Riba J, Rodriguez-Fornells A, Barbanoj M (2002) Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively. Psychopharmacology (Berl), 165: 18-28.
Eighteen volunteers (15 men, 3 women, mean age 25.7) received two doses of ayahuasca (freeze-dried, encapsulated) measured at 0.6 and 0.85 mg/kg DMT. All participants reported having used psychedelic drugs on at least 5 occasions and were healthy and free of mental illness as established through medical history and psychiatric interview. Participants initially received placebo in a single-blind condition to familiarize them with the setting and procedures. (Data gathered from the same sample is presented in a subsequently published paper (see below). The P50 evoked response potential (ERP) to pure-tone auditory stimuli was measured via 19-electrode electroencephalography (EEG) and pre-pulse inhibition (PPI) of acoustic startle was also assessed, with P50 assessed 1.5 hour post-drug and PPI assessed 2 hours post-drug. Subjective effects were assessed via Spanish-language versions of the Hallucinogen Rating Scale (HRS) and Altered States of Consciousness Questionnaire. Both 0.6 and 0.85 mg/kg DMT decreased the difference in P50 in response to the first and second (C and T) stimuli, and both doses of ayahuasca also reduced percentage P50 suppression. There was a trend for decreased latency (time until appearance of) P50 peak for 0.6 and 0.85 mg/kg DMT. 0.85 mg/kg was associated with a non-significant increase in startle magnitude. However, ayahuasca (at either 0.6 or 0.85 mg/kg) neither inhibited nor facilitated pre-pulse inhibition of auditory startle when compared with placebo. Both 0.6 and 0.85 mg/kg DMT increased all ASC scores ("oceanic boundlessness," or positive derealization, "anxiety over ego loss" or fear of losing control, and "visual restructuring" or perceptual alterations). All HRS scores save "volition" (capacity to interact with self and environment) were increased by 0.6 and 0.85 mg/kg DMT. These scales include "affect," "cognition," "perception," "somasthenia' and "intensity." Effects lasted for 4 to 6 hours, with peak effects reported between 90 and 120 minutes after drug administration. Participants reported experiencing closed-eye imagery, but only distortions in the visual field with eyes open, and they reported alterations in sound, but no auditory hallucinations. An increase in rapidity of thought and free association and a decrease in ability to focus or concentrate were experienced along with changes in emotion, including increased excitation and happiness. None of the participants lost insight into the drug-induced nature of these effects. Changes in P50 suppression were not correlated with any of the subjective effects listed above.
The study indicates that ayahuasca can be safely administered in humans, and that ayahuasca alters some markers of sensory gating without altering others. Since d-amphetamine and yohimbine (an alpha2-antagonist that increases norepinephrine release) reduce P50 suppression, it is possible that reduced P50 suppression after ayahuasca is associated with increased catecholamine (norepinephrine and dopamine) transmission, as a result of the MAOI in ayahuasca. Lack of changes in PPI are surprising, as the 5HT2A agonist psilocybin and MDMA (a serotonin releaser) facilitate PPI in humans, and amphetamine and bromocryptine (dopamine agonists) reduce PPI. It may be that the AMO inhibiting effects of ayahuasca counter the potential facilitation of PPI through action on serotonin 5HT2A receptors. Findings of tolerability are still limited to samples with prior experience with psychedelic drugs, but no adverse events occurred in this or the prior study in a smaller sample, and no medical intervention was needed.