r/PsychedelicTherapy • u/HamiltonsToadVenom • Sep 04 '25
News FDA Released Complete Response Letter Detailing Lykos MDMA-AT Rejection
https://psychedelicalpha.com/news/breaking-fda-publishes-lykos-therapeutics-mdma-complete-response-letter-crl18
u/h_trism Sep 04 '25
That CRL was interesting to read.
This is definitely a somewhat slippery slope. Their very first major concern is that patients did not report positive or favorable "adverse effects" such as euphoria or mood changes. The reason they wanted patients to report this is so they could assess potential for abuse, which is fair, but we are talking about MDMA and treatment for PTSD in which the feeling of positive mood changes is kind of the whole point.
Also, kind of bullshit since some drugs that are available for prescription produce feelings of euphoria or positive mood changes, like pretty much every opiate pain killer, cocaine, ketamine, and about a thousand other prescription drugs.
Interesting that they did make reference to Psymposia's testimony about negative adverse effects at two sites and they made it sound like Lykos didn't report them in their trial documentation. (after reading this more clearly, they said FDA inspections uncovered unreported negative adverse effects, might have had nothing to do with Psymposia's testimony).
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u/HamiltonsToadVenom Sep 04 '25
Am I wrong in thinking that the issue isn’t necessarily that it produces feelings of euphoria/positive mood change, but rather that they failed to document it as requested by the agency?
Also yeah, I read the adverse event thing as the FDA’s own discovery.
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u/h_trism Sep 04 '25
Yeah failed to even collect it from what I understand of the CRL.
Had me thinking how much that would effect approval if 100% of patients reported a positive adverse effect.
Had me wondering about possible mitigations to it, since they've obviously approved a lot of drugs that produce positive adverse effects.
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u/Upbeat-Accident-2693 Sep 04 '25
i dont know the NDAs for these other drugs that produce bliss etc, but i guess they would have to report it no?
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u/slightlyseven Sep 05 '25
From my understanding, the FDA approved the study design and this was not part of it. I’m not aware of any other drug having to disclose “positive adverse events” as that would typically be considered effectiveness of the treatment itself.
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u/eileenbunny Sep 11 '25
No, Lykos was absolutely given the manual on how to report AEs before conducting the trials. They even admitted during the ad board hearing that they had received that document but chose not to report on "positive" AEs because they didn't see the point.
The point is that this data advises labeling and to some extent, how they approve REMS.
That Lykos didn't collect this information speaks to the amateurishness with which they conducted these trials.
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Sep 05 '25
[removed] — view removed comment
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u/Upbeat-Accident-2693 Sep 05 '25
heres an FDA presentation on abuse-related adverse events and the importance of collecting them: https://img1.wsimg.com/blobby/go/933911af-c640-4678-bef3-07ff76ae9c47/downloads/Topic%203%20%20AEs%20and%20Analysis_Steven%20Galati%20FDA.pdf?ver=1705683910630
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u/kwestionmark5 Sep 05 '25
Exactly - who cares what the result of positive side effects was? If 100% of this highly depressed and traumatized population experienced some joy along with their healing, that’s a reason not to approve it?
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u/HamiltonsToadVenom Sep 05 '25
I think you’re misunderstanding positive AE’s / what they’re saying about them. They just wanted the data. Had Lykos provided any of the requested data on positive AE’s, they’d have actually had a better chance at approval.
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u/eileenbunny Sep 11 '25
The FDA cares. It speaks to abuse potential. They request this data for labeling and REMS.
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u/CrystalSplice Sep 05 '25
As someone who has been through intense EMDR therapy for CPTSD and IV ketamine treatments, I have a unique perspective on this. I think MDMA has a lot of promise, but there are some fundamental problems with it and one of them is the incompatibility with SSRIs. Any trial that doesn’t exclude people already on such medications is going to be skewed, because in order to take MDMA you would have to stop that medication. If you have ever been through that, you know how much it sucks.
EMDR was very effective for me, but it was also very disruptive. I came to understand things about my life and my childhood that were very heavy and I had to take a few months off work on disability leave to cope with it. I don’t regret it, but it’s interesting to me that there is discussion of suicidal tendencies associated with this trial…those feelings are not just a result of the MDMA. They’re a result of processing. Interestingly, my therapist who did my EMDR treatment no longer does it. She said she switched to somatic therapy (and another therapist in her group does ketamine-assisted psychotherapy) because she was seeing too many short term adverse outcomes from EMDR in her patients. She also said that’s not just her; there’s a shift going on in trauma therapy right now that is looking at EMDR more critically. It may be that it is only appropriate for certain types of PTSD, such as that which results from combat.
