420
Founder
There have been hundreds of studies on the medical uses of cannabis since its introduction to western medicine in the early nineteenth century. A review of the literature reveals over 65 human studies, most of them in the 1970's and early 80's.
* The best established medical use of smoked marijuana is as an anti-nauseant for cancer chemotherapy. Marijuana's efficacy was demonstrated in studies by half a dozen states, involving hundreds of subjects. Most research has found smoked marijuana superior to oral THC (Marinol). Many oncologists are currently recommending marijuana to their patients.
* Marijuana is widely used to treat nausea and appetite loss associated with AIDS, but the government has blocked research in this area. Studies have shown that marijuana helps improve appetite, and Marinol has been FDA approved for treatment of AIDS wasting syndrome. Nearly 10,000 PWA's were reported to be using marijuana through the San Francisco Cannabis Buyers' Club. However, the government has blocked efforts by Dr. Donald Abrams of the University of California at San Francisco to proceed with an FDA-approved study of marijuana and AIDS wasting syndrome, by refusing to grant him access to research marijuana. Research is badly needed on the relative merits of smoked and oral marijuana versus Marinol.
* There is much evidence, largely anecdotal, that marijuana is useful as an anti-convulsant for spinal injuries, multiple sclerosis, epilepsy, and other diseases. Similar evidence suggests marijuana may be useful as an analgesic for chronic pain from cancer and migraine as well as for rheumatism and a variety of auto-immune diseases. There is a conspicuous lack of controlled studies in this area; further research is needed.
* Cannabidiol, a constituent of natural marijuana not found in Marinol, appears to have distinctive therapeutic value as an anti-convulsant and hypnotic, and to counteract acute anxiety reactions caused by THC.
* It has been established that marijuana reduces intra-ocular pressure, the primary object of glaucoma therapy. Due to its psychoactivity, however, marijuana has not gained widespread acceptance in this application.
* Many patients report using marijuana as a substitute for more addictive and harmful psychoactive drugs, including prescription painkillers, opiates, and alcohol. Marijuana and Marinol have also been found useful as a treatment for depression and mood disorders in Alzheimer's and other patients. More research is needed.
Overview of Medical Marijuana Research
In its position paper, "Use of Marijuana as a 'Medicine,'" the California Narcotics Officers Association refers to "10,000 studies... documenting the harmful physical and psychological effects of smoking marijuana." This myth has been effectively debunked in a letter to Dr. Lester Grinspoon from NIDA's marijuana research librarian at the U. of Mississippi, Beverly Urbanek, who writes, "We are totally in the dark as to where the statement that there are 10,000 studies showing the negative impact of marijuana could have originated." She explains that while her library has some 12,000 citations on cannabis, they cover a broad spectrum of economic, legal, horticultural, enforcement, and other non-health issues, and are not categorized by negative or positive effects. Pursuing the issue further, it is possible to enumerate an impressive number of studies on marijuana's therapeutic uses. There is no space here to list or summarize all of them. The book, "Cannabinoids as Therapeutic Agents," edited by Dr. Raphael Mechoulam (CRC, 1986), includes copious references to research articles on cannabis' pharmacological effects, as follows:
Pharmacohistory of Cannabis Sativa - 90 references;
Therapeutic Potential of Cannabinoids in Neurological Disorders -155
Ocular Effects - 70
Cannabinoids as Antiemetics in Cancer - 91
Cannabinoids and Analgesia - 136
Bronchodilator Action of Cannabinoids - 67
Of course, there are some duplicates, and by no means all of these 609 references actually detail medicinal benefits of marijuana, but it certainly seems reasonable to estimate that there have been 100's of studies on medical use of marijuana.
Human Studies
Following is a summary of the human clinical and epidemiological studies on marijuana's therapeutic applications. We have not attempted to detail the great bulk of research, which consists of animal and in vitro studies that are of more dubious relevance to human health. However, we have tried to include all human studies reported in the recent medical literature.
(1) Anti-Nauseant for Cancer Chemotherapy:
This is by far the best substantiated use of medical marijuana. There have been at least 31 human studies of marijuana and/or oral THC for cancer chemotherapy,1 beginning with the pathbreaking work of Sallan and Zinberg, the first modern study of medical marijuana2. This doesn't count the studies in which the sponsors of Marinol got it FDA approved as "safe and effective" for cancer chemotherapy. Smoked marijuana was shown to be an effective anti-nauseant in 6 different state-sponsored clinical studies: 3 New Mexico (250 patients),4 New York (199 patients),5 California (98),6 Tennessee (27),7 Georgia (119),8 and Michigan (165).9
Smoked marijuana was found to be superior to oral THC in the New Mexico and Tennessee studies, with efficacy rates of 90%. In New York and Tennessee, it was effective in patients who had not been helped by Marinol. In Michigan, patients found smoked marijuana preferable to a conventional prescription anti-nauseant (Torecan). Other researchers have also reported smoked marijuana to be superior to THC.10
The California study was the least satisfactory, being highly biased towards oral THC (2000 patients were given oral THC, versus only 98 for marijuana): still, it found that marijuana was effective in 59% of patients, vs 57% for oral THC; however, 30% rated oral THC "highly effective," versus only 17% for marijuana. This is the only state study showing smoked marijuana inferior to Marinol.11
A survey of oncologists by Doblin and Kleiman reported that 44% of 1035 respondents had recommended marijuana to their patients (54% favored making it a prescription drug).12
(2) Glaucoma:
It is generally accepted - by the National Academy of Sciences and others - that marijuana/THC reduces intraocular pressure (IOP), the basic aim of anti-glaucoma therapy.13
This was shown in a series of experiments by Robert S. Hepler of UCLA, stemming from research aimed at finding out whether marijuana dilated pupils.14 Hepler found a "statistically significant" drop in IOP in 429 subjects treated with marijuana or THC; a subset of 29 patients showed continued benefits during 94 days of treatment with no signs of tolerance.15 The effects of THC/marijuana in reducing IOP were explored in a half-dozen other studies.16
Nonetheless, ophthalmologists have been reluctant to accept marijuana/THC because of its high psychoactivity. Efforts to develop topical cannabinoid eye drops as a non-psychoactive alternative have so far proven unfruitful.
The California Research Advisory Panel established a glaucoma research protocol under its cannabis research program of 1979-89, after finding interest in marijuana in its survey of ophthalmologists. The program flopped: only nine patients were treated; all chose to take Marinol instead of marijuana; and all eventually abandoned treatment.
(3) AIDS & APPETITE STIMULATION:
There have been no clinical studies on the use of marijuana for AIDS. Of course, one reason for this is that the government has blocked the study of Dr. Donald Abrams at the University of California at San Francisco by denying him access to research marijuana.
Nonetheless, Marinol has been FDA-approved as an appetite stimulant for treating AIDS wasting syndrome.17
There is also an extensive literature on smoked marijuana and appetite stimulation, including 4 clinical studies in which marijuana enhanced food intake and weight gain.18
Medical marijuana is widely used by AIDS patients. 80% of the SF Cannabis Buyers' Club's 11,000 customers are said to be PWA's.19 A recent survey of HIV-positive gays in Australia found that one-quarter were using marijuana therapeutically.20
Many AIDS patients prefer smoked marijuana to oral THC, due to its quickness of action, ease of controlling the dose, and absence of side-effects. In addition to appetite stimulation, many AIDS patients use marijuana for pain associated with neuropathy, shingles, etc.
An important concern about smoked marijuana that critics emphasize is the danger of respiratory infection in AIDS patients due to smoking. In particular, critics have cited a worrisome study by Caiaffa et al,21 showing a twofold increase in the rate of pneumonocystis carinii pneumonia (PCP) among HIV positive injection drug users who smoke illegal drugs (88% marijuana, 26% cocaine, 9% crack). There are a few problems with the study, notably that almost all of the subjects also smoked cigarettes; therefore, it's difficult to say whether the PCP was really due to marijuana.
In any case, these problems can be avoided by ingesting marijuana orally, which many AIDS patients in fact do. It's not clear whether oral marijuana has any medical benefits over Marinol, though it could certainly be more economical.
Another problem that critics like to emphasize is the supposed threat to PWA's posed by the immuno-suppressive properties of marijuana. Of course, these objections apply equally well to oral THC, which has been approved for treatment of AIDS. Studies of THC's effects on immunity have been contradictory, and do not lend themselves to easy interpretation.22 There are hints that THC might actually help stimulate the immune system in some ways.23
Epidemiological studies have found no relation between marijuana use and development of AIDS.24 One recent study of 354 HIV-positive males actually found marijuana to be associated with a decreased rate of progression to AIDS, though the difference was not significant when adjusted for parameters reflecting the initial health of the study subjects.25
(4) Muscle Spasticity, MS, Epilepsy & Spinal Injuries
The treatment of convulsions was the first major application of cannabis in Western medicine, attested by 19th-century authorities such as Dr. William O'Shaughnessy, the Ohio State Medical Committee, and Dr. John Russell Reynolds (who prescribed it to Queen Victoria for menstrual cramps).26 Although well authenticated in traditional practice, modern research into this usage has been scant, except for animal studies.
