Study shows psilocybin gives comparable long-term antidepressant effects to standard antidepressants

Head-to-head comparisons of the experimental hallucinogen psilocybin with standard SSRI antidepressants have shown similar improvements in depression symptoms, but psilocybin has additional long-term benefits.

A comparison of psilocybin (the active ingredient in “magic mushrooms”) and the SSRI escitalopram showed similar long-term improvements in depressive symptoms over a six-month period, but patients taking psilocybin also reported improved psychosocial functioning, including a greater sense of meaning in life and psychological connectedness.

This work is, ECNP Conference in MilanA related paper is scheduled to be published in the journal Clinical Medicine For conference presentations.

Lead researcher Tommaso Barba, a PhD candidate at Imperial College London, said: “This is the first study to compare the long-term effects of these two medications, not just in terms of freedom from depression but overall well-being. Previous studies have found that at six weeks, both treatments produced comparable improvements in reducing symptoms of depression, such as sadness and negative emotions.”

“But this study does show that psilocybin is superior to escitalopram on several measures of well-being, meaning in life, and work and social functioning. These results appear to be maintained over a six-month follow-up period. Furthermore, in previous studies we also found that psilocybin increases libido, in contrast to SSRIs, which tend to decrease it in many patients. So overall, it appears that psilocybin may have additional positive effects on mental health.”

SSRI drugs (selective serotonin reuptake inhibitors) such as Prozac, Paxil and Zoloft are among the main medications used to treat depression, however, around one-third of patients do not respond to SSRI treatment and for such patients, psilocybin may be an alternative, although it was not studied in this trial.

Barba added: “SSRIs, while highly effective, don’t work for everyone and are associated with some side effects. However, this study suggests that psilocybin generally offers a genuine alternative, and even additional benefits, for people who are concerned about taking traditional antidepressants.”

Researchers at Imperial College London conducted a six-month study (a two-phase, double-blind, randomized controlled trial) of 59 people with moderate to severe depression. Thirty people received a single dose of psilocybin, and 29 people received six weeks of escitalopram. Each group received similar psychological support for a total of about 20 hours.

Both groups saw significant improvements in their depression symptoms up to six months after treatment (the researchers stopped monitoring at six months), but the group given psilocybin also saw greater improvements in their social functioning and psychological connectedness, which they reported were even greater benefits.

“This is important because improving connection and having more meaning in life can significantly enhance a person’s quality of life and long-term mental health,” said co-first author Dr David Elizo, clinical director and deputy director of the Centre for Psychedelic Studies at Imperial College London.

“This study suggests that psilocybin therapy may be a more holistic treatment option for depression, addressing both depressive symptoms and overall health. This could make a difference to the overall well-being and daily activities of people suffering from depression, offering a more integrated approach to mental health treatment.”

The researchers note that patients were treated for only six weeks, and many of them received additional treatment during the six-month follow-up period.

Dr Elizo warned: “Psilocybin is still an experimental drug and has not yet been approved for general use. Psilocybin is administered in highly controlled and protected environments. Such precautions are not seen with recreational use of psychedelics, which are known for their unpredictable and potentially harmful effects, especially for vulnerable people suffering from mental health issues.”

Johan Lundberg, adjunct professor of psychiatry in the Department of Clinical Neurosciences at Karolinska Institutet, Stockholm, who was not involved in the study, commented, “This report is an important attempt to compare the clinical value of psilocybin with state-of-the-art treatments for major depression. The results come with some caveats, including the lack of a non-inferiority analysis and the failure to report other interventions during the follow-up period. Nonetheless, as hypothesis-generating material, it has the potential to be of great benefit to the field.”

“At present, we do not know whether psilocybin will ever be approved for the treatment of severe depression, and even if it is approved, it will not work for everyone. In the future, some patients may prefer treatment with psychedelics over SSRIs, but others may be frightened by the dramatic changes in perception and difficult emotions that psychedelics can cause.”