Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists.
Trevor Sharp, Aurelija Ippolito
British Journal of Pharmacology May 23, 2025 DOI: 10.1111/bph.70050 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Serotonin |
| Keywords | 5‐ht2a receptor Antidepressant Psychedelics hallucinogens Entheogens Neuroscience serotonin Brain research Mental health antidep |
| Citations | 8 |
| Key findings | A new class of 5-HT2A receptor agonists may retain the therapeutic potential of psychedelics without inducing hallucinatory experiences, with increased neuroplasticity offering a likely account of their common therapeutic effects. |
Abstract
Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that they can produce long-lasting improvements in health across a wide variety of mental illnesses, including major depression, addictions and anxiety disorders. These drugs interact with many different 5-HT receptor subtypes but the powerful psychedelic experience, which (depending on set and setting) includes profound alterations in perception, mood and cognition, accompanied by vivid hallucinations, is now widely considered mediated by an agonist action at 5-HT2A receptors. However, the link between the psychedelic experience, 5-HT2A receptor agonism and therapeutic effects is currently uncertain. Indeed, recent research has revealed a new class of 5-HT2A receptor agonists which appear to retain the therapeutic potential of psychedelics drugs without inducing disorienting hallucinatory experiences. Biased signalling, partial agonism and non-selectivity at the 5-HT2A receptor are amongst the possible explanations for the differential properties of these drugs, whereas increased neuroplasticity offers a likely account of their common therapeutic effects. This article explores the neuropsychopharmacological properties of hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists in the context of their promise as novel drug treatments in psychiatry.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cited by 7
- Simple Analogs of the LSD D-Ring: A Consideration of Structure-Activity Relationships and Their Potential as Therapeutics. ACS Chemical Neuroscience November 5, 2025
- The serotonin 1B receptor as a target for the treatment of depression and anxiety Expert Opinion on Therapeutic Targets September 21, 2026
- 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
- Effects of an international ceremonial ayahuasca retreat on the diversity and community composition of the human gut microbiome: A preliminary observational single-arm pre-post study Brain Behavior and Immunity Integrative July 1, 2026
- Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms. Behavioural Pharmacology July 1, 2026
and 2 more in the library
Cites 71
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- 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 66 more in the library