Original ContributionsAutonomic, Neuroendocrine, and Immunological Effects of Ayahuasca A Comparative Study With d-Amphetaminedos Santos, Rafael G. MS*†‡; Valle, Marta PhD†‡§; Bouso, José Carlos MS*†‡; Nomdedéu, Josep F. MD∥; Rodríguez-Espinosa, José MD, PhD¶; McIlhenny, Ethan H. MS#; Barker, Steven A. PhD#; Barbanoj, Manel J. MD, PhD✠†‡; Riba, Jordi PhD*†‡ Author Information From *Human Experimental Neuropsychopharmacology, IIB Sant Pau; †Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau; ‡Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM; §Pharmacokinetic and Pharmacodynamic Modelling and Simulation; and Servei ∥Laboratori d'Hematologia and ¶Servei de Bioquímica Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; and #Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA. Received December 17, 2010; accepted after revision June 13, 2011. Reprints: Jordi Riba, PhD, Human Experimental Neuropsychopharmacology, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, St Antoni Maria Claret, 167, Barcelona 08025, Spain (e-mail: [email protected]). ✠Dr Barbanoj is deceased. This work was supported by grant SAF 2002-02746 from the Spanish Ministry of Education and Science and a private donation by Richard Wolfe. Journal of Clinical Psychopharmacology: December 2011 - Volume 31 - Issue 6 - p 717-726 doi: 10.1097/JCP.0b013e31823607f6 Buy Metrics Abstract Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-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 the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that 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 the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were 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. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users. © 2011 Lippincott Williams & Wilkins, Inc.