Drug Abuse

Research Findings on Medicinal Properties of Marijuana

by Kevin B. Zeese, Esq.

President, Common Sense for Drug Policy

I. Background to the Medical Marijuana Debate

With the passage of initiatives in California and Arizona the debate about the medical utility of marijuana is in the spotlight once again. On December 30, 1996, the federal government announced that it intends to use their authority to stop doctors from recommending or prescribing marijuana to their patients and is planning a public relations campaign to demonstrate marijuana has no medical value.

The memorandum describing their policy stated that: a practitioner's action of recommending or prescribing Schedule I substances is not consistent with the public interest' (as that phrase is used in the federal Controlled Substances Act) and will lead to administrative action by the Drug Enforcement Administration to revoke the practitioner's registration." Further if a physician does not have a bona fide doctor patient relationship when recommending or prescribing marijuana they will face criminal prosecution.

In addition to threatening doctors for giving medical advice to their patients the Clinton Administration is undertaking a public-relations offensive" which will include a campaign to discredit the notion that smoking marijuana has medicinal benefits." In their December 30 memorandum, the Administration described a public relations effort with medical associations and the public reenforcing the

messagethat marijuana has no medical value. On December 29, 1996 retired General Barry McCaffrey, the nation's drug czar, claimed in a column syndicated by the Scripps-Howard News Service that No clinical evidence demonstrates that smoked marijuana is good medicine." He has consistently described medical marijuana as Cheech and Chong medicine."

The purpose of this compilation is to provide policy makers, health professionals and the public with the published literature and reports filed with the Food and Drug Administration that demonstrates that doctors have a basis for recommending marijuana as a medicine to their patients.

II. The Long History of Marijuana as Medicine

Marijuana has long been recognized as having medical properties. Indeed its medical use predates recorded history. The earliest written reference is to be found in the fifteenth century B.C., Chinese Pharmacopeia, the Ry-Ya. Between 1840 and 1900, more than 100 articles on the therapeutic use of cannabis were published in medical journals. The federal government in its 1974 report Marihuana and Health states:

The modern phase of therapeutic use of cannabis began about 140 years ago when O'Shaughnessy reported on its effectiveness as an analgesic and anticonvulsant. At about the same time Moreau de Tours described its use in melancholia and other psychiatric illnesses. Those who saw favorable results observed that cannabis produced sleep, enhanced appetite and did not cause physical addiction.

The 1975 report of the federal government began its discussion of medical marijuana by stating Cannabis is one of the most ancient healing drugs." The report further noted: One should not, however, summarily dismiss the possibility of therapeutic usefulness simply because the plant is the subject of current sociopolitical controversy."

The list of medical uses of cannabis from historical references includes:

Anorexia Asthma Nausea

Pain Peptic Ulcer Alcoholism

Glaucoma Epilepsy Depression

Migraine Anxiety Inflammation

Hypertension Insomnia Cancer

Interestingly, relief of many of the symptoms marijuana was used for in these illnesses are many of the same symptoms that have been proven in modern research. This should not be surprising unless we want to assume that all of the experience of thousands of years did not have some factual basis.

III. Modern Research Findings on Medical Marijuana

As can see from this compilation there has been a tidal wave of published research demonstrating marijuana's medical usefulness. Indeed, it is stated in the research studies conducted by various states under FDA protocol that the research being conducted was in the final phase of approval by the FDA. When the federal government stopped research on the medical use of marijuana in 1992 the drug had nearly completed the requirements for new drug approval.

Drug Czar Barry McCaffrey's assertion in his Scripps-Howard News Service column that No clinical evidence demonstrates that smoked marijuana is good medicine" is inconsistent with the facts. Whether this is an intentional deception, as part of the federal government's stated public relations offensive against medical marijuana, or whether it is based on ignorance does not matter. The reality is General McCaffrey's statements are not consistent with the facts.

The research reprinted in this compilation includes randomized, double-blind, placebo controlled studies, research using a variety of objective and subjective measurements and a range of research protocols. Doctors have a sound basis on which to recommend marijuana for use by their patients. Indeed, physicians are well aware of the medical value of marijuana. One study, a scientific survey of oncologists found that almost one half (48 percent) of the cancer specialists responding would prescribe marijuana to some of their patients if it were legal. In fact, over 44 percent reported having recommended the illegal use of marijuana for the control of nausea and vomiting.

