New Study of Ayahuasca Users Shows Placebo Effect in Action

The ayahuasca study also demonstrates how psychiatry co-opts and misunderstands indigenous rituals.

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A study on the mental health effects of the psychedelic drug ayahuasca found that the drug was no better than a placebo. The researchers suggest that the ceremonial aspects of the ayahuasca ritual are far more important than any proposed biological action of the drug.

The researchers randomly assigned 30 experienced ayahuasca users to receive either the drug or placebo. Then they checked outcomes of anxiety, depression, and stress. They found that mental health outcomes improved—in both groups. There was no difference between the ayahuasca group and the placebo group.

The researchers write, “Symptoms reduced in both groups after the ceremony, independent of treatment.”

Detail of a drum on the ground and the other in the hands of a player: The music that is played afd a ceremony with the use of ayahuascaIn fact, both groups experienced about the same level of psychedelic effects, too. The researchers write that “participants in both groups experienced altered states of consciousness during the ceremony.”

The researchers write that this is why placebo-controlled trials are so important:

“These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.”

The study was led by M. V. Uthaug at Maastricht University in the Netherlands, and it was published in the journal Psychopharmacology.

According to the authors, ayahuasca as a treatment for mental health problems is growing in popularity, and researchers have studied its effects by observing psychedelic retreats. However, they write that these researchers generally do not control for the placebo effect, which could explain the positive initial findings.

Ayahuasca “treatment” often includes a ritual or ceremonial aspect, as well as a group of like-minded people who all expect it to have an effect. These are factors that strongly enhance the placebo effect.

This study also demonstrates how indigenous ritual beliefs are co-opted and misunderstood by the medical model of psychiatry. In psychiatry, it is assumed that the drug’s biological aspect causes the improvement; however, in indigenous cultures, the ritual itself is responsible for the improvement.

According to the researchers:

“It should also be noted that for many indigenous traditions, it is not necessary for the participants to consume ayahuasca. The belief held is that the shamans perform their work to aid those in the ceremony, even if they have not consumed the brew.”

The study had one massive limitation: the participants did not meet the criteria for psychiatric disorders. But this is also true of other naturalistic studies on the drug, which appeared more promising because they did not control for the placebo effect.

Similarly, a recent paper revealed that another psychedelic, touted as a “miracle cure” for mental health problems, esketamine, actually failed five of its six clinical trials and was associated with significant harm.

 

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Uthaug, M. V., Mason, N. L., Toennes, S. W., Reckweg, J. T., de Sousa Fernandes Perna, E. B., Kuypers, K. P. C., . . . & Ramaekers, J. G. (2021). A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats. Psychopharmacology, 238, 1899-1910. (Link)

10 COMMENTS

  1. https://screenshot-media.com/the-future/science/mental-health-blood-test/

    Please someone here respond to this article and supposed test for something that does not exist. Does this article fail to rule out the external factors causing stress and mislabel them bipolar?

    Article: “The study, as noted by Al Jazeera, delves into the biological basis of mental health concerns by developing a blood test using ribonucleic acid (RNA) markers that help distinguish the type of condition a person has. Drawing on 15 years of previous research into how psychiatry relates to blood gene expression biomarkers, the team—led by Doctor Alexander Niculescu—has proved that it’s possible to diagnose depression and bipolar disorder with a blood test. The blood test has clinical utility, is able to distinguish between the two conditions and can eventually match people to the right medications.”

    I am suffering so much 100% imposed panic and terror, and financial devastation, in America My Criminal Psychiatric Fuck in Hell Without End.

    https://ginafournierauthor.com/

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  2. A study on the mental health effects of the psychedelic drug ayahuasca found that the drug was no better than a placebo

    Err, no it didn’t.

    What it actually found was …

    There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca.

    And the moral of the story is; when reading analyses by commentators with an agenda always check primary sources.

    But you’re probably right about ketamine/esketamine.

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  3. “In fact, both groups experienced about the same level of psychedelic effects, too. The researchers write that “participants in both groups experienced altered states of consciousness during the ceremony.”

    That’s not at all what it says either. ‘Contact highs’ are a thing, so you’d expect both groups to experience altered states. But unless the dose is quite small they would definitely not experience the same level of psychedelic effects. And sure enough, according to Fig 2 the ayahuasca group experienced significantly greater psychedelic effects than the placebo group in all categories except ‘Ego Dissolution Inventory’ and ‘reduction of vigilance’.

