The potent hallucinogen DMT, when taken orally, is inactivated by peripheral monoamine oxidase-A, an enzyme found in the lining of the stomach, whose function is precisely to oxidize molecules containing an NH2 amine group, like DMT. There are thus two ways to ingest DMT, or plants containing DMT, and experience psychoactive effects — by parenteral ingestion through nasal inhalation, smoking, injection, or rectal insertion; or by mixing the DMT with an MAO inhibitor that prevents the breakdown of DMT in the digestive tract. Let’s look at these one at a time.

• Inhalation   A number of indigenous peoples around the Orinoco basin in Venezuela ingest a snuff called epená, made from the sap of several trees in the genus Virola which contain large amounts of DMT; and the Guahibo of the Orinoco basin use a snuff called yopo, also called cohoba, vilca, and huilca, made from the DMT-rich plant Anadenanthera peregrina.
• Smoking   Contemporary North American users smoke synthetic DMT as the free base. Burning DMT has a harsh, unpleasant, unforgettable taste and smell, variously described as being like mothballs or burning plastic.
• Injection   In a well-known series of experiments, psychopharmacologist Rick Strassman administered DMT to his volunteer subjects using intravenous injection. Intramuscular injection was rejected because it gave an effect that was slower in onset and less intense than the smoked route. The smoked route was rejected because of uncertainty as to how much DMT was actually being absorbed, and questions about what DMT combustion products the volunteers might actually be inhaling.
• Rectal insertion   I know of only one person who has reportedly tried this. Krystle Cole mixed 600 mg of DMT with butter, melted it, and inserted the mixture rectally, in three 200-mg doses, with a syringe, after having used an enema. She reports that the experience was not enjoyable.
• Mixture   The ayahuasca vine (Banisteriopsis caapi) contains the ß-carboline harmaline, which is a potent inhibitor of MAO-A. Three plants of the Upper Amazon have leaves that are rich in DMT — the shrub chacruna (Psychotria viridis), the closely related shrub sameruca (Psychotria carthaginensis), and a vine variously called ocoyagé, chalipanga, chagraponga, and huambisa (Diplopterys cabrerana). Boiling the leaves of these compañeros, companion plants, along with the MAO-inhibiting ayahuasca vine produces a drink that allows the DMT to produce its hallucinogenic effect when orally ingested — a unique solution which apparently developed only in the Upper Amazon.

How in the world did they come up with this? Many mestizo shamans will claim, of course, that the plants themselves taught humans how to do this. Other commentators point to some mysterious ecological wisdom found only in indigenous peoples. I think the answer is simpler. I think people were looking for a better way to vomit.

It is harmaline, one of the ß-carboline components of the ayahuasca vine, that makes the ayahuasca drink such a potent emetic and purgative. These gastrointestinal effects appear to be related to the ability of harmaline to inhibit peripheral MAO; overdosing on an MAO inhibitor — they are sometimes used as antidepressants — is known to cause nausea and vomiting. Harmaline is also found in Syrian rue (Peganum harmala), from which it was first isolated and after which it was named; like the ayahuasca vine, Syrian rue has been used as an emetic and vermifuge. Doses of harmaline as small as 200 mg orally produce nausea, vomiting, and diarrhea in human volunteers. Five grams of Syrian rue seeds produce mild nausea and vomiting; higher doses produce both vomiting and diarrhea, in some cases serious enough to be incapacitating.

Now, I have found no direct evidence that any of the traditional companion plants has emetic or purgative properties. However, it is noteworthy that two Psychotria species, P. ipecacuanha and P. emetica, are widely used emetics, the former in Brazil and the latter in Perú. P. ipecacuanha is, of course, the source of the widely used emetic called syrup of ipecac. In the Colombian Vaupés, a shrub whose leaves are added to the ayahuasca drink, and which Schultes and Hofmann have identified as ocoyagé, is called by the Tukano “the ayahuasca that makes you vomit.”

If the companion plants have emetic properties of their own, it is plausible to hypothesize that the ayahuasca vine and its companion plants were first combined in order to synergize or modulate their emetic and purgative effects, with the serendipitous result of creating an orally effective delivery form for DMT.

Not quite so mysterious, but still, I think, pretty clever.