC recommendations even though those decisions are part of an as of yet unapproved meeting. Between May 12th and 16th I found my access to marijuana an uncertain affair. Dr. Merritt was verbally disauthorized and reauthorized numerous times. FDA’s Office of Drug ABuse has, for the moment, ceased in its attempts to implement DARAC’s policies. I am unsure what the future will bring. 

It is mad for such irrational, impulsive, and ill considered recommendations to interfere with my health. It strikes me as frightening that FDA cannot construct a research program which is humane or respectful of Constitutional rights. It is my hope you will instruct FDA’s Office of Drug Abuse to cease any further attempts at implementing DARAC’s decisions. I would also ask that you speak with members of this almost non-existent group and request that they reconsider the implications of their policies. Should DARAC fail to re-evaluate its position I will be forced to administratively appeal. If that should fail I am ready, though not willing, to go to court and secure myself and my eyesight from further bureaucratic harassment.

Thank you for your attention to this most important area. I am hopeful that reason will dominate FDA’s further involvement in my medical future. 

Sincerely yours,

Robert Randall

Exhibit Number 14

Department of Health, Education and Welfare

Public Health Service

Food and Drug Administration

Rockville, Maryland 20852

July 11, 1977

Mr. Robert Randall

209-A 8th Street, S.E.

Washington, D.C. 20003

Dear Mr. Randall: 

Your letter addressed to The Commissioner of the Food and Drug Administration, Dr. Donald Kennedy, was referred to my office for reply. I am also replying to the letter which you addressed to my office concerning the same topics which include the decision of the Drug Abuse Research Advisory Committee. 

From your letters there seems to be some misunderstanding concerning your status in the study of marihuana for glaucoma. You are one of a group of volunteer research patients of Dr. John Merritt at Howard University. The only legal way marihuana can be distributed is through a research study. Marihuana has not been scientifically demonstrated to be safe or effective for any therapeutic condition and is not available for use in the treatment of any condition. I have included a copy of an article by Marion J. Finkle, M.D., Associate Director for New Drug Evaluation which presents information on the need for unbiased scientific information. The study of marihuana for any therapeutic purpose including glaucoma is in late Phase I or early Phase II according to the classifications in the enclosed article. 

The FDA is responsible for determining the safety and efficacy of drugs prior to their introduction into the commercial market. This is accomplished through the monitoring of research studies during the development of drugs. Our primary concern is the safety of the volunteer patient, and evaluating the research protocol and conditions under which the study will be performed prior to the initiation of the study. We accomplished the second responsibility through monitoring the progress of the study, and in evaluating the results. In this way, the action of a drug may be scientifically determined and the proper assessment of its potential benefits and risks may be made. 

Marihuana is being studied in several research institutions throughout the United States for potential benefit in reducing the nausea and vomiting following cancer chemotherapy. The take-home policy in those studies is to allow one dose to be taken the day following chemotherapy. No additional drug is taken out of the clinic in those studies. There is only one clinical study currently for the use of marihuana for the treatment of glaucoma. This is the study in which you participate, under Dr. John Merritt at Howard University. The protocol calls for initial hospitalization to determine the proper dose and dosage form for which each individual patient will be studied, and one day’s take-home except for weekends. During the early stages of investigations, it is important that the dose and dosage regimen be very rigidly controlled in order to adequately assess the effects of the drug. Without such control it is impossible to conclude the effects which are seen are due to the drug regimen which is being tested. Until these effects are clearly documented, and the studies have been confirmed by other investigators, the effects of the drug can not progress beyond the stage of interesting observation. The limitation of one day’s supply is based on the need to assure that the volunteer stays within recommended dosage regimen, as much as possible. This decision is a compromise between the requirement for continued hospitalization, which would provide the most reliable scientific data and unrestricted take-home of drug which would provide no controlled scientific data. Allowing a supply of the drug to be taken home for periods beyond one day creates an uncontrolled situation where the dose and dosage regimen is at the discretion of the volunteer patient and, therefore, the results are subject to question and validity. 

The Food and Drug Administration does not, and can not, authorize the use of a drug for treatment of a condition which has not been approved for such use. The FDA can, and does, authorize investigators to study drugs for the potential benefits in treating some conditions. The responsibilities of the FDA are primarily toward the interstate shipment of materials throughout the United States. We also have concern for individual patients like yourself, and our concern in your case resulted in our expediting the application of Dr. Merritt through the process of obtaining the IND. I hope this clarifies your understanding of the situation regarding the study of marihuana for the treatment of glaucoma and your position as a volunteer in the study for Dr. Merritt. 

Sincerely yours, 

Edward C. Tocus, Ph.D.

Chief, Drug Abuse Staff

Division of Neuropharmacological 

Drug Products

Bureau of Drugs

Exhibit Number 15

Department of Health, Education and Welfare

Public Health Service

Food and Drug Administration 

Rockville, Maryland 20852

August 2, 1977

Mr. Robert Randall

709-A 8th Street, S.E.

Washington, D.C.

Dear Mr. Randall:

Your letter addressed to The Honorable Joseph Califano, Secretary, Health, Education, and Welfare, dated June 4, 1977 has been directed to my office for reply. Similarly issues were raised in your letters to Drs. Kennedy, Focus, and Scigliano in May, 1976. The Drug Abuse Staff, of Which Dr. Tocus is Chief, is one part of the Division of Neuropharmacological Drug Products, which also regulates all drugs in Psychopharmacology and Neurology. 

In your letter to The Secretary, you imply that FDA and the Drug Abuse Research Advisory Committee have interfered with your medical treatment and violated your constitutional rights. Just how the FDA and DARAC has caused these effects, is not clearly defined. You are free to obtain treatment for your condition of open angle glaucoma from any ophthalmologist who is willing to accept you as a patient. Neither the FDA nor the DARAC has interfered in this respect with your freedom to seek medical treatment. Perhaps the name of the Advisory Committee has caused some confusion, in terms of the activities of the Committee. I believe Dr. Scigliano of my division, has sent a description of the Committee and a list of the members in response to your letter to him. The information which you received states that the Drug Abuse Research Advisory Committee advises FDA on action to be taken on Notices of Claimed Investigational New Drugs for substances with abuse potential. This statement clearly authorizes the Committee to advise the FDA on matters concerning marijuana being investigated under the Investigational New Drug Regulations. 

You were advised by Dr. Tocus in his response to your letter addressed to him that you are receiving marijuana under the Investigational New Drug Application of Dr. John Merritt of Howard University. You volunteered as a subject in this research program, and you are free to withdraw at any time. I understand that you have been receiving your standard glaucoma medication throughout the period of investigation in which the marijuana cigarettes are being studied. Whether or not such cigarettes have been beneficial can not be concluded from the data which has been obtained thus far. 

Your conclusions, therefore, that the use of marijuana cigarettes is beneficial and critical are not valid. In any event, there has been no attempt to have you withdrawn from the study, or to deprive you of the experimental portion of Dr. Merritt’s investigation.

The FDA is interested in obtaining the most valid scientific data which results from controlled studies, in order to reach the best decisions regarding the use of marijuana in the treatment of open angle glaucoma. 

We appreciate your contribution as a volunteer in obtaining this scientific data. We look forward to future reports from Dr. Merritt regarding the results obtained from his study.

If you have specific problems concerning your condition, or questions concerning the conduct of the research, I suggest you discuss these with Dr. Merritt who is responsible for the study. 

Sincerely yours,

Ronald Kartzinel, M.D., Ph.D.

Acting Director

Division of Neuropharmacological 

Drug Products

Bureau of Drugs

Exhibit 16

Minutes

Drug Abuse Advisory Committee

FY 78-1 Meeting Thursday, 11 August 1977

Parklawn Building, Conference Room “D”

Rockville, Maryland 20857

Attendees

Committee Members

Robert B. Forney, Ph.D., Chairman

Loretta P. Finnegan, M.D.

