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10/3/2014 Cannabinoid Poisoning

Background
Cannabis sativa is the hemp plant from which marijuana (leaves, stems, seeds) are derived. The term marijuana
became popular in the 1930s; it was originally a slang word for the medicinal part of cannabis smoked by Mexican
soldiers. Hemp refers to the roots, stalk, and stems of the plant, which can be used to make rope and twine. The
most potent form of this plant's extracts is hash oil, a liquid. The dried resins are referred to as "hashish". The dried
flowering tops and leaves are smoked as a cigarette, known as a "joint" or a "reefer". This plant has been used for
several thousands of years both recreationally and medicinally. See the image below.

Flowering top of cannabis plant.

Likewise, cannabinoids can be used as biological warfare, as they produce predominately behavioral effects.
Although they are not a likely choice in warfare, cannabinoids have many active metabolites that can prolong their
effects.

More than 400 active compounds have been isolated from the C sativa plant. Sixty active compounds are unique to
the plant and are collectively known as cannabinoids. Delta-9-tetrahydrocannanbinol (THC) is the most psychoactive
cannabinoid, producing euphoria, relaxation, intensification of ordinary sensory experiences, perceptual alterations,
diminished pain, and difficulties with memory and concentration.

The "Gateway" theory of the development of abuse describes the escalation of drug use from adolescence to
adulthood. According to this theory, one progresses from legal drugs, such as alcohol and cigarettes, to illicit drugs,
such as marijuana. A cross-sectional study conducted recently demonstrated that a twin who used cannabis by age
17 was 2-5 times more likely to use other drugs, or develop alcohol dependence than his non-cannabis using twin.

Pathophysiology
The most potent cannabinoid, THC, was isolated in the 1960s. Nearly 3 decades later, in the early 1990s, the
specific cannabinoid receptors were discovered, CB1 (or Cnr1) and CB2 (or Cnr2). The CB1 receptors are
predominantly located in the brain with a wide distribution. The highest densities are found in the frontal cerebral
cortex (higher functioning), hippocampus (memory, cognition), basal ganglion and cerebellum (movement), and
striatum (brain reward). Other brain regions in which the CB1 receptors are found include areas responsible for
anxiety, pain, sensory perception, motor coordination, and endocrine function. This distribution is consistent with the
clinical effects elicited by cannabinoids.

The CB2 receptor, on the other hand, is located peripherally. Specifically, it is involved in the immune system
(splenic macrophages, T and B lymphocytes), peripheral nerves, and the vas deferens.

Both the CB1 and CB2 receptors inhibit adenylate cyclase and stimulate potassium channels. As a result, the CR1
receptors inhibit the release of several neurotransmitters, including acetylcholine, glutamate, norepinephrine,
dopamine, serotonin, and gamma–aminobutyric acid (GABA). CR2 receptor signaling is involved in immune and
inflammatory reactions.

Potency
In the last decade, the average THC potency of cannabis has increased due to more sophisticated plant breeding
and cultivation.[1] In the 1970s, the average marijuana cigarette contained approximately 10 mg of THC. Today, a
comparable cigarette contains 60-150 mg. Because the effects of THC are dose dependent, modern cannabis users
may experience greater morbidity than their predecessors.

Cannabis is available in the following forms:

Marijuana is a combination of the C sativa flowering tops and leaves. The THC content is 0.5-5%. Two
preparations are possible:
Bhang – Dried leaves and tops
Ganja – Leaves and tops with a higher resin content, which results in greater potency
Hashish is dried resin collected from the flowering tops. The THC concentration is 2-20%.
Hash oil is a liquid extract; it contains 15% THC.
Sinsemilla is unpollinated flowering tops from the female plant. THC content is as high as 20%.
Dutch hemp (Netherweed) has a THC concentration as high as 20%.

Absorption

The route of administration determines the absorption of the cannabis product.

Smoking – Onset of action is rapid (within minutes); it results in 10-35% absorption of the available THC; peak
plasma concentrations occur within 8 minutes.
Ingestion – Onset occurs within 1-3 hours (unpredictable); 5-20% is absorbed due to stomach acid content
and metabolism; peak plasma levels occur 2-6 hours after ingestion.
Synthetic forms include the following[2, 3] :
Dronabinol (Marinol) – 10% absorption; peak concentration 2-3 hours after ingestion
Nabilone (Cesanet) – Up to 90% absorption; peak concentration in 2 hours after ingestion

Behavioral effects

THC produces euphoria, or "high," including feelings of intoxication and detachment, relaxation, altered
perception of time and distance, intensified sensory experiences, laughter, talkativeness, decreased anxiety,

