Part of the reason that people with SMI and family history of the same are excluded from these trials is that hallucinogen use is thought to be much riskier for this group, as it may exacerbate or precipitate these conditions. I worry that the tenor of the hype will give people who should be very cautious about their use an exaggerated sense of the potential benefits and a false sense of safety. The disclaimers are in the fine print--most people will just hear that it's "medicine for mental health problems". I think this has happened in places that legalized marijuana--because the risks had been so exaggerated and the arguments for restriction so weak, people were almost innoculated against the idea that the substance can cause harm, especially to certain groups. The push for medical use in lieu of what was usually recreational use led to a lot of claims about benefits for mental health conditions on flimsy evidence, that are now largely thought to be false, and the evidence that marijuana contributes to mental health problems, especially psychosis, is mounting. I think the case for psychedelics in some conditions is more promising and the risks less significant for most people, but I see the same pattern playing out. Not only will this likely not benefit people with SMI, it stands to cause harm.
It seems your criticism amounts to "It's early days, and won't help everyone."
Per the latter point, what does? Clearly the treatments we have for run of the mill anxiety, depression, addiction, and PTSD are inadequate. These conditions are becoming more common, not less.
Also, psychedelics have a fundamental discordance with allopathic research which can never be overcome. The placebo problem is unsolvable. And these medicines are customarily adjuvant to non-directive therapy, and ongoing integration. We'll never be able to quantify those things in a trial format the same way we can for a blood pressure pill. Finally, we know set and setting matter with these medicines. Which means an interventional supportive environment. Not staring at people like lab rats in an exam room.
But know what? They work. Trial data are mostly positive. As are the anecdotes. And the adverse events are minimal, and crucially if these medicines are going to work they'll work -- or not -- within a few months. No ineffective SSRI cocktail until the crack of doom, or expensive weekly psychotherapy for years at a time.
Does that mean allopathic psychiatry should disdain these medicines? Fine by me. So long as the infrastructure stops getting actively in the way of other people doing healing work that matters.
It sounds like you see psychedelic therapy as an alternative medicine which will never really fit into the allopathic/Western/medical model of mental illness.
Interesting to hear this point of view and I suspect you’re not the only one who feels these drugs should operate in a different sphere.
Medicalization is controversial within the plant medicine space itself. Those against it fear it's either a dead end, because these medicines can't by their nature reproduce reliably in the setting of a randomized controlled trial. There's too many variables, and many of them are extremely subjective. MAPS/Doblin purposely selected MDMA and PTSD to avoid some of these problems: It's synthetic, so dosing is reliable. Sessions themselves aren't too long. Not much works for PTSD, anyway, for those recalcitrant to exposure therapy. There are long-standing outcome tools everyone accepts in PTSD. And -- per one of your points -- they actually did go out of their way to work 'tough' patients.*
Also importantly, per the people who don't want medicalization: MDMA and the therapeutic modalities adjacent to it promise to be more easily patentable. And that's the other thing those against medicalization fear: Capture by pharma, thereby reducing access and concentrating profits.
Now, personally, I get that everyone has gotta' make a living. So that part doesn't bother me.
But I am struck by how most of the reasonable objections being raised to these therapies in an allopathic setting have to do with *how these medicines work.* They simply do not work like conventional drugs. One does not get the same response from a person every time the same drug and dose are administered.
In which case one can just say "Well, treat them like psychology/psychotherapy modalities. People try those out all the time absent any clinical data at all, and the data that do exist are usually unreplicable." Nobody loses their shit over that, right? Well, at least they don't until we get some sort of Satanic Cult scare because of allegedly repressed memories.
But, of course, the problem there is with psychedelic therapy a 'drug' is, indeed, involved.
Oregon's experiment is interesting. In that it has been medicalized, there. But, at the same time, the actual medical establishment is entirely kept out of it. So much so that if you're an MD in that environment it's actually illegal for you to do MD things in that environment, and represent one's self as a doctor.
