Ayahuasca: physiological and subjective effects, comparison with d-amphetamine, and repeated dose assessment.

Abstract

Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase (MAO)-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual and medicinal purposes by the indigenous peoples of the region. More recently the syncretistic religious use of ayahuasca has expanded to many countries in Europe and the Americas._x000D_ In view of the expanding use of ayahuasca worldwide, two clinical studies were conducted to further characterize the human pharmacology of ayahuasca. In study 1 we explored: a) the physiological impact of acute ayahuasca administration in terms of autonomic and neuroendocrine effects; and b) the potential effects of ayahuasca on cell-mediated immunity. In study 2 we assessed the pharmacology of ayahuasca in repeated doses and the potential occurrence of acute tolerance or sensitization. Both studies were conducted in healthy young volunteers with experience with psychedelics, using an encapsulated freeze-dried formulation of ayahuasca administered according to randomized double-blind designs._x000D_ In study 1 an ayahuasca dose equivalent to 1.0 mg DMT/kg body weight was compared vs. a placebo and vs. a positive control (20 mg d-amphetamine) in 10 volunteers. Autonomic, neuroendocrine and immunomodulatory effects were measured in addition to DMT blood concentrations, subjective and neurophysiological effects (secondary variables). Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects which were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine; and cortisol was increased by both, with ayahuasca leading to higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased and NK cells increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation and a time-dependent modulatory effect on cell-mediated immunity._x000D_ In study 2, nine volunteers received the two following treatment combinations at least one week apart: a) a lactose placebo and then 4 hours later an ayahuasca dose; and b) two ayahuasca doses 4 hours apart. All ayahuasca doses were equivalent to 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were assessed. DMT plasma concentrations, scores in subjective, and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second dose. In conclusion, whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

Date of Award	3 Feb 2012
Original language	English
Supervisor	Jordi Riba Serrano (Director)