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decreased alertness, and depression. These effects depend on the dose, expectations of the user, mode of
administration, social environment, and personality.
THC triggers dopaminergic neurons in the ventral tegmental area of the brain, a region known to mediate the
reinforcing (rewarding) effects. This dopaminergic drive is thought to underlie the reinforcing and addicting
properties of this drug.
Dysphoric reactions to cannabis are not uncommon, especially in naive users. Reactions can include severe
anxiety or panic, unpleasant somatic sensations, delirium, mania, or paranoia. Anxiety and/or panic are the
most common reactions; they are of sudden onset during or shortly after smoking, or they can appear more
gradually 1-2 hours after an oral dose. These anxiety/panic reactions usually resolve without intervention.
Flashbacks occasionally occur in which the original drug experience (usually dysphoria) is relived weeks or
months after use.

Mental effects

Short-term memory is impaired even after small doses in both naive and experienced users. The deficits
appear to be in acquisition of memory, which may result from an attentional deficit, combined with the inability
to filter out irrelevant information and the intrusion of extraneous thoughts.
Chronic use can be associated with subtle impairment in cognitive function, which is dependent on dose and
duration of use. At present, most of the available data indicate that these cognitive deficits are reversible after
more than a week of abstinence.

Immune system effects

Cannabis use can impair the immune system's ability to fight off microbial and viral infection.
In a dose-dependent fashion, lung macrophage functions, including phagocytosis, migration, and cytokine
production, appear to be compromised by cannabis use. This has been demonstrated in limited human in
vitro studies.
Although cannabinoid receptors are found on human T and B lymphocytes, to date, no conclusive effects
have been found on the use of cannabis and the clinical effects related to the presence of these receptors.

Cardiovascular effects

Naive users may experience a sudden 20-100% rise in heart rate, lasting up to 2-3 hours.
Peripheral vasodilatation causes postural hypotension, which may lead to dizziness or syncope.
Cardiac output increases by as much as 30%. In addition, the cardiac oxygen demand is also increased.
Tolerance to these effects can develop within a few days of use.
Naive users can experience angina. In addition, users with preexisting coronary artery disease or
cerebrovascular disease may experience myocardial infarctions, congestive heart failure, and strokes.

Respiratory effects

Transient bronchodilatation may occur after an acute exposure.


With chronic heavy smoking, users experience increased cough, sputum production, and wheezing. These
complaints are augmented by concurrent tobacco use.
One study sites that the rate of decline of respiratory function in an 8-year period was greater among
marijuana smokers than among tobacco smokers.
Aside from nicotine, marijuana cigarettes contain the same components as tobacco smoke, including
bronchial irritants, tumor initiators (mutagens), and tumor promoters. The amount of tar in a marijuana
cigarette is 3 times the amount in a tobacco cigarette when smoked, with one-third greater deposition in the
respiratory tract.
Chronic cannabis use is associated with bronchitis, squamous metaplasia of the tracheobronchial epithelium,
and emphysema. These problems have been reported more frequently in cannabis-only users than in
tobacco-only users.
Several case reports strongly suggest a link between cannabis smoking and cancer of the aerodigestive
system including the oropharynx and tongue, nasal and sinus epithelium, and larynx.
Most illegally obtained marijuana is contaminated with Aspergillus species, which can cause invasive
pulmonary aspergillosis in immunocompromised users.

Reproductive effects

High-dose THC in animals causes a drop in testosterone levels, decreased sperm production, and
compromised sperm motility and viability.
THC alters the normal ovulatory cycle.
Cannabis administration during pregnancy reduces birthweight in animals. However, studies are equivocal in
humans. No evidence exists that cannabis increases the risk of birth defects.
A growing body of evidence suggests permanent, though subtle, effects on memory, informational
processing, and executive functions in the offspring of women who use cannabis during pregnancy.
Children younger than 1 week of age born to mothers who used cannabis during pregnancy had increased
incidence of tremors and staring. Children of chronic users (>5 joints per wk) were found to have lower verbal
and memory scores at age 2 years.
Three studies have demonstrated a possible increased risk of nonlymphoblastic leukemia,
rhabdomyosarcoma, and astrocytoma in children whose mothers reported using cannabis during their
pregnancies.