James W. Gibb, Ph.D. 

Michael M. Hart, Ph.D., M.D.

Marilyn E. Hess, Ph.D.

Kay R. Jamison, Ph.D.

Jorge Perez-Cruet, M.D.

Coy W, Waller, Ph.D.

James H. Woods, Ph.D.

FDA Staff

W. Danny Brown, Ph.D. 

Glenna Fitzgerald, Ph.D. 

Ferdinand Hui, Ph.D.

Ronald Kartzinel, M.D., Ph.D.

(Acting Director, DNDP)

Denis J. McGrath, M.D.

Doris C. Morrow

Barry Rosloff, Ph.D.

John A. Scigliano, Ph.D.

(Executive Secretary)

E.C. Tocus, Ph.D.

(Chief, Drug Abuse Staff)

David Blake, Ph.D., Consultant

Arthur A. Wykes, Ph.D., Consultant

NIDA

M.C. Braude, Ph.D.

Phyliss Lessin

R. Phillipson, M.D.

Heinz Sorer, Ph.D.

Stephen Szara, Sc.D., M.D.

DEA
Ronald Buzzeo

Judith Lawrence, Ph.D.

Guests
S.J. Black, Ph.D. (G.D. Searle)

Robert Randall, Research Subject

Jonathan Shapiro, lay person

Emanuella I. Dobrin (G.D. Searle)

Meredith Sykes, lay person

Mrs. Tepper, Court Stenographer,

ACE - Federal Reporters, Inc.

The first meeting of FY 78 of the Drug Abuse Research Advisory Committee (DARAC) was called to order by the Chairman, Dr. Robert B. Forney, at 8:30 a.m. He announced that the OPEN PUBLIC HEARING would be in session from 8:30 to 9:30 a.m. There were several people from the public present and the Chairman explained the process of input from the public sector during the period, and called for any questions or any contributions. There was no response from the public and the Chairman closed the OPEN PUBLIC HEARING.

The Chairman next announced the opening of the business portion of the meeting.

He introduced the new members: Drs. Hart, Jamison and Perez-Cruet. They each identified their institutional affiliation, areas of expertise and research interests. Also, other visitors were identified. Following this the attention of the Committee was directed to the Agenda. 

Minutes of May 22, 1977 meeting.

The minutes were approved with corrections of the mostly “typographical” errors reported. 

Proceeding to the review of research protocol, the Executive Secretary, Dr. John A. Scigliano, informed the DARAC that Drs. Freemon and Stickney notified his office that they would not be able to attend but furnished written reports. These reports had been furnished to the Chairman prior to the meeting.

Dr. Waller reported to the Chairman that the minutes of the previous meeting were “very well done.”

The Executive Secretary made the following announcements:

1. That Dr. Julius Richmond was confirmed as Assistant Secretary of Health and the Surgeon General of the USPHS; and

2. That there appeared in the American Pharmaceutical Association newsletter an item “About a dozen victims of cancer, glaucoma and multiple sclerosis have petitioned the U.S. Attorney General Griffin Bell to have marihuana reclassified from its present Schedule I category so that it can be used for medical treatment.

The Chairman then proceeded to the review of research protocols, amendments and progress reports.

Reviews:

VII-A Human Pharmacology using Radiolabelled Cannabinoids: smoked tritiated THC; and the effect of intravenous THC on testosterone levels. Evaluation of a progress report.

The objective of the study was to augment information which has been obtained on the effects of CBD on the absorption of ∆-9-THC administered. 

A very brief summary statement was included which indicates some preliminary results. The THC has been administered in two different dosages and have plasma, urine and fecal samples to analyze. No data on the samples are presented. A cursory report on the effects of THC on plasma testosterone levels was also included.

Critique: Although the investigators are well qualified, have the necessary facilities to carry out the outlined experiments and the experiments are pertinent to a better understanding of metabolism of the cannabinoids and the influence of CBD on the metabolism of THC, a number of questions were raised and additional information was sought. 

1. Reviewers claimed the Informed Consent Document was not appropriate for the currently proposed study as: this amendment involves CBD & THC whereas the earlier study involved titrated THC; this amendment collects only blood samples whereas earlier urine and fecal samples were collected; and finally the amount of radioactivity is less in the amendment than in the earlier study. It was concluded that an updated “informed consent form” is needed to reflect the above. 

2. Reviewers claimed the progress reports to be inadequate as the following information should be included: The cigarette smoking schedule; rationale for changing both the dose of THC smoked and the total amount of radioactivity; the time period at which plasma, urine and fecal samples are taken; the plot data on chemical analysis; and reason for the delay in doing the chemical analysis. Further, for the I.V. THC study of effects on plasma testosterone levels, the Committee would like to see the data from the study; methods of statistical analysis the safety data on the intravenous formulation (THC in human serum albumin); normal saline is considered not the proper placebo (human serum albumin should be used); and they questioned whether the relatively short periods of time in which it was studied. 

*illegible* that the FDA communicate the above questions to the *illegible* -quest that the missing data be furnished. 

The next review included three protocols covered under a single IND number. These would be designated A, B, & C followed by the research titles. 

1. “Extension of effects of THC on catecholamine excretion after smoking, oral or intravenous administration.” This protocol involves plasma concentrations of THC and the urinary excretion of the norepinephrine metabolite MHPC (3-methoxy-4-hydroxy-phenylglycol) following smoking, oral and i.v. administration. Absolute bioavailability of THC administered by smoking or orally has not been worked out, although early estimates indicate that the drug was about 3 times as potent when smoked as when taken orally. Subsequent studies of the kinetics of radiolabelled THC indicated that those for smoking were similar to what might be expected from i.v. administration. With the availability of accurate methods for determining plasma concentrations of THC, the investigator will test more systematically the bioavailability of THC after administration by smoking or orally. Intravenous administration of the drug will be the standard. 

The dosage forms will be: 

Smoking - 19 mg cigarettes

Oral        -  20 mg chocolate cookies (Brownies)

I.V.   -     5 mg THC in 95% ETOH (slowly injected over 2 minutes) 

Into injection part of a rapidly flowing i.v. infusion of NSS. 

The total of 55 ml of blood will be taken at each session through the heparin lock; taken at various intervals after drug. Spontaneously voided urines will be collected during the 24 hour period prior to the drug trial, as well as on the day of the drug trial. The content of MHPC will be measured. 

Clinical evaluation of drug effects will be made, including pulse rate, conjunctival injection, rating scores as to degree of “hig”, and the card-sort version of the ARC inventory will be completed in the same sequence as the “high” rating scale. 

1. “Interactions of THC with Cannabidiol and Cannabinol by oral route – cookies.” 

Though THC is considered the major active component of cannabis, in the plant it exists with varying amounts of 2 other major components (CBD and CBN) which, though without psychic effects, may have pharmacologic activity and could interact with THC. Both animal and human studies of such a possible interaction have been contradictory. Some evidence suggests that if any interaction occurs, it might be between THC and CBD and this is probably of small degree. 

The possibility of being able to measure concurrently plasma concentrations of these cannabinoids provides another point of inquiry into such interactions especially of a pharmacokinetic nature. Three trials will be run with THC + CBN; THC + CBD; and THC + placebo. Criteria for patient selection; clinical evaluation of drug effects and determinations of plasma concentration of cannabinoids will follow that proposed in Protocol A. 

1. “The differences in urinary metabolites and pharmacokinetics of THC in “heavy” and “light” users of cannabis.”

Apparently there now seems little doubt that “heavy” users of cannabis develop tolerance to the effects of the drug. Although tolerance has been much more difficult to demonstrate in “light” users.

The nature of the tolerance is not known, although it may be metabolic. Early studies using radiolabelled THC indicated that chronic users had a shorter plasma-disappearance-time for the label, than naive users. It would now be appropriate to test this idea using a specific plasma determination for THC.

