The neuropsychological effects of naturally occurring psychoactive substances have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals, such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic effects of LSD, and the observations that LSD and the endogenous neurotransmitter serotonin share chemical and pharmacological pro fi les, led to the suggestion that biogenic amines like serotonin were involved in the psychosis of mental disorders such as schizophrenia. Understanding the mechanism by which hallucinogens elicit unique neurobehavioral effects may open up new avenues in drug abuse research, as well as contributing to the understanding of the endogenous psychosis of psychiatric diseases. Here we summarize recent advances in our understanding of the molecular mechanism of action of hallucinogenic drugs, as well as fi ndings obtained in animal models.