Altogether, there appear to be:
5 human case studies, involving a total of 8 patients, in which marijuana was reported to be useful for: epilepsy, multiple sclerosis, injury, and Tourette's syndrome;27
1 study in which 5 out of 8 spinal cord injury patients reported benefits from marijuana;28
3 more studies of THC for multiple sclerosis (total: 30 patients), in which benefits tended to be more subjective than objectively measurable;29
1 case study of THC for spinal cord injury30
2 clinical studies in which cannabidiol (CBD), a component of natural marijuana not found in Marinol, was found beneficial for grand mal epilepsy (15 subjects, double blind controls)31 and dystonia (5 patients, no controls).32
1 study in which a THC-related cannabinoid benefitted 2 out of 5 severely epileptic children;33
1 survey of 308 epileptic patients found that marijuana use appeared to delay the first onset of complex partial seizures.34
1 survey of 43 spinal cord injury patients at VA hospitals found that 56% smoked marijuana, and 88% reported that it reduced their muscle spasms.35
There have also been a couple of negative studies, finding no benefits of marijuana for Parkinsonism36 or CBD for Huntington's corea.37 Paradoxically, marijuana/THC has been reported to exacerbate spasticity or epilepsy on occasion, perhaps because of a rebound effect.
In a purported recent negative study on marijuana and multiple sclerosis, Dr. Harry Greenberg et al. at U. of Michigan reported that marijuana impaired posture and balance in patients with spastic MS.38 This should come as no surprise, since marijuana/THC also impairs balance in normal patients. In any event, MS patients don't use marijuana for posture/balance, but to reduce tremors and pain.
Cannabidiol:
There is considerable evidence from animal studies that CBD has distinctive anti-convulsant properties not found in THC.39
In addition, there is evidence that CBD can reduce the risk of panic reactions associated with THC. A study by Zuardi found that CBD reduces the anxiety-stimulating effects of THC, a leading cause of adverse reactions to Marinol.40 This may be a reason why many patients prefer natural cannabis.
A controlled study of 15 insomniacs found that CBD helped subjects sleep better.41
(5) Analgesia & Pain
Many patients report using marijuana for some form of pain relief. Cannabis was used as an analgesic from ancient times through the nineteenth century. This usage declined with the introduction of more potent opiates such as injected morphine. Cannabis continued to be regarded as a drug of choice for migraine into the 20th century.
Modern research is scant. Animal studies have tended to show analgesic effects, while human studies have been more conflicting:
In a preliminary study by R. J. Noyes, patients reported that marijuana relieved migraine, menstrual cramps, postsurgical pain. 42
In a follow-up, Noyes found oral THC relieved chronic pain in 10 cancer patients. 43
In a second follow-up with 36 cancer patients, THC was as effective as codeine, but had more side-effects.44
2 other studies found marijuana and THC effective in reducing experimentally induced pain.45
1 study reported that 3 patients began to experience migraines only after giving up marijuana.46
Negative results have also been reported:
1 study failed to find THC benefical for cancer pain, though it did help with depression and appetite.47
1 study found THC useless for artificially induced pain.48
1 study found marijuana increased sensitivity to electrically induced pain.49
1 study found CBD useless for neuropathic pain (10 patients).50
Inflammatory Diseases:
Marijuana is used by many patients for a wide variety of diseases characterized by inflammation. These include arthritis, rheumatism, lupus, multiple sclerosis, colitis, Crohn's disease, inflammatory gastritis, scleroderma, endometriosis, psoriasis, and pruritis. These diseases are thought to be auto-immune in nature. It is possible that the supposed immune suppressive properties of cannabis are beneficial for such conditions.
Unfortunately, there have been no clinical studies of this phenomenon. However, a variety of animal and laboratory studies have shown that cannabinoids have anti-inflammatory properties.51 One mouse study even suggested that a non-cannabinoid ingedient of marijuana may be involved.52
Asthma:
Although this isn't (and shouldn't be) an indication of choice for medical marijuana, three human studies have shown that smoking marijuana produces bronchodilation, thereby relieving asthma attacks.53 Two other studies confirmed the same effects with THC.54 Efforts to develop a smokeless THC inhaler proved unsuccessful.
Depression & Mental Illness:
Opponents of medical marijuana such as the CNOA have charged that marijuana causes depression. In fact, marijuana is more often used to treat depression; hence its notorious reputation as a euphoriant. Human studies have been inconsistent. One study found that marijuana helped relieve depression in cancer patients;55 another found no benefit for clinical depression.56
A survey of 79 mental patients found that those who used marijuana reported relief from depression, anxiety, insomnia, and physical discomfort, as well as fewer hospitalizations;57 a second survey also found fewer hospitalizations in schizophrenics who used marijuana.58 Some psychiatrists are currently prescribing Marinol for depression.
A recent pilot study by the Unimed Corporation found that Marinol helped relieve mood disturbances and anorexia in 12 Alzheimer's patients.59
Violence
Many opponents absurdly charge that marijuana aggravates violence. To this, the best answer is that of the National Academy of Science in Marihuana and Health (1982, p. 128):
"Both retrospective and experimental studies in human beings have failed to yield evidence that marijuana use leads to increased aggression. Most of these studies suggest quite the contrary effect. Marijuana appears to have a sedative effect, and it may reduce somewhat the intensity of angry feelings and the probability of interpersonal aggressive behavior."
Alcoholism & Drug Dependence
Cannabis is often used as a substitute for other, more dangerous drugs, including prescription narcotics, opiates and alcohol. Cannabis has been proposed as a treatment for alcoholism as well as opiate addiction.60 However, a single controlled study of cannabis to treat alcoholics proved unsuccessful.61 There is some epidemiological evidence that substitution of marijuana for alcohol and other drugs tends to reduce drug abuse and accident costs.62 Many cannabis buyers club members say they use marijuana as a substitute for prescription narcotics.63
References
Raphael Mechoulam, ed., Cannabinoids as Therapeutic Agents (CRC Press, Boca Raton) 1986.
Lester Grinspoon and James Bakalar, Marihuana, the Forbidden Medicine, (Yale U. Press) 1993.
Sidney Cohen and Richard Stillman, ed., The Therapeutic Potential of Marihuana (Plenum, NY) 1975.
Tod Mikuriya, Marijuana Medical Papers (Medicomp Press, Berkeley) 1973. Robert Randall, Marijuana, Medicine and the Law (Galen Press, Wash. DC) 1989 (2 Volumes).
National Academy of Sciences, Marijuana and Health, Report of the Institute of Medicine (National Academy Press) 1982. (NAS Report)
Laura Murphy and Andrzej Bartke, ed., Marijuana/Cannabinoids: Neruobiology and Neurophysiology (CRC Press, Boac Raton) 1992.
M.C. Braude and S. Szara, ed., Pharmacology of Marihuana, NIDA Monograph (Raven Press, NY) 1976 (2 Volumes).
References on Glaucoma:
Martin Adler & Ellen Geller, "Ocular Effects of Cannabinoids,"
Chapter 3 in Mechoulam.
Chapts 4-6 "Ophthalmic Effects," in Cohen & Stillman.
References on Anti-Convulsant Properties:
P Consroe & R Sandyk, "Potential Role of Cannabinoids for Therapy of Neurological Disorders," Chapter 12 in Murphy & Bartke.
Paul Consroe & Stuart Snider "Therapeutic Potential of Cannabinoids in Neurological Disorders," Chap 2 in Mechoulam.
References on Analgesia:
Mark Segal, "Cannabinoids and Analgesia," Chap. 6 in Mechoulam
FOOTNOTES
1 Includes (a) 25 studies of oral THC listed in M. Levitt, "Cannabinoids as Antiemetics in Cancer Chemotherapy," in Mechoulam, p. 73; (b) 6 state studies of marijuana listed below.
2 S. Sallan, N. Zinberg and E. Frei, "Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy," New England Journal of Medicine 295: 795 (1975).
3 For a summary, see Robert Randall, ed., Marijuana, Medicine and the Law, Vol . 2 (Galen Press, Wash. DC) 1989, pp. 36ff.
