Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans
European Neuropsychopharmacology – March 26, 2016
Source: OpenAlex
Summary
Ayahuasca significantly alters brain oscillations and subjective experiences, with 12 healthy participants showing EEG power decreases in delta, theta, and alpha bands after consumption. Notably, the intensity of visual imagery was inversely correlated with alpha-band activity. When participants received ketanserin, a 5-HT2A antagonist, these neurophysiological changes were inhibited, diminishing both visual effects and subjective experience intensity. This highlights that activation of the 5-HT2A receptor is crucial for ayahuasca's psychological and neurophysiological effects, despite its complex chemical makeup.
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.