Do Psychological Benefits from Psilocybin Last?

Eight years ago, scientists at New York University Langone Medical Center and Johns Hopkins University described an extraordinary pilot study. Both research groups reported that cancer patients could get dramatic relief from depression and anxiety related to their prognosis from taking psilocybin in a clinical setting (Journal of Psychopharmacology, Dec. 2016). These benefits from psilocybin were unexpectedly strong.

How Well Do Psychological Benefits from Psilocybin Last?

Scientists from New York University Langone Medical Center published a follow-up after four and half years (Journal of Psychopharmacology, Feb. 2020). They found that the benefits from psilocybin therapy stuck with 60 to 80 percent of the surviving participants. (The numbers are small; of the original 29, 16 are still alive and 15 agreed to answer the investigators’ questions.)

The volunteers reported feeling less afraid of dying and less hopeless than those who took placebo. They were overwhelmingly positive about their psilocybin-assisted therapy and rated it as a personally meaningful and spiritually significant experience.

Confirmation That Antidepressant Benefits from Psilocybin Can Last Years:

A new study confirms that some people get lasting relief from severe depression with a single dose of psilocybin, the hallucinogen in magic mushrooms (Cancer, June 15, 2025). Like the one described above, this trial was small, just 30 patients with cancer and depression. The follow-up period was two years long, less than the previous study but much longer than most depression studies. There was no control group; the volunteers started with four weekly psychotherapy sessions. Then they had a single six-hour session during which they took 25 mg of psilocybin in a supportive environment. After that, they had four more psychotherapy session a week apart.

At that point, 80% of the patients were significantly less depressed. After two years, 50% still had significant reduction in their depression scores on a validated questionnaire. 25% of these participants had had no further treatment for their depression.

The authors suggest psilocybin may eventually offer an alternative to antidepressants for some people with cancer:

“These findings demonstrate robust antidepressive activity from a single 25 mg dose of psilocybin combined with psychotherapy and suggest a potentially paradigm-changing alternative to traditional antidepressants requiring further study.”

A Different Study Compared Psilocybin to Lexapro (Escitalopram) for Major Depression:

This 6-month follow-up study was conducted in the UK (eClinical Medicine, Sept. 21, 2024). It really is worth a moment to read the long title of the article published in one of The Lancet journals:

“Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial“

That’s a mouthful…but it does reveal what the researchers did. They describe the value of the study this way:

“This study represents a preliminary attempt in understanding the long-term therapeutic profiles of PT [psilocybin therapy] and ET [escitalopram treatment] for depression, providing data from a six-month follow-up period. It is the first to compare the long-term antidepressant effects of these two treatments as well as global mental health measures such as work and social functioning, connectedness, and meaning in life. The findings suggest that while both PT and ET may have comparable long-term effects on depressive symptomatology, PT may be associated with greater improvements in overall mental health.”

OK, that’s pretty technical. Here is my interpretation:

These investigators compared the hallucinogen psilocybin [P Therapy] to a standard antidepressant called escitalopram [E Treatment], also known as Lexapro. That alone is pretty radical. It’s unusual to find a study comparing an “alternative” treatment with a standard antidepressant medication. Even more unusual is the long-lasting nature of this research with follow-up.

All the patients were suffering from “moderate to severe depression.” They were randomly assigned to get either psilocybin (one dose at two weeks and another dose at four weeks) or escitalopram (10 mg daily for the first three weeks and then 20 mg a day for the next three weeks). Psychological support was provided for both groups and follow-up was continued for six months.

The Benefits from Psilocybin Were Better Than Escitalopram:

The authors summarize the implications of their research. In essence, psilocybin therapy (PT) and escitalopram treatment (ET) were comparable when it came to easing depressive symptoms. This is pretty extraordinary given that psilocybin was only taken twice, whereas the antidepressant escitalopram was taken daily.

One more thing. The authors state that PT may have provided additional benefits:

“There are several relevant implications from these findings. Clinically, they suggest that PT and ET could be effective over a six-month period for treating depression, with PT possibly providing additional benefits including enhanced functioning, connectedness, and meaning in life.”

The authors reinforce these findings:

“Overall, the results suggest that although PT and ET may have comparable long-term effects in depression symptomatology, PT might be linked to sustained higher levels of global mental health beyond mere symptom reduction.”

Caveats and Cautions:

This was intriguing research, but it was a relatively small study. The six-month follow-up data were intriguing, but what about longer term? We need larger studies that last longer. There was also missing data in this study that could have impacted the results and the conclusions.

Psychological support was a key part of both treatment programs. The authors point out that psychotherapy alone is valuable:

“In meta-analysis, the odds of depression relapse following psychotherapy alone are approximately half of those associated with medications alone—meaning patients are more likely to relapse after pharmacotherapy.”

Do Not Try This at Home!

Various researchers have warned that people should not adopt a do-it-yourself stance on magic mushrooms. They suggest that the therapeutic environment is important for the benefits from psilocybin. In sum, that could be very difficult to duplicate without trained therapists ready to guide people through a potentially harrowing experience.

To learn more about this research, you may wish to listen to our interview with Dr. Jeffrey Guss, a member of the original NYU team. It is Show 1084: Psilocybin, Cancer and Spiritual Awakening. You might also be interested in Show 1188: The Healing Potential of Psychedelic Drugs–LSD Without Hallucinations?