This is the world’s first study to test if the main psychological and physiological effects of ayahuasca still persist after the ketanserin blockade. In previous studies with psilocybin, pretreatment with ketanserin completely abolished subjective effects. 12 participants who had previous experience with psychedelics were subject to EEG and questionnaire assessments on two occasions: under the effect of ayahuasca (0.75 mg DMT/kg body weight) alone, and also together with ketanserin (40 mg).
Usually ayahuasca induces very strong visual experiences. These correlate with the decrease in the alpha oscillations (brain waves of the 7.5–12.5 Hz frequency) at the back of the cortex (visual and other sensory areas, but also memory). In this study, those decreases were impeded by ketanserin and this markedly reduced ayahuasca’s visual effects. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation may be the main contribution to its psychotropic effects.
An unexpected finding was that while ketanserin decreased the overall intensity of the subjective experience, it did not completely block the subjective effects. One possible explanation is that DMT interacts with receptors other than 5-HT2A, but also has effect on the cellular transporters. The uptake of DMT into the cells when 5-HT2A sites are blocked by ketanserin could potentially lead to intracellular accumulation and later release.
Our studies confirm the crucial role of 5-HT2A receptors in the effects of ayahuasca, but stress the importance of investigating other mechanisms of action of this substance.
You can read the accepted version of the paper online here.
Psilocybin for Depression
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