Sorry about the ramble. Ultimately, I do agree with you, even as an advocate for these medicines. From within an allopathic medicine frame psychedelic therapy likely won't solve any crises. But, from a *public health* frame, I certainly think they can help a lot.
*Setting aside the understanding of most psychedelic practitioners that recent mania or suicidal ideation, psychosis, and family history of schizophrenia are contraindications to psychedelic therapy.
I agree with most of what you write about psychedelics, but you also write: “until we get some sort of Satanic Cult scare because of allegedly repressed memories.” Not sure what this indicates about your understanding of repressed memories and dissociative amnesia, but if you doubt the existence of dissociative amnesia or the validity of traumatic memory, I suggest you give ‘dissociative amnesia’ a little study. It’s been in the DSM since 1980 and known about since the 1800s. It’s only controversial because it’s the kind of concept that people fight against. (But maybe it’s only the “Satanic Cult” scare you’re referencing. I’ve heard of it but don’t know much about it. Perhaps I’ll look it up.)
I didn't mean to suggest repressed memories are all fake. But I did mean to suggest all the satanic cult nonsense pegged to alleged repressed memories were fake.
Your comment led me to read a few online articles. Very interesting! It turns out there is a Church of Satan. History.com says: "The 1980s Satanic Panic saw Christian fundamentalists push the idea that Satanic cults were systematically abusing children in rituals and committing widespread murder, and successfully convince the general public through sensational news coverage. Christian groups typically misrepresented the Church’s beliefs and practices in order to fabricate a real-world villain behind the conspiracy for the media." A NYTs article, https://www.nytimes.com/2021/03/31/us/satanic-panic.html, describes how, in the original McMartin Preschool case, it was the police who bungled the investigations, fueling the panic.
The placebo problem isn't unsolvable. Just use actually-naive subjects and a better active placebo (something that has the anticipated reality-distorting effects via another mechanism) than the usual choice of a light sedative.
I'm not familiar with all the options, but another psychedelic that we have good reason to believe doesn't have psychiatric benefits and doesn't have the same underlying mechanism of action, or a dissociative. At moderate doses I doubt a naive user could guess they are taking psilocybin versus, eg, dextromethorphan, DMT, or even THC. I just don't know if any of these are safe enough for a review board or well characterized enough to differentiate placebo effect from some actual benefit they might have.
Oh, dear ... DMT is something else entity. And the effects are of a much shorter duration. And THC is interesting, but tons of people have taken THC at this point, and know what it feels like. And for many of the relevant indications both THC and DMT are under investigation. Wouldn't reviewers like they just met say "All you've proven is your psychedelic is better than weed and/or DMT?"
Dextromethorphan is an interesting thought, tho. But is it safe enough to use as an alternative to placebo?
Well written and thought out article, thank you for this. As someone experienced in the realm of psychedelics but also with a family member who has CPTSD and autism who suffers from delusional thinking, the thought of her taking psychedelics is terrifying. I’m pretty sure she’d never come back mentally. It’s not for everyone. Many people need more help to be “here” in their body, feeling safe to accept their present reality rather than enter more hallucinogenic states that psychedelics induce.
Thanks for this thoughtful essay that balances the hope against the hype! The therapeutic potential of psychedelics is exciting, but implementing it without harming people will require the wisdom of Solomon.
I think that finding the set of patients most likely to respond in a positive way to a medicine or procedure has a very long tradition. You may screen out people with a family history of psychosis in trials now, but hope to include them in years to come. And I wonder if there is anyone with severe depression who doesn’t have suicidal ideation. If I wanted to be in a trial, I would lie and say I hadn't considered suicide. Seems to me we shouldn’t ‘pretend’ that we know what and who psychedelics might work for and not work for—and keep up the research. As you say, we're in desperate need of new treatments. (Of course, we should fund inpatient treatment too.)
True! I do wonder whether participants might be less than wholly honest when it comes to meeting other inclusion/exclusion criteria of these studies - eg downplaying previous psychedelic use.