    “This study also demonstrates how indigenous ritual beliefs are co-opted and misunderstood by the medical model of psychiatry. In psychiatry, it is assumed that the drug’s biological aspect causes the improvement; however, in indigenous cultures, the ritual itself is entirely or primarily responsible for the improvement.”

    That’s only partially true too.

    It’s true that only the shaman takes ayahuasca in traditional healing ceremonies and true that Western ayahuasca ceremonies co-opt and misrepresent indigenous ones. But it’s completely false to claim the ritual itself is primarily responsible for the improvement.

    In fact the shaman uses the ayahuasca to ‘get behind’ the objective physiological symptoms of the problem so she can address the entire disorder – which has physiological, emotional, social and spiritual components (not that non-Enlightenment cultures would make such distinctions). Without the drug the shaman would be unable to fully grasp the disorder and exercise her healing art upon it.

    It’s also misleading to imply ‘ritual effect’=’placebo effect’. In fact the ritual has important socio-spiritual components that serve to reintegrate the sufferer with his community and environment, thereby addressing aspects of disorders typically neglected by Western medicine.

    I really think Peter should consider rewriting or withdrawing this article. Some of his errors are attributable to misunderstanding but others are harder to find innocent explanations for. At the very least it seems he didn’t closely read the research he’s reviewing.

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  4. “The study had one massive limitation: the participants did not meet the criteria for psychiatric disorders. But this is also true of other naturalistic studies on the drug, which appeared more promising because they did not control for the placebo effect.”

    The study had another massive limitation – which it explicitly acknowledges in the discussion section.

    “In previous placebo-controlled studies, oral doses containing 0.36mg/kg DMT were administered to depressed patients (Palhano-Fontes et al. 2019) and freeze-dried oral doses containing 0.75mg/kg DMT (Dos Santos et al. 2012; Valle et al. 2016) and 1 mg/kg DMT (Dos Santos et al. 2011) to experienced users of ayahuasca. In the present study, doses were not adjusted for body weight. However, for an average individual of 70 kg, the equivalent dose would be between 0.20 (7 capsules) and 0.29 mg/kg (10 capsules). Therefore DMT doses in the present study were lower than a therapeutic dose of DMT as administered in a clinical setting. “

    In other words they were using sub-therapeutic doses, so it would have been quite surprising to see a strong drug-mediated response, especially as the subjects weren’t even suffering from the disorders used as response measures.

    So I guess the title of this article ‘New Study of Ayahuasca Users Shows Placebo Effect in Action‘ is less misleading than the text. But a similar study using sugar pills instead of sub-clinical doses of ayahuasca could have been expected to show the same thing and resulted in an even less misleading title and article.

    That said, it’s important to remember that it’s not the drug that effects healing in psychedelic therapy. The drug (in sufficiently high doses) merely temporarily knocks down the ego so the sufferer can gain insights into her condition that were obscured by her own self-image and notions of how she relates to her suffering and the aspects of her self/experience/environment that give rise to it. It’s up to the sufferer herself to decide what to do with those insights.

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  5. Dear Cabrogal,

    Thank you for your critique. I would like to clarify some of the issues you brought up.

    1. I wrote “A study on the mental health effects of the psychedelic drug ayahuasca found that the drug was no better than a placebo”

    You wrote, “Err, no it didn’t.”

    Yes, it did. The drug was no better than placebo on the outcomes of anxiety, depression, or stress. Yes, the researchers tested all sorts of outcomes (for instance, measures of “mindfulness”; padding their study so that something—anything at all—is likely to be positive, just by chance) and there was one outcome that showed a difference. That, as you correctly noticed, was “emotional empathy,” which I considered to be irrelevant, poorly operationalized, and likely a false positive anyway, so I did not think it even worth mentioning.

    To be clear: They found one irrelevant outcome to be slightly better for ayahuasca in a study with many outcomes, including highly relevant ones, that were no different between placebo and drug.

    On the RELEVANT outcomes, the researchers wrote: “Compared to baseline, symptoms reduced in both groups after the ceremony, INDEPENDENT OF TREATMENT” (emphasis mine).

    2. I wrote: “In fact, both groups experienced about the same level of psychedelic effects, too. The researchers write that “participants in both groups experienced altered states of consciousness during the ceremony.”

