Psilocybin May Offer Profound Relief From Cancer Depression

M. Alexander Otto, PA, MMS

April 28, 2023

Depression among cancer patients is common, but standard treatment options — antidepressants and therapy — often don't help very much.

This problem has led a team of researchers to try a novel approach to treating cancer depression: the psychedelic psilocybin.  

The results of a new phase 2 study, published online April 13 in JAMA Oncology, were "profound."

After 30 adult patients with cancer — all with a major depressive episode and 16 with incurable metastatic disease — took a one-time 25-mg dose of psilocybin (COMP360, Compass Pathways) under medical supervision, half had complete remission of their depressive symptoms and 30% showed sustained improvements at 8 weeks. The treatment was safe, with no treatment-related serious adverse events.

"Participants experienced clinically meaningful, rapid, and sustained improvement in symptoms of depression over 8 weeks following a single treatment of psilocybin therapy," the investigators write.

After 15 years of treating patients with cancer, "I have never seen anything that can affect somebodies' attitude and the way they think about themselves and their emotional health in such a short span," oncologist and lead investigator Manish Agrawal, MD, told Medscape Medical News.

"I'm cautious because the days are still early and it's not a magic bullet, but the stories of transformation are profound," said Agrawal, who is now CEO of Sunstone Therapies in Rockville, Maryland, which is working to develop psychedelic treatment centers for patients with cancer.

Charles White, PharmD, who was not involved with the study, said: "The evidence from preliminary studies like this is mounting that psychedelics, particularly psilocybin, could be an effective therapy for depression in patients with cancer."

But he agreed that the research is still young. The next step would be a randomized trial that pits psilocybin against placebo or traditional therapies, such as selective serotonin reuptake inhibitors.

"Future phase 3 clinical trials need to address the major weaknesses in the literature" to date, said White, chair of pharmacy practice at the University of Connecticut, Mansfield, and an author of a meta-analysis published in March exploring psychedelics for cancer depression and anxiety.

The Patient Experience: Hearing the Crickets 

Agrawal came to psilocybin for cancer depression because, after about two decades years in practice, he became frustrated with seeing his patients with depression not benefit much from the usual therapies.

Although initially skeptical of psilocybin given the hype surrounding its use in medicine, Agrawal ultimately decided to explore whether the psychedelic could help assuage his patients' emotional pain and feelings of despair.

The team conducted a single-center, fixed-dose, open-label phase 2 study to assess the safety of psilocybin and whether it can improve patients' depression.

Using the 60-point Montgomery–Asberg Depression Rating Scale, patients had a mean baseline score of 25.9 points, indicating moderate depression, and some patients scored in the severe range. 

Eight weeks posttreatment, patients exhibited a significant improvement in depression severity, with a mean reduction of 19.1 points from baseline.

Patients also reported an average improvement of 48% in depression symptoms and an average 53% drop in depression severity.

"I didn't believe it until I saw it myself," Agrawal said. "We actually found that people who have" the worst depression are helped the most.

Agrawal acknowledged that psilocybin treatment is intense and often grueling for patients, especially at the 25-mg dose used in the study.

But the experience can also be joyful. 

Although the details are different for each patient, the general outcome is a major shift in perspective. Patients are not as caught up in living their story; instead, they're able to see their story from the outside and how it fits into a larger context, Agrawal said.

Agrawal recalled one patient in the study who had metastatic renal cancer. 

It was hard for her to explain her trip, except that she went through her own death and came out on the other side knowing she could face anything, he said.

A couple of days after her session, she sat beside a lake on a warm summer evening marveling at how loud the crickets were chirping. She felt at peace. 

Slowly, an awareness came over her that, come winter, all the crickets would die, but that a whole new crop of crickets would come in the spring, and that it is the same for people.

"When she was born, there were all these humans, and they have died over her lifetime, and she'll die, and then there will be a new crop of humans. It's part of the natural cycle, and it's not personal," Agrawal said.

"Her psilocybin experience allowed her to have this sort of insight. You talk to patients about death being a natural part of life," but it's just a thought, he said. "For her, to feel it somewhere inside and not just cognitively, that is the thing that helped her," he added.

White has also found that when psilocybin therapy is successful, patients can "have a cathartic experience." They can process their emotions instead of repressing them and gain greater acceptance.

This perspective "helps them see that their problems are really small in the grander scheme of things and opens them up to [moving forward in ways] they were not able to think about before," White said.

Setting, Patient Selection Are Key

While such stories are powerful, White cautioned that "the same hallucinations" that can be so therapeutic "can also cause terrors and self-harm if the environment is not right."

Patients need to be prepared for the experience, guided during it, and counseled afterward to make sense of it. The setting needs to feel safe, calm, and supportive.  

Guiding patients through the process requires expertise, which is why Agrawal and his company are developing dedicated treatment centers.

The current study represents a dry run of how such treatment centers may operate. Patients were treated on the third floor of the Aquilino Cancer Center, in a spa-like setting surrounded by soft lighting, natural wood, and soothing music. People reclined on couches during their treatment session with eye masks and their therapist by their side.

Three to four patients received treatment at once in adjoining rooms. They had a group therapy session and individual therapy beforehand to prepare them for what to expect, followed by group and individual therapy afterward to help them process and benefit from the experience. 

But Agrawal and White agreed that even in the right setting, psilocybin therapy isn't for everyone. One concern is that in people with a history of psychotic thinking, hallucinations, or schizophrenia such symptoms could be made worse by the experience. Psilocybin might also exacerbate pre-existing heart arrhythmias. The emotional work of psychedelic therapy can also raise blood pressure significantly, a concern for people with cardiovascular issues.

There were no such problems in Agrawal's study. Adverse events were mild or expected and included headache (n = 24), nausea (n = 12), altered mood (n = 8), and anxiety (n = 7).

Still, this experience "requires you to be able to go inside and be internal and be quiet and still, and some people just can't do that," Agrawal said. If people are looking for a magic bullet, this is "probably not going to be it."

The work was funded in part by Compass Pathways, which manufactures the psilocybin used in the study. The company was involved in the study design but not its conduct, interpretation, or manuscript approval. One investigator has reported receiving grants from Compass; another has reported receiving nonfinancial support from the company and holding stock in Sunstone. White has reported no relevant financial relationships.

JAMA Oncol. Published online April 13. Research letter

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is also an MIT Knight Science Journalism fellow. Email:

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