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Science paper Enhancing mindfulness and compassion through an ayahuasca-inspired formulation containing N,N-DMT and harmine
- Thread starter murklan
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Pure science papers to share and discuss.
This is certainly an interesting paper, but it does raise some important considerations. So here are my thoughts.
While the title doesn’t explicitly suggest this is an intervention aimed at people with mental health issues, it naturally raises the question of whether these findings would generalize to populations that aren’t as healthy. After all, it would be particularly compelling if this approach also worked in individuals who actually suffer from the issues being addressed. So for all self medicators, this is not proof
Additionally, my bias is that I’ve always had doubts about what mindfulness actually is, or not, the references don’t really change my opinion or help.
In studies involving psychedelics, a true double-blind setup is mostly impossible, I mean once you take a psychedelic, you know it. That awareness alters the blinding mechanism, making the placebo control far less robust.
Another point worth noting is the post hoc grouping of the “Low Responders.” That raises concerns about p hacking, it feels like an effort to find statistical significance that may not have been there initially. When you look at the variability in the data, it’s considerable. And interestingly, the Low Responders even seem to show a slight negative trend compared to the placebo baseline.
What also stands out is the lack of critical discussion in the paper regarding these statistical and methodological issues. That’s somewhat understandable, but still disappointing, especially given how common and problematic such steps can be in studies like this. Impact factor is good.
Furthermore this raises the possibility that the observed effects might not be pharmacological, but rather the result of subjective experience and expectation. In that sense, they might be measuring something closer to a nocebo/placebo effect. That’s particularly relevant given the challenges around blinding in this context.
Thanks again for sharing it, definitely an interesting read.
While the title doesn’t explicitly suggest this is an intervention aimed at people with mental health issues, it naturally raises the question of whether these findings would generalize to populations that aren’t as healthy. After all, it would be particularly compelling if this approach also worked in individuals who actually suffer from the issues being addressed. So for all self medicators, this is not proof
Additionally, my bias is that I’ve always had doubts about what mindfulness actually is, or not, the references don’t really change my opinion or help.
In studies involving psychedelics, a true double-blind setup is mostly impossible, I mean once you take a psychedelic, you know it. That awareness alters the blinding mechanism, making the placebo control far less robust.
Another point worth noting is the post hoc grouping of the “Low Responders.” That raises concerns about p hacking, it feels like an effort to find statistical significance that may not have been there initially. When you look at the variability in the data, it’s considerable. And interestingly, the Low Responders even seem to show a slight negative trend compared to the placebo baseline.
What also stands out is the lack of critical discussion in the paper regarding these statistical and methodological issues. That’s somewhat understandable, but still disappointing, especially given how common and problematic such steps can be in studies like this. Impact factor is good.
Furthermore this raises the possibility that the observed effects might not be pharmacological, but rather the result of subjective experience and expectation. In that sense, they might be measuring something closer to a nocebo/placebo effect. That’s particularly relevant given the challenges around blinding in this context.
Thanks again for sharing it, definitely an interesting read.
I generally agree with you, @Varallo . However,
I do agree that if the subjective experience were to be the main or even an important cause of any posterior change, that would make it imperative to standardize set and setting in a study to the highest degree possible.
I'm not very optimistic overall that psychedelics will ever fit well in standardized medicine. I think the key component of most of their positive or negative long term effects is the experience and thus the experiencer. This makes them too complex and unreliable if your intention is to get people other than you to use them with the intention of a certain outcome. But I see this as a good thing in general, as I wouldn't like if such powerful tools could be reliably used to change people.
If many or most of the potential benefits of psychedelics turned out to not be directly pharmacological but a result of the experience they (pharmacologically) induce, which I think it's likely to be the case, why would it detract from their usefulness? And the subjective content of psychedelic experiences could be considered a pharmacologically amplified placebo or nocebo effect indeed, hence the importance of set and setting.
I do agree that if the subjective experience were to be the main or even an important cause of any posterior change, that would make it imperative to standardize set and setting in a study to the highest degree possible.
I'm not very optimistic overall that psychedelics will ever fit well in standardized medicine. I think the key component of most of their positive or negative long term effects is the experience and thus the experiencer. This makes them too complex and unreliable if your intention is to get people other than you to use them with the intention of a certain outcome. But I see this as a good thing in general, as I wouldn't like if such powerful tools could be reliably used to change people.
The problem with this, I think, is that the effects are often highly subjective and based on personal experience. A big part of how we’re influenced comes down to the intention behind it, or the story or idea surrounding it. So in that sense, it sets something in motion that doesn’t necessarily function better, or even as well, as a placebo.
Whether that’s a bad thing or not, I honestly don’t have a strong opinion. I actually think the placebo effect is a wonderful thing. If one of my kids has a headache and I give them a peppermint instead of paracetamol, and I tell them it works really well, then it actually does work really well.
So in that sense, it’s harmless. There’s really not that much wrong with it, as far as I’m concerned.
It becomes much more difficult when you’re an medical professional and you’re treating patients, then I think it’s better to have tools that go beyond the placebo effect.
