FDA "Breakthrough" Ruling on Magic Mushrooms, Explained by Scientists

The US Food and Drug Administration has given a group of psychiatrists its blessing to dose patients with magic mushrooms in therapy sessions. This week, the FDA granted “Breakthrough Therapy” designation to COMPASS Pathways’ psilocybin-assisted therapy for treatment-resistant depression. The London-based life sciences company, backed in part by Peter Thiel, will use the psychedelic drug psilocybin, the active chemical extracted from psychedelic mushrooms, to treat patients in Europe and North America in a Phase 2b trial to determine the optimal dose of the drug.

For scientists that study psychedelic drugs, the FDA’s move is welcome news. The Breakthrough Therapy designation, first established in 2012, allows the FDA to closely assist researchers in the development of a promising drug to treat serious conditions or diseases.

Roland Griffiths, Ph.D., a professor of psychiatry and behavioral sciences at Johns Hopkins University, heads the lab that conducted the first contemporary FDA-approved clinical trial on psilocybin in 2000. He’s encouraged by the news.

“This is a significant positive development in the potential future regulatory approval of psilocybin, a classic psychedelic drug, for medicinal purposes,” Griffiths tells Inverse. “After a decades-long hiatus of research with psilocybin and related psychedelic drugs, investigators in the United States and Europe have demonstrated the safety and preliminary signs of efficacy of psilocybin for a variety of therapeutic applications.”

Kelan Thomas, Pharm.D., an associate professor of clinical sciences at Touro University California, co-authored a Journal of Psychoactive Drugs review of psilocybin-assisted therapy in 2017, in which he and his team predicted the compound’s role in the future of psychiatry.

“I was very surprised that the FDA has already granted Breakthrough Therapy designation just two months after they approved the study design,” Thomas tells Inverse. “Usually the FDA wants to evaluate data from the drug sponsor’s phase 2b trials before granting Breakthrough Therapy designation, but perhaps data from the previous psilocybin clinical trials that were summarized in my 2017 review article were sufficient evidence.”

But Griffiths explains that the Breakthrough Therapy designation doesn’t necessarily indicate that the FDA will approve psilocybin for widespread human use. What it does mean is that the FDA sees psilocybin-assisted therapy as a novel approach to specifically treating treatment-resistant depression, a condition that affects as many as 50 percent of patients with clinical depression.

Matthew Johnson, Ph.D., an associate professor of psychiatry and behavioral sciences at Hopkins who works with Griffiths on psilocybin research, agrees that this news is significant.

“FDA Breakthrough status is a big deal,” he tells Inverse. “It implies that the FDA recognizes the treatment is potentially one with a large impact on a largely under-treated condition. It also means that the FDA works more closely with the sponsor given the potential public health benefit, and goes beyond the typical ‘Just the facts, ma’am’ relationship they typically have with a pharmaceutical sponsor.”

This means that instead of just scrutinizing the results of COMPASS’s clinical trials, the FDA will make constructive recommendations in a more timely manner than it would with typical drug trials.

The FDA would not offer any comment on the news, citing the confidential status of Breakthrough Therapy applications. But COMPASS Pathways announced the development itself on Tuesday.

To Johnson and Griffiths, the news suggests that the FDA has grown willing to look at psilocybin from the perspective of science and public health, rather than a stance of fear or misunderstanding. This change has been slow, as the psychedelic heyday of the ‘60s sparked a culture of fear around psychedelic drugs, which meant mainstream scientists couldn’t touch them for decades.

“We don’t have an area of science — except possibly chemical weapons or germ warfare — where there’s a cultural consensus that this is so dangerous that we shouldn’t do anything with them,” says Griffiths. But due to the work done in the past 18 years at Johns Hopkins, Imperial College London, New York University, and other academic institutions around the world, this cultural consensus is shifting, and the FDA’s decision is evidence. Johnson says the Breakthrough Therapy designation indicates the FDA will not be “prejudiced against [psilocybin] for non-scientific, political reasons.”

“I think this is an important advance in bringing these compounds out of the dark ages into the light of potential cultural acceptability to systematically explore further applications,” says Griffiths.

All of this is becoming possible because scientists have established enough of a basic understanding of psilocybin to confidently move forward with human trials, knowing that there’s a low likelihood that they’ll do serious harm to volunteers.

This summer, Griffiths, Johnson, and their colleagues published a lengthy analysis of psilocybin’s potential to harm people in the journal Neuropharmacology. In the paper, they conclude that psilocybin has a very low potential for abuse and addiction, and a low potential to harm people who take it.

They also recommended that psilocybin should be moved to Schedule IV of the Controlled Substances act — the category that includes drugs like Xanax and Ambien. Currently the drug is designated Schedule I — along with heroin — meaning it has no medicinal value and high potential to harm people. But as the research piles up, the law will be forced to catch up.

Griffiths is keen to caution, though, that psilocybin is not always harmless. In a 2016 survey in the Journal of Psychopharmacology, the Hopkins team found that out of 1,993 people who had had challenging psychedelic experiences (“bad trips”), 7.6 percent of them ended up seeking professional treatment for psychological symptoms that lasted long after the drugs wore off.

“Although the addiction liability of these drugs is low,” Griffiths says, “that doesn’t mean they’re safe, and they certainly need to be regulated in some fashion. FDA will ultimately be responsible for determining the parameters of that regulation.”

It remains to be seen whether this looks like a central pharmacy that dispenses drugs directly to psychiatrists, or perhaps something else, but Griffiths is pretty sure of one thing:

“It seems unlikely that these are compounds that will be dispensed at a pharmacy.”