Lykos Therapeutics experienced a double blow this week, with the FDAās rejection of their proprietary MDMA-assisted therapy for PTSD and the retraction of three articles on MDMAās supposed efficacy.
In a way, neither of these events is surprisingāthe research has been marred by controversy for years and the FDA advisory committee in June voted against approval. But in another sense, these are surprising wins for science in a world that is dominated by industry marketing.
Still, we are just beginning to consider the down-the-road implications of this decision.
MDMA, the club drug known as ecstasy or molly, has long been the poster child for the possible approval of illegal psychedelics as medical interventions for psychiatric conditions. The trials of this drug, beginning in the early 2000s, seemed to bring a sense of ārealā medical research to a field plagued with small sample sizes, lack of control groups, unblinding, and other major methodological limitations. By late 2023, the general public perception was of two strong phase 3 trials that demonstrated the treatmentās efficacy in healing those with PTSD.
But when subjected to the FDA advisory committeeās scrutiny, the supposed strengths of these trials fell apart. That appearance of methodological rigor was revealed to be an illusion. And the ethical concerns that dogged the trials finally blew up for the journal Psychopharmacology, which realizedāperhaps thanks to the advocacy of a few whistleblowersāthat the researchers conducting these studies had hidden unethical conduct and protocol violations, and failed to fully disclose all their financial relationships.
According to a Medpage Today article about the FDAās decision: āIn a 9-2 vote, theĀ Psychopharmacologic Drugs Advisory Committee said available data failed to show that MDMA was effective in treating patients with PTSD. The committee also voted 10-1 that the risks outweigh the benefits, even with a proposed risk evaluation and mitigation strategy (REMS).ā
Some of the concerns were medical, involving the harmful cardiac effects of the drug. Some concerns were methodological: concerns about efficacy largely rest on the small sample size and the fact that almost all patients could tell whether they received the placebo or the drug. (An Institute for Clinical and Economic Review (ICER) report calls the studies āfunctionally unblinded,ā meaning that the supposed methodological rigor of these trials just isnāt there.)
But other concerns raised by the advisory committee involved the allegations of unethical conductāincluding sexual assaultāthat occurred in the MDMA trials. For one, the safety data was reported by the psychedelic guides, rather than by unblinded reviewers, and concerns were raised about sexual assault and suicidality going unreported. (Lykosā MDMA protocol explicitly encourages the āguideā to engage in physical touch with the participant, which is particularly concerning when the participant is in an altered state from a drug known to break down boundaries.)
As the ICER report notes, āEven in carefully controlled clinical trials with two therapists of different sexes, therapist misbehavior occurred. We heard concerns about much greater risks if MDMA-AP is administered outside of such controlled settings.ā
These are the concerns that led to Psychopharmacologyās retractions. The retraction notice takes strong language:
āThe Editors have retracted this article after they were informed of protocol violations amounting to unethical conduct at the MP4 study site by researchers associated with this project. The authors have subsequently confirmed that they were aware of these violations at the time of submission of this article, but did not disclose this information to the journal or remove data generated by this site from their analysis. Additionally, the authors also did not fully declare a potential competing interest. Several of the authors are affiliated with either the Multidisciplinary Association for Psychedelic Studies (MAPS) or MAPS Public Benefit Corporation (MAPS PBC), a subsidiary that is wholly owned by MAPS. As is stated in the Funding declaration, MAPS fully funded and provided the MDMA that was used in this trial, and MAPS PBC organised the trial.ā
Still, the pressure on the FDA to approve Lykosā application was strong. A bipartisan group of over 60 politicians signed on to a letter urging the approval of MDMA-assisted therapy. Moreover, the evidenceātwo phase 3 trials that both found a positive effect of the drug treatment group compared to the placebo groupāseemed more powerful than that in other recent FDA approvals, such as those for esketamine and aducanumab.
And the FDA is not required to follow the advice of its advisory committees.
Aducanumab and Esketamine
The case of Alzheimerās drug aducanumab provides an example. By 2019, two Phase 3 trials of aducanumab were terminated early because the drug wasnāt improving outcomes and was clearly causing harm (a large percentage of the participants were experiencing brain bleeding known as ARIA). Yet the FDA worked secretly with drugmaker BiogenĀ for two years to findĀ new ways to analyze the data. Eventually, they managed to massage the data into showing a statistically significant effect in a subgroup of patients in one of the trials.
The FDAās advisory board rejected this evidence, voting 10-0 (with 1 āuncertainā) against approving the drug. But theĀ FDA approved the drug anyway based on a surrogate outcome that researchers have criticized for lack of clinical significance.