Whether that’s a bad thing or not, I honestly don’t have a strong opinion. I actually think the placebo effect is a wonderful thing. If one of my kids has a headache and I give them a peppermint instead of paracetamol, and I tell them it works really well, then it actually does work really well.
So in that sense, it’s harmless. There’s really not that much wrong with it, as far as I’m concerned.
It becomes much more difficult when you’re an medical professional and you’re treating patients, then I think it’s better to have tools that go beyond the placebo effect.
Seen as a medication, yes, I agree with you. Seen as a therapy, not really. Insight into one's mind, life history, patterns, etc. goes much beyond mere placebo. For example, I was starting to abuse pregabalin, and I quit after starting having Ayahuasca regularly. It was not because I thought "I had Ayahuasca and its effect has removed my incipient dependency from pregabalin", that for example would likely be placebo. It was that I could see the incipient dependency and understand it's main causes and consequences, so I decided to stop that pattern. In that sense, it was not merely placebo and not merely pharmacological, but a pharmacologically mediated experience of insight. That insight could have happened without it as well, but the substance made it easier and more powerful.
I think we agree, I mostly wanted to clarify it in case we actually don't. Precisely because those results come from a very complex experience with many many variables, it's not something a doctor could just order you to take in order to "cure" depression, addiction or any other psychological issue.
Here&Now
Titanium Teammate
Right, I think there is a lot of hidden value in psychedelics for their ability to literally turn up the dial on the intensity of awareness itself, which I don't believe we currently have any reliable methods for objectively measuring. A "pharmacologically mediated experience of insight" is a good way to put it.
murklan
Established member
Regarding this. I've read that they in some studies give niacin as the non-psychedelic substance. The flush that it can give makes at least some, psychedelic naive, persons the impression that they have in fact been given the active substance.
Great thoughts also. I think there are some major changes coming around how we understand placebo and medicine in general. But psychedelics might be extra tricky since work with and through so many systems.
Ah yes I have heard of that, also there’s some studies that use very low doses as an proxy for an “placebo”. I think you’re correct about our understanding of placebo effects and their value, especially when psychedelics are involved.
Thanks for this, this idea aligns well with my thoughts on the subject. I think that psychedelics in a therapeutic setting are/can function as amplifiers of the therapy itself, they don’t cure on their own but they amplify the therapeutic process.
Anyway after the summer I have been thinking about making an table with all the papers that I can find on the subject of, therapeutic effects and psychedelics, and see if it’s possible to work out some trends. If so it would be possible to write it down as an paper and then publish it.
In the discussion the authors never talk about the reduction of functional connectivity in the default mode network by psychedelics such as DMT. I found it odd since this is the most supported mechanism behind therapeutic change and it would also explain the increase in mindfulness- and compassion-related capabilities the study focuses on.
I agree with blig-blug's pharmacology-mediated experience of insight. I think they can't be separated. The pharmacological action and the subjective experience can't exist without each other. I guess that even non-hallucinogenic psychedelic compounds with antidepressant or antiaddiction potential would make people experience subjective effects. I don't think one can modulate a brain network without making the brain experience it.
Couldn't the low-responders in the study be low-responders also from a pharmacological point of view?
Maybe, it’s not included in the article but I would not be surprised, also the dosage is very conservative (I made an mistake see edit) on the harmine, but subjectively (100mg nasally) high in dmt, so that could probably have implications ont the responses.
Overall very nice study.
Edit: this article by the same authors is clearing up the dosage, a very interesting read. Frontiers | Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine
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Looking forward to your forthcoming review paper or meta-analysis
Well, I’ve been thinking about it for a while now, and I think it could be interesting to see if there’s an opportunity here for the upcoming year. So far, I’ve been working on a script that uses an LLM to read academic papers and fill a large table with extracted information. At this point, it categorizes papers based on type, theme, and also things like sample size (N=), among other details.Looking forward to your forthcoming review paper or meta-analysis
I’m now thinking of adding a web check to pull in impact factor data, and I’d also like to include some visual elements, maybe something that shows all references and authors in a visual format. Like a large network.
Anyway, it’s still very much an idea in my head, but I hope to get something on paper after the summer. Co-authors welcome
This is very interesting. If you share the script in some repository not linked to your real identity (I recommend Codeberg, avoid GitHub if possible) I'd be interested in helpingWell, I’ve been thinking about it for a while now, and I think it could be interesting to see if there’s an opportunity here for the upcoming year. So far, I’ve been working on a script that uses an LLM to read academic papers and fill a large table with extracted information. At this point, it categorizes papers based on type, theme, and also things like sample size (N=), among other details.
I’m now thinking of adding a web check to pull in impact factor data, and I’d also like to include some visual elements, maybe something that shows all references and authors in a visual format. Like a large network.
Anyway, it’s still very much an idea in my head, but I hope to get something on paper after the summer. Co-authors welcome
Ow thanks, that would be great, in time I will come back to it and contact youThis is very interesting. If you share the script in some repository not linked to your real identity (I recommend Codeberg, avoid GitHub if possible) I'd be interested in helping
or I could just share the python code here
Maybe share it here in the new coding subforum, it could kickstart sharing relevant or useful code snippets thereOw thanks, that would be great, in time I will come back to it and contact you