Is Psychedelic Therapy Ready for FDA Approval?

Added: 2026-05-30

[00:00:00]The secret source of this treatment is in that combination of a drug action that opens up the mind, makes it more plastic. By simple logic, you have a plastic state. You got to do the right thing with that. You know, it's more shapable. So, shape it right.

[00:00:15]>> I am here with Robin Carheart Harris.

[00:00:17]Robin, thanks for joining me again.

[00:00:19]>> Thanks for having me on.

[00:00:20]>> So, um, remind people where you are, um, doing your research on psychedelics.

[00:00:26]>> I'm at the University of California, San Francisco. I have my lab there. And >> and what's the focus of your research at this point?

[00:00:33]>> It's consciousness science and how it's encoded in brain activity. That's a big part of it. How can we use psychedelics to try and tackle that question? Um and it translates into therapeutic applications of psychedelics as well. I also look at harms. Um yeah, so try and cover the much of the sort of full gamut of psychedelic science and research.

[00:00:58]>> Yeah. Well, I want to get into all of that. Um I guess big picture to start.

[00:01:04]How what are your impressions of of the state of the field at this point? Where are we with um research on psychedelics and therapeutic potential and safety?

[00:01:15]And I mean, how vulnerable are we to um having the the rug pulled out from under all of this by some new new regime of um there being a war on drugs? I mean, what's your what's your perception of the field high level?

[00:01:30]>> Well, it's it's rich and complex. Uh we rode a wave through a kind of peak of a hype cycle perhaps after Michael Polland's bestseller, How to Change Your Mind, published in 2018. And yeah, there was a a period of some correction, you might say. There was a bit of a push back on this space for different reasons. And I think there was a market correction as well. Some of the psychedelic medicine companies had gone up to a pretty high valuation, a couple of billion dollars I think one of them.

[00:02:03]And they're certainly not there now. So, so something's happened. Uh we had Lyos close to seemingly close to getting FDA approval for MDMA therapy for post-traumatic stress disorder, but that was denied by the regulators by the FDA.

[00:02:21]Um and so that put a another dent in the road.

[00:02:25]>> Um I do think that there are reasons to be optimistic though. If if you look at the research, there's a heck of a lot of research. I mean there's more than ever uh the publication you know rate and volume is is higher than ever year on year and you know more quality trials bigger trials so I I still feel that yeah we're knocking on the door if if FDA approval is the is the you know prime milestone I still think that that's achievable and probably quite close.

[00:03:01]>> Mhm. Yeah. So, what's the um what's your sense of all of the research to date that we're relying on to um kind of organize our intuitions about the therapeutic value of psychedelics? I mean, much of it I think is probably underpowered and and many things probably haven't been replicated.

[00:03:24]There's just, you know, widespread in in science now. there's a a greater sensitivity to the the possibility that results will not replicate. There's obviously replication crisis uh so so branded in uh the social sciences and psychology. What's your what's your state of just the the quality? What's your sense of the quality of the the evidence uh that we're hurling at uh the FDA or likely to hurl in the near future so as to argue for the therapeutic value and you know legalization? Well, there's a lot of small studies published, you know, a few of them have come from uh myself and my colleagues and what's happened historically is that, you know, this space has been up against it. So, we've done everything that we can to raise money and much of that's come from philanthropy and typically, you know, running an in investigator study, so not a uh industry sponsored study or trial.

[00:04:26]uh you've got a limited budget and you set something up and it's 20 patients and you kind of sew the seed and so that's what we did uh back in 2016 with psilocybin therapy for treatment resistant depression. Um so most of the trials have in this modern era have been published in the last 20 years really.

[00:04:52]The first clinical trial in the clinical population was 2006 that was Franchesco Moreno looking at psilocybin for obsessive compulsive disorder. Mhm.

[00:05:04]>> And uh yeah, so uh there are probably now I would estimate a couple of dozen small trials and a couple of biggies.

[00:05:15]You know, we've got um uh the phase 2b work of compass pathways and we're also hearing the topline findings from their phase three works. So that takes us into the hundreds uh in a a single trial albeit multi-sight.

[00:05:34]>> Which are these for psilocybin or >> this is psilocybin therapy for treatment resistant depression >> and that's the most advanced that's the closest to um a breakthrough I would say with the regulators.

[00:05:48]Um, yeah, they're talking about this rolling submission where, you know, not all of the data necessarily has to be submitted for a decision to come. On the face of it, that sounds pretty optimistic.

[00:06:00]>> Um, but then I'm hearing mixed messages as well.

