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8. The therapeutic effects of cannabinoids
8.1 Historical background
Cannabis has had a long history of medical and therapeutic use in India and the Middle East (Grinspoon and Bakalar, 1993; Mechoulam, 1986; Nahas, 1984) where it has been variously used as an analgesic, anti-convulsant, anti-spasmodic, anti-emetic, and hypnotic. Cannabis was introduced to British medicine in the mid-nineteenth century by O'Shaugnessy (1842) who had gained clinical experience with the drug while an Army surgeon in India (Mechoulam, 1986; Nahas, 1984). He recommended its use for the relief of pain, muscle spasms, and convulsions occurring in tetanus, rabies, rheumatism and epilepsy (Nahas, 1984). Partly as the result of his advocacy, cannabis came to be widely used as an analgesic, anti-convulsant and anti-spasmodic throughout the middle part of the 19th century in Britain and the USA.
The medical use of cannabis declined around the turn of the present century. Because the active constituents of cannabis were not isolated until the second half of the twentieth century, cannabis continued to be used in the form of natural preparations which varied in purity and, hence in effectiveness. The use of cannabis was largely supplanted by other pharmaceutically purer drugs, which could be given in standardised doses to produce more dependable effects. These included the opiates, aspirin, chloral hydrate, and the barbiturates (Mechoulam, 1986; Nahas, 1984). In the early part of the century, the medical use of such crude cannabis preparations was further discouraged by laws which treated cannabis as a "narcotic" drug and severely restricted its availability. It finally disappeared from the American pharmacopoeia in the early 1940s after the passage of the Marijuana Tax Act (Grinspoon and Bakalar, 1993), although it continued to be used in Australia into the 1960s (Casswell, 1992).
THC, the major psychoactive ingredient of cannabis, was not isolated until 1964 (Goani and Mechoulam, 1964), shortly before cannabis achieved widespread popularity as a recreational drug among American youth. Its widespread recreational use, and its symbolic association with a rejection of traditional social values, undoubtedly hindered pharmaceutical research into its therapeutic uses. Consequently, the rediscovery of some of its traditional therapeutic uses was largely serendipitous, as was the discovery of some newer uses. For example, its value as an anti-emetic agent in the treatment of nausea caused by cancer chemotherapy seems to have been rediscovered by young adults who had used cannabis recreationally prior to undergoing chemotherapy for leukemia (Grinspoon, 1990).
From the mid-1970s some clinical research on the therapeutic value of cannabis and cannabinoids was undertaken. On the whole, however, this research has been very thin and uneven, and, consequently, many of the claims for the therapeutic efficacy of cannabinoids rely heavily, and, in the case of rare medical conditions, solely upon anecdotal evidence, that is, the testimonies of individuals who claim to have derived medical benefit from its use (e.g. Grinspoon and Bakalar, 1993; Randall, 1990), and small numbers of cases reported by physicians (e.g. Consroe et al, 1975; Meinck et al, 1989).
Evidence will be reviewed for the best-supported therapeutic uses of cannabinoids. The review begins with the evidence on the effectiveness of cannabinoids as anti-emetic drugs for nausea caused by cancer chemotherapy, and as agents to control intra-ocular pressure in glaucoma. Briefer reviews are provided of the evidence in favour of other putative therapeutic uses of cannabinoids which are less well supported by clinical evidence, chief among which are its uses as an anti-convulsant, an anti-spasmodic, and an analgesic agent. The value and limitations of the largely anecdotal evidence of efficacy in these latter conditions will also be briefly considered. The review will include a discussion of the controversy in the United States about "marijuana rescheduling" which has coloured much recent discussion of the issue. This controversy concerns the vexatious issue of whether smoked cannabis should be available for medical use in addition to synthetic cannabinoids such as THC.