4 New Mexico: 250 patients; 90% relieved; only 3 adverse reactions (all w/THC): testimony of Daniel Dansak, MD in Robert Randall, ed., Marijuana, Medicine and the Law, Vol 1, pp. 125-33; Vol 2 , pp. 36-8.
5 New York: 199 patients evaluated; all had failed previous anti-nauseants (some also failed THC); marijuana 89.7%-100% effective at 3 hospitals. ACT Official State Reports, Vol II, Exhibit 15, "Evaluation of the Antiemetic Properties of Inhalation Marijuana in Cancer Patients Receiving Chemotherapy Treatment," NY Dept of Health, Office of Public Health, Chapter 810, Laws of 1980 Article 33-A, Public Health Law, Septermber 1981; ACT Exhibit 16-C, "Impressions from the National Conference on the Therapeutic Applications of Cannabinoids". Cited in Randall Vol 2, pp. 46-54.
6 California: 98 patients received marijuana; 59% found effective against strong emetics; 57% of 257 patients found THC-only effective; 17% rated marijuana "very effective" vs 30% for THC. "Cannabis Therapuetic Research Program," Report to the Cal. Legislature by California Research Advisory Panel, Jan. 1989. See also Randall, Vol 2, pp. 55-63.
7 Tennessee: 27 patients evaluared of 43 who had failed other therapy, including THC; 90.4% successful on marijuana; 66.7% on oral THC. ACT Official State Reports, Vol II, Exhibit 17, "Annual Report: Evaluation of Marijuana and Tetrahydrocannabinol in the Treatment of Nausea and/or Vomiting Associated with Cancer Therapy Unresponsive to Conventional Anti-emetic Therapy: Efficacy and Toxicity," Board of Pharmacy, State of Tennessee, July 1983. Cited in Randall, Vol 2, p.55.
8 Georgia: 119 evaluable patients; THC or marijuana 73% effective; marijuana had 6 adverse reactions from smoke-intolerance; THC had 6 panic reactions. Michael H. Kuttner, "Evaluation of the Use of Both Marijuana and THC in Cancer Patinets for the Relief of Nausea and Vomiting Associated with Cancer Chemotherapy After Failure of Conventional Anti-Emetci Therapy: Efficacy and Toxicity," report for the Composite State Board of Medical Examiners, Georgia Dept of Health, by researchers at Emory Univ 1/20/83. Cited in Randall Vol. 2, pp. 38-43.
9 Michigan: randomized crossover, marijuana vs Torecan; 165 patients; marijuana 71% effective - similar to Torecan, but patients preferred marijuana. ACT Official State Reports, Vol. II, Exhibit 9, "Evaluation of Marijuana as an Antiemetic in Patients Being Treated with Cancer Chemotherapy," Protocol Trial A, IND # 17-193. Cited in Randall, Vol. 2, p. 43.
10 e,g., Sallan and Zinberg (cited in Randall, vol. 2, p. 35), and AE Chang et al, "Delta-9-thc as an Antiemetic in Cancer Patients Receiving High-Dose Methotrexate: A Prospective Randomized Evaluation," Annals of Internal Medicine 91 (1979) 819-24.
11 For another study in which oral THC was found superior to smoked marijuana in 20 subjects, see: M. Levitt et al, "Randomized double-blind comparison of delta-9-tetrahydrocannabinol (THC) and marijuana as chemotherapy antiemetics," ASCO Abstracts, 3: 94 (1984); cited in Mechoulam, p. 73.
12 Rick Doblin & Mark Kleiman, "Marihuana as Anti-emetic Medicine: A survey of Oncologists' Attitudes and Experiences," Journal of Clinical Oncology 9:1275-80 (1991).
13 NAS Report, "Marijuana and Health," pp. 140-142.
14 R.S. Hepler & I.R.Frank, "Marihuana smoking and intraocular pressure," JAMA 217:1392 (1971). Hepler, RS, Frank, IM, and Ungerleider, JT "Pupillary constriction after marijuana smoking," Am J Ophthalmol. 74: 1185-90, 1972. RS Hepler, IM Frank, IM, and Petrus, R, "Ocular effects of marihuana smoking," in Braude & Szara, Vol. 2: 815-24 (Raven, NY) 1976.
15 Robert S Hepler and Robert J Petrus, "Experiences with administration of Marihuana to Glaucoma Patients, "Chap 5 (pp 63-94) in Cohen & Stillman.
16 Shapiro, D. "The ocular mainfestations of the cannabinols," Ophthalmologica 1974 168:366-9; Purnell, W.D. & Gregg, J.M. "Delta-9 Thc, euphoria and intraocular pressure in man," Annals of Ophthalmology, July 1975; Greeen, K. & Podos, SM "Antagonism of arachidonic acid-induced ocular effects by delta-thc" Investigative Ophthalmology, June 1974; Flom, M.C., Adams, A.J. and Jones, R.T.: "Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenom?", Invest. Ophtalmol., 14:52 (1975); Cooler, P. & Gregg, J.M. "Effect of delta-9-thc on introacoular pressure in humans," South Med J. 70: 954, 1977; Paul Cooler & John Gregg, "The effect of delta-9-thc on intraocular pressure in humans," Chap 6 in Cohen & Stillman; Merritt, J.C., et al: "Oral delta-9-thc in heterogeneous glaucomas," Ann. Ophthalmol., 12:947 (1980); Perez-Reyes, M. et al: "Intravenous administration of cannabinoids and intraocular pressure," in Braude & Szara, p 829; "Jones, R, Benowitz, N, and Herning, RI, "Clinical relevance of cannabis tolerance and dependence," J Clin Pharmacol, 21:143S (1981).
17 TF Plasse, RW Gorter, SH Krasnow, et al "Recent Clinical Experience with Dronabinol," Pharmacology, Biochemistry and Behavior 40 (1991) 695-700.
18 LE Hollister, "Hunger and Appetite after Single Doses of Marihuana, Alcohol, and Dextroamphetamine," Clinical Pharmacology ajnd Therapeutics 12 (Jan-Feb 1971) 44-9. 27 marihuana users and 10 controls - gained weight in hospital ward : Greenberg et al, "Effects of Marihuana Use on Body Weight and Caloric Intake in Humans," Journal of Pscyhopharmacology (Berlin) 49 (1976) 79-84. 9 subjects gained weight smoking marihuana rather than placebo cigarettes:RW Foltin et al, "Behavioral Analysis of Marijuana Effects on Food Intake in Humans," Pharmacology, Biochemistry and Behavior 25 (1986) 577-82. 6 subjects increased caloric intake 40% over 13 days: RW Foltin et al, "Effects of smoked marijuana on food intake and body weight in humans living in a residential laboratory," Appetite 1988: 11:1-14.
19 Personal communication.
20 228 subjects: Prestage, Garrett et al, "Use of Treatments and Health-Enhancement Behavior Among HIV-Positive Men in a Cohort of Homosexually-Active Men," XI International Converence on AIDS, Vancouver, B.C., Canada, July 1996.
21 W.T. Caiaffa et al, "Drug Smoking, Pneumonocystis Carinii Pneumonia, and Immunosuppression Increase Risk of Bacterial Pneumonia in Human Immunodeficiency Virus-seropositive Injection Drug Users," Am J Respir Crit Care Med, 150: 1493-8 (1994).
22 Leo Hollister, "Marijuana and Immunity," Journal of Psychoactive Drugs 20(1): 3-8 (Jan/Mar 1988)
23 One study of 10 healthy subjects found significantly higher T-cell counts after exposure to marijuana: D. Tashkin, "Cannabis 1977," Ann. Intern. Med. 89:539-49 (1978). Recenty lab studies have variously found that THC (1) decreases interleukin-6, while increasing tumor necrosis factor-alpha: SC Shivers et al, "Delta-9-THC modulates IL-1 bioactivity in human monocyte/macrophage cell lines," Life Sciences 54(17) 1281-9 (1994); or (2) inhibits TNF-alpha: H Friedman et al, "Marijuana, receptros and immunomodulation," Advances in Experimental Medicine and Biology 373: 103-113 (1995); or (3) stimulates production of interleukin 2 in rats: Susan Pross at the Univ. of South Florida, Tampa (personal communication).
24 Richard A Kaslow et al, "No Evidence for a Role of Alcohol or Other Psychoactive Drugs in Accelerating Immunodeficiency in HIV-1 Positive Individuals," JAMA 261:3424-9 (June 16, 1989); M.S. Ascher et al, "Does drug use cause AIDS?," Nature 36: 103-4 (March 11, 1993).
25 Di Franco et al, "The Lack of Association of Marijuana and Other Recreational Drugs With Progression to AIDS in the SFMHS," XI International Conference on AIDS, Vancouver, B.C., Canada July 1996.
