Pharmacology and potential therapeutic uses of cannabis.

Throughout history, cannabis has been used as a natural therapeutic herb. Indeed the discovery of the remains of a young girl in Jerusalem who died in childbirth sometime around the third century AD, revealed residues of cannabis in the pelvic region. This strongly suggests that cannabis was used in medical practice in early human civilizations. Cannabis was first used as a medicine in Britain in the mid-nineteenth century by O’Shaugnessy, an army surgeon. While in India O’Shaugnessy witnessed at first hand the use of cannabis for a wide range of medical conditions such as rabies, epilepsy and muscle spasms, and for pain relief. On his return to Britain, O’Shaugnessy advocated its use and cannabis was widely accepted as a medicine for about 70 years. 63 In this article we shall review the pharmacology of cannabinoids and their therapeutic potential. In particular, we shall discuss their use as antinociceptive/ analgesic agents. The reader is referred to several excellent review articles and books on this subject. 8 22 37 45 50 63 69 95 The major psychoactive constituent of Cannabis sativa was first isolated in 1964. The compound was identified as -tetrahydrocannabinol ( -THC, fig. 1), and when administered to humans produced a spectrum of effects, including increased pulse rate, decreased blood pressure, muscle weakening, increased appetite, euphoria followed by drowsiness, depersonalization, altered time sense and decreased memory recollection; hearing became less discriminative and visual signals were sharper but distorted. The effects of -THC at the biochemical level were virtually unknown until recently. Pharmacological studies suggested that -THC and other active cannabinoids might act at specific receptor sites, 68 but the high lipophilicity of these compounds made their use in binding assays very difficult. Some researchers were initially of the opinion that the effects observed with -THC were attributable to perturbation of membrane structures. However, these proposals were refuted and early attempts to identify specific cannabinoid receptor binding sites in brain membranes showed encouraging results. As early as 1984, Howlett and co-workers showed that cannabinoids caused inhibition of adenylyl cyclase. It was subsequently shown that this effect