It’s Zero Hour For Psychedelic Medicine

Ecstasy, the psychedelic club drug that lawmakers and the Department of Veterans Affairs hope can help veterans with PTSD, is about to have its make-or-break moment.

A Food and Drug Administration panel will decide Tuesday whether to recommend the agency grant approval. A thumbs up from the FDA could open up a massive shift to psychedelic medicine, not only for veterans, but also all Americans with mental illness. A thumbs down will upend a burgeoning industry — and crush a lot of hopes.

"MDMA is going to revolutionize treatment of mental health in this country,” said Rep. Lou Correa, a Democrat who’s traveled from his southern California district to Tijuana, Mexico, to visit a clinic there that provides psychedelic drugs to veterans who can’t get them here.

The VA cites research finding 7 percent of veterans will suffer from PTSD at some point in their lives. It can cause flashbacks, nightmares and anxiety brought on by traumatic events — like combat. Nearly one in four vets who seek care at a VA facility have the condition, had it, or will get it.

Lykos Therapeutics, whose application the FDA panel of expert advisers will consider, is making the case that MDMA, the scientific name for ecstasy, along with therapy can take the pain away. VA officials are hoping it’s right.

In May, the VA’s undersecretary for health, Dr. Shereef Elnahal, raised the expectations of psychedelic enthusiasts at a conference in New York put on by the Horizons Center Public Benefit Corp., which promotes the drugs.

“We keep proving the science. We keep surprising the folks who are skeptical,” he told the crowd.

But there’s a problem with the rosy forecasts.

Lykos has come under fire for allegedly slanting its studies to make the case for approval. The head of the National Institute on Drug Abuse, Nora Volkow, last month compared the hype for psychedelics as a cure for mental illness to belief in “fairy tales” in Senate testimony.

In March, an independent, nonpartisan group that evaluates new drug applications found Lykos’ trials suspect.

"We have substantial concerns about the validity of the results," the Institute for Clinical and Economic Review wrote in a draft report. The panel cited safety, ethical and cost concerns and projected difficulty in widely implementing the treatment.

The institute also critiqued the psychedelic community, which it said treats psychedelic drugs "more like a religious movement than like pharmaceutical products," feelings the report said "were sometimes inculcated in patients participating in the trials."

In April, a citizen petition from psychedelic researchers critical of Lykos called on the FDA to hold an extended open public hearing so that the advisory committee could hear the public's concerns.

In a comment to the institute, Lykos CEO Amy Emerson said its critics discount “significant unmet medical need” and that the FDA was best equipped to evaluate its treatment’s safety and efficacy.

The FDA will decide after its advisers’ meeting whether to grant approval.

Promising results

Lykos' data is striking.

Sixty-seven percent of participants with severe PTSD who received MDMA combined with therapy no longer met the diagnostic criteria for the disorder, compared with 32 percent in the group that received therapy and a placebo, according to Lykos' Phase 3 study, which was published in Nature Medicine in 2021.

In its 2023 trial, 71 percent of participants who received the combo therapy no longer met the criteria for PTSD.

The FDA decision is a huge moment for psychedelic research, said Andrew Penn, a psychiatric nurse practitioner and clinical professor at the University of California, San Francisco who’s previously worked with Lykos. If the FDA says "yes," it will likely galvanize support for early-stage psychedelic research. If the FDA says "no," it could give those same researchers pause, he said.

Researchers don't fully understand why MDMA helps some people with PTSD.

One theory is that the amygdala, the small, almond-shaped part of the brain that controls emotions, especially fear, quiets down on MDMA. It could make therapy more productive if patients feel comfortable talking about topics that otherwise upset them.

Therapy can be difficult for people who’ve been traumatized. Some become overwhelmed or triggered. Others dissociate or shut down, Penn explained. MDMA can create what’s known as a “window of tolerance,” a zone in which people with PTSD are able to operate from a calm, engaged state.

Another theory is that MDMA increases activity in the prefrontal cortex, the front part of the brain that coordinates and directs thinking, motor skills and behavior, and provides a sense of safety and trust, which people with PTSD often struggle with.

In that altered state, it may be easier for people with PTSD to benefit from therapy.

There's a profound need for better PTSD treatments. Current options are notoriously ineffective, with many people with PTSD left white knuckling through daily life.

But recent history suggests that getting a psychedelic treatment to the masses — safely — may be easier said than done.

The FDA approved a version of ketamine that Johnson & Johnson developed for treatment-resistant depression in 2019. Ketamine, an anesthetic that can distort people's senses and cause them to feel detached from their environment, soon became widely available off label, especially after looser pandemic-era telemedicine rules allowed clinics to prescribe it virtually. Patients reported getting addicted to the drug as well as bladder damage.

MDMA comes with its own health risks, including heart problems.

In its initial review of the application released Friday, the FDA said that data was "challenging to interpret" and cited MDMA's heart risks and abuse potential as safety concerns. The agency also noted that it's hard to discern how much of study participants' improvement came from MDMA combined with therapy, versus therapy alone.

The FDA review also offered hope for advocates of the treatment: "Based on the clinical trial data submitted with this application, participants appear to experience rapid, clinically meaningful, durable improvement in their PTSD symptoms," the review says.

The advisory committee will vote on two questions on June 4: whether the drug is effective in patients with PTSD, and whether its benefits outweigh its risks. (The FDA has proposed a risk-mitigation strategy that will be included in the second question.)

The FDA typically follows the advice of its advisers in deciding whether to approve a new treatment. It expects to decide by mid-August.

Support in Congress

Former Navy SEAL Morgan Luttrell, a Republican in his first term from a suburban Houston district, credits a different psychedelic therapy, ibogaine and 5-MeO-DMT, with helping him overcome trauma after his Black Hawk helicopter went down during a training mission in 2009.

He called the advisory committee meeting a "major step forward in getting these emerging therapies in our toolbox for veterans."

The Tijuana clinic Correa visited on a fact-finding trip earlier this year also offers ibogaine, a psychedelic derived from an African shrub, and another mind-altering drug, 5-MeO-DMT, which comes from plants as well as the Colorado River toad, to veterans with PTSD, depression or anxiety.

Correa urged the FDA to approve Lykos' application, regardless of which way the committee goes. "Veterans swear by it. Mental health advocates are saying it works. Housewives are taking it with or without the research," he said of psychedelics. "What are we waiting for?"

And Rep. Jack Bergman (R-Mich.), who has joined Correa in sponsoring legislation to advance psychedelic research, said we've only scratched the surface of psychedelic treatment for mental illness.

"Once MDMA-assisted therapy receives full approval, it is imperative that entities like the VA and HHS move quickly to craft guidelines and procedures to ensure safe access to these treatments," Bergman said.