This publication addresses research that has been published in three areas: cancer, glaucoma and muscle spasticity. All of the materials herein were published after 1970. The materials enclosed are either published in peer review journals, government publications or are reports submitted to the federal government by state agencies.

A. Published Research Studies

There have been several studies which have been published which focus on the medical value of smoked marijuana and cancer therapy. These include:

• Vinciguerra et al., Inhalation Marijuana as an Antiemetic for Cancer Chemotherapy," The New York State Journal of Medicine, pgs., 525-527, October 1988 involved 56 patients who had no improvement with standard antiemetics. When treated with marijuana 78 percent demonstrated a positive response. No serious negative side effects were seen.
• Chang et al., Delta-9-Tetrahydrocannabinol as an Antiemetic in Cancer Patients Receiving High Dose Methotrexate," Annals of Internal Medicine, Volume 91, Number 6, pg. 819-824, December 1979 is a randomized, double-blind, placebo controlled trial of THC and smoked marijuana which found a 72 percent reduction in nausea and vomiting. The research found that smoked THC (marijuana) was more reliable than oral THC.
• Foltin, R.W., Brady, J.V. and Fischman, M.W. 1986. Behavioral analysis of marijuana effects on food intake in humans. Pharmacology, Biochemistry and Behavior. 25: 577-582 and Foltin, R.W. et al., 1988 Effects of Smoked Marijuana on Food Intake and Body Weight of Humans Living in a Residential Laboratory," Appetite 11:1-14; Greenberg, et al. 1976 Effects of Marijuana use on Body Weight and Caloric Intake in Humans," Psychopharmacology 49: 79-84. All demonstrate that marijuana increases appetite and food intake.
• Doblin et al., Marijuana as Antiemetic Medicine: A Survey of Oncologists' Experiences and Attitudes," Journal of Clinical Oncology, Vol. 9, No. 7, July 1991. A random survey of clinical oncologists found that 44 percent of respondents report recommending the (illegal) use of marijuana for the control of emesis and 48 percent would prescribe marijuana to some patients if it were legal.
• Sallan, S.E., Zinberg, N.E. and Frei, D., Antiemetic Effect of Delta-9-tetrahydrocannabinol in Patients Receiving Cancer Chemotherapy," New England Journal of Medicine, 293(16): 795-797 (1975). The researchers conducting this study of THC noticed that some patients were dropping out of the research and choosing to use marijuana from the street instead. They followed up on these patients. In their conclusion they reported on the marijuana patients and stated that natural marijuana was more successful than synthetic THC for some patients.

The cancer research is relevant to marijuana as a useful therapy for AIDS patients. The same symptoms are needed to be controlled among AIDS patients: appetite, nausea and vomiting. There have been recent reports of AIDS and marijuana in the literature. A study with THC found relief of nausea and significant weight gain in 70 percent of patients. However, one-fifth of the patients did not like the psychoactive effective of synthetic THC, indicating marijuana is likely to be preferred by AIDS patients. This is consistent with a survey of people with AIDS conducted by a researcher in Hawaii in 1996. The survey found that 98.4 percent of AIDS patients were aware of the medical value of marijuana and 36.9 percent had used it as a antiemetic. Of those that had used is 80 percent preferred it over prescription drugs including synthetic THC. A study being conducted in Australia of HIV patients found that those who use marijuana had a better quality of life. In particular, those that were HIV positive for over ten years found marijuana to be critical. One patient told the researcher that he considered marijuana to his savior."

Regarding glaucoma, there have been published studies which consistently show that marijuana is effective in lowering intraocular eye pressure. Heightened intraocular eye pressure is the cause of glaucoma. Thus published evidence indicates marijuana preserves the vision of people with glaucoma.

Finally, regarding the control of muscle spasm there is published literature demonstrating marijuana to be effective in controlling convulsions. The control of muscle spasm is important to patients with multiple sclerosis, epilepsy, spinal cord injury, paraplegia and quadriplegia.

B. State Health Department Studies

In addition to the published research there have been a series of six studies conducted by state health departments under research protocols approved by the U.S. Food and Drug Administration.The focus of these studies, conducted by six state health agencies was the use of marijuana as an anti-emetic for cancer patients. The studies, conducted in California, Georgia, New Mexico, New York, Michigan and Tennessee, compared marijuana to antiemetics available by prescription, including the synthetic THC pill, Marinol. Marijuana was found to be an effective and safe antiemetic in each of the studies and more effective than other drugs for many patients.