[00:06:04]>> What were the implications and consequences of um the FDA denial of the LICOS maps MDMA uh petition?

[00:06:16]>> Yeah. Um I mean it did cause this market correction. So you know companies were were their valuation dropped quite dramatically. Um and I think you know had that got through that would have caused a general uplift you know rising tide for everyone um in this space. Yeah. So it it's >> were the reasons for it uh intelligible and and justifiable or >> some of them and some of them weren't you know so um some of the data quality in terms of adverse events weren't fully reported apparently I think you know Lyos was the commercial face of MAPS >> uh and MAPS multi-disciplinary association of psychedelic studies headed up by Rick Dolblin uh and MAPS is in a sense a advocacy group uh for psychedelics generally. Um like Rick brings this incredible charisma um but it's not fundamentally I think it's fair to say an academic body say annex to an obvious academic institution is it's not really pure scientists sort of running things. Uh, and I I think that makes it a very easy target for this accusation of of bias. I mean, the bias is pretty >> pretty overt really.

[00:07:40]>> Yeah.

[00:07:41]>> Um, and so they were very vulnerable in in that regard. And so some of the data quality issues in terms of all AES being reported, I can sort of see how that could happen. and some of the some of the sites, you know, they weren't traditional clinical research uh um sites uh some of the dosings happening in people's, you know, homes. These are clinicians, but still, um it wasn't very much wasn't the traditional model. Um and so I can see how it went that way. I think the FDA made some errors in terms of their misunderstanding of psychedelic medicine and and therapy. Ultimately, they're a uh regulatory body that approved drugs, drugs as medicines.

[00:08:32]>> And um so they want to be able to look at the profile of a drug and as uh this treatment was presented to them, it was a combination treatment. you know, even in the framing of it, I think it was psychedelic assisted therapy or MDMA assisted therapy for post-traumatic stress disorder. So that's leaning emphasis on the therapy. And the FDA say, well, this isn't our remit. You know, we're not a body to approve psychotherapy, so this is confusing to us. And I think that tripped things up quite considerably, you know, so compass pathways with psilocybin are playing it very differently.

[00:09:13]How do how do you think about the promise of psychedelics? Is it inextricably bound up with the role of a therapist or a the some sort of therapeutic context or are you do you think the compounds and their utility are totally divorcable from context in that way?

[00:09:32]>> Certainly not. Um you know I've I've written a paper called psychedelics and the essential importance of context. So you know I'm very um out there on this perspective that I do see it as fundamentally a combination treatment.

[00:09:48]So you know maps like course how they presented it was right. It was transparent and it's in my view the reality of this treatment. It's the secret source of this treatment is in that in that combination of a drug action that opens up the mind makes it more uh plastic and then you um you know by simple logic you have a plastic state you got to do the right thing with that you know it's more shapable so shape it right um and so uh that's where the context really really matters and the the context we sometimes call it set and setting. Set being the mindset that you bring in in a sense the psychology that you bring in. Yes, expectations but a lot more than that.

[00:10:39]Um and the setting is the immediate environment for the experience. So these are just two ways to split up I suppose factors that contribute to context and that context really mattering with psychedelics on board. That's a strong assumption that we hold in this space.

[00:10:57]It's actually an assumption that I'm testing right now in my lab. Controlling context as a variable as a factor.

[00:11:05]>> What what are you controlling with respect to context? Are you talking about therapist versus no therapist or or variables with respect to set and setting? What what are you controlling?

[00:11:16]So it is more really this what the staff do, the quality of their preparation ahead of a dosing session, the quality of the way they hold the space and provide compassionate support if uh needed during a dosing session because the support is typically quite hands-off.

[00:11:40]>> Uh it's quite indirect. um it's more like a holding rather than something directive. There's there's often uh quite little talking going on. So it's not traditional psychotherapy. It's not traditional >> talking therapy in the session itself but it is in the prep and it is in what we call the integration which is the therapy the psychological support that comes after the dosing session. might come the next day, it might come the next week, you know, plus maybe one or two sessions on top of that uh is how we tend to do it in the field. So we we do control that quality of psychological support both its amount and its quality and we have a protocol to follow for that. We control music listening as a variable. We either have it on or off. uh with colleagues we've referred to music as a hidden therapist.

[00:12:40]>> Mhm.

[00:12:40]>> Because the sessions are so nondirective.

[00:12:44]You ask the question, well, is there any nudging, any kind of coaxing going on here?

[00:12:49]>> Yeah. No, the music the music can be quite an overwhelming experience. Yeah.

[00:12:53]>> Can't it? And and it gets enhanced in its emotionally uh evocative uh Yeah. properties.

