Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics

Abstract

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebocontrolled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine 2A agonist activity, with monoamine oxidase (MAO)-inhibiting ␤-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. C max values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. T max (median) was observed at 1.5 h after both doses. The T max for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

“…In recent years, the use of ayahuasca has spread outside South America to some religious groups established in the United States and in several European countries, including Germany, Great Britain, Holland, France and Spain (Riba et al, 2003). As an increasing number of people have come into contact with this psychotropic tea, the beverage has begun to attract the attention of researchers interested in its pharmacological and toxicological aspects (Callaway, 2005;Callaway et al, 1999;Gable, 2007;Riba & Barbanoj, 2005;Riba et al, 2003).…”

“…DMT is active when administered parenterally, but not orally because the gastrointestinal tract contains the enzyme monoamine oxidase (MAO), which metabolizes orally ingested DMT (Tupper, 2008). DMT is, therefore, only active in the presence of β-carbolines, such as harmine, harmaline and tetrahydroharmine, since these are potent monoamine oxidase (MAO) inhibitors (Callaway, 2005;Callaway et al, 1999;Gable, 2007;Riba & Barbanoj, 2005;Riba et al, 2003;Tupper, 2008). The synergistic interaction of these alkaloids is the basis of the psychotropic action of ayahuasca (McKenna, 2004;Riba et al, 2003;Tupper, 2008).…”

“…N,N-dimethyltryptamine (DMT) is an hallucinogenic indole alkaloid, structurally related to the neurotransmitter serotonin (Callaway, 2005;Callaway et al, 1999;Gable, 2007;Riba & Barbanoj, 2005;Riba et al, 2003;Tupper, 2008). DMT has high affi nity for 5-HT2A and 5-HT2C receptors in the brain and moderate to low affi nity for the 5-HT1A receptor (Keiser et al, 2009).…”

“…As an increasing number of people have come into contact with this psychotropic tea, the beverage has begun to attract the attention of researchers interested in its pharmacological and toxicological aspects (Callaway, 2005;Callaway et al, 1999;Gable, 2007;Riba & Barbanoj, 2005;Riba et al, 2003).…”

“…It was initially used by indigenous peoples in shamanic rituals for spiritual purposes and in folk medicines. Its use has since expanded beyond the indigenous culture, being used in Brazilian-based syncretic religious groups, such as "União do Vegetal" and "Santo Daime", where the beverage is reported to be used to facilitate self-knowledge and introspection (Carlini, 2003;Riba et al, 2003).…”