Psychedelic Research Recap January 2025

Psychedelic Research Recap January 2025

Welcome back to our monthly update on psychedelic research!

Five studies have been testing how psychedelic treatments work in practice. One trial found that a single dose of psilocybin helped people with severe depression who hadn’t improved with other treatments. Another showed that combining psilocybin with group mindfulness sessions helped reduce stress and depression in healthcare workers. We’ve also learned that ketamine nasal spray works faster and longer than traditional antidepressants, and that adjustable doses of ketamine can help reduce anxiety.

Looking at the bigger picture, researchers have been studying how these treatments work in the real world. A large review of ketamine nasal spray found modest benefits for hard-to-treat depression, though it raised some safety questions. However, another study found that the treatment did help reduce hospital visits and medical costs compared to usual care. Other studies looked at how psilocybin therapy works, including its ability to change negative thought patterns and improve well-being.

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Check out the research link overview for all the studies we didn’t add to the database.

Interventional Studies on Psychedelic Therapy

Last month, five studies reported on clinical trials to test how psychedelic treatments work in patients. We begin with two trials that report original findings. The rest are secondary analyses that offer new insights by reexamining trial data. Together, these studies shed light on different treatment approaches for hard-to-treat depression and other conditions.

In a small open-label trial at a hospital, a single dose of 25 mg psilocybin was given to 12 patients with severe treatment-resistant depression (TRD). The results showed a clear drop in depression scores at both three and twelve weeks after treatment. The study also noted that aspects of the psychedelic experience, such as strong feelings of oneness, were linked to better outcomes. Patients with additional post-traumatic stress symptoms (PTSD) did not respond as well.

A randomized trial looked at group-format psilocybin-assisted therapy combined with mindfulness-based stress reduction for frontline healthcare providers suffering from depression and burnout during the pandemic. In this study, participants who received both therapies experienced a greater drop in depression and burnout scores than those who only took part in mindfulness training. These findings align with a December study of frontline clinicians, which also found that psilocybin therapy significantly reduced depression symptoms compared to a control group. The group approach may also offer benefits by fostering a sense of support among colleagues. No serious side effects were seen in either group, making this combined treatment a promising option for stressed healthcare workers.

A secondary analysis of a Phase IIIb trial compared esketamine nasal spray plus an SSRI/SNRI with quetiapine XR (extended-release) plus an SSRI/SNRI in patients with treatment-resistant depression. In this study of 676 patients, those treated with esketamine reached remission faster and maintained it longer than those receiving quetiapine. The safety findings were similar between the two groups.

Another secondary analysislooked at the effects of subcutaneous (injection under the skin) ketamine on anxiety in people with treatment-resistant depression (for which the results are published in this study). In this trial, one group of patients received a flexible dose of ketamine and showed a significant reduction in anxiety scores at the end of treatment. In contrast, a fixed low dose did not yield meaningful improvements. The reduction in anxiety was partly linked to improvements in depression scores. However, the benefits on anxiety did not last long after the treatment ended.

A reanalysis of a Phase II trial examined personality changes in patients with alcohol use disorder (AUD) after psilocybin-assisted therapy. The study found that patients who received psilocybin had lower levels of neuroticism and higher levels of extraversion and openness compared to those who received an active placebo. In addition, a decrease in impulsiveness was related to less alcohol use after treatment. These results point to the possibility that psilocybin therapy may help adjust personalitytraits that contribute to alcohol problems.

Healthcare Utilisation, Observations, and Mechanisms

Next to clinical trials in patients, six more studies caught our eye this month. These studies use observational methods and secondary analyses to explore how psychedelic treatments work, their safety, cost aspects, and support strategies. The research here dives into drug action, patient outcomes, and even real-world cost use to offer a deeper view of treatment processes.

A systematic review and meta-analysis of esketamine as an add-on treatment for treatment-resistant depression found only modest improvements (effect sizes between 0.15 and 0.23). The authors raised concerns about abuse potential and regulatory issues. Notably, this study used lower doses than those common in clinical practice; however, sensitivity analyses confirmed its modest efficacy, which counters the prevailing view on ketamine’s effectiveness.

Alongside this meta-analysis, a large retrospective study of patients with major depressive disorder (MDD) and acute suicidal ideation (SI) revealed that esketamine nasal spray led to lower acute care use and reduced medical costs compared to electroconvulsive therapy and antipsychotic augmentation. Together, these studies provide a balanced look at both the clinical benefits and economic impacts of esketamine treatment.

A secondary analysis of a trial in 31 healthy male volunteers tested a new formulation combining DMT and harmine. The study showed that intranasal DMT, paired with buccal harmine (together also referred to as ‘pharmahuasca’), produces consistent drug levels and safe, well-tolerated effects similar to those seen with ayahuasca, with subjective experiences lasting about 2–3 hours. This controlled approach may offer a standardised and safer alternative to traditional preparations.

An observational study from a retreat with 83 participants looked at factors influencing the outcomes of psilocybin-assisted therapy (with psilocybin-containing truffles). The study found that a single high dose of psilocybin reduced symptoms of anxiety, depression, and PTSD over three months while boosting traits like openness and conscientiousness. It also noted that the quality of the psychedelic experience—such as mystical feelings, emotional breakthroughs, and a sense of personal growth—played a role in how well patients improved.

A descriptive study introduced the Compass Psychological Support Model used in clinical trials for psilocybin treatment in serious mental health conditions. This model outlines how trained therapists prepare participants, provide minimal support during the dosing session, and guide patients through integration sessions afterwards. The structured approach aims to ensure a safe and meaningful psychedelic experience while maintaining high standards of therapy delivery.

Finally, in a single-blind study with 11 healthy participants, researchers examined changes in belief confidence after psilocybin dosing. They found that a 25 mg dose reduced the strength with which participants held negative self-beliefs, and this change predicted improvements in well-being four weeks later. This work – which we previously covered in July 2022 as a pre-print – provides the first psychological support for the REBUS model, suggesting that loosening rigid negative beliefs may be a key factor in the lasting benefits of psychedelic therapy.