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ARCHIVE:  February 1, 2002

Ayahuasca and MAO Inhibitors

Dear Dr. Shulgin:

There are two popular MAOI additives used in making Ayahuasca to promote the oral activity of Psychotria viridis. One is Banisteriopsis caapi (Yaje) and the other is Peganum harmala (Syrian Rue). I have had much success with the latter, but I am considering switching, having heard about the neurotoxic quality of Harmaline. Trusted friends claim that lethargy seems to be part of P. harmala's baggage (I have not found this to be so), and that B. caapi is more uplifting. Any opinions to share on health or spiritual value of either would be appreciated. Peace.

-- Cosmic Joke

 

Dear Dr. Shulgin:

There are a lot of references in literature on ayahuasca containing the MAOI harmine and harmaline. Is harman, a very widespread chemical in nature, expected to have the same effect?

-- RK

 

Dear Cosmic Joke and RK:

I have combined your two questions as both of them refer to the monoamine oxidase inhibitors (MAOI) that allow N,N-dimethyltryptamine (DMT) in Ayahuasca to become orally active. Ayahuasca is the accepted name for a South American decoction made up of two separate plant components. One of these contains the psychotropic drug DMT, which is quickly destroyed by natural protective enzymes in our body, and the other one contains compounds that effectively block these destructive enzymes. Either plant taken separately is inactive. Together they form a rather remarkable combination that is widely accepted as a medicine and as a spiritual guide.  

There are three structurally related compounds that are inevitably brought into any discussion of natural MAOI's dealing with the oral activity of Ayahuasca. These are the three related beta-carbolines. There is (1) the totally aromatic Harmine, (2) the partially reduced Harmaline, and (3) the totally reduced Tetrahydroharmine. Let me refer to these as simply 1, 2, or 3 in this discussion. It is generally accepted that both 1 and 2 are potent MAOI's that protect DMT from being destroyed, thus allowing it to release serotonin at receptor sites, and 3 contributes to this neuroactivity by the inhibiting the reuptake of serotonin that would effectively remove it from these receptor sites. The end results of these actions are the same, the increase of available serotonin, but the mechanisms for achieving them are different.

My limited personal experience with Ayahuasca has always been with materials that have used the Banisteriopsis recipe, and I have carefully saved and assayed small samples of every decoction I had used. In each case the beta-carboline components have been largely 1 and 3, with only a trace amount of 2 present. However I have analyzed the Peganum harmala alkaloid mixtures as well, and they have always shown largely 1 and 2, with little if any 3. This blush of superiority is clouded by the fact that there are two additional alkaloids that usually appear as gratuitous components in these latter samples, namely, Vasicine and Desoxyvasicine. I have no knowledge what these Syrian Rue quinazoline compounds might contribute, positively or negatively, to the Ayahuasca experience, but my gut feeling would be to avoid them until you know their pharmacological properties.

The second question relates to yet another beta-carboline alkaloid, Harman. This is a structural analogue of Harmine that has been stripped of its methoxyl group. It is widely found in plants and foods, and has been shown in experimental animals to be a vasodilator and a hypotensive agent. It also interacts directly with DNA and is thus a possible mutagenic agent. But these findings are in animal studies at levels much greater than those found in fried fish and cigarette smoke. As a natural component in our environment, this all can be ignored. And I know of no reports of an MAOI effectiveness of Harman that would justify exploring it as an Ayahuasca component.

-- Dr. Shulgin

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