New Mexico: This study involved 250 patients.The study compared marijuana to THC capsules. The research protocol was approved by the FDA in 1978. In order to participate in the research the patient had to be referred by a physician and had to have failed on at least three other antiemetics. Patients were permitted to choose marijuana or the THC pill. Both objective (e.g., frequency of vomiting, amount of vomiting, muscle biofeedback, blood samples and patient observation) and subjective measures were made to determine the effectiveness of the drug.

The study concluded that marijuana was not only an effective antiemetic but also far superior to the best available conventional drug, Compazine, and clearly superior to synthetic THC pill." The study found that [m]ore than ninety percent of the patients who received marijuana . . . reported significant or total relief from nausea and vomiting." The study found no major adverse side effects. Only three patients reported adverse reactions, none of these reactions involved marijuana alone. The 1984 report concluded . . . the data accumulated over all five years of the program's operation do show that marijuana smoked resulted in a higher percentage of success than does THC ingested."

Michigan: The Michigan research compared marijuana to Torecan. It involved 165 patients. Upon admission to the program patients were randomized into control groups with some randomized on the conventional antiemetic Torecan and the remainder randomized to marijuana. When failure on the initial randomized drug occurred, patients could elect to crossover to the alternate therapy. This procedure allowed the Michigan Department of Health to evaluate how well patients responded to both drugs and allowed patients to register their preference.

The Michigan study reported 71.1 percent of the patients who received marijuana reported no emesis to moderate nausea. Ninety percent of the patients receiving marijuana elected to remain on marijuana. Only 8 of 83 patients randomized to marijuana chose to alter their mode of antiemetic therapy. This was almost the inverse of patients randomized to Torecan, there more than 90 percent - 22 out of 23 patients - elected to discontinue use of Torecan and switched to marijuana.

Very few serious side effects were found related to marijuana use. The most common side effect was increased appetite - reported by 32.3 percent of patients - this was a positive effect. The most common negative effects were sleepiness, reported by 21 patients and sore throat, reported by 13 patients.

Tennessee: This study involved an evaluation of 27 patients. The patients had all failed on other forms of antiemetic therapy including oral THC. The study found an overall success rate of 90.4 percent for marijuana inhalation therapy. In comparison it found a 66.7 percent success rate for THC capsules. In the under 40 age group, the study found a 100 percent success rate for marijuana inhalation therapy.

The report concludes:

We found both marijuana smoking and THC capsules to be effective anti-emetics. We found an approximate 23 percent higher success rate among those patients administered THC capsules. We found no significant differences in success rates by age group. We found that the major reason for smoking failure was smoking intolerance; while the major reason for THC capsule failure was nausea and vomiting so severe that patient could not retain the capsule.

New York: In describing the purpose of the marijuana research program the New York Department of Health stated: [t]he program is a large-scale (Phase III) cooperative clinical trial . . . ." The central question addressed is [h]ow effective is inhalation marijuana in preventing nausea and vomiting due to chemotherapy in patients . . . who have failed to respond to previous antiemetic therapy?"

By 1985, the New York program had extended marijuana therapy to 208 patients through 55 practitioners. Of that, 199 patients were evaluated. These patients had received a total of 6,044 NIDA-supplied marijuana cigarettes which were provided to patients during 514 treatment episodes.

In percentage terms the results were stunning:

• North Shore Hospital reported marijuana was effective at reducing emesis 92.9 percent of the time;
• Columbia Memorial Hospital reported efficacy of 89.7 percent;
• Upstate Medical Center, St. Joseph's Hospital and Jamestown General Hospital reported 100 percent of the patients smoking marijuana gained significant benefit.

The report concludes: Patient evaluations have indicated that approximately ninety-three (93) percent of marijuana inhalation treatment episodes are reported to be effective' or highly effective' when compared to other antiemetics." The New York study reports no serious adverse side effects. No patient receiving marijuana required hospitalization or any other form of medical intervention. See, Evaluation of the Antiemetic Properties of Inhalation Marijuana in Cancer Patients Receiving Chemotherapy Treatment," New York Department of Health, Office of Public Health (Annual Reports).

Georgia: The Georgia program evaluated 119 patients. It compared THC to standardized smoking of marijuana and with patient-controlled smoking. To enter the program a patient had to have failed on other antiemetics. Patients were randomized to either patient-controlled smoking of marijuana, standardized smoking of marijuana or THC pills.