The case of esketamine, too, showcased an approval despite evidence of harms and lack of efficacy. Though there were six four-week efficacy trials of the drug for treatment-resistant depression, it failed to beat placebo in five. The drug eked out statisticalāthough not clinicalāsignificance in one of the six trials, and the FDA considered that evidence strong enough to approve the drug.
Yet both of those decisions led to an outcry in the research world. Erick Turner, who was on the FDAās advisory committee that approved esketamine, said that āAccepting just one short-term trial as being enough is a historic break from precedent.ā In the same publication, antidepressant researcher Glen Spielmans added, āBased on the evidence provided in Janssenās application, the FDA should not have approved the drug.ā
After aducanumabās approval, three advisory board membersĀ resigned in protest, and one of them called it āthe worst drug approval decision in recent U.S. history.ā A congressional inquiry into the approval āraise[d] serious concerns about FDAās lapses in protocol,ā and concluded that Biogen was planning to offset the negative press about the drugās harms and ineffectiveness with billions of dollars in marketing.
The ultimate conclusion of the aducanumab scandal was thatĀ āThe FDA is failing the American people.ā
Perhaps it was to avoid a similar blowback and congressional investigation that the FDA was more cautious with Lykosā application. Or perhaps the rejection of Lykosā drug reveals something else: the powerful influence of the traditional pharmaceutical lobby at the cost of the upstart psychedelic industry.
The FDA usually bends over backwards to approve new drugs, particularly psychiatric drugs. Yet, in this instance, the advisory board complained about a lack of blinding and possible underreporting of harms. That is surely a problem, but itās also a documented problem for other drugs. Why isnāt this concern raised about, say, antidepressants? After all, the FDA also just approved an expansion of escitalopram for seven-year-olds with anxiety, despite lack of benefit and clear evidence of increased suicidality in youth.
Perhaps because MDMA-assisted therapy isnāt a simple drug to be prescribed by psychiatrists. Moreover, Lykos is a small company bringing it to market, one that emerged out of a psychedelic research nonprofit (MAPS). And since SSRIs are prescribed for PTSD, this would be a treatment competing with pharmaceutical giants. Could their pressureāpharma giantsā influence on the FDAāhave led to this decision? We may never know.
Where Might This All Lead?
Still, in this case the FDA followed the evidence, in a startling break from two recent decisions, and rejected Lykosā treatment. Certainly, psychedelic promoters and the psychedelic industry will consider this a problem. And there are those who believe that the FDA should have no role in safeguarding the consumer from expensive and potentially harmful treatments that canāt clearly show benefit. But thereās another problem, too, and thatās how the industry is going to interpret this decision.
Already, writers are arguing that the next FDA submissions for psychedelic treatment are going to involve the drug alone, thereby omitting the troubling ethical concerns about providing therapy.
If the industry takeaway from the FDAās rejection of MDMA-assisted therapy is to focus on the drugs and drop the therapeutic component, that would be a shame. Lykos didnāt fail because it included therapy, it failed because individual psychotherapy is a poor substitute for the psychedelic ritual. The focus on including therapy ironically revealed the emptiness of the current cultural understanding of psychedelics in Western medicine.
Maybe the real takeaway from this decision should be that the techno-utopianism of psychedelics as medicineāushered through the bureaucratic regulatory system as part of a for-profit industryāis at odds with the life-changing profundity that many people report experiencing from these drugs. The rituals that bind indigenous communities together are diametric opposites of the psychiatric use of drugs as individual medical treatments for āmental illness.ā Those ancient rituals make space for, even deliberately create, extreme statesāof revelation, of intense connection with others, and of connection to the secret power of the universeāthat are more akin to the very experiences psychiatry considers pathological.
Indeed, psychiatryās goal with esketamine and other drugs is to tap into a supposed chemical healing power these drugs have without engendering an extreme experience. Esketamine nasal spray is meant to be a treatment you can do in complete isolation, without ever leaving your home, and supposedly without causing the dissociative state that has led to ketamine’s popularity as a recreational drug.
In a way, then, Lykosā MDMA treatment is a bridge between these two worlds, the world of individual drug treatment sans experience, and the world of a ritual connecting you to others. But itās a false bridge because the core belief is firmly rooted on the side of Western medicineāseeking FDA approval as a medical treatment will do that. Lykosā words about āintegrating the experienceā and āintuitionā are merely colonized language: co-opting the language of a true psychedelic ritual without bothering to include the ritual itself. Mixing psychotherapy with a drug ends up still being a dismissal of the importance of the ancient psychedelic ritual. Itās a hubristic notion, that individual psychotherapy can easily substitute for a community-binding extreme experience.
