Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists?
Jan Kehler, Morten Skøtt Thomsen Lindskov
Journal of Psychopharmacology May 5, 2025 DOI: 10.1177/02698811251330741 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Serotonin |
| Keywords | Lisuride Psychedelics hallucinogens Entheogens Psychoactive drugs Neuroscience neuropharmacology Brain science Neural receptors Serotonergic compounds 5-ht2a |
| Citations | 3 |
| Key findings | There is no basis for claiming that lisuride or ergotamine are non-hallucinogenic at relevant concentrations in the brain. |
Abstract
The recent resurgence of classical psychedelic compounds, specifically 5-HT2A receptor agonists, as potential therapeutics has led to numerous initiatives aimed at better understanding the mechanisms underlying their effects. Psychedelic compounds are commonly known as hallucinogens. One of the major outstanding questions in the field is whether altered states of consciousness-the hallucinogenic or psychedelic experience-is a prerequisite for the therapeutic effect. As a result, several academic and commercial efforts are focused on developing 5-HT2A receptor agonists that are speculated not to have these consciousness-altering effects. However, these efforts largely rely on chemical analogs of supposedly non-hallucinogenic 5-HT2A receptor agonists, such as lisuride and ergotamine. Our review of the literature indicates that there is no basis for claiming that lisuride or ergotamine are non-hallucinogenic at relevant concentrations in the brain. This does not invalidate current efforts to produce non-hallucinogenic 5-HT2A receptor agonists for the potential benefit of patients, but it calls for caution in the reliance on animal data in the pursuit of such compounds and highlights the need for rigorous determination of target engagement in humans before claiming that 5-HT2A receptor agonists are non-hallucinogenic.
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 4
- Effects of LSD, DMT and psilocybin on cognitive and psychological functions: A systematic review of the literature Journal of Psychopharmacology February 16, 2026
- Pharmacological characterisation of psilocybin and 5-MeO-DMT discriminative cues in the rat and their translational value for identifying novel psychedelics Journal of Psychopharmacology August 27, 2025
- Structure-based design of subtype-selective psychedelic analogs Nature Communications September 17, 2026
- Serotonergic psychedelics and amphetamine shift male rat ultrasonic vocalizations toward call patterns associated with positively valenced states. Progress in Neuro-Psychopharmacology and Biological Psychiatry September 18, 2026
Cites 30
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects ACS Pharmacology & Translational Science December 10, 2020
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
and 25 more in the library