26 W.B. O'Shaughnessy "On the Preparation of the Indian Hemp or Gunja," (1839), Report of the Ohio State Medical Committee on Cannabis Indica (1860) and J.R. Reynolds, "Therapeutical Uses and Toxic Effects of Cannabis Indica," in Tod H Mikuriya, ed., Marijuana: Medical Papers
27 1 MS patient: D B Clifford, "Thc for Tremor in Multiple Sclerosis," Annals of Neurology 13 (1983) 669-71. 1 MS patient: HM Meinck, FW Schlone & B Conrad, "Effects of Cannabinoids on Spasticity and Ataxia in Multiple Sclerosis," Journal of Neurology 236 (1989) 120-2. 1 epileptic: Consroe, GC Wood & H Buchsbaum, "Anticonvulsant Nature of Marihuana Smoking," JAMA 234 (1975) 306-7. 3 Tourette's cases: R Sandyk & G Awerbuch, "Marijuana and Tourette's Syndrome," J Clin Psychopharmacol. 8: 444 (1988). 1 MS, 1 injury patient: DJ Petro, "Marijuana as a therapeutic agent for muscle spasm or spasticity, "Psychosomatics 221: 81 (1980)
28 M Dunn & R Davis, "The perceived effects of marijuana on spinal cord injured males," Paraplegia 12:175 (1974).
29 13 MS patients - THC had subjective, but not objective effects: T Ungerleider et al, "Delta-9-THC in the treatment of spasticity associated with multiple sclerosis," Adv Alcohol Substance Abuse 7:39 (1987) 5 of 8 MS patients had subjective benefits, 2 of 8 objective: DB Clifford, "Thc for tremor in multiple sclerosis," Ann Neurol 13:669 (1983). 9 MS patients double-blind reduced spasms; also 3 w/ tonic spasms: D J Petro & C Ellenberger, "Treatment of human spasticity with delta-9-thc," J Clin Pharmacol 21: 413S, 1981.
30 M. Maurer et al, "Delta-9-thc Shows Antispastic and Analgesic Effects in a Single Case Double-Blind Trial," European Archives of Psychiatry and Clincial Neuroscience 240 (1990) 1-4.
31 J.M.Cunha et al, "Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients," Pharmacology 21 (1980) 175-85.
32 P Consroe & R Sandyk, "Open label evaluation of cannabidiol in dystonic movement disorders," Int J Neurosci, 30: 277 (1986)
33 J.P. Davis & HH Ramsey "Antiepileptic Action of Marijuana-active Substances," Federation Proceedings 8 (1949) 284-5.
34 WR Ellison et al, "Complex partial seizure symptoms affected by marijuana abuse," Journal of Clinical Psychiatry 51: 439 (1990).
35 J Malec, RF Harvey & JJ Cayner, "Cannabis Effect on Spasticity in Spinal Cord Injury," Archives of Physical and Medical Rehabilitation 63 (March 87) 116-8.
36 J.P. Frankel, et al, "Marijuana for Parkinsonian tremor," J. Neurol. Neurosurg. Psychiatry 53:436 (1990).
37 P Consroe et al., "Controlled clinical trial of cannabidiol in Huntington's disease," Pharmacol Biochem Behav 40: 701 (1991).
38 Harry S. Greenberg et al, "Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers." Clin Pharmacol Therap March 1994: 55:324-8.
39 Consroe and Sandyk, "Potential Role of Cannabinoids for Therapy of Neurological Disorders," Chapter 12 in Murphy & Bartke, pp. 482-3.
40 8 human subjects: A.W. Zuardi et al, "Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects," Psychopharmacology 76: 245-50 (1982).
41 E.A. Carlini and J.M. Cunha, "Hypnotic and Antiepileptic Effects of Cannabidiol," Journal of Clinical Pharmacology 21: 4175-275 (1981).
42 R. J. Noyes, Jr and D.A. Baram, "Cannabis analgesia," Compr Psychiatry 15:531 (1973).
43 R J Noyes et al, "The Analgesic Effect of Delta-9-thc," Journal of Clinical Pharmacology 14 (Feb/Mar 1975) 139-43.
44 R J Noyes et al, "The Analgesic Properties of Delta-9-thc and Codeine," Clinical Pharmacology and Therapeutics 18 (1975) 84-9.
45 Analgesic effects on thumbnail test: SL Milstein et al, "Marijuana-produced Changes in Pain Tolerance: Experienced and Non-experienced Subjects," International Pharmacopsychiatry 10:177-182 (1975); 4 subjects tested with thermal pain: Zeidenberg et al, "Effects of oral administration of delta-9-thc on memory, speech and perception of thermal stimulation": Compr. Psychiatry 14:549 (1973).
46 R S El-Mallakh, "Marijuana & migraine," Headache 27, 442 (1989).
47 Regelson et al, "Delta-9-thc as an effective antidepressant and appetite-stimulating agent in advanced cancer patients," in Braude& Szara, pp. 763-76.
48 D Raft et al, "Effects of intravenous thc on experimental surgical pain," Clin Pharmacol Ther 21:26 (1977).
49 Hill et al, "Marijuana and pain," J Pharmacol Exp Ther 188:415 (1974).
50 P Lindstrom et al, "Lack of effect of cannabidiol in sustained neuropathic [pain]," Marijuana'87, Int. Conf. on Cannabis, Melbourne 1987.
51 M.L. Barret et al, "Isolation from Cannabis sativa L. of Cannflavon - a novel inhibitor of prostaglandin production," Biochem. Pharmacol. 34: 2019 (1985); S.H. Burstein et al, "Antagonism to the actions of platelet activating factor by a nonpsychoactive cannabinoid," J Pharmacol. Exp. Therap. 251: 531-5 (1989); R.D. Sofia, "Antiedemic and analgesic properties of delta-9-THC compared with three other drugs," Eur. J. Pharamacol. 41: 705-9 (1989).
52 E.A. Formukong, A.T. Evans and F.J. Evans, "Analgesic and antiinflammatory activity of constitutents of Cannabis sativa L." Inflammation 12#4: 361 (1988).
53 D.P. Tashkin, B.J. Shapiro and I.M. Frank, "Acute effects of smoked marijuana and oral delta-9-thc on specific airway conductance in asthmatic subjects," Am Rev Respir Dis 109: 420-8 (1974); D. P. Tashkin et al, "Effects of smoked marijuana in experimentally induced asthma," Am Rev Respir Dis 112:377-86 (1975); L. Vachon et al, "Bronchial effects of marijuana smoke in asthma," in Braude & Szara, pp 777ff.
54 D.P. Tashkin, B.J. Shapiro and I.M. Frank, "Acute Pulmonary Physicologic Effects of Smoked Marihuana and Oral Delta-9-Thc in Healthy Young Men," New England Journal of Medicine, 289: 336-41 (1973). ; L Vachon, A Robins and EA Gaensler, "Airways Response to Aerosolized Delta-9-Thc: Preliminary Report," Chapter 8 in Cohen and Stillman.
55 Regelson et al, "Delta-9-thc as an effective antidepressant and appetite-stimulating agent in advanced cancer patients," in Braude& Szara, pp. 763-76.
56 8 controlled depression patients: Kotin et al, "Delt-9-Thc in depressed patients," Arch Gen Psychiatry 28:345-8, 1973.
57 Richard Warner et al, "Substance Use Among the Mentally Ill," American Journal of Orthopsychiatry, Jan. 1994.
58 KT Meuser et al, "Prevalence of substance abuse in schizophrenia," Schizophrenia Bulletin 16: 31-56 (1990).
59 Study by Dr. Ladislav Volicer of Boston Univ: press release by Unimed Pharmaceuticals, Buffalo Grove IL, July 29, 1996.
60 Tod Mikuriya, "Cannabis Substitution: An Adjunctive Therapeutic Tool in the Treatment of Alcoholism," Medical Times 98 #4: 187-91 (1970); reprinted in Mikuriya, Marijuana Medical Papers; also, Chaim Rosenberg, "The Use of Marihuana in the treatment of alcoholism," Chapter 13 in Cohen and Stillman.
61 C.M. Rosenberg et al, "Cannabis in the treatment of alcoholism," J Stud. Alcohol 39:1955-8 (1978).
62 Frank Chaloupka and Adit Laixuthal, "Do Youths Substitute Alcohol and Marijuana? Some Econometric Evidence," National Bureau of Economic Research Working Paper No. 4662, Cambridge, Mass. 1993; Karyn Model, "The Effect of Marijuana Decriminalization on Hospital Emergency Room Episodes," Journal of the American Statistical Association 88:423 737-47 (1993) ; see also Peter Passell, "Less Marijuana, More Alcohol?," New York Times June 17, 1992, p. C2.
