Many of the items on that list are not about “negative effects of psychedelics” at all, unless one applies a broad and eccentric notion of “negative effects” according to which, e.g., Big 5 personality shifts associated with successful SSRI treatment for depression also count as “negative effects”.
This is a study about the effects of psilocybin on personality traits when used therapeutically in patients with treatment‐resistant depression.
Changes in personality traits have previously been observed in depressed patients undergoing successful treatment with standard antidepressants such as SSRIs. This study found that broadly similar changes occur when psilocybin is used for treatment-resistant depression, although the relative extent of the changes to the individual Big 5 traits was possibly somewhat different in this case[1].
Effects on depression itself were studied in a separate report on the same trial; psilocybin was highly effective at reducing depression for these patients[2] (who had tried other pharmaceutical treatments without success). The treatment was also “generally well tolerated” with “no serious adverse events.”
This is a Newsweek article about this paper, a systematic review of psychedelic effects on personality.
The paper summarizes a large number of other studies, and is thus difficult to summarize, but here are a few fairly representative quotations from summaries of individual studies:
“The authors concluded that these results indicated that, compared to the control group, UDV[3] members had reduced impulsivity and shyness, and were more reflective, confident, gregarious and optimistic. This study also reported an absence of current psychiatric diagnosis among the UDV members, as well as no evidence of cognitive deterioration.”
“Compared to placebo, LSD administration acutely improved mood and psychosis-like symptoms, and significantly increased Optimism (P = 0.005, corrected) and Openness (P = 0.03, corrected) scores two weeks after the experimental sessions.”
The paper’s abstract ends with the line “These [personality] changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.”
This is a web forum post responding to a list of quotations from people who reported “long-term beneficial effects” from Ayahuasca in the 2025 ACX survey.
Some of the quotations report belief and/or personality changes that some might find concerning (e.g. “Obliterated my atheism [...] no longer believe matter is base substrate [...]”). Others seem unambiguously and strongly positive (e.g. “Stopped using drugs and drinking for 6 years”).
The forum commenter speculates that even some of the reported positive changes might actually be negative changes. The following is the entirety of their commentary on the quotations: “I am pretty sure that people who could write some of those responses have had bad things happen to them, and just have no idea. If you can write nonsense like ‘put right and left hemispheres in order’, this might not be good.”
In principle, this is of course possible! Self-reports are not always reliable, people sometimes develop different views of their situation in hindsight than what they believed at the time (or are perceived one way by others and another way by themselves), etc.
But this proves too much: the same arguments could be used to cast doubt on any self-report whatsoever, including e.g. the self-reports of depressed patients who say they are less depressed after treatment with SSRIs, MAOIs, or other standard pharmacotherapies.
Surely a list of self-reported positive effects, followed by a broad skeptical comment about the reliability of self-report, does not constitute evidence for the occurrence or ubiquity of negative effects...?
Re: the specific comment about hemispheres, here’s the relevant part of the quote being critiqued: “put right and left hemispheres in proper order (only really understood 6 years later when reading McGilchrist).”
McGilchrist here is presumably Iain McGilchrist, author of The Master and his Emissary.
I have not read this book and do not know much about it, but a few quick searches revealed that (a) it is fairly controversial but (b) it has been brought up previously on LW/SSC/ACX a number of times, usually without anyone dismissing the person bringing it up as a peddler of obvious “nonsense” (see e.g. this comment and its response tree, or the brief mention of the book in this ACX guest post).
I don’t know if “put[ting] right and left hemispheres in order” is actually something McGilchrist himself talks about, but in any event the forum comment itself does not convincingly justify the commenter’s assessment of this phrase as “nonsense.”
This is, uh… about the psychological effects of supplemental estrogen. Which is not a psychedelic.
The author does mention psychedelics, but mostly as part of a line of speculation about how the effects of supplemental estrogen might resemble the effects of low psychedelic doses, except sustained continuously.
I have no idea what this one is doing on this list.
Several of the other links are more legitimately concerning, such as this single report of lasting negative effects from Ayahuasca; several links about HPPD (Hallucinogen-persisting perception disorder); and, arguably, this study about shifts in metaphysical beliefs. However—as with any other major life choice, e.g. starting a course of SSRIs or another psychiatric medication, conceiving a child, getting married, getting divorced, changing careers, etc. -- the undeniable risks must be tallied up against the potential benefits, some of which have been (inadvertently?) surveyed in this very list.
If the claim is merely that psychedelic drugs have a side effect profile worth taking seriously and reflecting upon with care, then I agree, they certainly do—just as with SSRIs, pregnancy, etc., etc. Should all these be “considered harmful,” then?
“Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. [...]
”Overall, the detected pre‐ to post‐treatment changes in both trait and facet scores in our trial corresponded well with observations from a study of patients who successfully underwent pharmacotherapy, mostly with selective serotonin reuptake inhibitors (SSRIs), for major depression. More specifically, the same four of ‘the Big Five’ traits changed in the two trials and in the same direction – that is toward the personality profile of healthy populations (although Conscientiousness only at trend‐level in our study).”
“Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen’s d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen’s d = 1.5 and 1.4, respectively, both p < 0.001). [...]
“Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort.”
União do Vegetal, a religious group that practices ritual use of Ayahuasca. (There are, of course, obvious confounding concerns with this line of evidence.)
Unlike those other things you list, psychedelics have almost no benefits. Almost all of even the claimed benefits are actually bad things.
Anyhow, you comment on 4 links out of 14. Do you then have no quarrel with the other 10 links? You agree that they show negative effects of psychedelics?
I ask because my response will differ substantially based on whether you think that these four are just individually bad examples, or what. (I intend to respond on the substance in any case, but I need to be clear on what claim I’m responding it.)
Anyhow, you comment on 4 links out of 14. Do you then have no quarrel with the other 10 links? You agree that they show negative effects of psychedelics?
I commented on 8 links, describing 4 of the 8 as “more legitimately concerning.”[1] So, yes, I think some of the links document negative effects of psychedelics—as was clear in the comment you’re replying to.
Unlike those other things you list, psychedelics have almost no benefits. Almost all of even the claimed benefits are actually bad things.
I would be very interested to hear your justification for this, and in particular, what you make of the reported efficacy as a treatment for depression.
There were two links about HPPD, which I grouped under “several links about HPPD” in the parent comment. The other 6 of the 8 were explicitly hyperlinked in the parent comment.
Hm… I see two other ones now that I look closely (they’re not list entries), but can’t find the last two… well, not a big deal.
So, yes, I think some of the links document negative effects of psychedelics—as was clear in the comment you’re replying to.
It actually wasn’t clear, so I definitely appreciate the clarification.
Anyhow, I will address your criticisms more substantively in an upcoming comment.
Unlike those other things you list, psychedelics have almost no benefits. Almost all of even the claimed benefits are actually bad things.
I would be very interested to hear your justification for this, and in particular, what you make of the reported efficacy as a treatment for depression.
Many of the items on that list are not about “negative effects of psychedelics” at all, unless one applies a broad and eccentric notion of “negative effects” according to which, e.g., Big 5 personality shifts associated with successful SSRI treatment for depression also count as “negative effects”.
For example:
https://pmc.ncbi.nlm.nih.gov/articles/PMC6220878/
This is a study about the effects of psilocybin on personality traits when used therapeutically in patients with treatment‐resistant depression.
Changes in personality traits have previously been observed in depressed patients undergoing successful treatment with standard antidepressants such as SSRIs. This study found that broadly similar changes occur when psilocybin is used for treatment-resistant depression, although the relative extent of the changes to the individual Big 5 traits was possibly somewhat different in this case[1].
Effects on depression itself were studied in a separate report on the same trial; psilocybin was highly effective at reducing depression for these patients[2] (who had tried other pharmaceutical treatments without success). The treatment was also “generally well tolerated” with “no serious adverse events.”
https://www.newsweek.com/just-one-psychedelic-drug-trip-can-cause-changes-personality-could-last-years-828884
This is a Newsweek article about this paper, a systematic review of psychedelic effects on personality.
The paper summarizes a large number of other studies, and is thus difficult to summarize, but here are a few fairly representative quotations from summaries of individual studies:
“The authors concluded that these results indicated that, compared to the control group, UDV[3] members had reduced impulsivity and shyness, and were more reflective, confident, gregarious and optimistic. This study also reported an absence of current psychiatric diagnosis among the UDV members, as well as no evidence of cognitive deterioration.”
“Compared to placebo, LSD administration acutely improved mood and psychosis-like symptoms, and significantly increased Optimism (P = 0.005, corrected) and Openness (P = 0.03, corrected) scores two weeks after the experimental sessions.”
The paper’s abstract ends with the line “These [personality] changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.”
https://www.datasecretslox.com/index.php/topic,13040.msg624204.html#msg624204
This is a web forum post responding to a list of quotations from people who reported “long-term beneficial effects” from Ayahuasca in the 2025 ACX survey.
Some of the quotations report belief and/or personality changes that some might find concerning (e.g. “Obliterated my atheism [...] no longer believe matter is base substrate [...]”). Others seem unambiguously and strongly positive (e.g. “Stopped using drugs and drinking for 6 years”).
