Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans
Marta Valle, Ana Maqueda, Mireia Rabella, Aina Rodríguez‐pujadas, Rosa María Antonijoan, Sergio Romero, Joan Francesc Alonso, Miguel Ángel Mañanas, Steven A. Barker, Pablo Friedländer, Amanda Feilding, Jordi Riba
European Neuropsychopharmacology March 26, 2016 DOI: 10.1016/j.euroneuro.2016.03.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Healthy, experienced psychedelic users |
| Interventions | Ayahuasca Ketanserin |
| Dose | 0.75 mg DMT/kg body weight (ayahuasca), 40 mg (ketanserin) |
| Topics | Ayahuasca Serotonin |
| Keywords | Ketanserin Hallucinogen Placebo 5-ht2 receptor Pharmacology |
| Citations | 175 |
| Key findings | 5-HT2A receptor activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans. |
Abstract
Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.
Comparable studies
Other randomized controlled trials on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Patients with treatment-resistant depression | 2018 | Randomized controlled trial | n = 29 |
| Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Volunteers with prior experience in the use of psychedelics | 2003 | Double-blind placebo-controlled clinical trial | n = 18 |
| Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers Healthy male volunteers with prior experience using ayahuasca | 2001 | Single-blind crossover placebo-controlled clinical trial | n = 6 |
| Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant Male volunteers with prior experience in the use of psychedelics | 2006 | Randomized controlled trial | n = 15 |
| Human brain effects of DMT assessed via EEG-fMRI. Healthy volunteers | 2023 | Within-subjects, placebo-controlled design | n = 20 |
Citations in the library
Cited by 147
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology December 25, 2017
- Neural correlates of the DMT experience assessed with multivariate EEG. Scientific Reports November 19, 2019
- Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences January 28, 2019
and 142 more in the library
Cites 29
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and 24 more in the library