    You wrote: “That’s not at all what it says either. ‘Contact highs’ are a thing, so you’d expect both groups to experience altered states. But unless the dose is quite small they would definitely not experience the same level of psychedelic effects. And sure enough, according to Fig 2 the ayahuasca group experienced significantly greater psychedelic effects than the placebo group in all categories except ‘Ego Dissolution Inventory’ and ‘reduction of vigilance’.”

    Nope. There were two measures of the psychedelic experience, the EDI (ego dissolution inventory) and the 5-Dimensional Altered States of Consciousness Rating Scale (5D ASC). You correctly identified that there was no difference between ayahuasca and placebo on the EDI. However, you wrote that there were significantly greater psychedelic effects in subscales of the 5D ASC. I’m afraid that’s just not true. There are 16 different subscales of the 5D ASC, all reported on in the supplemental materials, and only one subscale reached p<0.05 (the most liberal definition of statistical significance)—and that was “audio visual synesthesia.” The other 15 subscales did NOT demonstrate a statistically significant difference between ayahuasca and placebo.

    The researchers themselves admit this: “Mean ratings of EDI and total 5D-ACS (dimensions and subscales) did not significantly differ between conditions and did not significantly interact with ayahuasca use experience of the study participants.”

    So, yes, it is accurate for me to write that the two groups experienced the same level of psychedelic effect.

    3. You wrote: “That said, it’s important to remember that it’s not the drug that effects healing in psychedelic therapy. The drug (in sufficiently high doses) merely temporarily knocks down the ego so the sufferer can gain insights into her condition that were obscured by her own self-image and notions of how she relates to her suffering and the aspects of her self/experience/environment that give rise to it. It’s up to the sufferer herself to decide what to do with those insights.”

    Except that this study explicitly showed that the drug DID NOT AFFECT EGO DISSOLUTION any more than the placebo did (see my response #2, above).

    4. You wrote: “It’s also misleading to imply ‘ritual effect’=’placebo effect’. In fact the ritual has important socio-spiritual components that serve to reintegrate the sufferer with his community and environment, thereby addressing aspects of disorders typically neglected by Western medicine.”

    This is an interesting comment. In this case, I used the term placebo effect/response for two reasons: one, that is how the researchers used it in this paper; and two, because the study was about comparing ayahuasca versus placebo drug specifically.

    The term placebo effect is generally used to include a variety of things, including expectation effects, and usually it also helps control for things like regression to the mean which, obviously, is not an “effect” of the placebo. In its strictest sense there is no such thing as a placebo “effect” because by definition, placebos are substances without an effect. But that usage strikes me as pedantic. The term placebo effect, when used to encompass all of the aspects of the difference between a drug group and a control group, is helpful and, I think, operationalized well enough to be clear.

    In a comparison like this, the response of the group taking the placebo includes the expectation effect, and one could argue that for most Americans, the medical field carries more expectation of benefit than a mystic ritual would. So I’d suggest that all medical placebo effects are due at least in part, and I’d say in my opinion greatly, to faith in medical science.

    Thus, the argument that the ritual shouldn’t be called a “placebo effect” is a semiotics question, but not a helpful distinction when the point of the study is comparing the drug + ritual versus the ritual alone.

    4. You wrote: “In other words they were using sub-therapeutic doses, so it would have been quite surprising to see a strong drug-mediated response, especially as the subjects weren’t even suffering from the disorders used as response measures.”

    This is true, and I think it is a legitimate limitation of the study. Good job noticing that one.

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    • This is just a comment on the comment I just read, not a critique of anyone’s arguments.

      I think it is relevant to note that “placebo effects” have taken on (largely due to pharmaceutical company pressures and narratives) a negative connotation, the implication being that “placebo effect” are not real or are imaginary. Placebos of many kinds, including group rituals, can have very powerful, very real effects. The only relevance of calling it a “placebo effect” is that the effect is not caused by the drug or whatever specific intervention is being looked at. I think this can create a negative emotional reaction when people hear “X appears to be a placebo effect” about something they’ve seen be effective.

      I think the placebo effect is FASCINATING and says a lot about what’s wrong with psychiatry’s narrative. If believing something can actually change outcomes, even if the “something” has no direct effect on the brain or body, it suggests that what we believe or imagine or strive for is FAR more important than the “brain=mind” theory can possibly begin to explain.