63 Dr. Tod Mikuriya, personal communication.
Dale Gieringer
(415) 563-5858
* The best established medical use of smoked marijuana is as an anti-nauseant for cancer chemotherapy. Marijuana's efficacy was demonstrated in studies by half a dozen states, involving hundreds of subjects. Most research has found smoked marijuana superior to oral THC (Marinol). Many oncologists are currently recommending marijuana to their patients.
* Marijuana is widely used to treat nausea and appetite loss associated with AIDS, but the government has blocked research in this area. Studies have shown that marijuana helps improve appetite, and Marinol has been FDA approved for treatment of AIDS wasting syndrome. Nearly 10,000 PWA's were reported to be using marijuana through the San Francisco Cannabis Buyers' Club. However, the government has blocked efforts by Dr. Donald Abrams of the University of California at San Francisco to proceed with an FDA-approved study of marijuana and AIDS wasting syndrome, by refusing to grant him access to research marijuana. Research is badly needed on the relative merits of smoked and oral marijuana versus Marinol.
* There is much evidence, largely anecdotal, that marijuana is useful as an anti-convulsant for spinal injuries, multiple sclerosis, epilepsy, and other diseases. Similar evidence suggests marijuana may be useful as an analgesic for chronic pain from cancer and migraine as well as for rheumatism and a variety of auto-immune diseases. There is a conspicuous lack of controlled studies in this area; further research is needed.
* Cannabidiol, a constituent of natural marijuana not found in Marinol, appears to have distinctive therapeutic value as an anti-convulsant and hypnotic, and to counteract acute anxiety reactions caused by THC.
* It has been established that marijuana reduces intra-ocular pressure, the primary object of glaucoma therapy. Due to its psychoactivity, however, marijuana has not gained widespread acceptance in this application.
* Many patients report using marijuana as a substitute for more addictive and harmful psychoactive drugs, including prescription painkillers, opiates, and alcohol. Marijuana and Marinol have also been found useful as a treatment for depression and mood disorders in Alzheimer's and other patients. More research is needed.
Overview of Medical Marijuana Research
In its position paper, "Use of Marijuana as a 'Medicine,'" the California Narcotics Officers Association refers to "10,000 studies... documenting the harmful physical and psychological effects of smoking marijuana." This myth has been effectively debunked in a letter to Dr. Lester Grinspoon from NIDA's marijuana research librarian at the U. of Mississippi, Beverly Urbanek, who writes, "We are totally in the dark as to where the statement that there are 10,000 studies showing the negative impact of marijuana could have originated." She explains that while her library has some 12,000 citations on cannabis, they cover a broad spectrum of economic, legal, horticultural, enforcement, and other non-health issues, and are not categorized by negative or positive effects. Pursuing the issue further, it is possible to enumerate an impressive number of studies on marijuana's therapeutic uses. There is no space here to list or summarize all of them. The book, "Cannabinoids as Therapeutic Agents," edited by Dr. Raphael Mechoulam (CRC, 1986), includes copious references to research articles on cannabis' pharmacological effects, as follows:
Pharmacohistory of Cannabis Sativa - 90 references;
Therapeutic Potential of Cannabinoids in Neurological Disorders -155
Ocular Effects - 70
Cannabinoids as Antiemetics in Cancer - 91
Cannabinoids and Analgesia - 136
Bronchodilator Action of Cannabinoids - 67
Of course, there are some duplicates, and by no means all of these 609 references actually detail medicinal benefits of marijuana, but it certainly seems reasonable to estimate that there have been 100's of studies on medical use of marijuana.
Human Studies
Following is a summary of the human clinical and epidemiological studies on marijuana's therapeutic applications. We have not attempted to detail the great bulk of research, which consists of animal and in vitro studies that are of more dubious relevance to human health. However, we have tried to include all human studies reported in the recent medical literature.
(1) Anti-Nauseant for Cancer Chemotherapy:
This is by far the best substantiated use of medical marijuana. There have been at least 31 human studies of marijuana and/or oral THC for cancer chemotherapy,1 beginning with the pathbreaking work of Sallan and Zinberg, the first modern study of medical marijuana2. This doesn't count the studies in which the sponsors of Marinol got it FDA approved as "safe and effective" for cancer chemotherapy. Smoked marijuana was shown to be an effective anti-nauseant in 6 different state-sponsored clinical studies: 3 New Mexico (250 patients),4 New York (199 patients),5 California (98),6 Tennessee (27),7 Georgia (119),8 and Michigan (165).9
Smoked marijuana was found to be superior to oral THC in the New Mexico and Tennessee studies, with efficacy rates of 90%. In New York and Tennessee, it was effective in patients who had not been helped by Marinol. In Michigan, patients found smoked marijuana preferable to a conventional prescription anti-nauseant (Torecan). Other researchers have also reported smoked marijuana to be superior to THC.10
The California study was the least satisfactory, being highly biased towards oral THC (2000 patients were given oral THC, versus only 98 for marijuana): still, it found that marijuana was effective in 59% of patients, vs 57% for oral THC; however, 30% rated oral THC "highly effective," versus only 17% for marijuana. This is the only state study showing smoked marijuana inferior to Marinol.11
A survey of oncologists by Doblin and Kleiman reported that 44% of 1035 respondents had recommended marijuana to their patients (54% favored making it a prescription drug).12
(2) Glaucoma:
It is generally accepted - by the National Academy of Sciences and others - that marijuana/THC reduces intraocular pressure (IOP), the basic aim of anti-glaucoma therapy.13
This was shown in a series of experiments by Robert S. Hepler of UCLA, stemming from research aimed at finding out whether marijuana dilated pupils.14 Hepler found a "statistically significant" drop in IOP in 429 subjects treated with marijuana or THC; a subset of 29 patients showed continued benefits during 94 days of treatment with no signs of tolerance.15 The effects of THC/marijuana in reducing IOP were explored in a half-dozen other studies.16
Nonetheless, ophthalmologists have been reluctant to accept marijuana/THC because of its high psychoactivity. Efforts to develop topical cannabinoid eye drops as a non-psychoactive alternative have so far proven unfruitful.
The California Research Advisory Panel established a glaucoma research protocol under its cannabis research program of 1979-89, after finding interest in marijuana in its survey of ophthalmologists. The program flopped: only nine patients were treated; all chose to take Marinol instead of marijuana; and all eventually abandoned treatment.
(3) AIDS & APPETITE STIMULATION:
There have been no clinical studies on the use of marijuana for AIDS. Of course, one reason for this is that the government has blocked the study of Dr. Donald Abrams at the University of California at San Francisco by denying him access to research marijuana.
Nonetheless, Marinol has been FDA-approved as an appetite stimulant for treating AIDS wasting syndrome.17
There is also an extensive literature on smoked marijuana and appetite stimulation, including 4 clinical studies in which marijuana enhanced food intake and weight gain.18
Medical marijuana is widely used by AIDS patients. 80% of the SF Cannabis Buyers' Club's 11,000 customers are said to be PWA's.19 A recent survey of HIV-positive gays in Australia found that one-quarter were using marijuana therapeutically.20
Many AIDS patients prefer smoked marijuana to oral THC, due to its quickness of action, ease of controlling the dose, and absence of side-effects. In addition to appetite stimulation, many AIDS patients use marijuana for pain associated with neuropathy, shingles, etc.
An important concern about smoked marijuana that critics emphasize is the danger of respiratory infection in AIDS patients due to smoking. In particular, critics have cited a worrisome study by Caiaffa et al,21 showing a twofold increase in the rate of pneumonocystis carinii pneumonia (PCP) among HIV positive injection drug users who smoke illegal drugs (88% marijuana, 26% cocaine, 9% crack). There are a few problems with the study, notably that almost all of the subjects also smoked cigarettes; therefore, it's difficult to say whether the PCP was really due to marijuana.
In any case, these problems can be avoided by ingesting marijuana orally, which many AIDS patients in fact do. It's not clear whether oral marijuana has any medical benefits over Marinol, though it could certainly be more economical.
Another problem that critics like to emphasize is the supposed threat to PWA's posed by the immuno-suppressive properties of marijuana. Of course, these objections apply equally well to oral THC, which has been approved for treatment of AIDS. Studies of THC's effects on immunity have been contradictory, and do not lend themselves to easy interpretation.22 There are hints that THC might actually help stimulate the immune system in some ways.23
Epidemiological studies have found no relation between marijuana use and development of AIDS.24 One recent study of 354 HIV-positive males actually found marijuana to be associated with a decreased rate of progression to AIDS, though the difference was not significant when adjusted for parameters reflecting the initial health of the study subjects.25
(4) Muscle Spasticity, MS, Epilepsy & Spinal Injuries
The treatment of convulsions was the first major application of cannabis in Western medicine, attested by 19th-century authorities such as Dr. William O'Shaughnessy, the Ohio State Medical Committee, and Dr. John Russell Reynolds (who prescribed it to Queen Victoria for menstrual cramps).26 Although well authenticated in traditional practice, modern research into this usage has been scant, except for animal studies.