And in a culture of hype for the ānext big thing,ā where psychedelics are taken behind closed doors, in sessions led by odd āscientistsā who think themselves gurus and act without accountability, in a culture of for-profit industry and publish-or-perish academia, the incentives for unethical behavior pile up.
Ultimately, Lykosā failuresāof ethics and of scienceāreveal that co-opting the powerful ritual experience that has been part of humanity for millennia and marketing it as medicine is a more difficult task than the techno-futurists hoped.
Peter, this is a thought-provoking takeaway and spot on. I’ve recovered from PTSD but harmed myself plenty trying to jump through the western medicine hoops. Psychedelics have re-centered me and I’ve often balked at the idea that I need someone in a controlled setting to administer and guide me. Another for-profit model trying to be shoved down our throats. There is real promise in MDMA but anyone who has taken it can speak to the very real side effects and risks. I support legalization 100 percent but not the current models being proposed. Hopefully we have someone brave enough in the near future to lead the path forward.
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It’s all just to control and manipulate people. They treat most adults like they are children who cannot make their own decisions in life. It has never been about caring about others. When you are trying to control and manipulate someone’s perception that is not caring behavior. That is unethical and immoral. People need to be free to interpret their own experiences and perceive their experiences independently of someone manipulating them and controlling them to make a profit. Its literally sickening how narcissist these people are
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I was touched by a MIA last year questioning the methodology and strict protocols around psychedelics, saying that the original healing in the 60s was because it was open and free.
The delusion is that a professional can fake deep caring, including via touch. When on a substance like MDMA or acid you know at some level when someone has a true bond with you. A professional therapist being paid for their services simply doesn’t have that. And there’s a laughably small filter preventing narcissistic or sociopathic personalities from becoming therapists. The biggest denial is how much being in the power position over people taking transformative substances is attractive to the wrong people.
I still see evidence that such substances can be healing but only if profit is kept out of it and the sacred quality is restored.
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They want to control peoples experiences. That is not the point of psychedelics at all. If people want someone else to control and manipulate their experience then psychedelics probably aren’t the best option. Having someone else influence your perception and perspective is missing the point completely. People need to be free to interpret their own experiences and express themselves without somebody manipulating and controlling them
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I don’t understand this obsession with mdma. Mushrooms are a much better option and they are natural. They have been used by humans for thousands of years. When used responsibility and in the right set and setting they have the potential to benefit peoples lives
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MDMA is not a psychedelic. It’s an amphetamine with psychedelic “tendencies”. If anyone has taken a psychedelic, they know the difference and that MDMA has nothing to do with psychedelics.
The voice and tone of the author make this an editorial, not a report.
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I wonder if the real reason its been rejected is because its not something to be taken daily for years on end. Its also a common street drug quite easily available for people. The FDA has approved loads of psychiatric drugs based on corrupted science based on vested interest and agency capture. Having said that i’m not fan of bringing yet another drug on the market because its all about locating issues inside the brain and bodies of individual’s rather than between whole people in relation to others all contained within a living breathing context that makes or breaks us.
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Tessa
Good to red that the FDA followed the evidence in this case.
Whether Big Pharm had a hand in it and wants to try to make its own product
is a good point.
Hyped up amphetamines ….just the concept gives the shivers.
But then, every manufactured psych drug gives me the shivers.
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Excellent article. I have been a consumer of SSRIS and other psychiatric meds off and on for the last twenty years, having been diagnosed with anxiety and depression after several life altering events. Working on my own mental health with support of family and friends has saved my life many times. Psychiatric meds are viewed by the medical community as a whole as a way to manage patients. Psychedelics are not the answer to life’s problems, especially with the elderly….they are already vulnerable to drug therapy as their physical health is naturally on the decline. Thanks, Peter for letting us know what’s going on out there. Thought provoking read.
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Iām disappointed that MDMA hasnāt been approved as it could really help people get in touch with their emotions in a way that no other drug could. It isnāt psychedelic nor is it a placebo aka anti depressants and neither is it a drug for life
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Two indirect thoughts came to mind as i read the article on the non-approval by the FDA of MMDA..
1. Time is actually one of the biggest healers. It does NOT heal all, but it doea allow for long term obsrrvation and intervention. In my case, between new research, new diagnoses, and some good luck, ( with bad luck that did cause significant problems, too), in the 47 years I’ve been in treatment for my ever-evolving and chanhing diagnoses (from completely incorrect schizophrrnia to the much better fitting, yet non-official dx of c-PTSD), I can honestly say, not only am i functioning better, but i am also feeling better. I have survived the initial onset of my illness almost 50 years, through times of despair and great hopelessness and some suicidal ideation, to reach a point in my life where i not only behave in a more normal functioning way, i feel more integrated in the world around me. Notice, I didn’t say i feel “Happy,” because i can’t say i do–however, I can say i feel “better,” and acknowledge that feeling better must include my current supprts of mrdications and weekly talk therapy.
