Psychedelic Research Recap December 2024

Welcome back to our monthly update on psychedelic research!

December saw a noticeable slowdown in new psychedelic research publications, with 14 studies added to the Blossom database compared to the monthly average of 20. This seasonal dip is not uncommon, as research efforts often wind down toward the end of the year. Despite this, our team added 130 more articles to the link overview, a significant number of which were reviews and preclinical studies using animal models.

This month’s recap covers key research across several categories. Clinical studies were prominent in examining psilocybin therapy for healthcare workers, the safety profile of 3-MMC, and the therapeutic potential of intravenous DMT. Re-analyses of earlier clinical data provided deeper insights into esketamine’s efficacy compared to quetiapine, the link between psilocybin-induced experiences and depression outcomes, and the personality changes facilitated by psilocybin therapy. Reviews tackled broader themes, including the variability in reporting standards for psychedelic-assisted therapy, the neural and pharmacological effects of psychedelics, and healthcare workers’ attitudes toward their clinical application.

Finally, broader perspectives addressed the practical challenges of establishing psychedelic research programs and the regulatory shift in Australia allowing psilocybin and MDMA for specific conditions. Together, these studies and discussions reflect the growing maturity of psychedelic science while underlining the need for standardization, broader education, and global collaboration to maximise its therapeutic impact.

This month’s recap is made possible by our supporting members.

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

Five Clinical Studies on Psychedelics

In a relatively slow month (only 14 studies were added), four studies covered clinical research.

The first is a randomized trial that investigated psilocybin therapy in 30 clinicians experiencing depression and PTSD after providing frontline care during the COVID-19 pandemic. Participants receiving psilocybin showed significant reductions in depression scores compared to those given niacin (active placebo), though improvements in PTSD symptoms and burnout were not statistically significant. This study emphasizes the potential for psilocybin therapy to address the mental health challenges faced by healthcare workers, offering a promising avenue for real-world implementation aimed at “healing the healer.”

We covered the second study as a pre-print last month. The placebo-controlled trial explored the safety and cognitive effects of 3-MMC, a synthetic cathinone, in 14 participants. The study reported dose-dependent increases in heart rate and blood pressure (within clinically safe limits), improved cognitive performance, and mild dissociative and psychedelic effects. Appetite suppression and transient increases in drug liking and wanting were also observed. These findings establish the safety profile of low to moderate doses of 3-MMC and underscore the need for further research on its risks at higher doses.

A crossover study examined the effects of continuous intravenous DMT infusions in 22 participants, with infusion rates ranging from 0.6 to 2.4 mg/min. Results revealed dose-dependent effects, with moderate doses (1.8 mg/min) producing tolerable and positive experiences, while higher doses led to anxiety and ego dissolution. Participants successfully self-titrated doses to their preferred intensity (which was relatively ‘high’), demonstrating the viability of flexible dosing protocols. This research advances understanding of DMT’s pharmacokinetics and its potential for controlled therapeutic use.

A final study investigated the neural and subjective dynamics of medium- and high-dose DMT under naturalistic conditions. Nineteen participants received 20 or 40 mg of freebase DMT, with neural activity monitored using EEG and subjective experiences tracked via time-sensitive measures. The higher dose produced more intense visual hallucinations and emotional responses, while neural analyses showed that alpha power reductions and entropy increases correlated with subjective experiences. The findings challenge assumptions about established neural markers of psychedelic states, offering new insights into DMT’s effects on consciousness.

Re-analyses of Clinical Data

Next to the new clinical results, another four studies analysed data from earlier trials through new lenses.

A new analysis of the ESCAPE-TRD Phase IIIb trial compared esketamine nasal spray (Spravato) to quetiapine extended release in 676 patients with treatment-resistant depression. Esketamine significantly outperformed quetiapine in achieving remission at week 8 and maintaining relapse-free status through week 32. Sensitivity analyses confirmed esketamine’s consistent superiority across varying definitions of remission and relapse. This head-to-head trial addresses a critical gap in psychedelic research, where direct comparisons between treatments remain rare, and highlights esketamine’s robust efficacy (at least in this trial) in managing treatment-resistant depression.

