Psilocybin may be as effective as common antidepressant in treating depression

• Psychedelics are substances that may be beneficial in treating mental illness.
• Research is ongoing about the effectiveness of using psychedelics such as psilocybin and how they compare to more traditional treatment options.
• Evidence from a recent review suggests that the psychedelic psilocybin at high doses was slightly more effective at treating depression than the common antidepressant escitalopram.

Depression is a widespread mental illness, impacting about 280 million people worldwide. Researchers are interested in expanding treatment options and finding the most effective medications. Using psychedelics to treat depression is one area of ongoing research.

A review and meta-analysis published in the BMJ compared the effectiveness of psychedelics to escitalopram.

The results of the review indicate that high doses of psilocybin were minimally more effective than escitalopram in relieving depressive symptoms and slightly more effective than the placebo results in escitalopram trials.

The results suggest that psilocybin may be comparable to current antidepressant treatment.

How do psychedelics stack up to other treatments for depression?

Psychedelics are psychoactive substances that have the potential to treat several mental illnesses like depression and post-traumatic stress disorder (PTSD). Common examples of psychedelics include psilocybin, LSD, and MDMA.

While psychedelics have shown promise in the treatment of depression, it can be challenging to do blinded studies because of the subjective effects of psychedelics. Thus, there can be differing placebo effects and possible bias.

The researchers of the current review wanted to compare monotherapy use of psychedelics with escitalopram , a common medication used to treat depression. To help get over some of the problems with the reduced placebo effects of psychedelics trials, the review authors made sure to distinguish between the placebo response in psychedelic studies and the placebo response in antidepressant studies.

This review and Bayesian network meta-analysis included randomized controlled trials with adult participants who had clinically diagnosed depression.

For all the data, they focused on changes in depressive symptoms as the primary outcome. Altogether, they were able to include data from 19 trials: 811 participants in psychedelic trials and 1968 participants in escitalopram trials.

Based on their synthesis of the data, researchers did find that the placebo effect in psychedelic trials was lower than the placebo effect in escitalopram trials.

Compared to the placebo results of escitalopram trials, high-dose psilocybin was slightly more effective. The researchers typically defined high doses of psilocybin as 20 mg or more. In addition, high dose psilocybin was also slightly more effective than escitalopram.

David Merrill, MD, PhD , board certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health, who was not involved in the study, noted the following about the review’s findings:

“This study used meta-analysis techniques to compare the effectiveness of psychedelics and escitalopram (Lexapro) for depressive symptoms. It’s notable that only high dose psilocybin showed greater effectiveness than escitalopram. High-dose psilocybin shows promise as a fast-acting, short-term treatment for depression. This is in comparison to antidepressants, which take weeks, if not months, to kick in and only continue to work with continued use,” he told Medical News Today.

“Though not addressed in this study, the clinical consensus is that benefits of high dose psilocybin can last for months and potentially years after the acute episode of treatments. At times even only one treatment session is needed for otherwise chronic intractable depression. This is part of why psychedelic-assisted psychotherapy under safe, controlled professional settings is gathering such momentum and enthusiasm in the field of psychology and psychiatry,” he added.

Review limitations

This review does have limitations. First, it’s essential to acknowledge that any study included in the review had limitations. For example, researchers acknowledge that the effects of psychedelics may be overestimated compared to internal trial placebos, which is why researchers chose to look at how psychedelics compare to antidepressant placebo effects and low dose psychedelics. They also acknowledge that participants receiving psilocybin were often also receiving psychotherapy or psychological support, which could have impacted the results.

The researchers also only focused on acute effects, so future research will need to evaluate long-term effects of all related medications.

Researchers chose to include a broad range of depression types and included studies with participants who had terminal illnesses or life threatening diagnoses and depressive symptoms alongside participants who had PTSD. Most participants in trials using MDMA had PTSD, while most participants in escitalopram trials had major depressive disorder (MDD). Since the two conditions are different, the results may not necessarily be translated. The review also included only a small number of trials.

The researchers were also limited by choosing to make comparisons to extremely low psychedelics, which is not a true placebo. The results may also have been affected by the struggles of direct and indirect evidence and direct evidence biases, which could have overestimated the effects of high dose psilocybin compared to other treatments.

The inclusion and exclusion parameters also limited the researchers, so future research could include different parameters and inclusion criteria.

Finally, the researchers acknowledge that their meta-analysis may not have enough statistical power to identify publication bias. Researchers also recognize that “Most of the certainty of evidence for treatment comparisons was moderate or low.”

Standardization in psychedelic treatment

The study authors suggest that improving blinding methods and having more standardized psychotherapies could help increase understanding of the effectivenesss of psychedelics.

Matthew W. Johnson, PhD , senior researcher at the Sheppard Pratt Center of Excellence for Psilocybin Research and Treatment, who was not involved in the study, was skeptical about the review’s findings and noted the following to Medical News Today:

“A major reason for my lack of confidence in this particular method is that the various studies differed too widely, including the population studied and the disorder treated (existential distress, MDD, PTSD), in order to directly compare them in a such a way.”

“When conducting aggregate analyses such as meta-analysis or the network analysis conducted here, it is important to make sure that the studies aggregated are similar enough to each other to make sense. Otherwise, such techniques can lead one to think they are getting a valid answer, but you are really basing it off of an apples-to-oranges comparison,” he explained.

More treatment options for people with depression

Despite the limitations of this review, the findings do potentially point to expanding treatment options for people with depression. This allows doctors and people with depression to choose from more therapies to find what works for the individual.

Based on this study, high dose psilocybin appeared to be similar to the effects of antidepressants in treating major depressive disorder. Thus, the researchers recommended that psilocybin should likely be used alongside psychotherapeutic support.

“These findings give hope to those with depression — especially those who find antidepressants to be ineffective or intolerable due to side effects. While there are always potential risks of using drugs to treat health conditions, this review shows that, with the proper mindset and treatment setting, high dose psychedelics can be used safely and effectively to treat depression, with results on par or better than seen with antidepressant medications.”
— David Merrill, MD, PhD

“Many in the field are working diligently to build a renewed evidence base to allow for the legalization and regulated approval of psilocybin and other psychedelic therapies for depression, PTSD, addiction, and other health conditions,” Merrill noted.