Psychosis association

Large doses of THC may produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation. Most
episodes are rapidly remitting.
Cannabinoid Poisoning
A clear relationship exists between cannabis use and mental health.[4]
Substance-abusing adolescents commonly suffer one or more comorbid health or behavioral
problems. Several studies have demonstrated marijuana abuse to coexist with attention deficit
Author:hyperactivity
Ani Aydin, MD; Chief Editor:
disorder, Robert G
other learning Darling, MD,
disabilities, FACEP and
depression, more...
anxiety. Cohort and well-designed
cross-sectional studies suggest a modest association between early, regular, or heavy cannabis use
Updated: Jul 11,
and2013
depression.
An association exists between cannabis use and schizophrenia. A prospective study of 50,000
Swedish conscripts found a dose-response relationship between the frequency of cannabis use by age
18 and the risk of a diagnosis of schizophrenia over the subsequent 15 years. Five prospective studies
with well-defined samples looked at cannabis use and psychosis and concluded an overall 2-fold
increase in the relative risk for developing schizophrenia. Yet, cannabis use appears to be neither
necessary nor sufficient to cause schizophrenia. Among people who already have schizophrenia,
cannabis use is predicted to worsen psychotic symptoms.

Metabolism and elimination

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THC is metabolized via the hepatic cytochrome P450 (CYP) system. THC is metabolized into an active compound,
11-hydroxy-THC (11-OH-THC), which is further metabolized into inactive forms.

The elimination half-life of THC can range from 2-57 hours following intravenous use and inhalation. The half-life of
11-OH-THC, the active metabolite of THC, is 12-36 hours. Intravenous use or inhalation results in 15% excretion in
the urine and 25-35% in the feces. Within 5 days, nearly 90% of THC is eliminated from the body.

Tolerance

Repeated use over days to weeks induces considerable tolerance to the behavioral and psychological effects of
cannabis. Several studies have noted partial tolerance to its effect on mood, memory, motor coordination, sleep,
brain wave activity, blood pressure, temperature, and nausea. The rate of tolerance depends on the dose and
frequency of administration. The casual cannabis user experiences more impairment in cognitive and psychomotor
function to a particular acute dose than heavier, chronic users. The desired recreational high from cannabis also
diminishes with use, prompting many users to escalate the dose.

Pharmacologically, chronic use results in the downregulation of the CR1 receptor in several regions of the rat brain.
No correlations have been made in human physiology.

Toxicity

Acute cannabis toxicity results in difficulty with coordination, decreased muscle strength, decreased hand
steadiness, postural hypotension, lethargy, decreased concentration, slowed reaction time, slurred speech, and
conjunctival injection. Although acute toxicity is benign in the average adult, the same cannot be said for children. A
250-1000 mg ingestion of hashish (up to 20% THC concentration) can result in obtundation within 30 minutes,
apnea, bradycardia, cyanosis, or hypotonia in children.[5, 6]

Adverse reactions

Chronic users may experience paranoia, panic disorder, fear, or dysphoria. Transient psychotic episodes may also
occur with cannabis use. Of great clinical significance, ventricular tachycardia has also been associated with use of
this drug.

Dependence and withdrawal

Nearly 7-10% of regular users become behaviorally and physically dependent on cannabis. Furthermore, early onset
of use and daily/weekly use correlates with future dependence. According to the National Institute on Drug Abuse
(NIDA), 100,000 people are treated annually for primary (may be self-perceived) marijuana abuse.[7]

Animal studies demonstrate withdrawal symptoms with use of CB1 receptor antagonists. However, in humans, the
withdrawal syndrome is not well characterized. Classically, associated symptoms include irritability, restlessness,
insomnia, anorexia, nausea, sweating, salivation, increased body temperature, tremors, and weight loss following as
little as 1 week of daily use.

Epidemiology
Frequency

United States

Marijuana became the major drug of abuse in the 1960s. Its use peaked in the late 1970s. According to the NIDA-
funded Monitoring the Future survey, the peak year of use occurred in 1979, with 60.4% of 12th-grade students
having used cannabis in their lifetimes, 50.8% in the preceding year, and more than 10.3% on a daily basis.
Cannabis use began a continuous decline, with the lowest use occurring in 1992. At that time, 32.6% of 12th-grade
students reported ever using cannabis, 21.9% reported use in the preceding year, and 1.9% reported using on a
daily basis. The decline in use was attributed to perceived risk and to personal disapproval of drugs.

From 1992-1997, marijuana use increased dramatically and then leveled off in the last 2 years. Figures from 1999
reveal that 22% of 8th-grade students and 49.7% of 12th-grade students reported ever using cannabis. Daily use
was 1.4% and 6%, respectively.[8]

In 1998, the NIDA-sponsored Community Epidemiology Work Group investigated the rates of emergency department
mentions of marijuana use in 20 metropolitan areas. Cities with the highest rates included Dallas (63.9%), Boston
(44.1%), Denver (40.0%), San Diego (35.1%), and Atlanta (31.1%).