The report found that both THC and marijuana were effective in providing antiemetic relief for patients who were previously unresponsive to antiemetics. The rate of success was 73.1 percent. Patient controlled smoking of marijuana was successful in 72.2 percent, standardized smoking was successful in 65.4 percent and THC was effective in 76 percent of the cases. In comparing the reasons for failure between marijuana and THC the report found:

The primary reasons for failure of THC capsules were due to either adverse reaction (6 out of 18) or failure to improve nausea and vomiting (9 out of 18). The primary reason for failure of smoking marijuana were due to smoking intolerance (6 out of 14) or failure to improve the nausea and vomiting (3 out of 14).

California: California conducted a series of studies from 1981 through 1989. Annual reports were submitted to the FDA, state legislature and Governor. Each year approximately 90 to 100 patients received marijuana. The California research was described as a Phase III trial."

The study protocol preferred THC pills by making it much easier for patients to enter that portion of the study. Patients who received marijuana had to be over 15 years of age (the THC pill patients had to be over 5 years of age); had to be marijuana experienced, use the drug on an in-patient basis (patients could only use marijuana in the hospital and not take the medicine home) and had to be receiving rarely used and severe forms of chemotherapy. Thus, the design of the study did not favor marijuana.

Even with this built in bias against marijuana, the study consistently found marijuana to be an effective antiemetic. In 1981 the California Research Advisory Panel reported: Over 74 percent of the cancer patients treated in the program have reported that marijuana is more effective in relieving their nausea and vomiting than any other drug they have tried." In 1982, a 78.9 percent effectiveness rate was found for smoked marijuana. By 1983 the report was conclusory in its findings stating:

The California Program also has met its research objectives. Marijuana has been shown to be effective for many cancer chemotherapy patients, safe dosage levels have been established and a dosage regimen which minimizes undesirable side effects has been devised and tested.

The California Research Advisory Panel continued to review data on marijuana until 1989 with similar results.

C. Studies of Marijuana Constituents

In addition to research on smoked marijuana there has been a host of research on constituents of marijuana. This research is relevant in measuring the effectiveness of marijuana.

The drug for which there has been the most research is the THC pill. This pill contains pure delta-9-tetrahydrocannabinol in sesame seed oil. This substance is now scheduled in Schedule II of the Controlled Substances Act. When the drug was rescheduled the Food and Drug Administration acknowledged: The effects of pure THC are essentially similar to those of cannabis containing THC in equivalent amounts." Thus, the federal government has acknowledged that THC, which is available as a medicine, adequately emulates the effectiveness to marijuana. In fact, the research described above shows that marijuana is in fact a more effective medicine than the THC pill.

The research which compares marijuana to the THC pill found that patients preferred marijuana to THC and that marijuana was more effective at treating symptoms. State studies in Michigan and New Mexico found that most patients who tried THC chose to use marijuana instead. The most common reasons for this choice was because THC was more psychoactive, erratic and unpredictable. Patients found they had more control and a quicker response with smoked marijuana than with oral THC. Patients found it difficult to swallow the pill when they were nauseous. Patients were also able to limit their use of marijuana to only the amount needed when it was smoked. For many cancer and AIDS patients this can involve smoking a very small quantity of the drug. With the THC pill the patient must ingest the whole pill and therefore cannot control the dose.

The Chang study published in The Annals of Internal Medicine found that marijuana was more consistent than the oral THC pill. As they note this was consistent with the observations of Sallan and his colleagues in their study published in The New England Journal of Medicine, Alfred Chang et al. stated:

Sallan and his co-workers considered inadequate drug absorption as a possible contributing factor to the lack of antiemetic response seen in some patients. We concur, since THC plasma concentrations appeared to be causally related to an antiemetic response in our study. To avoid this problem, we switched patients to the inhalation route of drug administration when vomiting occurred. Inhaled marijuana results in the same psychological effects as orally administered THC. In our patient populations, smoked THC was more reliable than oral THC in achieving therapeutic blood concentrations.

A final reason why marijuana cigarettes are superior to the THC pill is because it is not only delta-9-THC which provides positive medical effects. The bibliography includes research involving other components of marijuana, including various cannabinoids and delta-8-THC. This research indicates that it is not only delta-9-THC which has beneficial medical effects but other components of marijuana. Smoking marijuana provides the patient with the benefits of the combination of marijuana's active ingredients as opposed to the effects of only THC.