[00:13:03]um and we control um and manipulate the quality of the aesthetics. So in what we call this enriched condition, we have an enriched condition with all these psychedelic therapy elements included and we have an unenriched condition with them stripped out.

[00:13:20]>> So there's no music. the the sessions are staffed but really for basic safety monitoring, not for any kind of active uh emotional support unless there's an emergency. I mean, we're guided by do no harm, of course. Um uh and uh yeah, we control the aesthetic. So, in the enriched there's lovely glowing lighting and printed screens of beautiful nature scenes. And then in the unenriched, it's a standard consulting room in a clinical research unit.

[00:13:53]>> Yeah. All of this suggests that there's um a fair amount to get right or wrong with respect to how one promotes people into the role of being a therapist.

[00:14:05]Right. So, um I'm wondering about just kind of quality control there and screening and supervision and training.

[00:14:12]And I'm thinking of one story I heard of a um someone who I think was in a group setting. I don't even know what the compound was. May might have been psilocybin. It might have been Iwasa.

[00:14:23]But uh some somebody in the setting was feeling like they were remembering uh you know childhood sexual abuse. I think some some trauma from childhood that had not been conscious prior to taking the drug. But they were also uncertain as to whether it was a memory or whether they were just imagining it. And the therapist, you know, to to my ear who was um in charge at that point came in uh uh it was it was a heavily enriched uh uh context, but you might think it was enriched by this this therapist's, you know, dogmatism or delusion. um because they seem to be coming at at this with a a very strong sense of uh you know recovered memory being a you know very much a real thing and I believe they told this uh subject that you know the body never lies or the body never forgets or something something like that. So and this was very much the framing that that got um uh put forward and I and and seemed seemed to decisively shaped this person's experience. This person came away thinking okay they have recovered memories of childhood sexual abuse uh with the aid of this compound but their initial experience was was much more equivocal than that. I mean they were uncertain as to whether this was a memory or they were imagining it and they were then in the presence of a therapist who had very strong ideas about what was likely or almost certain to be true. All of that worries me given what um I believe about you know what we know about the certainly the the recovered memory under hypnosis uh legacy. I mean I you know I I'm fairly aware of that phenomenon and of how um you know how so many uh witnesses were led to believe things that in many cases almost certainly didn't happen. What's your what are your thoughts about quality control with respect to therapists and and just how we can build a culture that that that does no harm while giving people the support that they need?

[00:16:30]>> Yeah, it's a biggie. It's certainly a biggie. Um, so not knowing the specifics of that case, but but responding to how you relay it, it sounds like bad practice uh in terms of a therapist coming in and transferring in a sense their assumptions, their beliefs, their perspective onto, you know, the tender opened heart >> of a vulnerable uh individual.

[00:16:57]uh cases of alleged um uh recovered memory in this space are prevalent. Uh it's happened in our trials. It's happened in other major sites. Hopkins, I know they've had this.

[00:17:15]>> Um >> but let me just be clear on one thing lest I be misunderstood. I don't think it's this is this never happens or is never in fact veritical, right? I think it's I think it's possible to remember something for the first time that you experienced in in you know early childhood and and I mean that doesn't I'm not fundamentally skeptical about every story but I just know that this this mechanism or imagine mechanism has been abused by certainly by the the the hypnosis community back in the day and I I I worry that psychedelics could be hypnosis on steroids. I worry too. Um, and I think there's an angle here from uh, you know, legal professionals seeing an opportunity.

[00:17:58]>> Um, and uh, I I think that's a problem uh, future problem that we'll we'll clash into at some point. Um, but yes, it comes up and I I treat it in that way. uh you know we we go case by case and um we've had to manage patients uncertain about a recovered memory. Um I remember one in particular he's spoken openly about it um where he was confused about whether his one of his parents had had tried to smother him and kill him with a pillow. Um and yeah, we had to hold that very lightly uh in terms of its veriticality or otherwise. And that was hard for him. You know, he wanted some kind of closure there. He had classic ambivalence about this parental figure.

[00:18:54]>> Uh projected for a while that they were all good and then had this um jarring challenge to that come up as a apparent or possible uh recovered memory. And so what happened there is that there was extended therapy for that case. When you look at his data, actually sticks out like a sore thumb in our trial. It was our first psilocybin therapy for treatment resistant depression trial.

[00:19:21]And you can see there's a clinically meaningful increase in symptom severity.

