The abuse of synthetic psychoactive substances known as "designer drugs" or "new psychoactive substances" (NPS) is increasing rapidly. These drugs are manufactured as legal alternatives to traditional illicit drugs. Synthetic cathinones ("bath salts") and synthetic cannabinoids ("spice") have received substantial media attention. Low recreational doses can produce desirable effects, but high doses or chronic exposure often lead to dangerous medical consequences including psychosis, violent behaviors, tachycardia, hyperthermia, and death. Despite their popularity, there is a paucity of scientific data about these drugs. This review describes the mechanisms of action and neurobiological effects of synthetic cathinones and cannabinoids.
Hexahydrocannabinol (HHC), sold as a legal replacement for Δ9-THC, has two epimers: 9(R)-HHC and 9(S)-HHC. In adult male mice, 9(R)-HHC produced all four cannabimimetic effects (locomotor suppression, antinociception, hypothermia, and catalepsy) and fully substituted for Δ9-THC in drug discrimination, with similar potency except for greater hypothermia. 9(S)-HHC only produced effects in two tetrad measures, was less potent, and partially substituted for Δ9-THC. 9(R)-HHC likely has abuse liability in humans, while 9(S)-HHC may produce weak Δ9-THC-like psychoactivity. The ratio of epimers consumed may influence effects in human users.