2.Going back to the initial onset of my illness, when i was mis-diagnosed with schizophrenia..there still seems to be one criteria that is under-represented in all these trials which would be helpful in the determination of whether the treatment is effective, and that is giving more weight to how the “patient, client, receiver of treatment,” feels with or about the psychiatric and/or psychological treatment. Again, referring to my own experience, or case, after approximately two months on medication for schizophrenia, my Doctor seemed to have a positive take on the fact I was no longer experiencing my initial hospital intake symptoms, however, i was reporting feeling horrible. That was 47 years ago. Within the last 5 years, it has been found that the family of antipsychotic drugs, one of which i was on, causes a non-reversable negative brain change pretty quickly in those who take it. Considering i was one of many people that feel horrible on these drugs and the over-riding reason for their remaing use is the behavioral outcome of the patient, with relatively little consideration of how patients feel on it, and with the (sadly) now known long term negative brain change, if more weight were being placed on peopke’s subhectuve ferlings on drugs, this could have bern avoided. Also consider how research is now ppinting to the ineffectiveness of antidepressants.
With greater weight placed on patuent’s subjective experience in addition to observation, perhaps these outcomes of drug difficulties coukd have been avoided. Note how “time” led to learning about this negative observable outcomes
3. It is sad that taking time, a great healer, is so costly. If one cannot be making money to support one’s self, one becomes a cistly burden on others. Therefire, there are pills. Ir is only noticed in tije, how these pills (mit all of course) have been observed as less and less helpful. Sadly, ways to lower the cost of people who bedd time to heal, which usually involve placing these (we) people together, lead to warehousing, and actually spending less and less money to the point of spending as little money as possible on people who need time to heal, ends of being the result in this culture. This is quite depressing.
However, it seems in my case, truly time has veen a major factor in mybemotional improvement.
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“Those ancient rituals make space for, even deliberately create, extreme statesāof revelation, of intense connection with others, and of connection to the secret power of the universeāthat are more akin to the very experiences psychiatry considers pathological.”
Thank you very much indeed, Peter Simon’s, for yet another excellent essay.
If the universe has as yet largely secret healing power/s, as I believe it does, then we may learn to tap into those powers without entering any states other than those states of consciousness experienced when we are extremely relaxed AND alert.
I believe Carl Jung learned to grip the back of a chair with all his very considerable strength in order to quell what we might now call panic attacks.
I think?Chuck Jaeger managed to keep his foot to the floor.l, or pedal to the metal, or acceleration to max when threatened by the extreme vibration which had caused more timorous colleagues to baulk and decelerate.
Chuck, I believe, managed this to break through the sound barrier.
Carl, I believe, taught and wrote and spoke lessons we have not yet grasped.
We can do this – with OR without drugs other than what our brains and bodies can produce, so I believe.
Thank YOU!
Peace, comfort and joy!
Tom.
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I enjoyed reading the comments as much as the article. Lots to reflect on and much food for thought, thank you!
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https://blog.ted.com/the-debate-about-graham-hancocks-talk/
It seems there may be a connection or correlation, at least, between the exposure of human brains to above threshold levels of DMT – whether exogenous (via ayahuasca) or endogenous (as, perhaps, during “NDE,” “OBE,” and experiences of great danger and apparently imminent death or other – such as deep meditative? – altered states of consciousness?) – and life reviews, plus or minus accompanying resolutions to drastically alter one’s life.
What we call science I see as a child of that Western-style, “Judeo-Christian/Judeo-Pauline” and Greek and Roman thinking which saw humanity, Nature and the or any divine as being quite distinct.
This, for me, explains an anticipated Orthodox scientific rejection of any Gaia hypotheses, followed by a gradual acceptance of them.
https://courses.seas.harvard.edu/climate/eli/Courses/EPS281r/Sources/Gaia/Gaia-hypothesis-wikipedia.pdf
https://youtu.be/Kmo8sh77G6Y?si=37f-ZaJoL2UZgxP-
I believe quantum physics confirm that the “mere” observation of matter can and does alter it, a fact which has been similarly hard to accept.
