This paper is the most comprehensive review of psychedelics research up to 2016 by the eminent David E. Nichols.


“Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network.”

Author: David E. Nichols


This paper is included in our ‘Top 10 Articles for Psychedelic Novices

Summary of …

Psychedelics can engender ecstatic states with persistent positive personality change but can also cause adverse reactions, hallucinogenic persisting perception disorder, and NBOMe compounds. The mechanism of action of psychedelics is discussed in detail, including the evidence for antagonist or partial agonist action at serotonin 5-hydroxytryptamine 2A receptors, the production of tolerance, functional selectivity at the serotonin 5-hydroxytryptamine 2A receptor, and possible roles for other receptors.

To access this content, you must purchase one of the following memberships: Sprout Membership, Pro Membership or Pro Membership Unlimited. The membership will give you access to exclusive data, including summaries of psychedelic research papers, extended company info, and our member-only visualisations. Save yourself multiple hours each week by accessing Blossom’s resource library.

Study details

Compounds studied
Psilocybin LSD DMT Mescaline MDMA


Authors associated with this publication with profiles on Blossom

David E. Nichols
David E. Nichols is a researcher (specifically pharmacologist and medicinal chemist) at Purdue University (semi-retired in 2012). His psychedelics work has been ongoing since 1969.

PDF of Psychedelics