Molecular and Cellular Basis of Hallucinogen Action

Abstract The neuropsychological effects of naturally occurring hallucinogens have been recognized for millennia. Hallucinogens, which include naturally occurring compounds such as psilocybin and mescaline, as well as synthetic compounds such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, cognition, and mood. The discovery of LSD and the observation that LSD and the endogenous neurotransmitter serotonin share chemical and pharmacological profiles led to the suggestion that biogenic amines like serotonin were involved in the mechanism of action of hallucinogens as well as in psychotic mental disorders such as schizophrenia. Based on evidence from rodents and humans, the serotonin 5-HT 2A receptor appears to be responsible for the hallucinogenic effects of tryptamine, ergoline, and phenethylamine hallucinogens. In this chapter, we review existing literature on the molecular and signaling mechanisms involved in the behavioral effects of hallucinogens.