Altogether, there appear to be:
5 human case studies, involving a total of 8 patients, in which marijuana was reported to be useful for: epilepsy, multiple sclerosis, injury, and Tourette's syndrome;27
1 study in which 5 out of 8 spinal cord injury patients reported benefits from marijuana;28
3 more studies of THC for multiple sclerosis (total: 30 patients), in which benefits tended to be more subjective than objectively measurable;29
1 case study of THC for spinal cord injury30
2 clinical studies in which cannabidiol (CBD), a component of natural marijuana not found in Marinol, was found beneficial for grand mal epilepsy (15 subjects, double blind controls)31 and dystonia (5 patients, no controls).32
1 study in which a THC-related cannabinoid benefitted 2 out of 5 severely epileptic children;33
1 survey of 308 epileptic patients found that marijuana use appeared to delay the first onset of complex partial seizures.34
1 survey of 43 spinal cord injury patients at VA hospitals found that 56% smoked marijuana, and 88% reported that it reduced their muscle spasms.35
There have also been a couple of negative studies, finding no benefits of marijuana for Parkinsonism36 or CBD for Huntington's corea.37 Paradoxically, marijuana/THC has been reported to exacerbate spasticity or epilepsy on occasion, perhaps because of a rebound effect.
In a purported recent negative study on marijuana and multiple sclerosis, Dr. Harry Greenberg et al. at U. of Michigan reported that marijuana impaired posture and balance in patients with spastic MS.38 This should come as no surprise, since marijuana/THC also impairs balance in normal patients. In any event, MS patients don't use marijuana for posture/balance, but to reduce tremors and pain.
Cannabidiol:
There is considerable evidence from animal studies that CBD has distinctive anti-convulsant properties not found in THC.39
In addition, there is evidence that CBD can reduce the risk of panic reactions associated with THC. A study by Zuardi found that CBD reduces the anxiety-stimulating effects of THC, a leading cause of adverse reactions to Marinol.40 This may be a reason why many patients prefer natural cannabis.
A controlled study of 15 insomniacs found that CBD helped subjects sleep better.41
(5) Analgesia & Pain
Many patients report using marijuana for some form of pain relief. Cannabis was used as an analgesic from ancient times through the nineteenth century. This usage declined with the introduction of more potent opiates such as injected morphine. Cannabis continued to be regarded as a drug of choice for migraine into the 20th century.
Modern research is scant. Animal studies have tended to show analgesic effects, while human studies have been more conflicting:
In a preliminary study by R. J. Noyes, patients reported that marijuana relieved migraine, menstrual cramps, postsurgical pain. 42
In a follow-up, Noyes found oral THC relieved chronic pain in 10 cancer patients. 43
In a second follow-up with 36 cancer patients, THC was as effective as codeine, but had more side-effects.44
2 other studies found marijuana and THC effective in reducing experimentally induced pain.45
1 study reported that 3 patients began to experience migraines only after giving up marijuana.46
Negative results have also been reported:
1 study failed to find THC benefical for cancer pain, though it did help with depression and appetite.47
1 study found THC useless for artificially induced pain.48
1 study found marijuana increased sensitivity to electrically induced pain.49
1 study found CBD useless for neuropathic pain (10 patients).50
Inflammatory Diseases:
Marijuana is used by many patients for a wide variety of diseases characterized by inflammation. These include arthritis, rheumatism, lupus, multiple sclerosis, colitis, Crohn's disease, inflammatory gastritis, scleroderma, endometriosis, psoriasis, and pruritis. These diseases are thought to be auto-immune in nature. It is possible that the supposed immune suppressive properties of cannabis are beneficial for such conditions.
Unfortunately, there have been no clinical studies of this phenomenon. However, a variety of animal and laboratory studies have shown that cannabinoids have anti-inflammatory properties.51 One mouse study even suggested that a non-cannabinoid ingedient of marijuana may be involved.52
Asthma:
Although this isn't (and shouldn't be) an indication of choice for medical marijuana, three human studies have shown that smoking marijuana produces bronchodilation, thereby relieving asthma attacks.53 Two other studies confirmed the same effects with THC.54 Efforts to develop a smokeless THC inhaler proved unsuccessful.
Depression & Mental Illness:
Opponents of medical marijuana such as the CNOA have charged that marijuana causes depression. In fact, marijuana is more often used to treat depression; hence its notorious reputation as a euphoriant. Human studies have been inconsistent. One study found that marijuana helped relieve depression in cancer patients;55 another found no benefit for clinical depression.56
A survey of 79 mental patients found that those who used marijuana reported relief from depression, anxiety, insomnia, and physical discomfort, as well as fewer hospitalizations;57 a second survey also found fewer hospitalizations in schizophrenics who used marijuana.58 Some psychiatrists are currently prescribing Marinol for depression.
A recent pilot study by the Unimed Corporation found that Marinol helped relieve mood disturbances and anorexia in 12 Alzheimer's patients.59
Violence
Many opponents absurdly charge that marijuana aggravates violence. To this, the best answer is that of the National Academy of Science in Marihuana and Health (1982, p. 128):
"Both retrospective and experimental studies in human beings have failed to yield evidence that marijuana use leads to increased aggression. Most of these studies suggest quite the contrary effect. Marijuana appears to have a sedative effect, and it may reduce somewhat the intensity of angry feelings and the probability of interpersonal aggressive behavior."
Alcoholism & Drug Dependence
Cannabis is often used as a substitute for other, more dangerous drugs, including prescription narcotics, opiates and alcohol. Cannabis has been proposed as a treatment for alcoholism as well as opiate addiction.60 However, a single controlled study of cannabis to treat alcoholics proved unsuccessful.61 There is some epidemiological evidence that substitution of marijuana for alcohol and other drugs tends to reduce drug abuse and accident costs.62 Many cannabis buyers club members say they use marijuana as a substitute for prescription narcotics.63
References
Raphael Mechoulam, ed., Cannabinoids as Therapeutic Agents (CRC Press, Boca Raton) 1986.
Lester Grinspoon and James Bakalar, Marihuana, the Forbidden Medicine, (Yale U. Press) 1993.
Sidney Cohen and Richard Stillman, ed., The Therapeutic Potential of Marihuana (Plenum, NY) 1975.
Tod Mikuriya, Marijuana Medical Papers (Medicomp Press, Berkeley) 1973. Robert Randall, Marijuana, Medicine and the Law (Galen Press, Wash. DC) 1989 (2 Volumes).
National Academy of Sciences, Marijuana and Health, Report of the Institute of Medicine (National Academy Press) 1982. (NAS Report)
Laura Murphy and Andrzej Bartke, ed., Marijuana/Cannabinoids: Neruobiology and Neurophysiology (CRC Press, Boac Raton) 1992.
M.C. Braude and S. Szara, ed., Pharmacology of Marihuana, NIDA Monograph (Raven Press, NY) 1976 (2 Volumes).
References on Glaucoma:
Martin Adler & Ellen Geller, "Ocular Effects of Cannabinoids,"
Chapter 3 in Mechoulam.
Chapts 4-6 "Ophthalmic Effects," in Cohen & Stillman.
References on Anti-Convulsant Properties:
P Consroe & R Sandyk, "Potential Role of Cannabinoids for Therapy of Neurological Disorders," Chapter 12 in Murphy & Bartke.
Paul Consroe & Stuart Snider "Therapeutic Potential of Cannabinoids in Neurological Disorders," Chap 2 in Mechoulam.
References on Analgesia:
Mark Segal, "Cannabinoids and Analgesia," Chap. 6 in Mechoulam
FOOTNOTES
1 Includes (a) 25 studies of oral THC listed in M. Levitt, "Cannabinoids as Antiemetics in Cancer Chemotherapy," in Mechoulam, p. 73; (b) 6 state studies of marijuana listed below.
2 S. Sallan, N. Zinberg and E. Frei, "Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy," New England Journal of Medicine 295: 795 (1975).
3 For a summary, see Robert Randall, ed., Marijuana, Medicine and the Law, Vol . 2 (Galen Press, Wash. DC) 1989, pp. 36ff.
4 New Mexico: 250 patients; 90% relieved; only 3 adverse reactions (all w/THC): testimony of Daniel Dansak, MD in Robert Randall, ed., Marijuana, Medicine and the Law, Vol 1, pp. 125-33; Vol 2 , pp. 36-8.
