The health and psychological consequences of cannabis use - chapter 4

THIS DOCUMENT HAS BEEN RESCINDED: Chapter 4.7 Metabolism of cannabinoids.

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4. Cannabis the drug


4.7 Metabolism of cannabinoids

"Cannabinoids" is the collective term for a variety of compounds which can be extracted from the cannabis plant or are produced within the body after ingestion and metabolism of cannabis. Some of these compounds are psychoactive, that is, they have an effect upon the mind of the users; others are pharmacologically or biologically active, that is, have an effect upon cells or the function of other bodily tissues and organs, but are not psychoactive. Animal and human experimentation indicates that delta-9-tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis.

THC is rapidly and extensively metabolised in humans. Different methods of ingesting cannabis give rise to different patterns of absorption, metabolism and excretion of THC. Upon inhalation, THC is
absorbed within minutes from the lungs into the bloodstream. Absorption of THC is much slower after oral administration, entering the bloodstream within one to three hours, and delaying the onset of psychoactive effects.

After smoking, the initial metabolism of THC takes place in the lungs, followed by more extensive metabolism by liver enzymes which transform THC to a number of metabolites. The most rapidly produced metabolite is 9-carboxy-THC (or THC-COOH) which is detectable in blood within minutes of smoking cannabis. It is not psychoactive. Another major metabolite of THC is 11-hydroxy-THC, which is approximately 20 per cent more potent than THC, and which penetrates the blood-brain barrier more rapidly than THC. 11-hydroxy-THC is only present at very low concentrations in the blood after smoking, but at high concentrations after the oral route (Hawks, 1982). THC and its hydroxylated metabolites account for most of the psychoactive effects of the cannabinoids.

Peak blood levels of THC are reached very rapidly, usually within 10 minutes of smoking and before a joint is fully smoked, and decline rapidly to about 5-10 per cent of their initial level within the first hour. This initial rapid decline reflects the rapid conversion of THC to its metabolites, as well as the distribution of THC to lipid-rich tissues, including the brain (Fehr and Kalant, 1983; Jones, 1980; 1987). THC and its metabolites are highly fat soluble and may remain for long periods of time in the fatty tissues of the body, from which they are slowly released back into the bloodstream. This phenomenon slows the elimination of cannabinoids from the body.

The time required to clear half of the administered dose of THC from the body has been found to be shorter for experienced or daily users (19-27 hours) than for inexperienced users (50-57 hours) (Agurell, et al 1986; Hunt and Jones, 1980; Lemberger et al, 1970; 1978; Ohlsson, et al, 1980). Recent research using more sensitive detection techniques suggests that the half-life in chronic users may be closer to three to five days (Johansson et al, 1988). It is the immediate and subsequent metabolism of THC that occurs more rapidly in experienced users (Blum, 1984). Given the slow clearance, repeated administration of cannabis results in the accumulation of THC and its metabolites in the body. Because of its slow release from fatty tissues into the bloodstream, THC and its metabolites may be detectable in blood for several days, and traces may persist for several weeks.

While blood levels of THC peak within a few minutes, 9-carboxy-THC levels peak approximately 20 minutes after commencing smoking and then decline slowly. The elimination curve for THC crosses the 9-carboxy-THC curve around the time of the peak of the latter and subjective intoxication also peaks around this time (i.e., 20-30 minutes later than peak THC blood levels), with acute effects persisting for approximately two to three hours.