A large literature exists on the effects of cannabis plants, with many of the earlier studies conducted in human subjects (Mendelson et al., 1976; Jones, 1978; Hollister, 1986). Unfortunately, much of this research would now be regarded as inadequately controlled and poorly designed. Cannabis plants However, research on cannabis has been stimulated in recent years by the recognition that specific receptors exist in the brain that recognize cannabinoids, cannabis plant and by the discovery of a series of endogenous cannabinoids that act as ligands for these receptors. As was the case with opiate research in the 1970s, research on a psychoactive drug of plant origin has revealed a hitherto unknown physiological control mechanism. This review will focus mainly on the more recent literature in this field.
The cannabis plant system in brain
Exogenous cannabinoids and their receptors
The principal active component in the complex mixture of cannabinoids present in extracts of the plant Cannabis sativa is Δ9‐tetrahydrocannabinol (THC) (Mechoulam, 1970) (Fig. 1). THC is a sticky resin that is not soluble in water. Smoking remains the most efficient means of delivering the drug and experienced users can titrate the dose by adjusting the frequency and depth of inhalation (Iversen, 2000).
THC or cannabis extracts can also be taken orally in fat‐containing foods or dissolved in a suitable pharmaceutical oil, but absorption is delayed and variable (Iversen, 2000). A series of man‐made synthetic cannabinoids, some of which are more potent and more water soluble than THC, is also available (Pertwee, 1999) (Fig. 1). All of these compounds act as agonists at the CB1 cannabinoid receptor (Matsuda et al., 1990), which is the only one known to be expressed in the brain. A second cannabinoid receptor, CB2, is expressed only in peripheral tissues, principally in the immune system (Munro et al., 1993; Felder and Glass, 1998; Pertwee, 1999). THC and the synthetic cannabinoids also act to some extent as agonists at the CB2 receptor.
Following the discovery of specific cannabinoid receptors, a search was made for naturally occurring ligands of these receptors in mammalian tissues. This led to the discovery of a series of arachidonic acid derivatives with potent actions at cannabinoid receptors. These are: anandamide (N‐arachidonyl‐ethanolamine; Devane et al., 1992), 2‐arachidonylglycerol (2‐AG; Mechoulam et al., 1995; Sugiura et al., 1995; Stella et al., 1997) and 2‐arachidonylglyceryl ether (Hanuš et al., 2001) (Fig. 1). Of these, anandamide is the ligand that has been most extensively studied so far.