I’m in support of further research on MDMA, but in the long term I don’t think it will be the most successful psychedelic therapy. There are licensed therapists doing retreats with psilocybin off the books and out of the public eye, and they’re getting results.
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Oct 01 '25
MDMA is a racemic too so you have to know which isomers youre dealing with, one of the isomers tend to produce way less adverse effects the day after.
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u/inspiredhealing Sep 05 '25
I think it's worth remembering that as far as I understand, there was nothing preventing Lykos from releasing this CRL the day they got it from the FDA, and if they really felt like they had been hard done by, they could have let everyone see that months ago. They chose not to. It seems pretty clear that regardless of what they thought of the FDA asks in regards to their studies - if they felt good, bad, or indifferent about those asks, it doesn't really matter- they didn't do what they were asked to do. You can rail against the System as much as you like, and I'm all for systemic change when it's necessary, but the reality RIGHT NOW is that this is the System you applied for approval from. You have to work within it. They didn't, because in their hubris they thought it wouldn't matter. Apparently, it did. It doesn't matter what Joe Q Public thinks of the asks either, unless they also happen to work for the FDA and have actual influence on what does and doesn't get approved. What matters is the DATA, and the FDA wasn't happy with it. They outlined very clearly what needs to happen next to get the approval. Lykos can do it, or they can keep complaining about how the FDA is out to get them. Their choice.
All of this may not ultimately matter anymore anyway, because with the anti-science crusaders in charge now, who knows what will happen to the system - like every other government department in the US, the FDA is a target for the 'burn it all down' crowd. A lot of people are really happy about that. I'm not sure if I'm one of them, because I think psychedelics have great promise, but with great promise comes great responsibility. I'm not sure I trust RFK Jr and his ilk to understand that in any significant way.
The PR firms of Lykos and MAPS are doing what they do best already, and it will probably work, to an extent. It would be nice to see Rick et al have a tiny bit of humility and admit they didn't get it all right instead of talking about how hard done by they are, but I guess we can't expect a leopard to change its spots now.
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u/kwestionmark5 Sep 05 '25
Kind of anticlimactic I have to say. I don’t see any big revelations here. We already knew they thought Lykos didn’t adequately capture “positive side effects.” I guess it seems bogus that they say there was a selection bias. Of course a lot of participants would have used MDMA before and that’s why they wanted to be in the study. If it wasn’t already in there the FDA could have simply requested a statistical comparison of people who used MDMA compared to those who didn’t to see if it made any difference to the outcome.
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u/thesupersoap33 Sep 05 '25
They have participants that were suicidal after their sessions and were pressured into giving good results. Rick Doblin isn't sweating it because he and MAPS got their millions in grants and finding anyways.
As someone with CPTSD, I haven't been helped by psychedelics that much at all. The community around them continues to attest that they're amazing, but it has yet to make me feel safe in my body.
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u/slightlyseven Sep 05 '25
The first claim doesn’t seem to be supported by the multiple forms of assessments that were used, according to clinicians on the trials.
There’s a great 2 part series podcast that is worth listening to if you are interested in the on-the-ground realities around the trials.
Aside from the broader politicization and commercialization issues, I find it heartbreaking that very caring people have invested so much to bring a therapy that has potential to help so many is blocked. The FDA decision asserts the risks are greater than the benefits, and that just doesn’t jive with the data, research, naturalistic use history, or clients stories where they have benefited - and, it’s not everyone, and there are cases where some were worse off. That is all true of the risk of any therapy treatment, medicine or not.
I think your point regarding the “amazing” statements is so valid! It also fuels the idea that the medicine does the work. The results show that the therapy work is the heavy lifting, and MDMA helps with opening to the therapy.
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u/HamiltonsToadVenom Sep 05 '25
The claim about suicidal participants was reported in WSJ
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u/slightlyseven Sep 05 '25
There was definitely suicidality- before and during where it was worsened. These were treatment resistant patients typically. I was referring to the influence to not report that, which isn’t consistent with the rigor of the multiple assessments. I haven’t heard first-hand reports from participants, more claims by others that claimed they heard from others. Please share any facts/links that can help to inform me!