5 New York: 199 patients evaluated; all had failed previous anti-nauseants (some also failed THC); marijuana 89.7%-100% effective at 3 hospitals. ACT Official State Reports, Vol II, Exhibit 15, "Evaluation of the Antiemetic Properties of Inhalation Marijuana in Cancer Patients Receiving Chemotherapy Treatment," NY Dept of Health, Office of Public Health, Chapter 810, Laws of 1980 Article 33-A, Public Health Law, Septermber 1981; ACT Exhibit 16-C, "Impressions from the National Conference on the Therapeutic Applications of Cannabinoids". Cited in Randall Vol 2, pp. 46-54.
6 California: 98 patients received marijuana; 59% found effective against strong emetics; 57% of 257 patients found THC-only effective; 17% rated marijuana "very effective" vs 30% for THC. "Cannabis Therapuetic Research Program," Report to the Cal. Legislature by California Research Advisory Panel, Jan. 1989. See also Randall, Vol 2, pp. 55-63.
7 Tennessee: 27 patients evaluared of 43 who had failed other therapy, including THC; 90.4% successful on marijuana; 66.7% on oral THC. ACT Official State Reports, Vol II, Exhibit 17, "Annual Report: Evaluation of Marijuana and Tetrahydrocannabinol in the Treatment of Nausea and/or Vomiting Associated with Cancer Therapy Unresponsive to Conventional Anti-emetic Therapy: Efficacy and Toxicity," Board of Pharmacy, State of Tennessee, July 1983. Cited in Randall, Vol 2, p.55.
8 Georgia: 119 evaluable patients; THC or marijuana 73% effective; marijuana had 6 adverse reactions from smoke-intolerance; THC had 6 panic reactions. Michael H. Kuttner, "Evaluation of the Use of Both Marijuana and THC in Cancer Patinets for the Relief of Nausea and Vomiting Associated with Cancer Chemotherapy After Failure of Conventional Anti-Emetci Therapy: Efficacy and Toxicity," report for the Composite State Board of Medical Examiners, Georgia Dept of Health, by researchers at Emory Univ 1/20/83. Cited in Randall Vol. 2, pp. 38-43.
9 Michigan: randomized crossover, marijuana vs Torecan; 165 patients; marijuana 71% effective - similar to Torecan, but patients preferred marijuana. ACT Official State Reports, Vol. II, Exhibit 9, "Evaluation of Marijuana as an Antiemetic in Patients Being Treated with Cancer Chemotherapy," Protocol Trial A, IND # 17-193. Cited in Randall, Vol. 2, p. 43.
10 e,g., Sallan and Zinberg (cited in Randall, vol. 2, p. 35), and AE Chang et al, "Delta-9-thc as an Antiemetic in Cancer Patients Receiving High-Dose Methotrexate: A Prospective Randomized Evaluation," Annals of Internal Medicine 91 (1979) 819-24.
11 For another study in which oral THC was found superior to smoked marijuana in 20 subjects, see: M. Levitt et al, "Randomized double-blind comparison of delta-9-tetrahydrocannabinol (THC) and marijuana as chemotherapy antiemetics," ASCO Abstracts, 3: 94 (1984); cited in Mechoulam, p. 73.
12 Rick Doblin & Mark Kleiman, "Marihuana as Anti-emetic Medicine: A survey of Oncologists' Attitudes and Experiences," Journal of Clinical Oncology 9:1275-80 (1991).
13 NAS Report, "Marijuana and Health," pp. 140-142.
14 R.S. Hepler & I.R.Frank, "Marihuana smoking and intraocular pressure," JAMA 217:1392 (1971). Hepler, RS, Frank, IM, and Ungerleider, JT "Pupillary constriction after marijuana smoking," Am J Ophthalmol. 74: 1185-90, 1972. RS Hepler, IM Frank, IM, and Petrus, R, "Ocular effects of marihuana smoking," in Braude & Szara, Vol. 2: 815-24 (Raven, NY) 1976.
15 Robert S Hepler and Robert J Petrus, "Experiences with administration of Marihuana to Glaucoma Patients, "Chap 5 (pp 63-94) in Cohen & Stillman.
16 Shapiro, D. "The ocular mainfestations of the cannabinols," Ophthalmologica 1974 168:366-9; Purnell, W.D. & Gregg, J.M. "Delta-9 Thc, euphoria and intraocular pressure in man," Annals of Ophthalmology, July 1975; Greeen, K. & Podos, SM "Antagonism of arachidonic acid-induced ocular effects by delta-thc" Investigative Ophthalmology, June 1974; Flom, M.C., Adams, A.J. and Jones, R.T.: "Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenom?", Invest. Ophtalmol., 14:52 (1975); Cooler, P. & Gregg, J.M. "Effect of delta-9-thc on introacoular pressure in humans," South Med J. 70: 954, 1977; Paul Cooler & John Gregg, "The effect of delta-9-thc on intraocular pressure in humans," Chap 6 in Cohen & Stillman; Merritt, J.C., et al: "Oral delta-9-thc in heterogeneous glaucomas," Ann. Ophthalmol., 12:947 (1980); Perez-Reyes, M. et al: "Intravenous administration of cannabinoids and intraocular pressure," in Braude & Szara, p 829; "Jones, R, Benowitz, N, and Herning, RI, "Clinical relevance of cannabis tolerance and dependence," J Clin Pharmacol, 21:143S (1981).
17 TF Plasse, RW Gorter, SH Krasnow, et al "Recent Clinical Experience with Dronabinol," Pharmacology, Biochemistry and Behavior 40 (1991) 695-700.
18 LE Hollister, "Hunger and Appetite after Single Doses of Marihuana, Alcohol, and Dextroamphetamine," Clinical Pharmacology ajnd Therapeutics 12 (Jan-Feb 1971) 44-9. 27 marihuana users and 10 controls - gained weight in hospital ward : Greenberg et al, "Effects of Marihuana Use on Body Weight and Caloric Intake in Humans," Journal of Pscyhopharmacology (Berlin) 49 (1976) 79-84. 9 subjects gained weight smoking marihuana rather than placebo cigarettes:RW Foltin et al, "Behavioral Analysis of Marijuana Effects on Food Intake in Humans," Pharmacology, Biochemistry and Behavior 25 (1986) 577-82. 6 subjects increased caloric intake 40% over 13 days: RW Foltin et al, "Effects of smoked marijuana on food intake and body weight in humans living in a residential laboratory," Appetite 1988: 11:1-14.
19 Personal communication.
20 228 subjects: Prestage, Garrett et al, "Use of Treatments and Health-Enhancement Behavior Among HIV-Positive Men in a Cohort of Homosexually-Active Men," XI International Converence on AIDS, Vancouver, B.C., Canada, July 1996.
21 W.T. Caiaffa et al, "Drug Smoking, Pneumonocystis Carinii Pneumonia, and Immunosuppression Increase Risk of Bacterial Pneumonia in Human Immunodeficiency Virus-seropositive Injection Drug Users," Am J Respir Crit Care Med, 150: 1493-8 (1994).
22 Leo Hollister, "Marijuana and Immunity," Journal of Psychoactive Drugs 20(1): 3-8 (Jan/Mar 1988)
23 One study of 10 healthy subjects found significantly higher T-cell counts after exposure to marijuana: D. Tashkin, "Cannabis 1977," Ann. Intern. Med. 89:539-49 (1978). Recenty lab studies have variously found that THC (1) decreases interleukin-6, while increasing tumor necrosis factor-alpha: SC Shivers et al, "Delta-9-THC modulates IL-1 bioactivity in human monocyte/macrophage cell lines," Life Sciences 54(17) 1281-9 (1994); or (2) inhibits TNF-alpha: H Friedman et al, "Marijuana, receptros and immunomodulation," Advances in Experimental Medicine and Biology 373: 103-113 (1995); or (3) stimulates production of interleukin 2 in rats: Susan Pross at the Univ. of South Florida, Tampa (personal communication).
24 Richard A Kaslow et al, "No Evidence for a Role of Alcohol or Other Psychoactive Drugs in Accelerating Immunodeficiency in HIV-1 Positive Individuals," JAMA 261:3424-9 (June 16, 1989); M.S. Ascher et al, "Does drug use cause AIDS?," Nature 36: 103-4 (March 11, 1993).
25 Di Franco et al, "The Lack of Association of Marijuana and Other Recreational Drugs With Progression to AIDS in the SFMHS," XI International Conference on AIDS, Vancouver, B.C., Canada July 1996.
