The hallucinogenic concoction yage, also known as ayahuasca and caapi, has been used for centuries by shamans in the Amazon basin as an essential ingredient in their religious and healing ceremonies. Ayahuasca (ī-yə-hwäs-kə) is said to facilitate the participant's entrance into the world of the spirits and allow communication with long-dead ancestors. It is such an important part of life for some indigenous Amazonian tribes that it is called “La Medicina,” the medicine, and the “vine of the soul.”
Interest in ayahuasca in the United States as a recreational and therapeutic hallucinogen began in the 1940s when Beat Generation writers such as William S. Burroughs and Allen Ginsburg trekked through the South American rainforest in search of chemical enlightenment. Ayahuasca has become distinctly trendy over the past quarter-century.
Pop-up yagé parties have become common in hip areas such as San Francisco and Brooklyn, and ayahuasca tours to “traditional” ceremonies in Colombia, Ecuador, and Peru are a growing industry. Sometimes these “trips” end in tragedy, as reflected in a recent headline from The Guardian: “Colombia's Ayahuasca Ceremonies in Spotlight after Tourist's Drug Death.” (Aug. 31; http://bit.ly/2xr3x1K.)
The toxicology of the traditional ayahuasca brew is fascinating; the hallucinogenic effects depend on the synergistic interaction between chemicals contributed by two different plants. The leaves of the shrub Psychotria viridis contain the psychotropic drug N,N-dimethyltryptamine (DMT), an extremely potent agonist at the 5-HT2A serotonin receptor. DMT has a structure similar to other tryptamines such as LSD, ibogaine, psilocin, and 5-MeO-DMT (foxy methoxy).
The psychotropic effects of DMT occur rapidly when administered intravenously, peaking within five minutes and lasting about half an hour. The course of smoked DMT is roughly similar. It has almost no effect at all, however, when it is ingested. As it turns out, the enzyme monoamine oxidase—abundant in the gut and liver—deactivates DMT on the first pass before it reaches the systemic circulation and the brain.
That's where the second plant, Banisteriopsis caapi, comes in. That vine contains harmine and other beta-Carboline alkaloids in its bark. B. caapi has only mild mind-altering properties, but its main contribution to the ayahuasca potion is stemming its action as a monoamine oxidase inhibitor (MAOI). When both plants are mashed and boiled together to make the foul-smelling, nasty-tasting, violently emetic ayahuasca tea, harmine and other beta-Carbolines block first-pass deactivation of DMT, which then crosses the blood-brain barrier at full throttle. That's when the mystical visions begin.
Hallucinations and Depersonalization
In contrast to the rapid onset and short duration of action seen when DMT is injected intravenously, the hallucinogenic effects of ayahuasca tea peak at about 90-120 minutes after ingestion and last for approximately four to six hours. Ayahuasca tea also causes severe gastrointestinal upset. Some aficionados actually welcome the severe vomiting that invariably precedes psychedelic manifestation, seeing emesis as a therapeutic purge that helps eliminate evil spirits from the body and soul.
Aside from visual and sometimes auditory hallucinations, ayahuasca users report experiencing depersonalization, accelerated thinking, and distortions in their sense of time and space. Dysphoria, panic, and paranoia can turn the experience into a bad trip. Hypertension, hyperthermia, and tachycardia are usually mild and do not generally require specific treatment. Other frequent signs and symptoms are tremors, paresthesias, and mydriasis. Episodes of rhabdomyolysis and acute renal failure, although rare, have been reported.
A recent paper analyzing 538 calls to the National Poison Data System (NPDS) from 2005 to 2015 involving ayahuasca products found the most frequent effects were hallucinations, tachycardia, agitation, hypertension, mydriasis, and vomiting. (J Med Toxicol 2017;13:245; http://bit.ly/2Nq73DU.) There were four cardiac arrests, seven respiratory arrests, 12 episodes of seizures, and one death. The paper did not report whether additional medical factors or exposure to other drugs were involved in the more serious outcomes. I am not aware of any well-described case in which death resulted solely from direct effects of DMT or beta-Carbolines.
Patients presenting for medical attention won't know which drugs were in the potion they ingested, and you won't know either. The natural botanical ayahuasca preparations appear to be relatively safe, but some samples may contain much more dangerous synthetic sympathomimetic drugs such as 5-MeO-tryptamine (foxy-methoxy). They could also contain almost anything else. Patients should be evaluated to rule out hyperthermia, significant tachycardia and hypertension, rhabdomyolysis, and renal failure. Most patients in the series from the NPDS did well with observation alone, receiving fluids and benzodiazepines as needed.
DMT is a Schedule 1 drug, meaning it has no accepted medical use and a high potential for abuse. The U.S. government tried to ban the drug for religious purposes, but the Supreme Court ruled in 2006 that the government had failed to establish a compelling reason to do so. A branch of the Brazilian União do Vegetal Church in New Mexico incorporated ayahuasca into its religious services. Ayahuasca is hot, with increasing interest in investigating its potential for treating depression, anxiety, and post-traumatic distress syndrome.