[00:19:26]He's the only one who showed that >> uh in a couple in two or 3 weeks after the treatment. So we had to manage this um turbulence that he was going through where he was uncertain as to whether this happened or not. And we had to be very very careful and and professional not to either endorse or deny but rather just listen compassionately.

[00:19:49]And uh you know so if it if it's there as something imagined that's something to work with therapeutically. Uh if it really happened that's something to work with therapeutically. But but let's not make a call on its veriticality. I I will add though that there was another case where the abuse was known ahead of time that had actually been a >> a a case against this again a a parental figure, a father and it was sexual abuse and he was convicted. And so this was the trauma that this patient brought in >> uh to the session, treatment resistant depression again. And um so we didn't certainly didn't guide him there at all.

[00:20:34]Um as I said the therapy and the sessions is very hands-off. It's not directive in terms of talking at all.

[00:20:42]But he went there and uh he expressed to his therapist that I can see um my father abusing me. And so there the approach the response from the the therapist and one in particular was to gently suggest the going towards okay let's stay with that a while if you can >> is this on psilocybin or MDM >> solocybin high dos psilocybin >> very very painful for for him uh for the patient um but he did and and the abuser um was manifest as a monster with a gun.

[00:21:27]You know, that might be seen as symbolic and uh and incredibly menacing, terrifying.

[00:21:34]And then staying with this vision, um with the support, it it morphed and it morphed into something pathetic, almost pitiful.

[00:21:47]And there was almost some forgiveness and I'm sort of echoing the p the patient's words here. Um forgiveness might be you know too too much to say that but an understanding of sort of the pathetic you know weak nature of of the abuser and how they could have done something like this. And it was a breakthrough at the time. There was a lot of tears. there were there were you know sort of wet eyes with everyone in the room really and uh yeah it it was considered very beneficial to the patient to go through that.

[00:22:28]>> Yeah. I mean, so you're you're painting a picture of the obviously the other side of uh this therapy question, which is I mean, it has to be tremendously rewarding to be a therapist under these conditions where you're seeing people basically do you know a decade's worth of of psychological work in over the course of hours. I mean it's just this is this is not the normal experience of talk therapy where you can have a conversation with someone for 20 years and basically you're talking to the same person you did 20 years later. Um it has to be very rewarding in in success. What what do we know about people for whom psychedelics hold obvious therapeutic promise and people who should be uh who who should stay away? I mean, what are the exclusion criteria and and contraindications you're you're working with in research?

[00:23:22]And what do you think is just a ground truth in so far as we understand it for uh people out there in the public who probably shouldn't take any of these drugs? You might want to differentiate the the the various classes of drugs or specific compounds in with respect to risk, but what's your view of of who benefits and who who uh is cing obvious harm?

[00:23:47]>> Sure. Yeah. Well, I can respond to that empirically. Um, you know, while it's true that most of the studies that have been done are small, there are a lot of studies now and I I didn't speak to the reliability in terms of the clinical benefits because the results are very reliable. They've been very well replicated. Uh, positive results almost without exception. I think there was one uh negative result trial uh and you know again this would be in a couple dozen or close to that now um and they dosed the individual in a in a MR scanner and there was no psychological support. So for me that's quite telling very telling so very consistent positive results.

[00:24:34]>> Just to explain what why you would expect that I mean an MR scanner in terms of setting is is aesthetically pretty awful setting. I mean it's it's if you're claustrophobic at all you're going to freak out and it's also loud and >> uh you can't move in fact because they can't get data on someone who's moving.

[00:24:52]So it's just there are a lot of people who are not on drugs uh who can't take who can't get scanned in uh an MRI machine and you many people who can only if they take uh you know benzoazipam to to lower their anxiety you know so >> and then that's a big compound of course isn't it? Yeah. So, uh, yeah, it's not the best set in setting. It can be tolerated. I've done a lot of work putting people in scanners and giving them high doses of psychedelics.

[00:25:19]>> Um, but there's a way to do it. And, you know, it's not an optimal setting setting. It's not an optimal context.

[00:25:25]It's not obviously therapeutically supportive. There's no music listening that I'm aware of that they experienced.

[00:25:32]Um, so yeah, it's very very noisy, claustrophobic, and all the things you say. So, you know, looking at at the results at that high level, all of these depression trials, now there's a couple of um eating disorder trials, we've got one coming out very soon looking at psilocybin therapy for anorexia that uh reports positive results. Uh obsessive compulsive disorder. If we're including MDMA, the PTSD results are very promising.

[00:26:00]>> Very large positive effect sizes there.