Smoking and the intravenous route will be used. With their recommendation for approval the committee identified some areas which needed clarification. One had to do with the Informed Consent Document: the committee felt the document should be changed to reflect

1. That the sequence of frequency of collecting urine for a 24-hour specimen be clarified, and

2. That the specifics re assurance of compliance with the requirements of the protocol by the subject detailed. 

The other had to do with:

1. What is the cut-off point between “heavy” and “light” users when measuring urinary metabolites; and

2. What criteria is used for classifying “heavy” users by the measuring of metabolites.

FDA was instructed to communicate the above to the investigator.

VII-C Progress Report on the “Use of Marihuana in the Treatment of Alcoholism.”

This is a report of a recently concluded study examining the potential use of marihuana to treat alcoholism. The therapeutic prospects seem very low. 

The committee found the report to be acceptable. Further, they were interested in knowing if the subjects who remained at the clinic for longer periods of time belonged to a particular treatment group and if marihuana enhanced the length of time the alcoholics remained in the clinic. Also, the committee felt that if tables of data had been included in the report it would make it easier to follow. 

It was recommended that if such tables are available they be requested by FDA, for inclusion in the official file and for information to the committee.

VII-D “Evaluation of THC against nausea and vomiting, etc. via inhaled, intravenous and transdermal administration, and to evaluate psychological effects”. 

This is an amendment to extend the study of the antiemetic activity of THC. The primary objectives to compare the effects of three different routes of administration. 

Initial studies by this group considered only the inhalation route of administration of cannabis for its effect as an antiemetic and other effects were not studied systematically. Now they propose to study, among other things, the effects of the drug when administered by other routes on: 

1. Decreased nausea and vomiting 

2. Increased appetite 

3. Dysphoria

4. Euphoria

5. Sense of well being

6. Increased or decreased anxiety

7. Increased or decreased awareness of discomfort

Intravenous and inhalation studies will be done now; the transdermal study will be done when a safe dosage form has been developed.

The committee recommended approval and to direct certain questions to the investigator. These are:

1. Name the clinical psychologist or psychiatrist who will monitor and evaluate the psychological aspects and submit the credentials;

2. Indicate the method of analysis for THC in blood level determination;

3. If possible, include 50 subjects in each route of administration group and furnish the formulation of the intravenous form of THC and support with data of safety;

4. Will a control or a comparative group be included;

5. The patient selection criteria should state the type of cancer and chemotherapy invl=olved; and

6. Furnish a documentation of the approval of the local Human Research Committee.

The work session was interrupted for a return to OPEN Public Hearing to receive testimony from two members of the public: Ms. Meredith Sykes who stated she has suffered symptoms of multiple sclerosis for five (5) years and who has experienced spontaneous remission of the symptoms for two (2) years while smoking “street” marihuana; and Mr. Robert Randall who has a diagnosed glaucoma accompanied by an elevated intraocular pressure of five years’ duration. He assigns elevation of the pressure to smoking “pot” while continuing on physician prescribed standard glaucoma medication. 

Both appealed to the committee to explore legal avenues to make marihuana available other than through the IND procedure without breaking the law. The appeal may be identified with efforts to decriminalize marihuana possession and use. 

The Chairman, Dr. Forney, thanked Mr. Randall and Ms. Sykes for their testimony and emphasized with his comments that supplies of drugs are for research and not for treatment until good controlled studies have been done and published. No one really knows for sure at this time what the real benefit of marihuana (THC) itself is on either of the conditions of which Randall and Sykes are suffering.

The OPEN Public Hearing was again closed and the work session re-opened to consider the review of the balance of protocols. 

VII-E This amendment to an ongoing study, wherein the investigator has pursued the effects of smoking on flying, will look at “interpersonal effects of marihuana”. 

At a previous meeting the principal investigator presented a brief progress report of his research into the “interpersonal effects fo marihuana”. Based on the protocol submitted to that time and the data presented in his talk, the DARAC reviewers and the entire committee recommended that no further shipments of marihuana be made in support of this research project. This was communicated to him.

He then responded with a statement that his research had been accepted for presentation at a number of psychiatric meetings as evidence of professional support of the work along with a copy of a paper submitted to “Archives of General Psychiatry” concerning some aspects of the research.

The major thrust of the report is to suggest that marijuana smoking causes a relative decrease in ratings of interpersonal skills. The skills tested included empathy, acceptance, warmth and genuineness. Assessment of these skills was made under normal, placebo and active marihuana conditions. 

Conclusions drawn by the principal investigator are: 

1. Overall marihuana intoxication leads to a decrease in interpersonal skills;

2. “Decreased similarity of changes” in experimental subject’ and partners’ moods during experimental subject intoxication reflects a decrement in interpersonal skills; and

3. Marihuana-induced changes in specific Zuckerman affective adjective checklist items and the subjective high assessment scale items appear to reflect experimental subject insecurity, confusion and detachment as well as partner dysphoria. 

The critique of the report.

The two major conclusions of the principal investigator are not supported by the data reported; the discussion section is confusion, misleading and poorly written;

1. That marihuana intoxication significantly decreases interpersonal relationships – only one of 4 interpersonal skills were affected for both experimental subjects and partners;

2. The author notes there is no statistically significant changes in mood with intoxication; there are trends in changes of mood that may reflect a decrement in interpersonal skills – the statistics do not support this conclusion. Generally the committee stated that the overall design, rationale and methodology of the study seem weak; and strongly suggest that more objective and comprehensive measures be included as a minimum requirement for approval. The study is clearly not an assessment of the effects of marihuana in a natural social setting – this places major limitations on any generalizations which might otherwise derive from the study. 

The FDA was advised to communicate the above to the principal investigator and that the amendment was disapproved with request to resubmit. 

VII-F An amendment for a “Comparative Evaluation of THC and Compazine on Nausea, vomiting, anorexia and dysphoria due to cancer chemotherapy.” 

The extent of the amendment was to study a larger number of patients in an approved study. Approval was recommended. 

VII-G “Study of the effects of marihuana (THC) on the I.O.P. of glaucoma”, an amendment. 

The amendment introduced records of disposition of previously issued drugs; and justification of additional supplies. There was some direction given to daily issuance of marihuana cigarettes to out-patient subjects but this requirement could not be applied until arrangements have been completed for dispensing from a federal pharmacy. 

New supplies were approved. The supplier was instructed to ship. 

VII-H “The Effects of THC on Behavior”. A new study. 

This is an experiment with single doses of Nabilone compared to THC in various doses along with Diazepam in a situation involving anxious young adults on selected subjective, behavioral and physiologic variables. 

The DARAC recommended approval with communication of their findings of minor deficiencies in design, rationale and methodology. 

These matters could be cleared up with resolution of the following questions: 

1. What criteria will be used for diagnosing ‘psychoneurotic disorder, psychoneurotic personality disorders, and adult situational reactions?;

2. What degree of difference in anxiety and depression scores will be regarded as significant or necessary?;

3. How will the inclusionary criteria be assessed?;

4. What kind of psychiatric evaluation will be done?; and

5. Which drug is being studied? Is Nabilone the unknown and Diazepam and THC the controls? 

Other comments of an advisory nature are:

1. It is important to insure as much reliability and validity as possible; 

2. A non-anxious control group should be included; and

3. Female subjects are to be excluded.

The DARAC recommended that the study may start only after satisfactory resolution of the deficiencies. 

VII-I A new submission to study “The Use of THC in the treatment of glaucoma”.

This was reviewed by staff and found to be deficient on the basis that the application was most inadequate. A disapproval letter with request for resubmission was sent. This proposal and action taken was brought to the attention of the committee. 

VJJ-J An amendment to a submission to “Study the effects of marihuana on nausea, vomiting and anorexia associated with cancer chemotherapy” introducing the use of females into the study. 

