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 5HT
1A
receptors, as well as dopamine and glutamate systems. Investigations into the neurochemical and behavioural effects of this class of drugs have 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. In the past 30 years, there has been a renewed interest in conducting clinical studies with these drugs in healthy individuals and in patients with psychiatric conditions 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 the 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 effect 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 and human studies.