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Preparations of hemp, Cannabis sativa, have been used for thousands of years as recreational and therapeutic drugs. The most important constituents are the psychoactive (-)-trans-∆ 9 -tetrahydrocannabinol (THC), a partial agonist at cannabinoid (CB) receptors CB 1 and CB 2 , and the non-psychoactive pleiotropic cannabidiol (CBD). Both compounds are highly lipophilic, like the endogenous CB receptor agonists, the arachidonic acid derivatives anandamide and arachidonoyl glycerol. The CB receptors belong to the family of G protein-coupled receptors, and the first X‑ray crystal structures of both CB receptors subtypes have recently been obtained, which will facilitate the rational design of novel synthetic ligands. Besides the already largely established indications such as chronic pain, chemotherapy-induced vomiting, multiple sclerosis-associated spasms, and cachexia, there is preliminary evidence for several further cannabinoid effects, which will have to be confirmed by clinical studies.

The endocannabinoid system reduces sensitization processes. Low doses of cannabinoids may enhance the potency of opioid-drugs and reduce the risk of tolerance to opioids. So far no cannabinoid has been approved for the treatment of acute pain due to lack of consistent data. In contrast, a Cannabis Based Medicine spray consisting of delta9-tetrahydrocannabinol and cannabidiol has been approved for the treatment of neuropathic pain in patients with multiple sclerosis. The adjunct of cannabidiol and the oromucosal formulation increase the therapeutic index of delta9-tetrahydrocannabinol. The differentiation of analgetic effects and cannabimimetic effects may be increased while compounds--such as ajulemic acid--are used which preferentially act on peripheral cannabinoid receptors and exert receptor independent effects. A further approach in this direction is the use of enzymes which metabolize endocannabinoids.