As a person with severe mental illness, I hope to try psychedelics at some point. I've tried around 25 different psychiatric medications and none of them have helped. I have never tried amitriptyline because of my suicidal ideation - our established treatments have contraindications too. I've been in therapy for years and it's helping, slowly. I know we shouldn't believe the hype but isn't there room for hope as well.
Agree we need to have hope and that recovery from severe mental illness is possible for many people.
I personally don’t have hope in psychedelics from conditions like schizophrenia, bipolar disorder, psychotic depression, or personality disorders. I do hope other, better treatments are developed.
Totally agree regarding the psychoses, I think that no one researching psychedelics would think they are safe in people who have a history of psychosis. I think given the history of their use in substance misuse, we should see more trials assessing their benefit in addiction and/or confirming their safety in people with a substance misuse history.
I’m very interested to see if they could be of use in PD - borderline especially. PD is itself hardly a fixed and completely understood concept in psychiatry and is in a state of flux. It could be in a few years viewed as a solely a consequence of developmental trauma. Equally, there is the neurodivergent/social model of disability view, which looks at PD as an expression on the continuum of human experience and could well lead to us starting to view it as something that doesn’t need “curing” but merely help with the distressing consequences.
Anyway, my point is that I wonder if psychedelics could be useful in loosening unhelpful coping strategies that form a core part of the dysfunction in PD - whether from trauma or friction with the social environment. I think given the good evidence for the response of BPD to psychotherapy, there is some hope for psychedelic assisted psychotherapy. Having said that, I imagine the results will be much less dramatic.
I heard at a conference a while ago that there was something in the works but I’ve heard nothing since. I agree, risk and suicidality is a major problem. Again goes back to your point of who we are actually treating. The very distressed and uncontained individuals who we see most frequently in services would probably be better served by simple continuity of care in community services by professionals who are experienced and want to work with them, alongside access to psychotherapy in a timely manner. As we know, patients like this are often to risky/unstable for basic DBT-informed work let alone psychedelics. I would very much like the NHS to get waiting lists down for intensive psychotherapies for the vast number of traumatised people we work with.
It will be very interesting to see if this therapy will sit with a psychotherapy service or the affective disorder service. Locally to me the affective disorder team doesn’t have psychology and works on a receptor by receptor basis, and I know they would have little interest in sitting with someone for 4 hours on psilocybin!
I think it comes back to a wider point about psychedelics. They are not a drug in the same way as an SSRI is, because the mechanism of action is precisely to alter perception, and therefore the mindset and setting - I.e. therapeutic frame - is critical to their therapeutic success or harm. They should never be thought about divorced from psychotherapy.
Perhaps MDMA is a good candidate for BPD as it lacks the outright hallucinogenic effects and has a growing evidence base for trauma. This seems partially based on speeding up trust in the therapeutic relationship.
I guess my hope would be it could help with my PTSD symptoms, which I think many people with severe mental illness deal with. I could be wrong, but I don't think that any new treatment options are being explored for one of the diagnoses I have (AvPD). I understand that these drugs aren't really being developed for me, but neither were any of the other treatments I've tried, it seems.
Part of the reason that people with SMI and family history of the same are excluded from these trials is that hallucinogen use is thought to be much riskier for this group, as it may exacerbate or precipitate these conditions. I worry that the tenor of the hype will give people who should be very cautious about their use an exaggerated sense of the potential benefits and a false sense of safety. The disclaimers are in the fine print--most people will just hear that it's "medicine for mental health problems". I think this has happened in places that legalized marijuana--because the risks had been so exaggerated and the arguments for restriction so weak, people were almost innoculated against the idea that the substance can cause harm, especially to certain groups. The push for medical use in lieu of what was usually recreational use led to a lot of claims about benefits for mental health conditions on flimsy evidence, that are now largely thought to be false, and the evidence that marijuana contributes to mental health problems, especially psychosis, is mounting. I think the case for psychedelics in some conditions is more promising and the risks less significant for most people, but I see the same pattern playing out. Not only will this likely not benefit people with SMI, it stands to cause harm.