The prevalence of marijuana use has increased significantly in the early 2000s. A recent study found a 1.1% risk of
marijuana abuse and 0.3% dependence in 40,000 US adults surveyed for one year. In addition, a strong association
was noted between marijuana abuse/dependence and Axis I and II disorders.

International

Prevalence of cannabis use among young people has increased markedly over the last decade in the United
Kingdom. Surveys indicate that more than 40% of adolescents aged 15-16 years and 59% of students aged 18 years
have experimented at least once with marijuana.

In Canada, rates of use are lower, with a national telephone survey revealing that 23% of students reported ever
using cannabis.

Limited data on cannabis use in Africa, Asia, Central America, and South America, and Middle Eastern countries
suggest that these countries have lower rates of lifetime use than most western countries.

Mortality/Morbidity

No cases of mortality are reported from cannabis use in adults. One theory is that since cannabinoid receptors are
scant in the lower brain stem, where cardiovascular and respiratory functions are controlled, acute cardiorespiratory
dysfunction is unlikely.[9]

Race

No differences are reported in patterns of cannabis use according to racial or ethnic background.

Sex

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Little information is available regarding gender differences in cannabis use. In a 1995 US study, 6.5% of females and
10.5% of males aged 12 years and older reported marijuana use in the previous year.

Age

Most cannabis users begin use when younger than 20 years of age, with the peak incidence of onset between
16 and 18 years. Most stop using marijuana by their mid to late 20s. Only about 10% become daily users.
The Community Epidemiology Work Group, sponsored by NIDA, studied the rates of marijuana use in
patients evaluated in emergency departments of 20 metropolitan areas. The highest increase in use was
among adolescents aged 12-17 years.

Contributor Information and Disclosures


Author
Ani Aydin, MD Staff Physician, Department of Emergency Medicine, Bellevue Hospital/New York University
Medical Center

Ani Aydin, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Emergency Physicians, American Medical Association, Emergency Medicine Residents Association, and Society
for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)
Jessica A Fulton, DO Assistant Professor of Emergency Medicine, Assistant Residency Director, New York
University and Bellevue Hospital Center; Medical Director of Chemical Biological Radiological Nuclear Explosives
(CBRNE) Academy, Bellevue Hospital Center and New York City Department of Health and Mental Hygiene

Jessica A Fulton, DO is a member of the following medical societies: American College of Medical Toxicology

Disclosure: Nothing to disclose.

Specialty Editor Board


Suzanne White, MD Medical Director, Regional Poison Control Center at Children's Hospital, Program Director
of Medical Toxicology, Associate Professor, Departments of Emergency Medicine and Pediatrics, Wayne State
University School of Medicine

Suzanne White, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Clinical Toxicology, American College of Epidemiology, American College of Medical Toxicology, American
Medical Association, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rick Kulkarni, MD Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance,
Division of Emergency Medicine, Harvard Medical School

Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Emergency Medicine, American College of Emergency Physicians, American Medical Association, American
Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: WebMD Salary Employment

John D Halamka, MD, MS Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess
Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending
Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency
Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency
Medicine

Disclosure: Nothing to disclose.

Chief Editor
Robert G Darling, MD, FACEP Adjunct Clinical Assistant Professor of Military and Emergency Medicine,
Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director,
Center for Disaster and Humanitarian Assistance Medicine

Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency
Physicians, American Medical Association, American Telemedicine Association, and Association of Military
Surgeons of the US

Disclosure: Nothing to disclose.

Additional Contributors
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors,
Gregory R Bell, MD, and Alan H Hall, MD, to the development and writing of this article.

References
1. Wells DL, Ott CA. The "new" marijuana. Ann Pharmacother. Mar 2011;45(3):414-7. [Medline].

2. Forrester MB. Adolescent synthetic cannabinoid exposures reported to Texas poison centers. Pediatr
Emerg Care. Oct 2012;28(10):985-9. [Medline].

3. McGuinness TM, Newell D. Risky recreation: synthetic cannabinoids have dangerous effects. J Psychosoc
Nurs Ment Health Serv. Aug 2012;50(8):16-8. [Medline].

4. Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C. Continued cannabis use and risk of
incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. Mar 1
2011;342:d738. [Medline]. [Full Text].

http://emedicine.medscape.com/article/833828-overview#showall 4/5
10/3/2014 Cannabinoid Poisoning
5. Fitzgerald KT, Bronstein AC, Newquist KL. Marijuana poisoning. Top Companion Anim Med. Feb
2013;28(1):8-12. [Medline].

