REVIEW OF HUMAN STUDIES ON MEDICAL USE OF MARIJUANA
by Dale H. Gieringer, Ph.D.
August 1996
California NORML
2215-R Market St. #278
San Francisco CA 94114
(415) 563-5858 / canorml@igc.apc.org
SUMMARY: HUMAN STUDIES ON MEDICAL USES OF MARIJUANA
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.