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.

As with abuse of cocaine, opioids, and alcohol, chronic marijuana abusers may lose interest in common socially desirable goals and steadily devote more time to drug acquisition and use. However, THC does not cause a specific and unique “amotivational syndrome.” The range of symptoms sometimes attributed to marijuana use is difficult to distinguish from mild to moderate depression and the maturational dysfunctions often associated with protracted adolescence. Chronic marijuana use has also been reported to increase the risk of psychotic symptoms in individuals with a past history of schizophrenia. Persons who initiate marijuana smoking before the age of 17 may subsequently develop severe cognitive and neuropsychological disorders, and may be at higher risk for later polydrug and alcohol abuse problems.

Physical Effects
Conjunctival injection and tachycardia are the most frequent immediate physical concomitants of smoking marijuana. Tolerance for marijuana-induced tachycardia develops rapidly among regular users. However, marijuana smoking may precipitate angina in persons with a history of coronary insufficiency. Exercise-induced angina may be increased after marijuana use to a greater extent than after tobacco cigarette smoking. Patients with cardiac disease should be strongly advised not to smoke marijuana or use cannabis compounds.

Significant decrements in pulmonary vital capacity have been found in regular daily marijuana smokers. Because marijuana smoking typically involves deep inhalation and prolonged retention of marijuana smoke, marijuana smokers may develop chronic bronchial irritation. Impairment of single-breath carbon monoxide diffusion capacity (DLCO) is greater in persons who smoke both marijuana and tobacco than in tobacco smokers.

Although marijuana has also been associated with adverse effects on a number of other systems, many of these studies await replication and confirmation. A reported correlation between chronic marijuana use and decreased testosterone levels in males has not been confirmed. Decreased sperm count and sperm motility and morphologic abnormalities of spermatozoa following marijuana use have also been reported. Prospective studies demonstrated a correlation between impaired fetal growth and development and heavy marijuana use during pregnancy. Marijuana has also been implicated in derangements of the immune system; in chromosomal abnormalities; and in inhibition of DNA, RNA, and protein synthesis; however, these findings have not been confirmed or related to any specific physiologic effect in humans.

Tolerance and Physical Dependence
Habitual marijuana users rapidly develop tolerance to the psychoactive effects of marijuana and often smoke more frequently and try to secure more potent cannabis compounds. Tolerance for the physiologic effects of marijuana develops at different rates; e.g., tolerance develops rapidly for marijuana-induced tachycardia but more slowly for marijuana-induced conjunctival injection. Tolerance to both behavioral and physiologic effects of marijuana decreases rapidly upon cessation of marijuana use.

Withdrawal signs and symptoms have been reported in chronic cannabis users, with the severity of symptoms related to dosage and duration of use. These include tremor, nystagmus, sweating, nausea, vomiting, diarrhea, irritability, anorexia, and sleep disturbances. Withdrawal signs and symptoms observed in chronic marijuana users are usually relatively mild in comparison to those observed in heavy opiate or alcohol users and rarely require medical or pharmacologic intervention. More severe and protracted abstinence syndromes may occur after sustained use of high-potency cannabis compounds.

Therapeutic Use
Marijuana, administered as cigarettes or as a synthetic oral cannabinoid (dronabinol), has been proposed to have a number of properties that may be clinically useful in some situations. These include antiemetic effects in chemotherapy recipients, appetite-promoting effects in AIDS, reduction of intraocular pressure in glaucoma, and reduction of spasticity in multiple sclerosis and other neurologic disorders. With the possible exception of AIDS-related cachexia, none of these attributes of marijuana compounds is clearly superior to other readily available therapies.

Cocaine and Other Commonly Abused Drugs

• Cocaine and Other Commonly Abused Drugs: Introduction
• Cocaine
• Lysergic Acid Diethylamide (LSD)
• Methamphetamine
• Phencyclidine
• Polydrug Abuse