The committee recommended approval of the amendment conditional to the requirement that female subjects sign an appropriately worded consent form attesting to strict adherence to the conditions “...that women are no longer of childbearing potential when, because of the concurrent use of chemotherapeutic drugs which are teratogenic, it will result in the oncologist recommending a therapeutic abortion should they conceive.” Further, the investigator emphasized that “most women receiving cancer chemotherapy are unable to conceive because of the inhibitory effects of the drugs on ovulation. In a relatively small number of patients, pregnancy does occur. These patients are then advised to have the pregnancy terminated because of the potential teratogenic effects of these chemotherapeutic agents.”

Since the eligible women subjects are based on the conditions set by the principal investigator, the Informed Consent Document should include: informing the female subject that a NEW DRUG (marihuana/THC), whose absolute effect on the fetus is not known, will be given to her to study what effect it may have on nausea and vomiting associated with the cancer chemotherapy.

The recommendation was to communicate to the Principal Investigator the above and request a revised copy of the Informed Consent Document modified to reflect advice included above. 

Next the Staff actions associated with drug shipments were concurred with by the committee.

There were 115 preclinical and 17 clinical shipments. 

Dr. Gibb extended an invitation to DARAC to hold its next meeting at the University of Utah where there is research being conducted of particular interest to this committee and FDA. The studies and investigators are:

1. Brian Finkle, Ph.D., has a major contract with NIDA for LAAM. He is the principal investigator in a National Testing Center for study of LAAM and its metabolites;

2. Ralph Karler, Ph.D. is conducting a study of the anticonvulsant properties of THC, its congeners, and metabolites;

3. Michael Franklin, Ph.D. has studies ongoing into the metabolism of LAAM;

4. James W. Gibb, Ph.D. is studying the effects of methamphetamine and other drugs of abuse on catecholamine metabolism, and

5. Harold Wolfs, Ph.D. and Dean, School of Pharmacy, is conducting research on models for opiate tolerance and dependence involving interaction with reward pathways in the brain. 

All these studies are in animals and/or in vitro. To site visit the projects and be exposed to data from them would be of considerable interest to DARAC. 

No decision was made regarding the site of the February 1978 meeting. Staff will consider the matter of cost/benefits along with valid scientific reasons for selection of a meeting outside of Washington. The November 10th meeting will be in the Parklawn Building, Rockville.

The miscellaneous items under tab XI were briefly touched on by the Executive Secretary. He pointed out that:

Item A. was new chemistry data added to the Drug Master File on cannabis;

Item B. Herbal Teas, a potential problem of abuse discussed at an earlier meeting, have been regulated under the Bureau of Foods;

Item C. Merging of some and elimination of other FDA advisory committees have been discussed relevant to the OMB effort to reduce the number of public advisory committees throughout the Federal Government. It has been mentioned that there is a possibility that the Controlled Substances and Drug Abuse Advisory Committees may be merged. 

Item D. A copy of Djerassi paper on CF rescue of MTX (methotrexate) poisoning was included for information of the committee. This drug procedure has been involved in several studies recently reviewed;

Item E. The ne Commissioner’s “re-statement” on Special Government Employees (SGE) was made available to DARAC for information and guidance, especially to the three new members; and

Item F. The chronological summary of the D.C. based study, of the effect of THC on the intraocular pressure of glaucoma, was included in the book as information and for future reference for the committee. 

Because she was not present when the minutes of the May 12, 1977 meeting were discussed and approved, Dr. Braude, NIDA, asked the Chairman to reopen the discussion about the addendum which was appended. (Note: The addendum is a summary of the Dr. Hui, FDA, evaluation of toxicity data filed in the NIDA Drug Master File (DMF-1631). She disagreed with the conclusions drawn as they apply to the use of females of childbearing potential. 

Whereas Dr. Hui stated “The independent research published in scientific journals indicated results different from those reported by the National Institute on Drug Abuse.”

Continuing, Dr. Braude requested that it “be entered in the minutes that the review as presented was incomplete,” and that the review doesn’t present the state of knowledge of the effect of cannabinoids on pregnancy and on the fetus.

Dr. Tocus, Chief, Drug Abuse Staff, FDA, then solicited from NIDA an evaluation of the toxicity data available to them and recommendation for the safe use of ∆-9-THC in women of childbearing potential; upon which Dr. Braude requested a clarification and Dr. Focus replied that the summary memorandum represented FDA evaluation of toxicity data submitted to the FDA.

Whereas, Dr. Focus formally made an official request that the data which she was alluding to be furnished to FDA with a written evaluation of it. 

Dr. Braude said “The data is in the literature”. She did, however, agree to submit the material to the FDA in support of minutes for the 11 August 1977 meeting. 

The first item for discussion in the afternoon session was by Dr. F. Hui of FDA/DAS staff; a review of the marihuana guidelines for possible updating. The three guides considered were: The administration of THC or standard marihuana extract for a period of time exceeding 90 days (continuing use); safety data to support the multiple use of an intravenous THC product; and safety data to support chronic use of marihuana via the inhalation (smoking) route. 

From data submitted to the Drug Master File and for FDA review, Dr. Hui observed some adverse effects from 90-day studies; possible chemical problems relating to intravenous precipitation after administration and no safe parenteral product at present and some pulmonary pathologic changes due to chronic smoking of marihuana.

Following the presentation the chairman called for a vote on the three items of the guideline considered for revision.

Conclusions:

1. Continue to permit consecutive use (smoking and oral) of marihuana only for 90 days;

2. Allow at this time take-home medication on a weekly basis and proceed to a daily and weekend basis when suitable arrangements have been made; and

3. Restrict use of an intravenous form of THC to one dose only until formulae and safety data are submitted.

Further the committee recommended that an ad hoc group be named to look over the DMF & the literature and determine what is documented and what is deficient; pursue raw data from authors or published papers and recommend to FDA and NIDA what safety data is not available. It was recommended that an up-to-date toxicity report be prepared and presented at the February meeting with suitable visual aids (charts, graphs, etc.) with the objective of firming up the guidelines for use of marihuana in human research studies. 

The ad hoc group included Dr. Blake, chairman and Drs. Wykes and Waller as members.

The topic “Heroin for Treatment of Opiate Dependence” was presented by Dr. Focus. He stated that this is a subject about which there is a difference of opinion currently throughout both the government and among the scientific community. This difference exists because in the previous administration (in Washington) there was an unwritten edict that heroin would not be used for any conditions – and it wasn’t. In the current administration, the question of heroin use again has surfaced.

An example of what can happen at the state level is embodied in the New Mexico state plan to use heroin as a treatment drug; and Mishigan also is considering a state heroin plan. 

The FDA’s position is neutral in that should an investigator submit an adequate protocol to evaluate heroin as a possible treatment drug it would be considered on its own merit. We would pursue the evaluation in terms of therapy rather than a deterrent to “street” activity, i.e. consider heroin in terms of clinical utility of heroin for its own purpose, therapeutic, rather than an enforcement measure. The Avram Goldstein outline was briefly touched on, and was stated to be a stepwise approach to total treatment of the addict, starting with heroin on the street and progressing through the procedure, to a completely drug-free state. 

Continuing, Dr. Focus stated that Goldstein’s approach is still a viable complete treatment idea, requiring more discussion, but the part we are focusing in on is the first step.

From a presentation by Dr. DuPont before a Symposium on “the Drug Abusing Criminal Offender” some cost analysis figures were made available. It is estimated that drug abuse costs the U.S. approximately $10 billion each year, of which about 70% is from crimes from 400,000 heroin users, which might be looked at as, the cost due to heroin would be about $7 billion. 

The Federal Government spends about $700 million/year for drug abuse, and states and local governments spend an additional $400 million for a total of all government efforts of $1.1 billion. About 40% of federal effort is for supply reduction with the remainder for treatment, research and prevention. 

The current federal government’s (national policy) position to quote Dr. DuPont is “... to ensure that the price  of heroin remains high in order to discourage experimentation and the addictive use of the drug.”