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  6. Cabrogal, I actually have one more comment. I re-read the study yet again since I was thinking about this today, and I discovered that your point about the low dose of ayahuasca is not actually really a limitation.

    Yes, the researchers in this paper CALLED it a limitation. However, while the researchers called this a lower dose, there’s really nothing to compare it to. It’s not as if there is an established dose of ayahuasca for clinical work. So, the researchers note that their dose was just somewhat lower than in two other studies.

    However, the researchers also say that the amount they used was actually the *usual dose* of ayahuasca and they were not responsible for preparing it, the people in charge of the ritual were. So, really, this study used the standard dose of the drug—and those two other studies gave *excessive* amounts of the drug, which is actually a way of biasing a study. So, no, this is not a low/placebo dose, it is a standard dose, and it actually makes the study stronger.

    From the study: “Study participants received 7 capsules with the option of taking 3 additional ones as a booster, after about 2 h of the first dose. A dose of 7 capsules was portrayed by the host organization as similar to as [sic] regular volume of ayahuasca brew.”

    Thanks again for your questions. It’s an interesting topic.

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  7. The term placebo effect is generally used to include a variety of things, including expectation effects, and usually it also helps control for things like regression to the mean which, obviously, is not an “effect” of the placebo. In its strictest sense there is no such thing as a placebo “effect” because by definition, placebos are substances without an effect. But that usage strikes me as pedantic. The term placebo effect, when used to encompass all of the aspects of the difference between a drug group and a control group, is helpful and, I think, operationalized well enough to be clear.

    Obviously not.

    If ‘placebo effect’ exclusively meant “the aspects of the difference between a drug group and a control group” it would be impossible to do placebo controlled trials of non-drug therapies. That clearly isn’t the case.

    The trial you are reviewing was not of the traditional ayahuasca healing ceremonies of the people of the Amazon. To introduce them by claiming they rely on the placebo effect is just as gratuitous as if a pill doctor reviewing a placebo controlled neuroleptic trial claimed that therapeutic communities such as Soteria rely on the placebo effect because the patients (by and large) don’t take neuroleptics.

    To know whether the ceremonies you mentioned rely on the placebo effect you’d have to run a trial in which one arm used the actual ceremony and another arm used a sham ceremony which resembled it but lacked the aspects practitioners claimed were what brought about healing (e.g. by having the shaman take a sugar pill). The trial you review does no such thing, so to suggest it says anything about whether traditional ceremonies rely on the placebo effect is false. To suggest you know anything about whether such ceremonies rely on the placebo effect is also false because no such trials have been done (at least to my knowledge – please correct me if I’m wrong).

    “Yes, the researchers in this paper CALLED it a limitation. However, while the researchers called this a lower dose, there’s really nothing to compare it to. It’s not as if there is an established dose of ayahuasca for clinical work. So, the researchers note that their dose was just somewhat lower than in two other studies.”

    So if they gave a microdose – or even a zero dose – it wouldn’t have been a limitation because there’s no established benchmark to compare it to? Perhaps. If so it’s equally true to say there’s no dosage that would be relevant to the study because we don’t know which ones might be therapeutic. So it’s a non-study that shows nothing.

    But there is something to compare it to. The placebo controlled trials which had neither the limitation of subjects with no clinical symptoms to alleviate nor a lower dose than has been found to have therapeutic effects. And they found “significant antidepressant effects of ayahuasca when compared with placebo at all-time points”.
    https://pubmed.ncbi.nlm.nih.gov/29903051/

    Obviously if you lower the dose sufficiently from there you will eventually reach a point at which it doesn’t have significant effects, so if this trial hadn’t had the additional limitation of lacking depression symptoms to treat it would be reasonable to say it shows a sub-clinical dose of ayahuasca, not that it shows the placebo effect in action (or at least not any more than any placebo controlled trial of anything does).

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  8. Medical literature has been describing placebos and their effects for more than two hundred years, and the quest to understand the mechanisms and explore the applications is still expanding. Placebo for pain relief is perhaps the most well understood model with clearly defined neurobiological mechanisms. Brief explanation of placebo and nocebo effect is shown in the book by Randy Baker (net-boss org/the-power-of-the-placebo-effect-by-randy-baker)

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