[00:26:04]Um there are anxiety disorders. There's a phase three trial LSD therapy for general anxiety disorder. Uh there are addiction disorders, alcohol use disorder, um opiate use disorder, um cocaine, um out of Alabama. There's there's a lot um and I'll be missing things. And there's also the the weight of evidence in favor of betterment of you know well people or the worried well if you want so improvements in in well-being life satisfaction sense of meaning in life um flourishing uh these positive psychology domains um that's very reliable as well and also in a mixed methods approach what do I mean by that um so surveying people taking psych psych Psychedelics in the wild, as we say, meaning in every kind of context. They could be at Burning Man. They could be in their bedroom. They could have gone off to Oregon to have legal adult supervised um psilocybin experiences. We've looked at that, too. But, you know, across those different contexts when we pull the data, very positive results there.

[00:27:22]So, yeah. So most people is is the short answer seem to benefit but not everyone.

[00:27:29]So then the critical question is where is this bottom margin you know who falls into that? Who's at special risk? Who's at risk of being at you know in that outlier bracket where they don't improve and if if anything they get worse. where could this be iatrogenic, you know, as as they say, meaning it actually worsens >> uh your your health. Um, and there we have found empirically that people with a history of a diagnosis, I'm being very concrete here, but history of a diagnosis of a personality disorder who um and and what is that? Well, it's an emotional volatility.

[00:28:15]Um it can come in different forms but it can be a sort of um histrionic character presentation very volatile very splitty as we would say in psychology meaning jumping from positive projection everything is good or this person is all good entirely flawless to this one is all bad and entirely malevolent you know quite irrational but but people do that they make the world black and white and that kind of psychological volatility is a risk factor. We actually found that people with that history were four times more likely to fall into a bottom margin in our grouped data. So they were the worst cases. Um and uh another bit of detail that that group actually did okay numerically.

[00:29:09]um a a very slight improvement in well-being in in the short period after the experience, but then they fell off a cliff, so to speak. Then they further out they they showed a clinically meaningful um worsening in their in their mental health.

[00:29:27]>> And these were individuals taking psychedelics in the wild. So this wasn't in a control trial, right?

[00:29:33]>> This is sampling people taking yeah psychedelics in any kind of context. In the control trials, we actually screen those individuals out. So, this field could be accused, I think, fairly for cherrypicking uh the you know, a more more resilient populations.

[00:29:53]>> Um so, we we screen out people with a history of psychotic illness. In that same study, people with a history of say schizophrenia, they were twice as likely to fall into that bottom margin than everyone else. Um so personality disorder which is quite close to psychosis is sometimes called borderline personality disorder and that borderline means sort of borderline psychotic some some divorcement from reality um uh close to to being you know diagnosed psychotic. M >> um so that's that's the vulnerability space. Um and that's where we have to be especially careful and we are in the trials but by doing that we've arguably and I think fairly cherrypicked this this sample and um of the more resilient types. It's funny it's not funny but it's sort of ironic to say that about something like depression. Um but it's a certain kind of depression that doesn't have say psychotic features or features of of personality disorder this special volatility. Would you say that the same contraindications apply to for MDMA or is is that not a an issue like the a propensity toward um you know psychosis or you know something like borderline or or any of the other clinical conditions or risks you're talking about having a first order relative with with one of these conditions. Um, do you think MDMMA poses similar or or any uh risk?

[00:31:33]>> I think it poses some risk. Um, everything does. Um, but uh maybe it's more resilient to context MDMA somewhat.

[00:31:45]Um, it's less of a heaven and hell that you get with the classic psychedelics.

[00:31:50]Um, LSD, psilocybin, IASA, DMT. Um, you know, you can take MDMA at a at a rave and have a very good time quite reliably.

[00:32:00]>> You take LSD and it's much more unpredictable.

[00:32:04]>> I mean, there doesn't seem to be a distortion of cognition and perception in the same way with with >> it's subtle. Yeah. subtle um shift in perception, maybe a softening, maybe a softening of of ego, you might say, whereas the classic psychedelics are called ego dissolvers or disintegrators.

[00:32:25]>> Um yeah, people like to say that MDMA is a heart opener rather than a head opener.

[00:32:31]>> Um so it promotes relational uh exchange uh you know, social exchange. uh it's easier to open up with people. Uh you can talk more easily on MDMA versus a classic psychedelic like LSD. So you can do some somewhat conventional talk therapy improvements in in well-being, life satisfaction, sense of meaning in life. I'm worthless.

[00:32:59]Life is pointless. It's all pointless.

[00:33:01]I'm more valuable in the world if I'm skinny. And psychedelics seem to be like a heat-seeking missile for that kind of self-generated BS as I call it.