Ayahuasca

Ayahuasca is a psychoactive brew traditionally prepared in the Amazon basin, used for centuries in Indigenous and syncretic religious ceremonies. It is made by combining two plants: the Banisteriopsis caapi vine, which contains harmala alkaloids (harmine, harmaline, and tetrahydroharmine), and a plant such as Psychotria viridis or Diplopterys cabrerana that contains N,N-dimethyltryptamine (DMT). Neither plant produces the full effect alone — it is the combination that makes ayahuasca work, and that combination is also the source of its main risks. In recent years it has drawn scientific and popular attention for possible therapeutic effects in depression and other conditions, which remains an area of active research.

Ayahuasca's effect depends on a two-part pharmacological interaction. DMT, the primary psychedelic, is normally destroyed in the gut and liver by the enzyme monoamine oxidase (MAO), which makes it inactive when swallowed on its own. The harmala alkaloids in the B. caapi vine are reversible inhibitors of MAO-A (they are MAO inhibitors, or MAOIs), and by blocking that enzyme they allow orally ingested DMT to survive and reach the brain, where it acts mainly as an agonist at serotonin 5-HT2A receptors — the same target as other classic psychedelics. This same MAO inhibition is why ayahuasca carries serious drug-interaction risks.

Ayahuasca produces a psychedelic experience that typically comes on over 30 to 60 minutes and lasts several hours — longer than smoked DMT. Reported effects include vivid visual imagery, emotional and introspective experiences, and altered perception. A prominent and very common physical effect is intense nausea and vomiting (in ceremony this is often called "la purga," the purge) as well as diarrhea. Anxiety, fear, and psychologically challenging experiences also occur.

The most serious risk with ayahuasca comes from its MAO-inhibiting component, which can interact dangerously with many medicines and other drugs. Combining it with serotonergic antidepressants (SSRIs, SNRIs, and especially other MAOIs), certain migraine drugs (triptans), dextromethorphan (DXM), stimulants, or other serotonergic substances can raise serotonin to dangerous levels and cause serotonin syndrome, which can be life-threatening; fatalities have been reported when harmala alkaloids were combined with other serotonergic drugs. Traditional MAOI dietary cautions may also apply. Beyond interactions, the intense psychological experience can be destabilizing for people with a personal or family history of psychosis, and the cardiovascular stimulation is a concern for people with heart conditions. Ayahuasca itself does not appear to produce dependence or tolerance.