The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs
The International Journal of Neuropsychopharmacology – March 20, 2014
Source: OpenAlex
Summary
A potent hallucinogen from Ayahuasca, 5-MeO-DMT, profoundly disrupts brain function, offering neuroscience insights into Schizophrenia. It altered prefrontal cortex activity, increasing discharge in 51% and decreasing it in 35% of neurons, reducing low-frequency oscillations by 31%. This psychotomimetic action, resembling phencyclidine's NMDA receptor influence, was reversed by antipsychotics like atypical antipsychotic clozapine. Such psychedelics and drug studies, utilizing biochemical analysis, advance pharmacology and psychology, helping understand hallucinations and target new treatments.
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.