Several decades of irrational prejudice may have hampered clinical research on cannabis as a medicine, but work on the pharmacology of its active ingredients has been making steady progress. Just as the body has a natural counterpart to the opiate drugs, so too it makes its own endogenous cannabinoids. These act through receptors, of which two variants—CB 1 and CB 2—have been definitely identified and at least one other is suspected. The CB 1 receptors are located only in the brain; their CB 2 counterparts are found peripherally, and especially on the cells of the immune system. Cannabinoid receptors are present not just in vertebrates but also in molluscs, leeches, and other invertebrate groups that have been evolutionarily separate for 500 million years. The fact that natural selection has for so long conserved these receptors is an indication of their physiological importance.

Anandamide, the first natural cannabinoid to be isolated, came to light in 1992. Its precise role, and those of the other cannabinoids that have since been identified, remains uncertain; but evidence exists that all play a part in memory, appetite, the control of movement, and, especially, the modulation of pain. 1 With respect to the last of these, the sites of cannabinoid action in the central nervous system are confined to specific areas, most of which—the dorsal horn of the spinal cord, for example 2 3—are involved in processing pain signals. Clear parallels exist between cannabinoid and opiod receptors, and evidence is accumulating that the two systems sometimes interact, 4 and may operate synergistically. One unproved but intriguing idea is that endocannabinoids may set the “analgesic tone” of the body, with the level of their production acting as a kind of pain thermostat.