26 W.B. O'Shaughnessy "On the Preparation of the Indian Hemp or Gunja," (1839), Report of the Ohio State Medical Committee on Cannabis Indica (1860) and J.R. Reynolds, "Therapeutical Uses and Toxic Effects of Cannabis Indica," in Tod H Mikuriya, ed., Marijuana: Medical Papers
27 1 MS patient: D B Clifford, "Thc for Tremor in Multiple Sclerosis," Annals of Neurology 13 (1983) 669-71. 1 MS patient: HM Meinck, FW Schlone & B Conrad, "Effects of Cannabinoids on Spasticity and Ataxia in Multiple Sclerosis," Journal of Neurology 236 (1989) 120-2. 1 epileptic: Consroe, GC Wood & H Buchsbaum, "Anticonvulsant Nature of Marihuana Smoking," JAMA 234 (1975) 306-7. 3 Tourette's cases: R Sandyk & G Awerbuch, "Marijuana and Tourette's Syndrome," J Clin Psychopharmacol. 8: 444 (1988). 1 MS, 1 injury patient: DJ Petro, "Marijuana as a therapeutic agent for muscle spasm or spasticity, "Psychosomatics 221: 81 (1980)
28 M Dunn & R Davis, "The perceived effects of marijuana on spinal cord injured males," Paraplegia 12:175 (1974).
29 13 MS patients - THC had subjective, but not objective effects: T Ungerleider et al, "Delta-9-THC in the treatment of spasticity associated with multiple sclerosis," Adv Alcohol Substance Abuse 7:39 (1987) 5 of 8 MS patients had subjective benefits, 2 of 8 objective: DB Clifford, "Thc for tremor in multiple sclerosis," Ann Neurol 13:669 (1983). 9 MS patients double-blind reduced spasms; also 3 w/ tonic spasms: D J Petro & C Ellenberger, "Treatment of human spasticity with delta-9-thc," J Clin Pharmacol 21: 413S, 1981.
30 M. Maurer et al, "Delta-9-thc Shows Antispastic and Analgesic Effects in a Single Case Double-Blind Trial," European Archives of Psychiatry and Clincial Neuroscience 240 (1990) 1-4.
31 J.M.Cunha et al, "Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients," Pharmacology 21 (1980) 175-85.
32 P Consroe & R Sandyk, "Open label evaluation of cannabidiol in dystonic movement disorders," Int J Neurosci, 30: 277 (1986)
33 J.P. Davis & HH Ramsey "Antiepileptic Action of Marijuana-active Substances," Federation Proceedings 8 (1949) 284-5.
34 WR Ellison et al, "Complex partial seizure symptoms affected by marijuana abuse," Journal of Clinical Psychiatry 51: 439 (1990).
35 J Malec, RF Harvey & JJ Cayner, "Cannabis Effect on Spasticity in Spinal Cord Injury," Archives of Physical and Medical Rehabilitation 63 (March 87) 116-8.
36 J.P. Frankel, et al, "Marijuana for Parkinsonian tremor," J. Neurol. Neurosurg. Psychiatry 53:436 (1990).
37 P Consroe et al., "Controlled clinical trial of cannabidiol in Huntington's disease," Pharmacol Biochem Behav 40: 701 (1991).
38 Harry S. Greenberg et al, "Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers." Clin Pharmacol Therap March 1994: 55:324-8.
39 Consroe and Sandyk, "Potential Role of Cannabinoids for Therapy of Neurological Disorders," Chapter 12 in Murphy & Bartke, pp. 482-3.
40 8 human subjects: A.W. Zuardi et al, "Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects," Psychopharmacology 76: 245-50 (1982).
41 E.A. Carlini and J.M. Cunha, "Hypnotic and Antiepileptic Effects of Cannabidiol," Journal of Clinical Pharmacology 21: 4175-275 (1981).
42 R. J. Noyes, Jr and D.A. Baram, "Cannabis analgesia," Compr Psychiatry 15:531 (1973).
43 R J Noyes et al, "The Analgesic Effect of Delta-9-thc," Journal of Clinical Pharmacology 14 (Feb/Mar 1975) 139-43.
44 R J Noyes et al, "The Analgesic Properties of Delta-9-thc and Codeine," Clinical Pharmacology and Therapeutics 18 (1975) 84-9.
45 Analgesic effects on thumbnail test: SL Milstein et al, "Marijuana-produced Changes in Pain Tolerance: Experienced and Non-experienced Subjects," International Pharmacopsychiatry 10:177-182 (1975); 4 subjects tested with thermal pain: Zeidenberg et al, "Effects of oral administration of delta-9-thc on memory, speech and perception of thermal stimulation": Compr. Psychiatry 14:549 (1973).
46 R S El-Mallakh, "Marijuana & migraine," Headache 27, 442 (1989).
47 Regelson et al, "Delta-9-thc as an effective antidepressant and appetite-stimulating agent in advanced cancer patients," in Braude& Szara, pp. 763-76.
48 D Raft et al, "Effects of intravenous thc on experimental surgical pain," Clin Pharmacol Ther 21:26 (1977).
49 Hill et al, "Marijuana and pain," J Pharmacol Exp Ther 188:415 (1974).
50 P Lindstrom et al, "Lack of effect of cannabidiol in sustained neuropathic [pain]," Marijuana'87, Int. Conf. on Cannabis, Melbourne 1987.
51 M.L. Barret et al, "Isolation from Cannabis sativa L. of Cannflavon - a novel inhibitor of prostaglandin production," Biochem. Pharmacol. 34: 2019 (1985); S.H. Burstein et al, "Antagonism to the actions of platelet activating factor by a nonpsychoactive cannabinoid," J Pharmacol. Exp. Therap. 251: 531-5 (1989); R.D. Sofia, "Antiedemic and analgesic properties of delta-9-THC compared with three other drugs," Eur. J. Pharamacol. 41: 705-9 (1989).
52 E.A. Formukong, A.T. Evans and F.J. Evans, "Analgesic and antiinflammatory activity of constitutents of Cannabis sativa L." Inflammation 12#4: 361 (1988).
53 D.P. Tashkin, B.J. Shapiro and I.M. Frank, "Acute effects of smoked marijuana and oral delta-9-thc on specific airway conductance in asthmatic subjects," Am Rev Respir Dis 109: 420-8 (1974); D. P. Tashkin et al, "Effects of smoked marijuana in experimentally induced asthma," Am Rev Respir Dis 112:377-86 (1975); L. Vachon et al, "Bronchial effects of marijuana smoke in asthma," in Braude & Szara, pp 777ff.
54 D.P. Tashkin, B.J. Shapiro and I.M. Frank, "Acute Pulmonary Physicologic Effects of Smoked Marihuana and Oral Delta-9-Thc in Healthy Young Men," New England Journal of Medicine, 289: 336-41 (1973). ; L Vachon, A Robins and EA Gaensler, "Airways Response to Aerosolized Delta-9-Thc: Preliminary Report," Chapter 8 in Cohen and Stillman.
55 Regelson et al, "Delta-9-thc as an effective antidepressant and appetite-stimulating agent in advanced cancer patients," in Braude& Szara, pp. 763-76.
56 8 controlled depression patients: Kotin et al, "Delt-9-Thc in depressed patients," Arch Gen Psychiatry 28:345-8, 1973.
57 Richard Warner et al, "Substance Use Among the Mentally Ill," American Journal of Orthopsychiatry, Jan. 1994.
58 KT Meuser et al, "Prevalence of substance abuse in schizophrenia," Schizophrenia Bulletin 16: 31-56 (1990).
59 Study by Dr. Ladislav Volicer of Boston Univ: press release by Unimed Pharmaceuticals, Buffalo Grove IL, July 29, 1996.
60 Tod Mikuriya, "Cannabis Substitution: An Adjunctive Therapeutic Tool in the Treatment of Alcoholism," Medical Times 98 #4: 187-91 (1970); reprinted in Mikuriya, Marijuana Medical Papers; also, Chaim Rosenberg, "The Use of Marihuana in the treatment of alcoholism," Chapter 13 in Cohen and Stillman.
61 C.M. Rosenberg et al, "Cannabis in the treatment of alcoholism," J Stud. Alcohol 39:1955-8 (1978).
62 Frank Chaloupka and Adit Laixuthal, "Do Youths Substitute Alcohol and Marijuana? Some Econometric Evidence," National Bureau of Economic Research Working Paper No. 4662, Cambridge, Mass. 1993; Karyn Model, "The Effect of Marijuana Decriminalization on Hospital Emergency Room Episodes," Journal of the American Statistical Association 88:423 737-47 (1993) ; see also Peter Passell, "Less Marijuana, More Alcohol?," New York Times June 17, 1992, p. C2.
63 Dr. Tod Mikuriya, personal communication.
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