Cannabis: Botany and Pharmacology
Cannabis preparations, derived from the female Cannabis sativa plant, have been widely used for their psychotropic effects since the beginning of history. The drug is prepared in different ways in different parts of the world. The flowering tops and resin se-creted by the female plant contain the highest concentrations of ∆-9-tetrahydrocannabinol (∆-9-THC), the primary psychoactive component. Marijuana, the most common preparation, is made by drying and shredding the upper leaves, tops, stems, flowers and seeds of the plant. Hashish is a more potent preparation made by extracting and drying the resin and sometimes also the com-pressed flowers. Hashish oil, which is even more potent, is dis-tilled from hashish. Marijuana and hashish can be smoked either in the form of cigarettes or by using a pipe. Hashish, hashish oil and, less commonly, marijuana can be mixed with tea or food and taken orally (Ashton, 2001; Hall and Solowij, 1998).
Selective breeding and improved growing methods have produced cannabis plants that contain significantly higher ∆-9-THC concentrations than naturally occurring plants. Thus, although there is a great deal of variation, the potency of illicit can-nabis available in the USA has increased substantially, on average, over the last 30 years (Ashton, 2001; Hall and Solowij, 1998).
Intoxication occurs within minutes after smoking canna-bis and typically persists for several hours. After eating foods containing cannabis, intoxication occurs after approximately an hour and can persist for 8 to 24 hours. The onset of intoxication after drinking cannabis steeped in tea is shorter, but not as rapid as after smoking, and has an intermediate duration of intoxica-tion. Smoking cannabis induces intoxication more quickly than ingesting cannabis because first-pass metabolism in the liver is avoided and the combustion causes enhanced release of ∆-9-THC from pyrolysis of acids in cannabis preparations. Smoking is the predominant method of taking cannabis in most parts of the world, including the USA, probably because of the more rapid onset of action and because the potency of the drug when it is smoked is about three times that experienced when an equivalent amount is eaten (Ashton, 2001; Hall and Solowij, 1998).
∆-9-THC and other cannabinoids are highly lipophilic and are quickly and widely distributed throughout the body. ∆-9-THC can cross the placenta and enter breast milk; it may interact with other drugs by inducing liver enzymes and competing for plasma binding sites. ∆-9-THC is metabolized in the liver by hy-droxylation to at least 20 different metabolites. Some, such as 11-hydroxy-THC, are psychoactive and have half-lives exceeding 2 days. ∆-9-THC may also be conjugated to more water-soluble metabolites that are excreted predominantly into the gut where they may be reabsorbed, and also into the bile, urine, sweat and hair. ∆-9-THC is stored in adipose tissue from which it is released slowly; in regular users it can often be detected more than 30 days after the individual’s last exposure to cannabis (Johnson, 1990). If an individual uses cannabis regularly, the stores of ∆-9-THC in the adipose tissue result in a constant supply of cannabinoids to the body including the brain (Ashton, 2001).
There are two types of G-protein-coupled cannabinoid re-ceptors. CB1 receptors are found in the lipid membranes of neu-rons in the central nervous system, including the cerebral cortex, basal ganglia, thalamus and brain stem, with high densities in the hippocampus, cerebellum and striatum. CB2 receptors are found in the lipid membranes of various types of cells in the im-mune system. ∆-9-THC is a partial agonist, activating both CB1 and CB2 receptors (Hall and Solowij, 1998). Activation of can-nabinoid receptors mediates the inhibitory effect of adenylate cyclase, decreasing cyclic adenosine monophosphate, and also inhibits calcium and potassium transport. Receptor activation also mediates the excitatory effect of mitogen-activated protein kinase (Ameri, 1999). The cannabinoid system plays a modula-tory role in regulating many different functions including mood, motor control, perception (including pain perception), appetite, sleep, memory and cognition, reproductive function and im-mune response (Hall and Solowij, 1998). ∆-9-THC can potentiate the effects of alcohol, barbiturates, caffeine and amphetamines (Solomons and Neppe, 1989).