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Psychedelics advance toward FDA approval as studies confirm benefits for treating certain mental health patients

Psych Congress 2021 kicked off with an unusual—and quite personable—format. Conference co-chair Charles Raison, MD, internationally recognized psychiatrist and Professor, Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, hosted one-on-one conversations with fellow experts to discuss important updates on how the landscape of mental healthcare is changing. Or, as Dr. Raison put it, the conversations circled around “utterly novel” agents set to disrupt mental healthcare.

During this welcome session, titled Perspective on Mental Healthcare: Connecting to the Now and the Future, Dr. Raison chatted with Andrew Penn, MS, PMHNP, Associate Clinical Professor, University of California, San Francisco.

The spotlight was on the exploding topic of psychedelics.

Beginning on a high note, the conversation began by reviewing psychedelic assisted therapy trials and when psychedelics might see the light of day as approved treatments.

Long story short, there should be news soon, Penn said.

One candidate, already in a phase 3 clinical trial, is methylenedioxymethamphetamine (MDMA)-assisted therapy for patients with severe, chronic post-traumatic stress disorder (PTSD). The trial reports that 67% of participants who received three MDMA-assisted therapy sessions no longer qualified for a PTSD diagnosis and 88% experienced a clinically meaningful reduction in symptoms. Penn speculates that FDA approval for MDMA may come as soon as 2023.

Another candidate, currently in a phase 2 trial, is psilocybin, the active compound in magic mushrooms, for major depression.

While these two psychedelics are sharing the limelight right now, Penn was quick to add, “At last count, there are now 100 commercial entities that have entered the psychedelic space. Billions of dollars of investment capital have flowed in, and if you go to clinical trials.gov, the list of psychedelics that people are looking at is mind boggling.”

With options around the corner, it’s time to bone up on what separates psychedelic therapy from current therapies—aside from the obvious, of course.

“We all know that these agents quickly affect change. But the thing that’s really important is that they are highly contextual, highly relational agents. Because they need that contextual piece, they really are catalysts to psychotherapy—the human-to-human connection.”

And that connection, Penn explained, is an essential component of psychedelic therapy. “Depression is a state of disconnection; it’s a disconnection from one sense of self. It’s a disconnection from pleasure. It’s a disconnection from others. And it’s a disconnection from a sense of meaning. Conventional medications work to some extent, but they often make certain aspects of this disconnection worse.

“How many times have we had patients say, ‘I don’t feel as depressed anymore, but I don’t feel much of anything. I just feel numb.’ So yes, we may have reduced that PHQ-9 score, but did we really heal that person? I think that’s the provocative question that psychedelics pose: Is there potential for actual healing, not just symptom amelioration?”

Possibly, Penn suggests. He pointed to research that suggests that one dose of a psychedelic, which stays in the body for maybe six or eight hours, has the potential to help patients feel better for an extended period time.

While Penn was careful to not overpromise a “one and done model” for any psychedelic therapy, he did present a theory as to why this particular treatment may have lasting power. “I think psychedelics tend to change the relationship someone has with their illness. So, it’s not necessarily about making the depression go away, but more about a patient altering their relationship with the suffering that resulted from their depression.”

The distinction between depression and suffering caused by depression turns out to be a crucial distinction. And exactly how psychedelics change a patient’s relationship with their chronic depressive state is a multi-level story, Penn said.

“It’s important to understand that the psychedelic session is bookended by non-drug therapy. We have preparation therapy, and we have integration therapy. That’s absolutely critical, because that is where change happens. The drug session itself is often very inward—even unremarkable. It’s the time afterwards where we start to identify where somebody might want to make some shifts in the way they’re experiencing and connecting with life.”  

Those shifts, Penn said, are based on realizations triggered by the psycho pharmacologic agent. Someone might realize that the way they normally relate to other people is contributing to their unhappiness and sense of disconnection. “Someone might see demonstrable changes that can improve their life—from more exercise to less stress or even a better diet,” Penn added.

These sorts of quick realizations aren’t unique to psychedelics. Literature says that in psychotherapy, 40% of changes occur in what’s called a sudden gain—a sort of aha moment that brings a drop in depression score.

No one is suggesting that powerful psycho pharmacologic agents replace antidepressants, but psychedelics do appear to deliver a rare moment for healing realizations. “I think capitalizing on those brief moments is so valuable,” Penn concluded.


MAPS’ Phase 3 Trial of MDMA-Assisted Therapy for PTSD Achieves Successful Results for Patients with Severe, Chronic PTSD [news release]. MAPS; May 3, 2021. https://maps.org/news/media/9122-maps-phase-3-trial-of-mdma-assisted-therapy-for-ptsd-achieves-successful-results-for-patients-with-severe-chronic-ptsd. Accessed October 29, 2021.