“The cost to society with this policy is great, but the cost to society for a change in this policy would be even greater. The idea of the government competing with the pusher by giving away heroin, thereby taking the profit out of the heroin traffic and reducing heroin-related crime, holds no appeal for me (DuPont). In fact it divides public attention and diminishes program effectiveness.

“The most fundamental objection to the call for legalization of heroin is that such an effort would simply move the heroin-addict social cost out of the criminal area and into the health area.”  This approach, it is estimated, would cost $35 billion/year.

Again, quoting Dr. DuPont, Dr. Focus stated “On the other hand, I do not think the use of heroin as part of an American drug treatment program would derive patients out of current treatment programs any more than methadone maintenance has eliminated the demand for drug-free treatment. 

Neither do I think that heroin as a treatment drug has much to offer. Heroin is a short-acting drug which must be taken intravenously several times a day to avoid painful withdrawal symptoms. I will be willing to think more about it when proponents (of heroin treatment) can answer four simple questions.

1. Who is eligible to receive them?

2. How much heroin will the treated person be given?

3. How long will the person be permitted to take heroin before he is forced to switch to methadone and/or detoxify?

4. How will take-home heroin be handled?”

After considerable discussion which included: quick conversation of heroin to morphine in the body; the British Heroin Programs, etc., the question placed before the committee was:

“Is there any reason why DARAC would not approve a study if it were well-planned and the safety factors were taken into consideration to study this effect?”

The chairman replied “...I think there is no reason why we could not. No objections to the study being done!”

This concluded the agenda. The meeting was adjourned at 3:45 p.m.

I certify that I attended the FY 78-1 meeting of the Drug Abuse Research Advisory Committee of the Food and Drug Administration and that these minutes accurately reflect what transpired. 

John A. Scigliano, Ph.D.

Executive Secretary

Drug Abuse Research

Advisory Committee

Robert B. Forney, Ph.D.

Chairman

Drug Abuse Research 

Advisory Committee

National Organization for the Reform of Marijuana Laws

2317 M Street N.W.

Washington, D.C. 20037 / 202-223-3170

July 14, 1977

Bastille Day

Dr. Peter Bourne

Office of Drug Abuse

The White House

Washington, D.C. 20500

Dear Peter:

I would like to raise with you the general subject of marijuana’s potential therapeutic usefulness. 

I know that you are familiar with this subject, including the growing research data supporting the usefulness of marijuana for a number of conditions and diseases, including glaucoma, the side effects of chemotherapy, and asthma. As a result of the media coverage of this subject over the past few months, we are now beginning to accumulate a list of individuals from around the country with similar claims, including claims for marijuana’s usefulness in treating additional diseases, such as multiple sclerosis. 

You are also aware that NORML has been involved in a five year suit against the Drug Enforcement Administration aimed at reclassifying marijuana under federal law. It appears that H.E.W. will finally be scheduling much needed hearings on this subject in the near future.

In NORML’s efforts, we have always attempted to separate the question of marijuana’s usefulness as a therapeutic agent from the question of an individual’s right to smoke marijuana recreationally. I think there is very little debate concerning the former; there is obviously still considerable debate over the latter. 

Nonetheless, our experience over the past year and a half, based primarily on Bob Randall’s efforts, have demonstrated that the therapeutic question has also become politicized. To many people, a change in the law which would permit a physician to prescribe marijuana in situations where it is helpful, is seen as somehow giving in to the argument concerning recreational use. As a result, people’s legitimate medical needs are in some cases being ignored. 

Perhaps more than any other single factor, the reticence of your office and Dr. DuPont’s office to support a reclassification of marijuana under federal law has held back further progress in this area. 

I know that you are supportive of the concept that marijuana should be available to people who need it, if indeed that need can be validly demonstrated. I’m also aware of the F.D.A. regulations pertaining to new drugs which are sought to be placed on the market. However, it appears to me that this F.D.A. argument is currently being used as a ruse, misapplied to the situation of an individual who merely wants the legal right to self-administer marijuana. In other words, I am willing to concede that before any drug company can or should be permitted to legally market marijuana, the company should be required to go through the usual steps at F.D.A., including the Investigative New Drug Application, followed by the New Drug Application. This will take some time, of course, but the same standard should be applied to marijuana as is applied to all other drugs being proposed for marketing. 

However, there is no reason that these F.D.A. requirements pertaining to commercial sales should be applied to an individual’s right to self-medicate. What Bob Randall has been working toward, and what many other individuals are now actively seeking, is support from the Carter administration in reclassifying marijuana to a lower schedule under federal law so that it would be permissible for a physician to prescribe marijuana to an individual in those rare situations when traditional medication was not adequate. The marijuana could obviously be obtained from the federal government during the period before commercial sources have cleared F.D.A., since the amounts we are discussing would not be great. Thus far, it seems to me that the F.D.A. arguments have been misused to justify no reclassification. 

You are of course aware of the requirements for a drug to be classified in Schedule I under the Uniform Controlled Substances Act. Among those requirements are that the drug must have a high potential for abuse, as well as no accepted medical use. These requirements must all be met, or else the drug cannot rightfully be classified in Schedule I. Surely, in light of the massive scientific research which has now been conducted and gathered by the National Institute on Drug Abuse, you could no longer make an honest claim that marijuana has a high potential for abuse. Of course it can be abused, and undoubtedly marijuana does have some potential for harm. But to classify that potential as a “high potential” seems absurd on its face. I reiterate that unless marijuana meets this criteria of a high potential for abuse, it cannot properly be classified on Schedule I.

I must also argue the point concerning marijuana’s accepted medical use. While I recognize that the federal government does not at this moment recognize marijuana’s medical usefulness officially, that is a Catch-22 situation. In essence the government says there is no use for marijuana since marijuana is in Schedule I, a schedule which by definition does not have any usefulness. Absurd! Without debating the point in detail, based on 2,000 years of marijuana’s medical usefulness as well as current research indicating marijuana’s usefulness at least in limited situations, marijuana again fails this criteria and must legally be moved out of Schedule I. 

Assuming you concur in either of these last two points, then you must conclude, as I do, that marijuana more properly belongs in either Schedule 2,3,4, or 5. Even lowering marijuana only to Schedule 2 would assure that it is available in appropriate therapeutic situations. This simple reclassification to Schedule 2 would not cost anyone any political credibility, since it has nothing at all to do with the emotional issue of whether people should be permitted to smoke recreationally. The reclassification would, however, make marijuana available to the hundreds or perhaps thousands of individuals who currently have a very real need for it. I urge you to take a fresh look at this subject, and to come out firm and open on the side of letting doctors make the decision concerning  marijuana’s medical usefulness, not legislators. 

I would naturally be available at your convenience to discuss this in greater detail. We would very much appreciate your support as we move forward in this important area. 

Regards,

Kieth Stroup

National Director

RKS:pes

Exhibit Number 19

709-A 8th St SE

Washington,D.C.

December 5, 1977

Doctor Peter Bourne

Office of Drug Abuse Policy

The WHite House

Washington, D.C.

Dear Doctor Bourne:

I am writing to inform you of recent developments affecting my medical care, and to ask your assistance in the resolution of long standing problems brought into sharp focus by these events. In your roles as Special Assistant to the President for Health, and as the Director of ODAP, I believe such a request is both proper and warranted. 

Doctor John C. Merritt informed me last week that he will transfer his medical practice to the University of North Carolina at Durham on or about January 15, 1978. As the only Ophthalmologist licensed to certify my access to marijuana for the treatment of open angle glaucoma Doctor Merritt’s decision portends profound changes in my medical care. Doctor Merritt has indicated his intention to continue marijuana/glaucoma investigations at the University of North Carolina, pending the availability of funding. However, it is evident Doctor Merritt will not be able to attend to me over such a great distance. 