Agree!
It seems your criticism amounts to "It's early days, and won't help everyone."
Per the latter point, what does? Clearly the treatments we have for run of the mill anxiety, depression, addiction, and PTSD are inadequate. These conditions are becoming more common, not less.
Also, psychedelics have a fundamental discordance with allopathic research which can never be overcome. The placebo problem is unsolvable. And these medicines are customarily adjuvant to non-directive therapy, and ongoing integration. We'll never be able to quantify those things in a trial format the same way we can for a blood pressure pill. Finally, we know set and setting matter with these medicines. Which means an interventional supportive environment. Not staring at people like lab rats in an exam room.
But know what? They work. Trial data are mostly positive. As are the anecdotes. And the adverse events are minimal, and crucially if these medicines are going to work they'll work -- or not -- within a few months. No ineffective SSRI cocktail until the crack of doom, or expensive weekly psychotherapy for years at a time.
Does that mean allopathic psychiatry should disdain these medicines? Fine by me. So long as the infrastructure stops getting actively in the way of other people doing healing work that matters.
Thanks for leaving this comment.
It sounds like you see psychedelic therapy as an alternative medicine which will never really fit into the allopathic/Western/medical model of mental illness.
Interesting to hear this point of view and I suspect you’re not the only one who feels these drugs should operate in a different sphere.
Medicalization is controversial within the plant medicine space itself. Those against it fear it's either a dead end, because these medicines can't by their nature reproduce reliably in the setting of a randomized controlled trial. There's too many variables, and many of them are extremely subjective. MAPS/Doblin purposely selected MDMA and PTSD to avoid some of these problems: It's synthetic, so dosing is reliable. Sessions themselves aren't too long. Not much works for PTSD, anyway, for those recalcitrant to exposure therapy. There are long-standing outcome tools everyone accepts in PTSD. And -- per one of your points -- they actually did go out of their way to work 'tough' patients.*
Also importantly, per the people who don't want medicalization: MDMA and the therapeutic modalities adjacent to it promise to be more easily patentable. And that's the other thing those against medicalization fear: Capture by pharma, thereby reducing access and concentrating profits.
Now, personally, I get that everyone has gotta' make a living. So that part doesn't bother me.
But I am struck by how most of the reasonable objections being raised to these therapies in an allopathic setting have to do with *how these medicines work.* They simply do not work like conventional drugs. One does not get the same response from a person every time the same drug and dose are administered.
In which case one can just say "Well, treat them like psychology/psychotherapy modalities. People try those out all the time absent any clinical data at all, and the data that do exist are usually unreplicable." Nobody loses their shit over that, right? Well, at least they don't until we get some sort of Satanic Cult scare because of allegedly repressed memories.
But, of course, the problem there is with psychedelic therapy a 'drug' is, indeed, involved.
Oregon's experiment is interesting. In that it has been medicalized, there. But, at the same time, the actual medical establishment is entirely kept out of it. So much so that if you're an MD in that environment it's actually illegal for you to do MD things in that environment, and represent one's self as a doctor.
Sorry about the ramble. Ultimately, I do agree with you, even as an advocate for these medicines. From within an allopathic medicine frame psychedelic therapy likely won't solve any crises. But, from a *public health* frame, I certainly think they can help a lot.
*Setting aside the understanding of most psychedelic practitioners that recent mania or suicidal ideation, psychosis, and family history of schizophrenia are contraindications to psychedelic therapy.
Time will tell! It does feel as if we are at a bit of a crossroads at the moment. Let’s see how it all pans out.
