Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience
Thomas Pokorny, Katrin H. Preller, Rainer Kraehenmann, Franz X. Vollenweider
European Neuropsychopharmacology January 22, 2016 DOI: 10.1016/j.euroneuro.2016.01.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Healthy human subjects |
| Interventions | Psilocybin Buspirone Ergotamine |
| Dose | 170 µg/kg psilocybin p.o., 20 mg buspirone p.o., 3 mg ergotamine p.o. |
| Topics | Psilocybin Serotonin |
| Keywords | Buspirone Hallucinogen 5-ht1 receptor Partial agonist Ergotamine Serotonin agonist 5-ht1a receptor Pharmacology |
| Citations | 148 |
| Key findings | Buspirone significantly reduced psilocybin-induced visual hallucinations, suggesting 5-HT1A receptor modulation may be a target for treating visual hallucinations. |
Abstract
The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
Comparable studies
Other randomized controlled trials on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Healthy human subjects | 2004 | Randomized controlled trial | n = 8 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Healthy human subjects | 2013 | Randomized controlled trial |
Citations in the library
Cited by 116
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review Neuroscience & Biobehavioral Reviews September 1, 2022
- Effect of Psilocybin on Empathy and Moral Decision-Making The International Journal of Neuropsychopharmacology June 14, 2017
- Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity Biological Psychiatry January 13, 2020
and 111 more in the library
Cites 36
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects Journal of Psychopharmacology November 11, 2014
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