6. Wiegand TJ, Wax PM, Schwartz T, Finkelstein Y, Gorodetsky R, Brent J. The Toxicology Investigators
Consortium Case Registry--the 2011 experience. J Med Toxicol. Dec 2012;8(4):360-77. [Medline].

7. National Institute on Drug Abuse, National Institutes of Health, Centers for Substance Abuse Prevention and
Treatment. National Conference on Marijuana Use: Prevention, VA. Treatment and Research. NIH
publication. 1995: Arlington;38-49:no 96-4106. [Full Text].

8. National Institute on Drug Abuse. InfoFacts: Marijuana. Updated April 2006. [Full Text].

9. Pavarin RM, Berardi D. Mortality risk in a cohort of subjects reported by authorities for cannabis possession
for personal use. Results of a longitudinal study. Epidemiol Prev. Mar-Apr 2011;35(2):89-93. [Medline].

10. Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction. Nov
1996;91(11):1585-614. [Medline].

11. Ashton CH. Adverse effects of cannabis and cannabinoids. Br J Anaesth. Oct 1999;83(4):637-49. [Medline].

12. Ashton CH. Pharmacology and effects of cannabis: a brief review. Br J Psychiatry. Feb 2001;178:101-6.
[Medline].

13. Compton WM, Grant BF, Colliver JD, Glantz MD, Stinson FS. Prevalence of marijuana use disorders in the
United States: 1991-1992 and 2001-2002. JAMA. May 5 2004;291(17):2114-21. [Medline].

14. Degenhardt L, Hall W, Lynskey M. Exploring the association between cannabis use and depression.
Addiction. Nov 2003;98(11):1493-504. [Medline].

15. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet.


2003;42(4):327-60. [Medline].

16. Hall W, Solowij N. Adverse effects of cannabis. Lancet. Nov 14 1998;352(9140):1611-6. [Medline].

17. Hall W, Solowij N, Lemon J:. The Health and Psychological Consequences of Cannabis Use. Monograph
No 25. National Drug Strategy. Australian Government Publication Serv. 1994;15-20.

18. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor
localization in brain. Proc Natl Acad Sci U S A. Mar 1990;87(5):1932-6. [Medline].

19. Huestis MA, Mitchell JM, Cone EJ. Detection times of marijuana metabolites in urine by immunoassay and
GC-MS. J Anal Toxicol. Oct 1995;19(6):443-9. [Medline].

20. Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Prog
Neuropsychopharmacol Biol Psychiatry. Aug 2004;28(5):849-63. [Medline].

21. Khalsa JH, Genser S, Francis H, Martin B. Clinical consequences of marijuana. J Clin Pharmacol. Nov
2002;42(11 Suppl):7S-10S. [Medline].

22. Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP. Risk factors for adolescent
substance abuse and dependence: data from a national sample. J Consult Clin Psychol. Feb
2000;68(1):19-30. [Medline].

23. Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA, Nelson EC, et al. Escalation of drug use in
early-onset cannabis users vs co-twin controls. JAMA. Jan 22-29 2003;289(4):427-33. [Medline].

24. McGee R, Williams S, Poulton R, Moffitt T. A longitudinal study of cannabis use and mental health from
adolescence to early adulthood. Addiction. Apr 2000;95(4):491-503. [Medline].

25. McGuigan M. Cannabinoids. In: Goldfrank's Toxicological Emergencies. 8th ed. New York: McGraw-Hill
Professional; 2006.

26. Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in
long-term cannabis users. Arch Gen Psychiatry. Oct 2001;58(10):909-15. [Medline].

27. Robson P. Cannabis. Arch Dis Child. Aug 1997;77(2):164-6. [Medline].

28. Smith NT. A review of the published literature into cannabis withdrawal symptoms in human users.
Addiction. Jun 2002;97(6):621-32. [Medline].

29. Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, Miller M, et al. Cognitive functioning of long-term
heavy cannabis users seeking treatment. JAMA. Mar 6 2002;287(9):1123-31. [Medline].

30. Strang J, Witton J, Hall W. Improving the quality of the cannabis debate: defining the different domains.
BMJ. Jan 8 2000;320(7227):108-10. [Medline].

31. Vitale S, van de Mheen D. Illicit drug use and injuries: A review of emergency room studies. Drug Alcohol
Depend. Mar 15 2006;82(1):1-9. [Medline].

32. Wallace KL, Kunkel DB. Legal hemp products and urine cannabinoid testing. J Toxicol Clin Toxicol.
1999;37(7):897-8. [Medline].

33. Watson SJ, Benson JA Jr, Joy JE. Marijuana and medicine: assessing the science base: a summary of the
1999 Institute of Medicine report. Arch Gen Psychiatry. Jun 2000;57(6):547-52. [Medline].

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