The forum commenter speculates that even some of the reported positive changes might actually be negative changes. The following is the entirety of their commentary on the quotations: “I am pretty sure that people who could write some of those responses have had bad things happen to them, and just have no idea. If you can write nonsense like ‘put right and left hemispheres in order’, this might not be good.”
In principle, this is of course possible! Self-reports are not always reliable, people sometimes develop different views of their situation in hindsight than what they believed at the time (or are perceived one way by others and another way by themselves), etc.
But this proves too much: the same arguments could be used to cast doubt on any self-report whatsoever, including e.g. the self-reports of depressed patients who say they are less depressed after treatment with SSRIs, MAOIs, or other standard pharmacotherapies.
Surely a list of self-reported positive effects, followed by a broad skeptical comment about the reliability of self-report, does not constitute evidence for the occurrence or ubiquity of negative effects...?
Re: the specific comment about hemispheres, here’s the relevant part of the quote being critiqued: “put right and left hemispheres in proper order (only really understood 6 years later when reading McGilchrist).”
McGilchrist here is presumably Iain McGilchrist, author of The Master and his Emissary.
I have not read this book and do not know much about it, but a few quick searches revealed that (a) it is fairly controversial but (b) it has been brought up previously on LW/SSC/ACX a number of times, usually without anyone dismissing the person bringing it up as a peddler of obvious “nonsense” (see e.g. this comment and its response tree, or the brief mention of the book in this ACX guest post).
I don’t know if “put[ting] right and left hemispheres in order” is actually something McGilchrist himself talks about, but in any event the forum comment itself does not convincingly justify the commenter’s assessment of this phrase as “nonsense.”
https://www.greaterwrong.com/posts/mDMnyqt52CrFskXLc/estrogen-a-trip-report
This is, uh… about the psychological effects of supplemental estrogen. Which is not a psychedelic.
The author does mention psychedelics, but mostly as part of a line of speculation about how the effects of supplemental estrogen might resemble the effects of low psychedelic doses, except sustained continuously.
I have no idea what this one is doing on this list.
Several of the other links are more legitimately concerning, such as this single report of lasting negative effects from Ayahuasca; several links about HPPD (Hallucinogen-persisting perception disorder); and, arguably, this study about shifts in metaphysical beliefs. However—as with any other major life choice, e.g. starting a course of SSRIs or another psychiatric medication, conceiving a child, getting married, getting divorced, changing careers, etc. -- the undeniable risks must be tallied up against the potential benefits, some of which have been (inadvertently?) surveyed in this very list.
If the claim is merely that psychedelic drugs have a side effect profile worth taking seriously and reflecting upon with care, then I agree, they certainly do—just as with SSRIs, pregnancy, etc., etc. Should all these be “considered harmful,” then?
“Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. [...]
”Overall, the detected pre‐ to post‐treatment changes in both trait and facet scores in our trial corresponded well with observations from a study of patients who successfully underwent pharmacotherapy, mostly with selective serotonin reuptake inhibitors (SSRIs), for major depression. More specifically, the same four of ‘the Big Five’ traits changed in the two trials and in the same direction – that is toward the personality profile of healthy populations (although Conscientiousness only at trend‐level in our study).”
“Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen’s d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen’s d = 1.5 and 1.4, respectively, both p < 0.001). [...]
“Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort.”
União do Vegetal, a religious group that practices ritual use of Ayahuasca. (There are, of course, obvious confounding concerns with this line of evidence.)
Unlike those other things you list, psychedelics have almost no benefits. Almost all of even the claimed benefits are actually bad things.
Anyhow, you comment on 4 links out of 14. Do you then have no quarrel with the other 10 links? You agree that they show negative effects of psychedelics?
I ask because my response will differ substantially based on whether you think that these four are just individually bad examples, or what. (I intend to respond on the substance in any case, but I need to be clear on what claim I’m responding it.)
I commented on 8 links, describing 4 of the 8 as “more legitimately concerning.”[1] So, yes, I think some of the links document negative effects of psychedelics—as was clear in the comment you’re replying to.
I would be very interested to hear your justification for this, and in particular, what you make of the reported efficacy as a treatment for depression.
There were two links about HPPD, which I grouped under “several links about HPPD” in the parent comment. The other 6 of the 8 were explicitly hyperlinked in the parent comment.
Hm… I see two other ones now that I look closely (they’re not list entries), but can’t find the last two… well, not a big deal.
It actually wasn’t clear, so I definitely appreciate the clarification.
Anyhow, I will address your criticisms more substantively in an upcoming comment.
Yep, I will certainly comment on this also.