Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca.
Level 4 - case-series / case-control
Single-arm human pharmacokinetic and metabolic disposition study
PubMed 22514127 · doi:10.1002/dta.1344
What was done
Ten healthy male volunteers received a single oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Urine collected over 24 hours was analyzed via HPLC/ESI/SRM/MS/MS to characterize the metabolic disposition and excretion of DMT and harmala alkaloids (harmine, harmaline, tetrahydroharmine).
What was found
Less than 1% of the administered DMT dose was excreted unchanged in urine. Approximately 50% was recovered as indole-3-acetic acid and 10% as DMT-N-oxide along with other MAO-independent metabolites, yielding a total recovery of DMT plus metabolites of 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant, with combined recovery of each harmala alkaloid and its O-demethylated metabolite ranging widely from 9% to 65%.
Why it matters
This study provides the first systematic human data on ayahuasca alkaloid clearance, demonstrating that human DMT metabolism involves significant MAO-independent pathways and that harmala alkaloids undergo extensive O-demethylation and conjugation.
Limits
The study was limited by a very small, all-male sample (n = 10) and only measured urinary excretion over 24 hours, leaving 32% of DMT and up to 91% of certain harmala alkaloids unaccounted for without plasma or fecal measurements.
Cited by
- supports Ayahuasca combines dimethyltryptamine (DMT) with a monoamine oxidase (MAO) inhibitor, which prevents rapid metabolism in the gut and prolongs its duration of action.