I agree with most of what you write about psychedelics, but you also write: “until we get some sort of Satanic Cult scare because of allegedly repressed memories.” Not sure what this indicates about your understanding of repressed memories and dissociative amnesia, but if you doubt the existence of dissociative amnesia or the validity of traumatic memory, I suggest you give ‘dissociative amnesia’ a little study. It’s been in the DSM since 1980 and known about since the 1800s. It’s only controversial because it’s the kind of concept that people fight against. (But maybe it’s only the “Satanic Cult” scare you’re referencing. I’ve heard of it but don’t know much about it. Perhaps I’ll look it up.)
I didn't mean to suggest repressed memories are all fake. But I did mean to suggest all the satanic cult nonsense pegged to alleged repressed memories were fake.
Your comment led me to read a few online articles. Very interesting! It turns out there is a Church of Satan. History.com says: "The 1980s Satanic Panic saw Christian fundamentalists push the idea that Satanic cults were systematically abusing children in rituals and committing widespread murder, and successfully convince the general public through sensational news coverage. Christian groups typically misrepresented the Church’s beliefs and practices in order to fabricate a real-world villain behind the conspiracy for the media." A NYTs article, https://www.nytimes.com/2021/03/31/us/satanic-panic.html, describes how, in the original McMartin Preschool case, it was the police who bungled the investigations, fueling the panic.
The placebo problem isn't unsolvable. Just use actually-naive subjects and a better active placebo (something that has the anticipated reality-distorting effects via another mechanism) than the usual choice of a light sedative.
What would that reality-distorting placebo be? A different psychedelic?
I'm not familiar with all the options, but another psychedelic that we have good reason to believe doesn't have psychiatric benefits and doesn't have the same underlying mechanism of action, or a dissociative. At moderate doses I doubt a naive user could guess they are taking psilocybin versus, eg, dextromethorphan, DMT, or even THC. I just don't know if any of these are safe enough for a review board or well characterized enough to differentiate placebo effect from some actual benefit they might have.
Oh, dear ... DMT is something else entity. And the effects are of a much shorter duration. And THC is interesting, but tons of people have taken THC at this point, and know what it feels like. And for many of the relevant indications both THC and DMT are under investigation. Wouldn't reviewers like they just met say "All you've proven is your psychedelic is better than weed and/or DMT?"
Dextromethorphan is an interesting thought, tho. But is it safe enough to use as an alternative to placebo?
Good question that I don’t have the answer to. Maybe something like midazolam? I know that’s been used in trials of ketamine
Wasn’t there a novel approach to studying ketamine with patients under anesthesia?
Yes, yes there was https://www.nature.com/articles/s44220-023-00140-x
https://rationalpsychiatry.substack.com/p/the-powerful-and-the-damned
Definitely an interesting study design, though I don’t think ketamine would be considered a psychedelic by most
I wondered if the same approach could be used for psilocybin.
Just one small point: you write, "you have to question what it would take for an n=15 case series to be published in a leading psychiatric journal, if it didn’t have psilocybin in the title." But: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.19070720
I stand corrected! Have added this to my mistakes, thank you - https://rationalpsychiatry.substack.com/p/mistakes
Great piece. I have higher hope for the rTMS SAINT protocol and would like to see large scale studies asap. What do you think?
https://www.nature.com/articles/s41398-023-02707-9
I don’t know much about it - need to learn more!
Well written and thought out article, thank you for this. As someone experienced in the realm of psychedelics but also with a family member who has CPTSD and autism who suffers from delusional thinking, the thought of her taking psychedelics is terrifying. I’m pretty sure she’d never come back mentally. It’s not for everyone. Many people need more help to be “here” in their body, feeling safe to accept their present reality rather than enter more hallucinogenic states that psychedelics induce.
Thank you for this insightful comment and for sharing your experience. Completely agree that, for certain people, psychedelics should be avoided.
Thanks for this thoughtful essay that balances the hope against the hype! The therapeutic potential of psychedelics is exciting, but implementing it without harming people will require the wisdom of Solomon.
Agreed - and thank you for reading!