IV. State Laws Provide an Avenue to Resolve The Medical Marijuana Problem

There is strong scientific evidence that marijuana is a safe and effective medicine. The voters in California and Arizona have recognized this at the ballot box. It is time for the federal government to help resolve this problem rather than threaten doctors with sanctions for providing medical advice to their patients and denying seriously ill patients access to a much needed medicine.

The California and Arizona initiatives, as well as state laws in two dozen states, provide an opportunity to resolve the medical marijuana problem. Research on the safety and effectiveness of marijuana is in its final phase. All that is needed is late-Phase III research. These are broad-based research studies which result in large numbers of patients receiving marijuana.

The federal government, in its policy announcement of December 30, stated that it wanted to ensure the integrity of the drug approval process. Part of their plan to do so includes reviewing the research and seeking to fill gaps in research with new research.

Combining the Food and Drug Administration's need for late-Phase III research before they approve marijuana as a medicine, with the decision of voters in California and Arizona to make marijuana medically available, will satisfy two needs. It can make marijuana available to large numbers of people under a research umbrella. (In the early 1980s nearly 1,000 patients a year were using marijuana medically under federally approved research programs. In fact, one year California requested one million medical marijuana cigarettes from the FDA.) In addition, it could finally resolve the medical marijuana problem and make marijuana available as a medicine by prescription.

The Food and Drug Administration should contact the health departments of Arizona, California and other states which have expressed interest in medical marijuana and ask them to participate in the final Phase III studies needed to complete the new drug application process. Getting results from this research should take less than one year. If they are consistent with previous research it should result in marijuana becoming a prescription drug under Schedule II of the Controlled Substances Act. Such a process will restore the integrity of the medical scientific process of drug approval which has been undermined by the use of medical marijuana as a political tool by those favoring expanded drug war policies.

By taking a constructive approach, rather than a confrontational one, the federal government avoids conflict with state law, does not intrude on the doctor-patient relationship and ensures that, in the end, marijuana is only made available as a prescription medicine to the seriously ill. Arizona and California have presented an opportunity to resolve an issue that is long overdue for resolution.

Bibliography

Overviews of Marijuana's Safety and Effectiveness

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Medical Marijuana and Nausea, Vomiting and Appetite

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Greenberg, I., Kuehnle, J., Mendelson,J.H. and Bernstein, J.G. 1976. Effects of marihuana use on body weight and caloric intake in human. Journal of Psychopharmacology (Berlin) 49: 79-84.

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Foltin, R.W., Brady, J.V. and Fischman, M.W. 1986. Behavioral analysis of marijuana effects on food intake in humans. Pharmacology, Biochemistry and Behavior. 25: 577-582.

Foltin, R.W. et al., 1988 Effects of Smoked Marijuana on Food Intake and Body Weight of Humans Living in a Residential Laboratory," Appetite 11:1-14

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Medical Marijuana and Glaucoma

Hepler, R. and Frank, I., (1971). Marijuana smoking and intraocular pressure. JAMA, 217, 1932.

Hepler, R., Frank, I. and Ungerleider, J. (1972). Pupillary constriction after marijuana smoking. Am. J. Ophthalmol., 74, 1185-1190.

Shapiro, D. (1974). The ocular manifestations of the cannabinoids. Opthalmologica, 168, 366-369.

Hepler, R. and Petrus, R. (1976). Experiences with administration of marijuana to glaucoma. In The Therapeutic Potential of Marijuana. (Cohen and Stillman, eds.), 63-75.

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Medical Marijuana, Muscle Spasm and Convulsion

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Dunn, M. and Davis, R., (1974). The perceived effects of marijuana on spinal cord injured males, Paraplegia, 12, 175.

Turkanis, S., Cely, W., Olsen, D. and Karler, R. (1974). Anticonvulsant properties of cannabinol. Res. Comm. Chem. Path. Pharmacol., 8, 231-246.

Consroe, P., Wood, G., and Buchsbaum, H. (1975). Anticonvulsant nature of marijuana smoking. JAMA, 234, 306-307.

Karler, R. and Turkanis, S. 1976. The antiepileptic potential of the cannabinoids. In The Therapeutic Potential of Marijuana, (Cohen and Stillman, eds.), 383-396.

Feeney, D.M., Marihuana and epilepsy: paradoxical anticonvulsant and convulsant effects, Marijuana Biological Effects: Analysis, Metabolism, Cellular Responses, Reproduction and the Brain, (Nahas, GG., Paxton, M., Bruade, J.C., Hardillier, and Harvey, D.J. eds.) Pergamon Press, Oxford, England, 643-657.

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