A new insight into ayahuasca’s adverse effects: Reanalysis and perspectives on its mediating role in mental health from the Global Ayahuasca Survey (Dutch DMT Shop)

Ayahuasca is a decoction native to the Amazon, where it plays a central role in the traditional medicine of many local cultures, likely for millennia [1]. Ayahuasca is also the sacrament of some syncretic Brazilian religions, some of which have expanded internationally across all continents over the last four decades [2]. Ayahuasca itself has undergone a more recent process of globalization [3] to the point where both psychiatrists and priests have made respective calls to their colleagues to be more informed [4,5]. At the same time, scientific production of ayahuasca research is also exponentially increasing, although this mostly focuses on its potential benefits for mental health and less on its potential risks and adverse effects [6].

Ayahuasca is both the Quichua name for the vine Banisteriopsis caapi and for any decoction made with it. B. caapi contains harmala alkaloids (mainly harmine, harmaline, and tetrahydroharmine), which are MAOI inhibitors in the gastrointestinal tract [7]. The most common plants mixed with B. caapi are the leaves of the bush Psychotria viridis or the leaves of the vine Diplopterys cabrerana, both containing the amine N,N-Dimethyltryptamine (DMT). DMT is a partial agonist of serotonin receptors, mainly 5-HT2A and 5-HT1A, and is responsible for the hallucinatory effects of ayahuasca [8]. When administered in a laboratory, ayahuasca slightly increases heart rate and blood pressure [9,10], transiently increases prolactin and cortisol, and modifies immunological markers [11,12]. It induces decreases in EEG power in the delta, theta, and alpha frequency bands [12–14], reduces top-down control, and increases bottom-up information transfer in the brain [15]. It increases blood perfusion in the frontal and paralimbic brain regions in both normal [16] and depressed subjects [17], and decreases the activity of the default mode network [18].

In terms of subjective effects, ayahuasca increases dose-dependent responses compared to placebo on visual analog scales of “any effect”, “good effects”, “liking”, “visions”, “stimulated”, and “high”, without altering “drunkenness”. It increases the subscales of Affect, Cognition, Somaesthesia, Perception, Intensity but not Volition of the Hallucinogen Rating Scale (HRS), and the measures of stimulatory effects (A scale), euphoria (MBG scale), and somatic symptoms (LSD scale) from the Addiction Research Center Inventory (ARCI) questionnaire [9–12]. This profile of subjective effects has also been observed in naturalistic settings, alongside the induction of mystical experiences assessed with the Mystical Experience Questionnaire (MEQ) [19].