Chemistry/structural biology of psychedelic drugs and their receptor(s).
Ryan H. Gumpper, David E Nichols
British Journal of Pharmacology October 2, 2024 DOI: 10.1111/bph.17361 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Psilocybin |
| Keywords | Psychedelic research Drug development Molecular biology Receptor binding 5‐ht2a agonists 5‐ht2a receptor Psychedelic chemotypes Crystal structures Docking Ergolines Phenethylamines Structural biology Structure‐activity relationships Therapeutic potential Tryptamines |
| Citations | 9 |
| Key findings | Three chemotypes of classic serotonergic psychedelics—phenethylamines, ergolines, and tryptamines—have distinct structural features that determine their activity at the 5-HT2A receptor, and recent structural biology studies reveal the atomic basis for their pharmacological effects. |
Abstract
This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.
Comparable studies
Other narrative reviews on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The Pharmacology of Lysergic Acid Diethylamide: A Review | 2008 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| ADVERSE REACTIONS TO PSYCHEDELIC DRUGS. A REVIEW OF THE LITERATURE | 1984 | Review |
Citations in the library
Cited by 6
- The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects Molecular Psychiatry November 5, 2025
- Advancing Next-Generation Psychedelic Therapeutics through Selective 5-HT2A Activation, Precision Aerosol Delivery, and Optimized 5-MeO-DMT Treatment Paradigms ACS Medicinal Chemistry Letters July 10, 2026
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Exploring a Druggable Hydrophobic Tunnel in the 5-HT2A Receptor with Potent Phenethylamines Journal of Medicinal Chemistry September 25, 2026
- Emerging therapeutic opportunities for psychedelic and related drugs. British Journal of Pharmacology July 1, 2026
and 1 more in the library
Cites 41
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
and 36 more in the library