AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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.

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. 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%.

• 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: 
• • Dronabinol (Marinol) – 10% absorption; peak concentration 2-3 hours after ingestion
  • Nabilone (Cesanet) – Up to 90% absorption; peak concentration in 2 hours after ingestion

• 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, 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Large doses of THC may produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation. Most episodes are rapidly remitting.
• A clear relationship exists between cannabis use and mental health. 
• • Substance-abusing adolescents commonly suffer one or more comorbid health or behavioral problems. Several studies have demonstrated marijuana abuse to coexist with attention deficit hyperactivity disorder, other learning disabilities, depression, and anxiety. Cohort and well-designed cross-sectional studies suggest a modest association between early, regular, or heavy cannabis use and 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.

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.¹⁷

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. 

Race

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

Sex

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.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

• Physicians rarely diagnose cannabis dependence because it is deemed an insignificant drug in comparison to others.
• A motivational affect of heavy use is characterized by poor attention and goal-directed thinking or behavior.
• Physicians should screen for cannabis use because it may be used in conjunction with other drugs. The CAGE questions used for alcohol dependence can also be used to screen for marijuana use. The acronym CAGE stands for the main words of the 4 questions: cut, annoyed, guilty, and eye opener. Two or more positive responses to the following CAGE questions suggests dependence:
• • Have you ever felt you ought to cut down on your use?
  • Have people annoyed you by criticizing your use?
  • Have you ever felt guilty about your use?
  • Have you ever needed to use in the morning as an “eye opener”?

Physical

• Typically, marijuana use can present with conjunctival injection, increased drowsiness, euphoria, nausea, increased appetite, dryness or irritation of the nasal or oropharynx, hypertension, tachycardia, tachypnea, hypotonia, tremors, impaired motor function, slurred speech, impaired short-term memory, inability to perform complex tasks, acute psychosis, agitation or bizarre behavior, urinary retention, impaired reaction time, or decreased intraocular pressure.
• Less objective findings include the following:
• • Dose-dependent miosis may be present.
  • Balance or motor incoordination, as elicited by a positive Romberg sign, may be observed.
  • Impaired performance with cognitive functioning tasks, including serial addition/subtraction, and object recall may be observed.
  • Sensory function and pain perception appear to remain intact.

Causes

• Several factors are believed to contribute to the resurgence of cannabis use.
• • Perceived health risk and addiction from cannabis use among teenagers is falling.
  • Disagreeing authorities have different beliefs about the risks of cannabis use. Some physicians are calling for loosened sanctions against prescribing cannabis for medical purposes, and many experts debate the issues of cannabis dependence and withdrawal.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Conduct disorder
Attention deficit hyperactivity disorder
Dysthymic disorder
Major depression
Other substance abuse
Narcotics

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Urine immunoassays are used to detect a conjugated THC metabolite, 11-nor-delta-9-THC carboxylic acid. 
• • After a single, acute use, THC is detectable in the urine for 7 days.
  • With chronic use, THC is detectable in the urine for 10-30 days.
  • Enzyme-multiplied immunoassay technique (EMIT) can detect urine levels as low as 20-100 ng/mL.
  • These screening tests correlate with prior exposure not with the amount used or degree of clinical effect.
  • False-positive results can occur with ibuprofen, naproxen, dronabinol, efavirenz, and hemp seed oil.
  • False-positive results are unlikely to result from second-hand smoke inhalation or health-food store products containing hemp, unless the exposure occurs in an unventilated space.
• Quantitative assays for 11-nor-delta-9-THC carboxylic acid are available in most laboratories, but it must be specifically requested.
• Blood tests can also be used to detect THC; however, the levels correlate poorly with the clinical effects.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Emergency Department Care

• In all patients, the use and abuse of cannabis should be addressed. The negative consequences on the patient’s professional and social life should be stressed. Speaking with the patient with empathy and without passing judgment is especially important.
• Treatment depends on the clinical presentation, the age of the patient, and the presence of other legal or illicit substances. 
• Immediate management should be supportive, including cardiovascular and neurological monitoring, and placement in a quiet room.
• Gastric decontamination may be considered in children younger than 16 years with an acute ingestion less than 2 hours prior to presentation.
• Patients who are agitated or with psychosis should be treated with benzodiazepines. Patients with an acute psychotic episode should also undergo substance abuse counseling.
• Those patients who request counseling should be referred for treatment.
• Maladaptive behaviors associated with cannabis are more common in males, younger adolescents, patients in urban settings, patients presenting to emergency departments after midnight or on weekends, and patients with psychiatric comorbidities. These patients should be referred to substance abuse counseling.

Consultations

• Persons with cannabis dependency should be referred to social services.
• Treatment programs differ for adolescents and young adults.
• • Adolescents should be counseled in a family-based approach with a well-defined but flexible intervention. Both outpatient and residential treatment facilities are effective in this age group. Home-based programs are an alternative to those families who do not wish to go to treatment centers.
  • Adults should be taught coping skills in situations that present a risk of use. In this population, group discussions related to cessation and support groups are more effective than one-on-one interventions.

FOLLOW-UP

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Patient Education

• Educate all patients with cannabis use or abuse about the adverse effects of this drug. Encouraging cessation is equally important. 
• An effort should be made to educate patients on the adverse effects of cannabis use which include the following:
• • Impaired attention, memory, and psychomotor performance that occur while intoxicated
  • Subtle changes in attention and memory that occur with chronic use
  • Increased risk of motor vehicle collisions if driving while intoxicated.
  • Chronic bronchitis and histopathological changes of the cavity or respiratory tract that may be cancerous precursors
• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Biological Warfare and Personal Protective Equipment.

MISCELLANEOUS

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• The Drug Enforcement Administration (DEA) issued a final order in March 1992 stating that the plant marijuana currently has no accepted medical use.
• Marijuana is a Schedule I controlled substance.
• In 1999, the Institute of Medicine concluded that scientific data support certain therapeutic uses for cannabinoid-based drugs including pain relief, nausea and vomiting, and appetite stimulation.

ACKNOWLEDGMENTS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Flowering top of cannabis plant.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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Article Last Updated: Feb 11, 2008