The utility and success of my present treatment is not questioned by those physicians competent to render an informed opinion. Over two years ago Doctor Robert S. Hepler (UCLA) examined me and concluded that my use of marijuana served a valid and critical medical function. Even under extremely trying conditions this prognosis has proven correct. My use of marijuana has led to a stabilization of my disease and has prevented any progression in visual field decay. This is a biological reality which cannot be dismissed.

Doctor Merritt’s decision to leave Howard University does not alter this reality or the fact of my medical needs. It does, however, throw sharp focus onto my concerns for the propriety of the methods employed by NIDA, FDA and DEA in providing me access to marijuana for medicinal use. I am, to be blunt, tired of constantly shifting bureaucratic policies and the confusion inherent in the multi-agencied administration of my medical care. I am weary of and exhausted by overt and covert threats against the security and stability of my access to a medication which the courts have recognized as ‘necessary’ to my health. I have tolerated gross and unwarranted manipulations of a highly irregular nature. I cannot afford these political complications and expect to retain my sight. 

I do not elaborate my grievances to inflate tempers, but to suggest the degree of good faith and patience I have expended over this past year. I believe you to be a decent man trapped by circumstances not of your own making. You must recognize that I too am caught in the same web. In the past few months I have been heartened by developments, like your recent letter to Secretary Califano. My experiences in this area are those of a citizen with a genuine problem who has sought, in vain, for relief from a bureaucratic system designed to serve an entirely different purpose. My medical care has become a captive of laws intended to prevent the abuse of drugs. I cannot be expected to bear the burden of past policies which have been misdirected. I do not believe any reasonable individual would expect me to bear such burdens. 

I have little desire to find myself in conflict with my government over something as immediate and precious as my eyesight. In the few weeks which remain before Doctor Merritt’s departure I would appreciate an opportunity to meet with you or a representative from your Office in the hope that a satisfactory solution can be devised. I sincerely believe, even at this late juncture, that with good faith my immediate problems and the larger question of marijuana’s therapeutic utility can be resolved to the benefit of all concerned.

The failure to find an equitable administrative solution which is legal, cogent, and respectful of my medical needs will serve no one. I cannot afford the physical consequences of such a failure. Though I believe these problems could be resolved by Congress or through the Courts, I also believe they can be solved, and solved more rapidly and completely, through the existing administrative structures. 

I pray this letter impresses you with the sincerity of my concerns and with my very real desire to confront and resolve our mutual problems in a climate of good will. It is, I think, in our mutual interest to seek such a resolution. 

Sincerely yours,

Robert Randall

The White House

Washington

December 19, 1977

Dear Mr. Randall:

Thank you for bringing to my attention the changing status of Dr. Merritt’s glaucoma research, as well as your condition as it relates to that research. In attending to the issue of the Federal Government’s policy on such research, Dr. Richmond, Assistant Secretary for Health, and I have communicated on the subject of research utilizing marihuana as a possible treatment for glaucoma. We are working to establish the most effective means conducting this research.

As for the cessation of your treatment by Dr. Merritt, that issue should be resolved between you and Dr. Merritt. 

I, too, hope we can resolve this issue to everyone’s satisfaction in the near future. 

Sincerely,

Peter G. Bourne

Special Assistant to 

The President

Mr. Robert Randall

709-A 8th Street. S.E.

Washington, D.C.

Exhibit Number 21

Steptoe & Johnson

Attorneys at Law

March 20, 1978

BY HAND

Dr. Robert L. DuPont

Director - NIDA

Room 10-05

5600 Fishers Lane

Rockville, Maryland

Dear Dr. DuPont:

On behalf of my client, Bob Randall, I am writing to renew his request for your assistance in making available marijuana for the treatment of his glaucoma. 

Mr. Randall, as you may be aware, suffers from chronic open-angle glaucoma. His disease produces increasing intraocular eye pressure which, if uncontrolled for three weeks, causes permanent nerve damage eventually leading to blindness. He has been treated with the full variety of conventional drugs and has developed tolerances to all of them. The results of two independent, government-authorized research programs established that marijuana effectively controls Mr. Randall’s excessive eye pressure. Moreover, the side effects associated with use of this drug appear to be far less severe than those of many conventional glaucoma medications. And, of course, no such known risk even approaches in severity the permanent blindness that Mr. Randall faces without effective treatment of his condition.

Mr. Randall’s legal supply of marijuana (obtained through an authorized research program) recently was terminated when the physician in charge of the program left the area. FDA and DEA regulations preclude the dispensing or shipment of marijuana to Mr. Randall or his physician for the treatment of his condition. Although the regulations may allow for continued research of the drug, such an alternative, as it is conceived under existing regulations, has already proven to be inadequate. Limitations placed on the take-home supply of the drug, the attempt to force hospitalization at the patient’s expense solely to conduct tests for research purposes, the requirement of repeated doctor visits for the purpose of monitoring the research, and the request that the patient agree to the substitution of placebos for the medication without his knowledge may all be reasonable from a research perspective, but they are at best irrelevant to and, indeed, a threat to Mr. Randall’s interest in the treatment of his serious disease. My client thus faces the loss of his sight for want of an adequate remedy under the current regulatory scheme. 

What is needed is what the proposed Drug Regulation Reform Act of 1978 refers to as a “drug treatment investigation,” i.e., an active investigation intended primarily for the “treatment” of persons with a serious disease. Recognition of such an approach, or of a “compassionate use” of marijuana in Mr. Randall’s situation, would provide him or his personal physician with legal access to the only existing drug that can save his sight without the onerous restrictions attending Schedule I research programs. 

If you think it might be productive for us to discuss with you any such alternative to the currently existing regulatory format, we would be happy to do so. We would certainly prefer an administrative solution to this problem even on an interim basis to allow for a determination of whether long term arrangements for treatment could be agreed to. If none is forthcoming, however, we will be compelled by the circumstances outlined here to bring this matter to the court. Developments in constitutional law convincingly support Mr. Randall’s right to medical treatment with this drug as an extension of his right to privacy. It is difficult to believe that a court would compel him to go blind. Whatever the result, however, we will be forced to seek such a remedy next week if it is not possible for the various agencies which control marijuana to deal with this problem administratively. 

Please do not hesitate to call.

Sincerely,

Tom Collier

Cc: Peter G. Bourne. M.D.

Commissioner Donald Kennedy

The Honorable Peter B. Bensinger

Donald Miller, Esp.

Richard Cooper, Esq.

Nancy W. Soulen, Esq.

Edward C. Focus, Ph.D.

Robert E. Willete, Ph.D.

Department of Health, Education, and Welfare

Public Health Service

Alcohol, Drug Abuse, and Mental Health Administration

Office of the Director

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, Maryland 20857

Area Code 301 TEL: 443-6480

Thomas C. Collier, Jr.

Steptoe & Johnson

1250 Connecticut Avenue

Washington, D.C. 20036

Dear Mr. Collier:

This is in reply to your letter of March 20 on behalf of your client, Mr. Robert Randall. As we have indicated in the past and the efforts of the NIDA staff have demonstrated, we sympathize with Mr. Randall and have been and are prepared to do what we can to help him within the limits imposed by law. Unfortunately, the present status of cannabis precludes our supplying this drug except under the classification of an investigational new drug (IND).

At the request of Dr. Peter Bourne, the Public Health Service established an interagency committee to coordinate and foster research on new therapies associated with marijuana and other controlled drugs. It is clearly within the jurisdiction of this committee and the National Eye Institute to take whatever action is appropriate in order to pursue the effects of marihuana on glaucoma. 

I am sending a copy of your letter to the Chairman of that committee, Dr. Seymour Perry, and to Dr. Carl Kupfer, Director of the National Eye Institute, and urge that you and Mr. Randall contact either Dr. Kupfer or Dr. Douglas Gaasterland of the National Eye Institute regarding the availability of other research studies or appropriate treatment. We will be willing to participate in any discussions you may have with them in regard to facilitating any supply, if in their judgement such is warranted.

