Ayahuasca, the Psychedelic Antidepressant?

By Neuroskeptic | June 17, 2018 6:09 am

A traditional Amazonian psychedelic brew is an effective and rapid-acting antidepressant, according to a paper just published. But the new study revives some long-standing questions.

Ayahuasca is a mixture of herbs, traditionally used for spiritual and therapeutic purposes. The main active ingredients are N,N-DMT, a potent psychedelic, and several molecules that inhibit the enzyme MAO. The MAO inhibitors serve to prevent the N,N-DMT from being broken down by the digestive system, allowing it to enter the bloodstream and cause hallucinations and other alterations of consciousness.

In the present study, Brazilian researchers Fernanda Palhano-Fontes and colleagues gave ayahuasca to 14 patients with chronic depression who hadn’t responded to other antidepressants. Another 15 depressed patients received a placebo drink.

The ayahuasca group showed a strong improvement in their depressive symptoms, which persisted for at least a week (the last assessment was on day 7). The patients given placebo also improved but this effect was modest and short-lived. This graph shows the MADRS depression scale scores during the trial (lower is better):

ayahuasca_depression

Palhano-Fontes et al. conclude that ayahuasca could be a safe and effective antidepressant. No serious side effects occured, although “the ayahuasca session was not necessarily a pleasant experience”:

In fact, some patients reported the opposite, as the experience was accompanied by much psychological distress. Most patients reported nausea, and about 57% have vomited, although vomiting is traditionally not considered a side effect of ayahuasca, but rather part of a purging process.

In my view, this is a promising study, and well-designed. For instance, Palhano-Fontes et al. went to some lengths to make the placebo brew look, taste and smell like the real thing. They even added zinc sulfate to make the placebo cause gastrointestinal distress, like the ayahuasca (although no-one on placebo vomited.)

However – and regular readers can probably guess what I’m going to say at this point – I think it’s possible that ayahuasca’s antidepressant effects were themselves a kind of placebo response. This is because, as expected, the ayahuasca caused powerful psychedelic effects, such as ‘altered perception’ and ‘transcedence’.

Such potent subjective experiences could lead patients to have confidence in the treatment and thus drive placebo effects, if combined with expectations that ayahuasca will be beneficial. A profound experience could trigger improvement in other ways, as well, such as by giving patients a new perspective on their own mental state.

mystical_ayahuasca

Now, in the case of ayahuasca, this ‘psychological’ interpretation of the antidepressant effect is not necessarily a problem. I think most people (including the traditional ayahuasca users) already assume that the psychedelic experience is part of the therapeutic process.

However, let’s consider another mind-altering drug which is being researched as a rapid-acting antidepressant: ketamine. Ketamine, much like ayahuasca, produces powerful antidepressant effects when compared to placebo, and in my view this may well be because of psychological processes, including placebo-like ones. Ketamine and ayahuasca produce very different experiences, but in both cases the subjective effects are intense, profound and unmistakable.

The difference between ketamine and ayahuasca is that many ketamine researchers believe that the antidepressant properties of ketamine represent a direct pharmacological effect, mediated by the drug’s effect on glutamate signalling; on this view, the subjective effects of ketamine are a mere epiphenomenon.

Palhano-Fontes et al. do discuss possible specific pharmacological pathways that might underly the antidepressant effects of ayahuasca (e.g. sigma-1 receptors), but they also acknowledge that

Visions are common during the effects of ayahuasca, and are most frequent with the eyes closed… It has been suggested that visions may play an important role in the therapeutic effect of ayahuasca, as they may help bringing clarity to introspective events

I wonder if almost any drug that produces psychedelic or other profound subjective effects would perform as well as ketamine or ayahuasca.

It would be interesting to carry out a comparative trial with (say) ketamine, LSD, mescaline, ayahuasca and a few others. I would predict that, regardless of the specific pharmacology of each drug, the intensity of subjective effects would be the best predictor of outcome.

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  • Reinier Battenberg

    Sam Harris had a quite interesting conversation about this recently. https://samharris.org/podcasts/127-freedom-known/

    • Subhash Trivedi

      Thank you for sharing, @Reinier

  • http://www.mazepath.com/uncleal/EquivPrinFail.pdf Uncle Al

    MAO inhibitors gave been used to treat cafard. A side effect is having your brain rupture from acute hypertension after eating anything containing tyramine – anything aged. cured, smoked, pickled, or fermented. Death by sauerkraut, red wine, cheese, barbecue, hung meat.

    OTOH, eat passion fruit including eh rinds, then micro-ice plant. Blast-off!, then death by lox.

    • TLongmire

      The vomiting is essential to disoriente the billions of minds in your gut that correlate in the multiverse. Once you stand alone you see the difference. Bit of canabis swallowed sees the mirrored frogs obvious.

  • gwynwas

    An “active placebo,” that is.

  • stgeorge

    I read an excellent study done at the Rhinehart Medical Foundation in Oregon on alcoholism treatment with LSD. It was incredible. It is so sad that all of these thousands of treatments for all diseases, that work like miracles, are never actually available to patients. Unless you are in a study, you will never be allowed to receive the treatment. On a personal level, I have tried DMT (smoked it in crystal form). This was 8 months ago, and the effects are still with me. I have always had incredible dreams (I do not have the space or time to explain them), some would call them nightmares. I had already made the correlation of my dreams with a type of depression (not sadness, more like an anxiety attack, where I feel like I cannot breathe). Well, since this one dose of DMT, I no longer have my dreams, and this depression as well. ODDLY, I really miss my dreams. They were like a whole other life, available to me at night. Many of them were dreams of the immediate future. Many of them were dreams of what I call ‘the dead worlds’.

  • zosima

    Aren’t MAOIs already known to be potent antidepressants? Ones that are rarely prescribed due to their tendency to cause sudden death among patients?

    Why aren’t the researchers looking at the obvious explanation? Mixing prosac and lsd doesn’t make lsd an antidepressant.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      MAOis are antidepressants, but as far as I know, it is unlikely that a single dose of the MAOis in ayahuasca would be enough to have an effect. You normally have to take MAOis daily for them to have an effect.

      • zosima

        I’d be suspicious if they don’t have the control group take the ayahuasca without the dmt. Because the particular MAOIs in the ayahuasca mixture aren’t the ones that are typically prescribed, it seems plausible that they take different amounts of time to become effective.

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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