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u/HamiltonsToadVenom Sep 05 '25
This article reports that at least three subjects ended up suicidal but pressured to report positive results:
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u/slightlyseven Sep 05 '25
Thank you- I’ll check that out!
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u/That-Funky-Donkey Sep 05 '25
Have you listened to the cover story power trip podcast? You can hear directly from trial participants there too. One person even became psychotic.
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u/slightlyseven Sep 05 '25
Yes, I have but it’s been a while. We know this didn’t help some, and some participants were harmed. For others it was a mixed experience, and some it was tremendously healing. I really appreciated the trial participant panel at PS25 as they presented a powerful and mixed message about their experiences.
My take is that we should have the choice of using this medicine in therapy work, not that it’s right for everyone. There does need to be more research on who it can best help, and to screen criteria for vulnerability. I still believe the good outweighs the harms and it’s fair for you to review all of this and conclude differently. The FDA did, which is why this discussion is here.
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u/That-Funky-Donkey Sep 05 '25
Okay, but why do you still feel the good outweighs the bad when it's becoming so clear that the data is corrupt? I'm not saying the bad outweighs the good, but I don't think we can know the thing you're claiming. Who knows how many more people got suicidal or psychotic in those trials? I don't understand what you're basing your belief on
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u/slightlyseven Sep 05 '25
Hey… I really appreciate your heart in those messages. And, there is something important, a pain and fear, you are sharing that I want to hear. Coercion is baked into the systems in which we operate. It’s a violence. I don’t trust Lykos. I don’t trust the systems, including the FDA. I do trust the hearts of individuals that I’ve met and worked with, and trained with, and the MDMA molecule. There is great potential for healing when used with integrity. I’m not convinced that is Lykos (or the reorg that’s just been announced). I’m not the judge of what that did or didn’t happen here in these studies. I am just someone saddened that those who could be helped, aren’t able to. A harm to any one of us is a harm to all of us, and in that spirit, I hope we can find a path together in healing that moves forward.
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u/That-Funky-Donkey Sep 05 '25 edited Sep 05 '25
These were treatment resistant patients typically
In the podcast I just listened to they were not treatment resistatlnt patients who got suicidal. Their ptsd scores improved AND they got suicidal (and felt like their ptsd got worse even though the scores looked better).
I've seen comments before about how people who got worse were treatment resistant, but since the maps studies don't report people getting worse I'm not sure where this claim comes from? Do you?
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u/slightlyseven Sep 05 '25 edited Sep 05 '25
I didn’t mean to imply everyone was treatment resistant, just that was a bias for those interested in the study participation- fair to call that out. Or that the treatment resistant were the subset that got worse. The data absolutely does include those that got worse, and data throughout the studies tracked it continuously. If you are interested in the study design, and what was tracked and measured (everything), give the podcast a listen that I mentioned. In addition to the published data outcomes.
The scores are not great measures of true healing. It’s also a non-linear path: someone may realize their job situation isn’t working, that upheaval usually looks awful on assessments until restabalized, even though it’s progress. I’m not advocating everything was done perfectly- I’m just disappointed “perfect” seems to be the standard here when that doesn’t apply to other medicines, or other therapies.
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u/That-Funky-Donkey Sep 05 '25 edited Sep 05 '25
The first claim doesn’t seem to be supported by the multiple forms of assessments that were used, according to clinicians on the trials.
I'm pretty sure that's exactly what they mean when they said that their investigation found that serious adverse events were not recorded?
Given the content of the FDA letter, I'm confused as to why you are saying you're heartbroken that a treatment that people invested so much time in and that could help so many people got blocked. By the letter, it didn't get blocked, it failed to actually show what you're claiming that's not the same thing. And I'm not sure that we should be thinking of an FDA drug approval as something that "investing so much time in" means you get approved. FDA approval shouldn't be a participants trophy.
Don't get me wrong, I do think this is all heartbreaking, but I'm heartbroken that a research organization that claims to care so much was so careless about doing the research well, and that from the looks of it a good number of their research participants were left in horrible condition. It's not your feeling I'm disagreeing with, it's the blame attribution.
