Autonomic, Neuroendocrine, and Immunological Effects of Ayahuasca

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.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

“…Although nonsignificant, in the present study these effects were observed during a period ranging from 80 to 140 min after AYA administration, which is the time point when the subjective effects of AYA are peaking, as are DMT plasma levels. [8][9][10][11][12] The absence of statistically significant effects on BPRS-TD scores could be explained by the DMT concentration found in our AYA batch (0.08 mg/mL), which is lower than DMT doses used in previous studies that reported significant psychotropic effects of AYA (0.53 mg/ mL DMT). 9,12 The nonsignificant effects of AYA on the BPRS-TD subscale suggest that changes in sensory perception and thought content may not be essential for therapeutic effects.…”

“…6,[8][9][10][11] The psychoactive effects of AYA are produced by a combined action of peripheral (gastrointestinal and liver) monoamine oxidase A (MAO-A) inhibition by harmine and central 5-HT 1A/2A/2C agonist action of DMT on frontal and paralimbic brain areas. 8,9,12 Studies conducted among long-term (i.e., years or decades) members of religious groups that use AYA ritually suggest that this population does not present evidence of psychological, neuropsychological, or psychiatric harm caused by AYA.…”

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

“…Clinically, psilocybin has been extensively studied in laboratory studies in healthy subjects and substance-assisted psychotherapy in patients (Carhart-Harris et al, 2013;Griffiths et al, 2006;Grob et al, 2011;Hasler et al, 2004). Similarly, the acute psychotropic effects of DMT have been described in controlled studies in humans (Dos Santos et al, 2011;Gouzoulis-Mayfrank et al, 2005;Winstock et al, 2014).…”

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

“…Many studies also sought to describe the psychotomimetic effects of LSD but were not designed to measure any positive subjective effects. Modern experimental studies with hallucinogens in humans resumed in the 1990s with N-N-dimethyltryptamine (DMT, ayahuasca) (18)(19)(20)(21), ketamine (21)(22)(23), and psilocybin (24,25) but not with LSD. Both LSD and psilocybin have also been recently evaluated in pilot therapeutic studies as treatments for anxiety in patients with lifethreatening diseases (11,26).…”

“…Because of the continued popularity of LSD as a recreational drug and renewed interest in its therapeutic use (11,27), we reexamined the acute response to LSD in healthy subjects. To allow for a better characterization of the subjective effects of LSD, we used psychometric instruments that have been used with other psychotropic drugs, including hallucinogens, empathogens, and stimulants (20,21,(28)(29)(30)(31).…”