I believe the same Albert Einstein who observed that one may reasonably view either everything OR nothing as miraculous, suggesting to me that he realized that there can be no true, ultimate randomness or chaos in our universe/s, still recoiled from the notion of what he dubbed “spooky action at a distance,” the simultaneous reaction of one entangled particle to any measurement/observation made on its fellow regardless of the distance in between.
I’ve not read that Einstein was enthralled by the fact that it was ?only because the sun and moon are so nearly equal in size when viewed from Earth, and that those clouds parted for JUST long enough for the necessary photograph to be taken, that made possible the experimental confirmation of his theory of relativity…but I reckon he may well have been.
I believe he said or wrote the following or something very like it:
“Imagination is more important than knowledge. For knowledge is limited to all we now know and understand, while imagination embraces the entire world, and all there ever will be to know and understand.”
I doubt he had intuited that that into which the last big bang is expanding is our shared consciousness, but maybe he did. Or maybe he does, now, wherever he and Besso may be?
‘Besso died in Geneva, aged 81. In a letter of condolence to the Besso family, Albert Einstein wrote “Now he has again preceded me a little in parting from this strange world. This has no importance. For people like us who believe in physics, the separation between past, present and future has only the importance of an admittedly tenacious illusion.”[8] Einstein died one month and 3 days after his friend, on 18 April 1955.’
From https://en.m.wikipedia.org/wiki/Michele_Besso
How could our entire
cosmos possibly not be conscious?
Peter Simons, of you are there, thank you again for your superb essay, and sincere apologies for leaving your name mangled in previous comment.
“God” rest ye merry.
Tom.
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I am not surprised the drug didn’t make it through the assessement in the first place because the psychotherapists administering it were found to be abusive.
And by the way. If you’re looking for a safe and affordable practice that can help with stressful inner experiences that are a consequence of violence and abuse learn to pray, meditate, and practice an hour of yoga a day.
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It is shocking that the FDA would actually protect the public from a drug known to deplete serotonin and has formerly been used in mind control experiments. Why all of a sudden does the FDA have ethics and care for humanity?
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Peter Simons wrote:
“The FDAās advisory board rejected this evidence, voting 10-0 (with 1 āuncertainā) against approving the drug. But the FDA approved the drug anyway based on a surrogate outcome that researchers have criticized for lack of clinical significance.”
https://theconversation.com/what-allegations-of-alzheimers-research-fraud-mean-for-patients-187911
https://www.sciencealert.com/alzheimers-may-not-actually-be-a-brain-disease-expert-reveals
I feel some sympathy for Lykos Therapeutics, and sense that it may even be that they were at least as conscientious and well-intentioned as, say the FDA and many Alzheimer’s researchers have been, and even possibly more so, for all we know.
A significant flaw of contemporary science/medicine is its failure to thoroughly check āseminalā work, and to go ON checking: Kochās high standards are sometimes honored more in the breach, and the peer review process itself is liable to serious corruption.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420798/#:~:text=Abuse%20of%20peer%20review,the%20ideas%20of%20a%20competitor.
A vet colleague of mine decades ago laughed to tell me of some branch of some nerve in a horse’s leg which was faithfully illustrated in many generations of anatomy textbooks….before it was discovered that that particular branch was an anomaly which was not present in the vast, vast, vast majority of horses and ponies.
And “Despite encountering more than a decade of skepticism from the scientific community, Marshall was finally able to prove that H. pylori was not only associated with, but also the cause of peptic ulcer disease.”
– from https://asm.org/podcasts/mtm/episodes/the-self-experimentation-of-barry-marshall-mtm-144
And, even while a simple thought experiment (“Nothing’s either good nor bad But thinking makes it so”) should suffice to convince us that there can be no peripheral pain receptors but only brain/mind ones, the vice-versa which still pervades science/medicine.
Similarly, even though it may very soon seem as stupid to suggest that there could be any such thing as a “mental illness” as to suggest that one could have “a personality illness,” learned men and women still believe this nonsense as āconventional wisdom:ā “The MIND is maya!”
By dramatically drawing attention to flawed science, flawed research, flawed trials, flawed research, flawed data, flawed FDA’s, flawed and corrupt decisions, flawed advisory committees, noble sacrifices and the vast potential for and anticipation of corruption – at least thus far in our human evolution – when so many billions are at stake, perhaps Lykos Therapeutics has indeed done us all a very great service, after all?
And perhaps when any of us, either as individuals or as collectives, means well and puts out our very best intentions, however flawed, Nature conspires not only to fly to our aid, but to bring about benefits in excess of our wildest dreams?
I believe so and I hope so, for, otherwise, how could these be the best of all possible worlds?
Keep on rockin’ in the free world.
Tom.
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