Hallucinogenic Drugs

Hallucinogens are among the oldest drugs used by humanity, often in spiritual contexts. Classic hallucinogens like LSD, psilocybin, DMT, mescaline, and DOM produce perceptual changes, cognitive shifts, and emotional alterations primarily by acting as agonists at serotonin 5-HT2A receptors, with additional activity on dopamine and glutamate systems. These drugs also include non-classic agents like ketamine and MDMA. Negative effects include 'bad trips', rare flashbacks, and psychotic breaks. After a long hiatus, human clinical studies have resumed, building on earlier animal research to advance understanding of pharmacology and psychiatric conditions.

Study at a glance

Abstract

Abstract Hallucinogens constitute one of the oldest classes of drugs used by humanity, often in the context of spiritual practices. Classic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin, N,N ‐dimethyltryptamine (DMT), mescaline and 2,5‐dimethoxy‐4‐methylamphetamine (DOM) produce complex psychological and physical effects, including perceptual changes, cognitive shifts in reality and emotional alterations. These drugs primarily act on serotonin systems through 5‐hydroxytryptamine 2A (5HT 2A ) receptors, with additional activity through dopamine and glutamate systems. Investigation of the neurochemical and behavioural effects of this class of drugs has provided important insights into pharmacology and psychiatric conditions. Given their popularity as recreational drugs, investigation of their actions and effects continues to be an important endeavour. After a long hiatus, clinical studies in humans have resumed with these drugs in laboratories around the world. Key Concepts: Hallucinogens have been used for thousands of years by various societies, often in conjunction with spiritual practices. In present day, hallucinogens remain highly popular as recreational drugs. The chemical structure of hallucinogens consists of tryptamines (LSD and psilocybin) and phenethylamines (mescaline and DOM). The potency of hallucinogens is directly correlated to their ability to act as agonists at the serotonin receptor subtype, 5‐HT 2A . Drugs that act at sites other than 5‐HT 2A receptors can also produce hallucinogen‐like effects (e.g. ketamine, MDMA, salvinorin A, nitrous oxide, GHB). The signature effects of hallucinogens include perceptual changes, alterations in affect and shifts in cognitive ability. Negative responses associated with hallucinogens include ‘bad trips’ (severe anxiety and a disconnection with reality) as well as rare instances of ‘flashbacks’ and psychotic breaks. Human research with hallucinogens has recently been revitalised, augmenting the scientific advances made previously with animal studies.