Ayahuasca, a South American psychedelic beverage combining DMT with MAO-inhibiting beta-carboline alkaloids, produces significant subjective perceptual and mood effects peaking 1.5 to 2 hours after oral administration. In a double-blind placebo-controlled trial with 18 experienced psychedelic users, doses of 0.6 and 0.85 mg DMT/kg increased diastolic blood pressure by 9 mm Hg at the high dose, while systolic pressure and heart rate rose modestly but not significantly. Peak DMT blood concentrations (Cmax) were 12.14 ng/ml and 17.44 ng/ml for low and high doses, respectively, coinciding with subjective effect peaks. Urinary normetanephrine increased, but deaminated monoamine metabolites did not decrease, and harmine plasma levels were negligible, suggesting harmine acts primarily in the gastrointestinal tract and liver to prevent DMT breakdown and allow its entry into the brain.
A method to measure the four main alkaloids in ayahuasca (DMT, harmine, harmaline, and tetrahydroharmine) plus two major metabolites (harmol and harmalol) in human plasma is described. DMT is extracted with n-pentane and quantified by gas chromatography with nitrogen-phosphorus detection, achieving 74% recovery, precision and accuracy better than 9.9%, and a limit of quantification of 1.6 ng/ml. The beta-carbolines and metabolites are measured by high-performance liquid chromatography with fluorescence detection after solid-phase extraction, with recoveries above 87%, accuracy and precision better than 13.4%, and limits of quantification from 0.3 to 1.0 ng/ml. The methods allow adequate characterization of the pharmacokinetics of these compounds, including two major metabolites not previously described.