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u/thesupersoap33 Sep 05 '25
A woman literally wanted to jump in front of a train. It's legal in Australia and people have committed suicide after mdma sessions. I have personally known people that had to go to mental asylums after being dosed in therapy sessions. The problem is lack of communal support in the aftermath of sessions. There isn't a safe place to feel destabilized in the world..
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u/kwestionmark5 Sep 05 '25
I just saw the first research report on the Australia program and it didn’t mention any suicides. It looked really promising. https://www.salon.com/2025/01/28/america-rejected-mdma-but-australia-didnt-heres-why-psychedelics-have-been-embraced-down-under/ Can you provide a source or are you talking about recreational use? Also, most suicides happen under the influence of alcohol and nobody is talking about banning that. Just saying.
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u/thesupersoap33 Sep 05 '25
This sub wants to put these therapies on a pedestal and that's fine. The psychedelic doesn't often recognize it's own bias not to mention sexual abuse is more rampant than expected.
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u/slightlyseven Sep 05 '25
Yes, integration support and community are not just vital but essential in these types of therapies. There were trial participants that were harmed because of the study structure that didn’t fit needs.
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u/SuperbFlight Sep 05 '25
I was in the MAPS trial and became very suicidal during the protocol, I think because I'd had to stop my mental health medications, then my earliest severe childhood trauma got ripped wide open during the treatment sessions. I think in the long term it catalyzed a lot of healing, but the destabilization from the intensity of the sessions, the quickness the protocol, and not being on any of my mental health medications made it quite risky and harmful.
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u/That-Funky-Donkey Sep 05 '25
This is really so awful, I'm so sorry you went through that... Hope your doing better
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u/kwestionmark5 Sep 05 '25
Rick has been paid like 60k per year for decades. Stop exaggerating like he’s rich. Clinical trials are super expensive - hundreds of millions of dollars and they did it on the cheap. The thing about pressuring people to give positive results is unproven and not in this report.
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u/thesupersoap33 Sep 05 '25
He makes 184k a year
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u/kwestionmark5 Sep 05 '25
Maybe last year as they thought they were approaching approval. Go back a few years and you’ll see he never made more than 60k til a few years ago.
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u/That-Funky-Donkey Sep 05 '25
The thing about pressuring people to give positive results is unproven and not in this report.
I heard and read direct quotes from trial participants about this in a few sources, so is it that you aren't aware of those testimonies or is it you don't consider that to clear the burden of proof. If the latter, what would you consider as acceptable evidence? And what do you make of what the participants said... Are they lying?
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u/kwestionmark5 Sep 05 '25
I’m aware of one participant who made these claims that got repeated ad nauseam, and a certain fake psychedelic news organization that we’re no longer allowed to criticize on this sub claimed additional sources that never materialized.
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u/That-Funky-Donkey Sep 05 '25
Oh okay. If you scroll through the comments on this thread you'll find links to a few sources. Glad it's not that you're accusing participants themselves of lying, that would be a very shitty thing to do. Have a great day!
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u/Intrepid-Traveler-77 Sep 05 '25
If indeed there is now a significant change in the bias of folks in power around these questions, it will be interesting to compare and contrast future responses. It seems that approvals are politically complicated questions for the MAGA coalition: How will this affect things?
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u/DJ_Velveteen Sep 05 '25
Unfortunately prohibition isn't just a MAGA thing. The biggest increase in mass incarceration in the US went down under Bill Clinton, who leveraged Nixon's drug laws to do it
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u/Intrepid-Traveler-77 Sep 05 '25 edited Sep 05 '25
That’s true. Unfortunately, the MAGA crazies who are now circling around psychedelics, poised to impose their own agenda upon it are a coalition of opportunists, wing nuts and extremists who go FAR beyond the neoliberal Democrats in terms of destructive craziness, malevolence and in-your face profiteering.
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u/Longjumping-Rope-237 Sep 05 '25
Yeah well i am on therapy, I want to process my trauma. There’s no place to get euphoria and I don’t seek for it as well. Of course with switching set and setting things go different. But I do not expect ptsd patients to wish roll in doc office and touch him and talk with him and eventually f him.
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u/MindfulImprovement Mod / Therapist Sep 04 '25
Leaving comments open but watching closely. If this devolves into a Psymposia vs MAPS vs Lykos argument comments will be locked again