Marijuana and Cannabis Compounds

Cannabis sativa contains >400 compounds in addition to the psychoactive substance, delta-9-tetrahydrocannabinol (THC). Marijuana cigarettes are prepared from the leaves and flowering tops of the plant, and a typical marijuana cigarette contains 0.5 to 1 g of plant material. Although the usual THC concentration varies between 10 and 40 mg, concentrations >100 mg per cigarette have been detected. Hashish is prepared from concentrated resin of C. sativa and contains a THC concentration of between 8 to 12% percent by weight. "Hash oil," a lipid-soluble plant extract, may contain a THC concentration of 25 to 60% percent and may be added to marijuana or hashish to enhance its THC concentration. Smoking is the most common mode of marijuana or hashish use. During pyrolysis, >150 compounds in addition to THC are released in the smoke. Although most of these compounds do not have psychoactive properties, they do have potential physiologic effects.

THC is quickly absorbed from the lungs into blood and is then rapidly sequestered in tissues. It is metabolized primarily in the liver, where it is converted to 11-hydroxy-THC, a psychoactive compound, and >20 other metabolites. Many THC metabolites are excreted through the feces at a rate of clearance that is relatively slow in comparison to that of most other psychoactive drugs.

Specific cannabinoid receptors (CB1 and CB2) have been identified in the central nervous system, including the spinal cord, and in the peripheral nervous system. High densities of these receptors have been found in the cerebral cortex, basal ganglia, and hippocampus. B lymphocytes also appear to have cannabinoid receptors. A naturally occurring THC-like ligand has been identified in the nervous system, where it is widely distributed.

Prevalence of Use

Marijuana is the most commonly used illegal drug in the United States. Use is particularly prevalent among adolescents; studies suggest that 37% of high school students in the United States have used marijuana. Marijuana is relatively inexpensive and is often considered to be less hazardous than other controlled drugs and substances. Very potent forms of marijuana (sinsemilla) are now available in many communities, and concurrent use of marijuana with crack/cocaine and phencyclidine is increasing. Marijuana abuse by individuals from all social strata has been increasing.

Acute and Chronic Intoxication

Acute intoxication from marijuana and cannabis compounds is related to both the dose of THC and the route of administration. THC is absorbed more rapidly from marijuana smoking than from orally ingested cannabis compounds. Acute marijuana intoxication usually consists of a subjective perception of relaxation and mild euphoria resembling mild to moderate alcohol intoxication. This condition is usually accompanied by some impairment in thinking, concentration, and perceptual and psychomotor function. Higher doses of cannabis may produce behavioral effects analogous to severe alcohol intoxication. Although the effects of acute marijuana intoxication are relatively benign in normal users, the drug can precipitate severe emotional disorders in individuals who have antecedent psychotic or neurotic problems. As with other psychoactive compounds, both set (user's expectations) and setting (environmental context) are important determinants of the type and severity of behavioral intoxication.