Sincerely yours,

Robert L. DuPont, M.D.

Director

BY HAND

Dr. Robert L. DuPont

Director - NIDA

Room 10-05

5600 Fishers Lane

Rockville, Maryland

Dear Dr. DuPont:

I appreciate your response to my March 20 letter. As you recognized, it is unfortunate that marijuana cannot be made available to Mr. Randall for therapeutic purposes and is only available through an IND. Since my letter raised the possibility of making the drug available through a “compassionate use” or a program similar to a “drug treatment investigation” as proposed under the Drug Regulation Reform Act, I presume you have concluded that no such option is currently available.

As you suggested, I contacted Dr. Gaasterland at the National Eye Institute (NEI) “regarding the availability of other research studies or appropriate treatments.” Dr. Gaasterland was particularly kind and helpful. Although I had hoped he might be able to provide me with some information on research and treatment programs which would allow our client to use marijuana to treat his glaucoma, this was not the case. According to Dr. Gaasterland NEI neither conducts nor has any plans to conduct research on smoked marijuana’s effects on glaucoma.

Dr. Gaasterland, however, did make two treatment suggestions. The first, surgery, has been rejected by my client upon advice of his doctors because of the significant risks which accompany such procedures. It is possible, however, that his second suggestion, Timolol, could offer some relief to Mr. Randall in preventing the further deterioration of his sight. After discussing this medication with Dr. Gaasterland, I contacted its manufacturer, Merck, Sharp and Dohme, and was told that the drug is not under active research anywhere in the country and that the IND procedures have been completed. As I understand it, the drug is simply awaiting approval of an NDA which has been filed. 

Mr. Randall’s purpose in his extended efforts before this and other agencies has not been to legalize marijuana, but merely to save his sight. In order to do that, however, some medical alternative – whether it is Timolol (assuming it is effective and safe) or marijuana – must be made available to him immediately. 

My letter of March 20, 1978, informed you and several other interested persons that, absent a response by the week of March 27-31, we would seek judicial relief. Your April 5, 1978 letter reached us just prior to the planned filing of our action. Although your letter does not propose any means by which Mr. Randall might be able to acquire legal marijuana to treat his glaucoma, my discussion with Dr. Gaasterland concerning Timolol raises the possibility that such a medication might be an effective and safe alternative treatment. 

We urgently request, therefore, that Timolol be made available to Mr. Randall upon prescription by his personal physician even though an NDA has not been approved. Our request is once again rested upon a compelling need for the approval of a “compassionate use” of the drug. Prior to my client’s actual use of Timolol, both he and his physician would need to become thoroughly familiar with data on its safety and efficacy. Although a decision to approve the early use of Timolol is not within NIDA’s authority, by copy of this letter we are specifically requesting that all of those responsible for formulating national drug policy, including Commissioner Kennedy, consider our request. 

The risk that Mr. Randall will suffer further damage to his eyes increases with each day that passes. Although I apologize for pressing you, this situation creates the need for an immediate response. If we have not been informed by Wednesday afternoon that there is a substantial possibility that Timolol will be made available immediately to my client for the treatment of his glaucoma, we will proceed to file a Motion for a Temporary Restraining Order in the United States District Court. By this Motion we will request that the court take those actions necessary to ensure that Mr. Randall is permitted to receive and use marijuana to treat his glaucoma. 

As I explained to you in my last letter, it is my sincere desire that we find a resolution of this matter which does not require judicial intervention. Therefore, I look forward to hearing from you by Wednesday.

Sincerely,

Tom Collier

Cc: Peter G. Bourne, M.D; Commissioner Donald Kennedy; The Honorable Peter B Bensinger; Donald Miller, Esq.; Richard Cooper, Esq.; Nancy W. Soulen, Esq.; Edward C. Focus, Ph.D.l Robert E. Willette, Ph.D.

Exhibit Number 24

The Johns Hopkins Hospital 

Baltimore, Maryland 21205

March 22, 1976

Ben S. Fine

Room 702

915 19th Street Northwest

Washington, D.C. 20006 Re: RANDALL, Robert C.

Dear Doctor Fine, 

Thank you very much for referring Mr. Robert C. Randall to the Wilmer Institute. Basically, Mr. Randall presented to you in Washington in 1972 with an approximately two year history of episodes of painless loss of vision. He had been treated by you until 1975, when in December he was hospitalized in Los Angeles by Dr. Hepler and treated with P-40 Ocuserts and Glaucon. He has since been on Phospholine Iodide 0.03% twice a day in both eyes with pressures in the 20’s and 30’s by history but field loss has continued. The day of admission his vision without correction was 5 ft./200 in the right eye, 20/400 in the left eye, pinhole to 20/200. Wearing -6.25 sphere, he was 20/200 in the right eye; manifest at -6.75 sphere he was 20/100. In the left yee wearing -6 + 0.25 axis 150, he was 20/15 manifest no improvement. Dilated no improvement. He could read J-1 at 20 inches in the left and no J in the right. Externally he was white and quiet bilaterally with normal lids, lashes and lacrimals. Tensions by applanation were 42 in the right eye and 44 in the left eye. Phospholine Iodide having been taken seven hours before. Tensions were Schiotz’s were 5 in the right eye and 5.5 in the left eye over 10. Pupils were 1mm. and fixed. Cornea was clear bilaterally. The anterior chamber was deep without ray or cell and gonioscopy disclosed grade III 360 degree angles in both eyes with prominent iris processes and 2+ pigmented trabeculum. The lens was clear bilaterally. The Iris in the left eye had large radial vessels coming from the periphery at 3 and 9 o’clock to the iris sphincter. He was orthophoric with normal ductions and versions and his maculae, vessels, and periphery were normal bilaterally. He had a 95% cup in the right eye with a bare, pale, temporal rim. The cup in the left eye was 85 to 90% with a better temporal rim. There was profound nasalization of the vessels in both eyes. The assessment was chronic open angle glaucoma, not in control, question of mesodermal angle abnormality. 

At the time of admission fundus photos were taken and visual fields were also performed which disclosed loss of fixation in the right eye and nasal steps in the left consistent with glaucoma. The patient was discussed with Dr. Neil Miller and Dr. Irvin Pollack and it was decided to begin the patient on 4% Pilocarpine four times a day and 2% Glaucon twice a day to both eyes. The evening of admission his tension by applanation were 21 in the right eye and 19 in the left eye.

At 8:00 a.m. the next morning they were 34 and 30, at 1:00 p.m. 34 and 32 respectively, at 6:00 p.m. 20 and 16, and at 10:00 p.m. 32 and 32. The following morning at 7:00 a.m. his pressure were 25 in the right eye and 30 in the left eye. At this point Pilocarpine was discontinued and the patient was begun on 0.25% Phospholine Iodide twice a day to both eyes and the Glaucon was continued. At 6:00 p.m. that evening his tensions by applanation were 38 bilaterally, at 10:00 p.m. they were 28 in the right eye and 27 in the left eye, and at 7:00 p.m. the following morning they were 18 bilaterally. At noon the next day his pressures were 26 in the right eye and 35 in the left eye. At this point Diamox 250 mg. p.o. q.6 hours was begun and the Phospholine Iodide and Glaucon 2% were continued twice a day each to both eyes. His tension at 5:00 p.m. that day was 22 in the right eye and 23 in the left. At 10:20 p.m. that evening his pressures were 25 bilaterally, at 11:00 a.m. they were 21 bilaterally, at 5:00 p.m. they were 28 in the right eye and 26 in the left eye. At 10:00 p.m. his pressures were 21 in the right eye and 19 in the left eye and at 7:30 a.m. the next morning his pressures by applanation were 19 in the right eye and 18 in the left eye. It is fair to say that his pressures were definitely not controlled with Phospholine Iodide and Glaucon in the strengths used and there were instances when even on maximal medical therapy in our hands the patient’s pressures were above 21 mm. of mercury. 

