Psilocybin Looking “Rather Good” as an Anti-Depressant, Trial Data Shows – Technology Networks

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When the psychedelic compound psilocybin was subject to federal regulation in the US during the 1960s, it swiftly brought any “above ground” research working to deduce its therapeutic potential to a grinding halt.

During the psychedelic renaissance of recent years, there has been a revival of work exploring psilocybin’s utility for treating psychiatric conditions. Legal restrictions have eased, enabling this work to be conducted ethically across research institutions and private practice sites.

A new meta-analysis by UK researchers analyzed data from a collection of such studies to further address the question: is psilocybin effective as an anti-depressant? The research – published in the BMJ – reports “encouraging findings” according to the research team.

An estimated five percent of the global population suffer from depression, also referred to as major depressive disorder (MDD) or clinical depression. While anti-depressant medications are available and can offer some individuals relief, they are not universally effective, and alternative treatment options are desperately sought.

“Psilocybin would hopefully provide a more quick-acting and tolerable (in terms of side effects) treatment,” Athina-Marina Metaxa, a former researcher in the Nuffield Department of Medicine at the University Oxford who now works in the pharmaceutical industry, told Technology Networks. Metaxa is a co-author of the BMJ study, along with Professor Mike Clarke from the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University Belfast.

Metaxa and Clarke searched through databases looking for randomized controlled trials that compared psilocybin as a treatment for symptoms of depression with controls, including placebo, niacin (vitamin B) or microdoses of psychedelics. They found 7 trials, recruiting a total of 436 participants with an average age of 36–60 years, that met their inclusion criteria. The participants were roughly 50/50 male and female but were 90% white. This lack of diversity, Metaxa says, is common across psychedelic studies, and makes it challenging to generalize results.

“It would be great to see more initiatives to include non-white participants in research, as there might be very interesting race-related differences in treatment outcomes that we currently cannot detect,” Metaxa said.

The effects of psilocybin on depressive symptoms were measured using the statistical method Hedges’ g. Using this method, a score of 0.9 or more indicates a large effect.

Across the seven trials analyzed, Metaxa and Clarke found that psilocybin induced a significantly greater improvement in depressive scores compared to placebo or alternative treatments, with a Hedge’s g score of 1.64. 

“Evidence overall shows that psilocybin can reduce depressive symptoms, both in primary depression (typical depression patients) and secondary depression (patients with depression who also have a serious/life-threatening illness),” Metaxa said.

There were, however, several factors that influenced the level of a participant’s improvement after psilocybin treatment, including whether an individual was experiencing secondary depression, the type of assessment used in their style and their age.

Metaxa expanded on these findings: “It has been proposed that patients with secondary depression benefit more because they tend to be older or because they have more severe depression, so improvements are more pronounced,” she said. “However, patients with secondary depression did not differ in average age or symptom severity than primary depression patients in this study. It would be interesting to look at the neural correlation of psilocybin treatment for each patient group – maybe that could tell us more about psilocybin’s specific effects in each patient type.”

“Self-assessment scales have shown larger treatment effects compared to clinician-assessed scales across psychological literature, so this is not unique to psilocybin interventions. This may be because clinicians tend to underestimate the severity of depression symptoms at baseline assessment, leading to less pronounced pre- vs post-treatment differences identified in clinician-assessed scales,” she continued. In other words, a patient is more likely to rate their initial symptoms as “more severe” than a doctor would when making the same assessment.

“When it comes to older age, it could be because older people have more experience in managing negative emotions. Additionally, some studies have shown that older patients’ cognitive performance improves significantly more than that of younger patients following psilocybin treatment – thus, the higher decrease in depressive symptoms associated with older age could be attributed to a decrease in the cognitive difficulties experienced by older participants,” Metaxa added.

Combined, do these findings imply that creating and implementing a “one-size-fits-all” psilocybin treatment approach for depression would be challenging? “The findings are encouraging in that they showed that psilocybin is overall effective when we pool all the data together. This means that while it may be more effective for some patient ‘types’ it can still be overall beneficial across patients,” Metaxa explained. “It would also be interesting to consider that the ‘individualized’ component of psilocybin treatment comes from the therapeutic support the patient receives along the treatment, and not the drug itself.”

Implementing psilocybin-based treatments: Opportunities and challenges

Unfortunately, Metaxa and Clarke could not measure pre-treatment expectations and the extent to which participants knew they were being treated with psilocybin or placebo. This data was not collected in the majority of studies analyzed by the duo, Metaxa explained to Technology Networks. Dr. Paul Keedwell, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said that concerns surrounding this limitation are “tempered by the fact that improvements were maintained for up to 12 weeks in one study.” Regardless, Metaxa suggests that future research measures pre-treatment expectations, as they would provide “invaluable” insight into how the patient’s mindset might affect treatment outcomes.

“This systematic review and meta-analysis confirms what smaller studies, such as our earlier work (Carhart-Harris 2016 and 2021) suggested – psilocybin looks rather good as an antidepressant,” Professor David Nutt, the Edmond J Safra Chair and Head of the Centre for Neuropsychopharmacology in the Division of Brain Sciences at Imperial College London, said.

Metaxa and Clarke are encouraged both encouraged by their findings but also realistic in their expectations. “We argue that the complexity of psilocybin-based interventions would be a significant barrier to implementation – the patient needs to go to the clinic and remain there for hours while the treatment is administered, a specially designed room is required to ensure the patient is calm and comfortable, and a trained therapist must be present to assist,” Metaxa said.

This makes the intervention costly and challenging to implement in a standardized way. “Also, due to its high cost, such an intervention may not be readily reimbursed, so it would be difficult for most patients to access,” Metaxa added.

She is, however, optimistic: “I want to believe that if a treatment is effective, it will end up being used in practice. While there are barriers to treatment implementation, there are also many brilliant researchers working across academia and industry who are trying to find ways to make psilocybin treatment more cost-effective and easier to implement in clinical practice.”

“I hope this work will encourage researchers to examine patient- and study design-related factors that could modify psilocybin’s antidepressant effectiveness,” Metaxa concluded. “Additionally, this study would hopefully stimulate more interest in psilocybin research across research organizations and patient groups and would encourage participation in such trials.”

Athina-Marina Metaxa was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

About the interviewee:

After completing her MSc at the University of Oxford, Athina-Marina Metaxa now works in the pharma/life science consulting industry. She continues to engage in research on psilocybin and other innovative treatments for mental health conditions through academic research collaborations across the US and UK. Metaxa urges anyone interested in this type of research to contact her.

Reference: Athina-Marina Metaxa, Mike Clarke. Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ. 2024;385:e078084. doi: 10.1136/bmj-2023-078084

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