Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans
This double-blind randomised placebo-controlled within-subjects study (n=12) investigated whether the neurophysiological effects of orally administered ayahuasca (52.5mg DMT /70kg) can be selectively blocked via 5-HT2A antagonist ketanserin (40 mg/70kg). Selectively blocking of the 5-HT2A pathway inhibited the ayahuasca-induced alpha oscillations in the parieto-occipito-temporal cortex, as well as the intensity of its correlated visual effects, which is the hallmark of the ayahuasca experience.
Authors
- Jordi Riba
- Amanda Feilding
- Erich Studerus
Published
Abstract
Introduction
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.
Methods
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 (0.75 mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40 mg). 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.
Results
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.
Discussion
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.
Research Summary of 'Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans'
Introduction
Ayahuasca is a traditional Amazonian plant brew containing the psychedelic indole N,N-dimethyltryptamine (DMT) together with β-carboline monoamine-oxidase inhibitors (harmine, harmaline, tetrahydroharmine). Previous research has shown that ayahuasca produces robust subjective effects and broad-band reductions in spontaneous brain oscillatory power, particularly in the alpha band over posterior visual cortex; similar alpha reductions have been noted with other classical psychedelics such as psilocybin. However, while classical psychedelics are generally thought to act via the serotonin-2A (5-HT2A) receptor, the specific contribution of 5-HT2A activation to ayahuasca’s neurophysiological and psychological effects had not been experimentally tested in humans. Valle and colleagues designed a human pharmacological study to test the role of the 5-HT2A receptor in ayahuasca’s effects. The investigators hypothesised that despite ayahuasca’s multi-component chemistry, its characteristic psychedelic phenomenology and the decreases in cortical current density—especially in the alpha band—depend largely on 5-HT2A receptor activation. To test this, they combined oral ayahuasca with pretreatment using the selective 5-HT2A antagonist ketanserin in a double-blind, randomized crossover experiment and measured EEG oscillations, intracerebral current density estimates, and multiple subjective effect scales.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Valle, M., Maqueda, A. E., Rabella, M., Rodríguez-Pujadas, A., Antonijoan, R. M., Romero, S., Alonso, J. F., Mañanas, M. À., Barker, S., Friedlander, P., Feilding, A., & Riba, J. (2016). Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology, 26(7), 1161-1175. https://doi.org/10.1016/j.euroneuro.2016.03.012
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