Landmark review spotlights challenge of judging psychedelic therapies

• Psychedelics have major effects on brain activity, which is why they're tightly regulated and researchers to date have struggled to meet best scientific practices.

Driving the news: A Food and Drug Administration panel of outside experts on Tuesday will evaluate Lykos Therapeutics' application to use the drug known as ecstasy to treat PTSD.

• MDMA, ecstasy's chemical name, targets multiple neurotransmitters in the brain and was found in Lykos studies to deliver "meaningful improvement" in PTSD symptoms that appears to be durable.

Yes, but: PTSD is hard to treat, and it often involves combining medication like antidepressants with psychotherapy. That can make it difficult to assess how much benefit comes from the drug versus supervised counseling.

• The FDA doesn't regulate psychotherapy, and agency staff have raised concerns about how to attribute its effects, including on the drug's label.

Between the lines: The FDA as far back as 2016 expressed concern about bias in Lykos' trial design, because MDMA's notable effects would make patients know they got it as opposed to a placebo, and that could raise their expectations of benefiting from the treatment.

• A psychedelics researcher's citizen's petition to the FDA in April additionally cited shortcomings and safety risks surrounding Lykos' application.
• And last month, the influential Institute for Clinical and Economic Review questioned whether misconduct could have influenced outcomes and concluded publicly available evidence for MDMA-assisted therapy is insufficient.

An FDA staff report on Friday raised concerns about the safety of using the treatment, citing the potential for abuse and possible harmful side effects to the heart and liver.

• The document pointed to gaps in clinical trial data, adding that regulators couldn't entirely rely on anecdotal reports of illegal MDMA use to project risks from an approved treatment.

There's a significant push to use psychedelics as a treatment, especially for veterans with PTSD, who have high drop-out rates for psychotherapy alone.

• FDA staff noted Lykos' application includes evidence patients who received the drug experienced "statistically significant and clinically meaningful improvement" in their PTSD symptoms that could last at least several months.
• Disabled American Veterans said in comments for the meeting that "Lykos' current research indicates MDMA may make psychotherapy more effective."

If approved, the drug would need to be subject to drug safety restrictions known as REMS, including monitoring of a patient's vital signs and psychological state for at least eight hours until the individual is stable to be discharged, per the staff report.

• "We are particularly concerned that serious harm could result while patients are impaired," FDA staff wrote, noting that the exact nature of the short-term effects were not captured in the clinical trials.

The other side: Lykos CEO Amy Emerson said in a statement Friday that the company stands by its research and development program and would discuss it in more detail at Tuesday's meeting.

• "Given there has not been a new PTSD medication approved in the United States in over two decades for the 13 million people living with PTSD, we are deeply committed to making a difference by bringing a potential new treatment to patients," she said.

What's ahead: The FDA has fast-tracked review of Lykos' treatment and is expected to make a decision by Aug. 11.

• There are more psychedelics in the regulatory pipeline: The FDA in March granted breakthrough therapy status to an LSD treatment from MindMed for generalized anxiety disorder based on initial clinical studies. Compass Pathways previously received the designation for psychedelic mushroom-assisted therapy for treatment-resistant depression.
• There's also new large-scale research underway, including a recently launched EU project to study psilocybin, or magic mushrooms, in palliative care.