I think that finding the set of patients most likely to respond in a positive way to a medicine or procedure has a very long tradition. You may screen out people with a family history of psychosis in trials now, but hope to include them in years to come. And I wonder if there is anyone with severe depression who doesn’t have suicidal ideation. If I wanted to be in a trial, I would lie and say I hadn't considered suicide. Seems to me we shouldn’t ‘pretend’ that we know what and who psychedelics might work for and not work for—and keep up the research. As you say, we're in desperate need of new treatments. (Of course, we should fund inpatient treatment too.)
True! I do wonder whether participants might be less than wholly honest when it comes to meeting other inclusion/exclusion criteria of these studies - eg downplaying previous psychedelic use.
As a person with severe mental illness, I hope to try psychedelics at some point. I've tried around 25 different psychiatric medications and none of them have helped. I have never tried amitriptyline because of my suicidal ideation - our established treatments have contraindications too. I've been in therapy for years and it's helping, slowly. I know we shouldn't believe the hype but isn't there room for hope as well.
Agree we need to have hope and that recovery from severe mental illness is possible for many people.
I personally don’t have hope in psychedelics from conditions like schizophrenia, bipolar disorder, psychotic depression, or personality disorders. I do hope other, better treatments are developed.
Totally agree regarding the psychoses, I think that no one researching psychedelics would think they are safe in people who have a history of psychosis. I think given the history of their use in substance misuse, we should see more trials assessing their benefit in addiction and/or confirming their safety in people with a substance misuse history.
I’m very interested to see if they could be of use in PD - borderline especially. PD is itself hardly a fixed and completely understood concept in psychiatry and is in a state of flux. It could be in a few years viewed as a solely a consequence of developmental trauma. Equally, there is the neurodivergent/social model of disability view, which looks at PD as an expression on the continuum of human experience and could well lead to us starting to view it as something that doesn’t need “curing” but merely help with the distressing consequences.
Anyway, my point is that I wonder if psychedelics could be useful in loosening unhelpful coping strategies that form a core part of the dysfunction in PD - whether from trauma or friction with the social environment. I think given the good evidence for the response of BPD to psychotherapy, there is some hope for psychedelic assisted psychotherapy. Having said that, I imagine the results will be much less dramatic.
Given the FDA’s verdict yesterday, will be interesting to see what happens next with MDMA assisted therapy!
I worry that psychedelics would be destabilising in BPD - particularly with suicidality being so strongly associated.
Though it seems with such a wide variety of disorders undergoing clinical trials perhaps someone is trialling this somewhere!
I heard at a conference a while ago that there was something in the works but I’ve heard nothing since. I agree, risk and suicidality is a major problem. Again goes back to your point of who we are actually treating. The very distressed and uncontained individuals who we see most frequently in services would probably be better served by simple continuity of care in community services by professionals who are experienced and want to work with them, alongside access to psychotherapy in a timely manner. As we know, patients like this are often to risky/unstable for basic DBT-informed work let alone psychedelics. I would very much like the NHS to get waiting lists down for intensive psychotherapies for the vast number of traumatised people we work with.
It will be very interesting to see if this therapy will sit with a psychotherapy service or the affective disorder service. Locally to me the affective disorder team doesn’t have psychology and works on a receptor by receptor basis, and I know they would have little interest in sitting with someone for 4 hours on psilocybin!
I think it comes back to a wider point about psychedelics. They are not a drug in the same way as an SSRI is, because the mechanism of action is precisely to alter perception, and therefore the mindset and setting - I.e. therapeutic frame - is critical to their therapeutic success or harm. They should never be thought about divorced from psychotherapy.
Perhaps MDMA is a good candidate for BPD as it lacks the outright hallucinogenic effects and has a growing evidence base for trauma. This seems partially based on speeding up trust in the therapeutic relationship.
I guess my hope would be it could help with my PTSD symptoms, which I think many people with severe mental illness deal with. I could be wrong, but I don't think that any new treatment options are being explored for one of the diagnoses I have (AvPD). I understand that these drugs aren't really being developed for me, but neither were any of the other treatments I've tried, it seems.