We would, of course, leave all conclusions as to the ultimate outcome of medical therapy in this patient’s glaucoma treatment, but it is our conclusion that maximal medical therapy in our hands was not successful in controlling Mr. Randall’s pressures. 

If we can be of any further assistance to you, please do not hesitate to let us know. 

Exhibit Number 25

Department of Health, Education, and Welfare

Public Health Service

Food and Drug Administration

Rockville, Maryland 20857

April 20, 1978

Thomas C. Collier, Jr., Esq. 

Steptoe & Johnson

1250 Connecticut Avenue, N.W.

Washington, D.C. 20036

Dear Mr. Collier:

At the direction of Donald Kennedy, Commissioner of Food and Drugs, this letter responds to your letters dated March 20, 1978, to him and to me with which you enclosed a copy of your letter of that date to Dr. Robert L. DuPont, Director of the National Institute on Drug Abuse.

We are familiar with the medical problems of your client, Robert Randall; on several occasions, I have discussed the subject with him at our offices in the Parklawn Building and by telephone. As I am sure you are aware, Mr. Randall was able to receive marihuana pursuant to an investigational exemption granted to Dr. Merritt at Howard University only as a result of the closest and most considerate cooperation of the Food and Drug Administration, the Drug Enforcement Administration and the National Institute on Drug Abuse. The grant of that exemption, however, was wholly in accordance with applicable regulations. 

Your letter reflects an understanding of the legal restrictions imposed on the Food and Drug Administration by the Federal Food, Drug, and Cosmetic Act and the Controlled Substances Act. As I am sure you are aware, marihuana, as a controlled substance within Schedule I of the Controlled Substances Act, has been found to have a “high potential for abuse”. On two occasions in the past, however, it was made available for clinical investigation of glaucoma in accordance with applicable provisions of the Federal Food, Drug and Cosmetic Act and the Controlled Substances Act, (as it pertains to research with controlled substances in Schedule I). But, at this time, there are no such studies in progress within the United States. And, reference to the provisions of the “Drug Regulation Reform Act of 1978” is inapposite because it is merely a bill that is the subject of legislative consideration; its provisions are without the force and effect of law, and are irrelevant to the resolution of your client’s medical problem at this time. 

Investigations in animals and in man with marihuana for reduction of intraocular pressure from wide-angle glaucoma have indicated that tetrahydrocannabinol is the active ingredient. This substance has been prepared recently in eye-drop form by the National Institute on Drug Abuse. Eye drops may be a more acceptable dosage form for ophthalmologists who have been reluctant to conduct glaucoma research wit marihuana in cigarette form. 

We anticipate more applications for the study of glaucoma with the eye drops and consequently, more opportunities for individuals like Mr. Randall to participate voluntarily in such studies. We do not anticipate that restrictions on the eye drops will be as severe as those imposed with the cigarettes, although protocols for such investigations will have to be designed to eliminate bias in evaluating the results of use. 

I trust that this letter is responsive to the concerns which you expressed on behalf of Mr. Randall. Please feel free to contact us if you believe that we might be of assistance in securing proper medical care for your client. We believe the physicians on staff at the National Eye Institute have more expertise in ophthalmology and can better advise Mr. Randall about proper medical care and treatment. 

Sincerely yours, 

Edward C. Tocus, Ph.D.

Chief, Drug Abuse Staff

Division of Neuropharmacological 

Drug Products 

Bueau of Drugs

Exhibit Number 26

STEPJOHN WSH

WJ INFOMASTER 4-027084E126 05/06/78

ICSIPMMTZZ CSP

ZCZC 2028622629 TDMT WASHINGTON DC 134 05-06 0212P EST

TLX 892503 STEPJOHN WSH

TOM COLLINS, STEPTOE AND JOHNSON

WASHINGTON DC 20036

BT

THE FOLLOWING IS A COPY OF A TELEGRAM SENT TO DR BRUCE SHIELDS BY TOM COLLINS 5/6/78

Dear Dr. Shields,

Robert Randall explained to me the decision you reached yesterday May 5 1978, concerning Timolol. He stated that you determined that although Timolol initially reduced his IOP to within a safe range, that effect has diminished to the extent that Timolol is no longer effective in maintaining his IOP within a safe range. This determination is essential to judicial action we have planned for Monday, May 8, 1978. If the above statement concerning Timolol does not represent your conclusion, it is imperative that you clarify that determination immediately by telephone, telex, or collect telegram to Tom Collier, Steptoe and Johnson, 1250 Connecticut Ave. Northwest Washington, D.C. 20036 Phone 202-862-2141 Telex number 89-2503.

I sincerely apologize for the sense of emergency; however, it is inescapable. 

If you have any questions please call. Thank you for your assistance.

Regards,

Tom Collier

Steptoe and Johnson

ATTN D GERVASI 1250 Connecticut Ave. Northwest, Washington, D.C. 20036

NNNN

1423 EST

STEPJOHN WSH

Exhibit Number 27

Look in Project 50 archives, unavailable here. Was not included in files received before transcribing. -RAP St Nic

Exhibit Number 28

Edward C. Tocus, Ph.D. 

Chief, Drug Abuse Staff

Food and Drug Administration

5600 Fishers Lane

Rockville, Maryland 20857

Dear Dr. Tocus:

Thank you for your recent response on behalf of Commissioner Kennedy to my March 20 letter. The discussion of Tetrahydrocannabinol (THC) eye drops included in your letter was intriguing. We had learned earlier that no human research had yet been conducted with this drug. My phone call of April 28, 1978, therefore was intended to ensure that we had not been misinformed. I sincerely appreciated both your confirmation of our understanding and the additional information which you so kindly provided, that no IND for use of the THC eye drops in humans has yet been approved by the FDA – indeed, that no such application has even been submitted – and that even if such an application were submitted at this time, it would be for a late phase I or early Phase II IND. Our review of an article, Investigational New Drugs, by Finkel & Zatman, once sent by the FDA to Mr. Randall in an effort to explain the IND process, showed that Phase I trials are directed primarily at toxicity, while Phase II trials concern whether a drug may have a “potential value outweighing possible hazards.” As we understand this procedure, patients with severe conditions are not included in IND studies until they reach Phase III, involving extensive clinical trials. 

As I explained in our telephone conversation, and as I had earlier stated to Mr. Bill Hill, Mr. Randall is currently undergoing treatment with Timolol. Timolol initially reduced Mr. Randall’s IOP to within a safe range. Recently, however, a noticeable decline in this effect has occurred. We hope, but without reason, that this trend will reverse itself during the course of this week. Should Timolol fail effectively to control Mr. Randall’s glaucoma, we will have no choice but to institute court action requesting that marijuana be made available to treat Mr. Randall’s glaucoma. Although the government’s position has been unmistakable that any informal resolution of the matter is impossible, we ask that you urge reconsideration of the government’s position. 

Your letter of March 20 stated that the proposed Drug Regulation Reform Act’s provision for a therapeutic IND is both irrelevant and inapposite to Mr. Randall’s request. Although we recognize that this provision for a therapeutic IND is not yet law, we believe it is relevant in at least two ways: first, it serves as an indication that the administration recognizes the necessity, in order to prevent serious health consequences, of allowing the use of drugs not yet commercially available; second, it indicates that such an exception to the normal regulatory scheme will not adversely affect the integrity of the federal drug control system. We do not request an exemption under the provisions of the new Act, for obvious reasons. However, we do request, particularly in light of the apparent diminishing effectiveness of Timolol in controlling Mr. Randall’s IOP, the therapeutic availability of marijuana in a manner similar to that recognized by the new Act. 

Thank you again for your assistance. 

Sincerely, 

Tom Collier

TC: el

Cc: Bill Hill, Esquire