When we published our New highs for psychedelics in the clinic (2023), it looked like Lykos Therapeutics’ MDMA-assisted therapy for PTSD was soon going to make waves.
Two positive Phase 3 clinical trials (MAPP1 and MAPP2) supported an FDA New Drug Application for MDMA in the treatment of adults with moderate to severe PTSD. It was the first ever New Drug Application for a psychedelic.
With years of collaboration between Lykos and the FDA, and a $250 million investment, the application appeared to be a done deal.
But, in August 2024, the FDA turned down the application.
What went wrong?
In June 2023, after Lykos had completed both MAPP trials, and years after the trial designs had been finalised in collaboration with the FDA, the FDA issued new draft guidance on psychedelic drug development.
It was these guidelines against which Lykos’s data were judged, and fell short. This of course raised eyebrows – the guidelines were published far after Lykos’ trial design in extensive conversation with the FDA. But it did highlight some key issues, quite specific to the development of psychedelic drugs.
One was that of “functional unblinding” – where the participants in the trial could determine which arm of the trial they were on simply by the inevitable effect of the psychedelic treatment – the change in mood and perception induced by the drug.
Another was the ability to isolate the effect of treatment from the psychotherapy component – the effect of the drug independent of talking therapy. This was especially problematic given that the FDA does not provide any regulation on psychotherapy itself.
Perhaps as could be expected, there were also concerns over patient safety and the potential for abuse of these substances.
What did this mean for the development of psychedelic therapies?
Initially, the response was gloomy – Lykos cut its staff by 75% following the rejection. And it inevitably caused other companies in this field to re-think their approach.
But the conditions that psychedelics promise to treat have some of the highest unmet need in the clinic today. And so, the pharmaceutical development of psychedelics remains an important field. It is clear now that far from being the death knell on the introduction of psychedelics into the market, the new guidance from the FDA at least gives a clearer roadmap for the development of these drugs, and companies are adapting their studies to suit.
Lykos has themselves reported a “productive meeting” with the FDA in January 2025 regarding next steps for their new drug application, and independent third-party review of their data as well as additional Phase 3 trial data. They continue towards their “goal of bringing midomafetamine capsules to the estimated 13 million Americans suffering from PTSD”.
Since then, other psychedelics companies have been catching up. Compass Therapeutics recently reported positive Phase III trial results for the use of a different psychedelic substance, Psilocybin (the active component found in magic mushrooms), in the treatment of treatment-resistant depression. We published an interview with Prof. David Nutt, an advisor to Compass Therapeutics, in 2024, discussing how Psilocybin’s ability to “disrupt brain circuits” sets it apart from drugs such as SSRIs.
The route to success is not entirely straightforward. For example, even following those positive results, the share price in Compass Therapeutics fell in June 2025, with investors apparently not being convinced by the clinical trial data, and it remains to be seen whether clinical trial data can ultimately meet the requirements of the FDA.
However, recent announcements in the US also serve to keep the enthusiasm afloat.
A change in the political landscape
A recent announcement from President Donald Trump’s health secretary, Robert F. Kennedy Jr. has shifted the landscape. There is now a significant momentum to ramp up government-run clinical trials for psychedelics, and a belief that “this line of therapeutics has tremendous advantage if given in a clinical setting”. The Food and Drug Administration Commissioner Marty Makary has supported this – setting the exploration of psychedelics as a “top priority”. Dr Mike Davis has been appointed deputy director of the FDA’s Center for Drug Evaluation and Research and, with specialized medical practice in the areas of psychiatry and psychopharmacology, he is well suited to deliver this goal.
What’s next?
Despite the challenges specific to psychedelics, and initial setbacks, the shifting of the political landscape and overall change in perception of psychedelics, as well as the serious development of FDA guidelines on these drugs, make an approval in the near future appear far more likely. It is clear that the FDA is serious about the introduction of psychedelics into the market, and this will have impact worldwide.