A re-analysis of the COMPASS Phase IIb trial explored the relationship between psilocybin doses, subjective psychedelic experiences, and therapeutic outcomes in 233 individuals with treatment-resistant depression (TRD). Participants received one dose of 25 mg, 10 mg, or 1 mg of psilocybin (the latter as a control) alongside psychological support. Results showed that higher doses induced stronger psychedelic experiences, with therapeutic outcomes most closely tied to specific experiential dimensions such as Oceanic Boundlessness, Visual Restructuralization, and Emotional Breakthrough. These findings suggest that the quality and intensity of the psychedelic experience significantly mediate therapeutic effects, highlighting the importance of both dose and subjective experience in psilocybin treatment for depression.

A separate re-analysis examined the impact of psilocybin-assisted therapy on empathy in 51 patients with major depression. Participants who received a single psilocybin dose (15 mg/70 kg) during a 4-week psychological support program demonstrated significant increases in emotional empathy, particularly toward positive stimuli, compared to those receiving placebo. These effects lasted up to two weeks. While no direct correlation was found between changes in empathy and reductions in depressive symptoms, the increase in emotional empathy could enhance social interactions and improve therapeutic alliances, offering broader psychosocial benefits for individuals with depression.

In another study, a re-analysis investigated personality changes following a single high dose of psilocybin (25 mg) in 28 healthy, psychedelic-naïve volunteers. Results showed significant reductions in neuroticism one month after the session, with greater changes observed in participants who reported highly meaningful experiences or ego dissolution. Interestingly, neurophysiological markers such as alpha power and brain complexity were linked to the intensity of psychological insights but did not directly predict personality changes. These findings emphasize the role of subjective experiences in catalyzing lasting psychological transformations, suggesting that set, setting, and emotional breakthroughs are critical factors in achieving beneficial outcomes.

Understanding Psychedelic Therapy and Attitudes of Healthcare Workers

Taking a broader view than the individual studies, three systematic reviews investigate the therapeutic component, psychedelics’ effects on the brain and mind, and how healthcare workers view psychedelic-assisted therapy.

A systematic review of 45 studies highlighted the low completeness and high heterogeneity in reporting psychological interventions for psychedelic-assisted therapy. The analysis found that MDMA studies, guided by standardized manuals from MAPS, offered more procedural detail and consistency compared to studies on psilocybin, LSD, and ayahuasca. Across these studies, descriptions of preparatory sessions, dosing protocols, and integration processes varied widely, with limited information on therapist roles and training (now, writing in January, one more protocol study around the Compass trial has been published – but more information on the trial designs – and especially the therapeutic component is warranted). This lack of standardization raises concerns about replicability, safety, and the accurate interpretation of research outcomes. Enhanced reporting standards are critical to establishing evidence-based guidelines, improving the generalizability of results, and supporting the real-world application of psychedelic treatments.

Another systematic review and meta-analysis synthesized data on the phenomenology, neuroimaging, and pharmacology of psychedelics. Findings revealed that LSD induces higher ratings of visionary restructuralisation than psilocybin, particularly at medium and high doses, while also promoting stronger between-network functional connectivity in the brain. Pharmacologically, LSD was more potent in activating serotonin receptors compared to DMT and psilocin, though receptor selectivity was similar across substances. The review emphasized the non-linear relationships between subjective experiences, brain activity, and receptor dynamics, pointing to significant gaps in standardisation across studies. Integrating these domains through more uniform methodologies and advanced data modeling could deepen our understanding of how psychedelics produce their effects and enhance their therapeutic potential.

A systematic review of healthcare workers’ attitudes toward psychedelic-assisted therapy (PAT) for patients with serious illnesses revealed polarized views. While most healthcare workers acknowledged the potential benefits of psychedelics in addressing refractory distress, many expressed concerns about the current evidence base and called for further research. The review identified key themes, including the need for stronger clinical evidence, education on PAT, and team-based approaches to integrate psychedelics into existing care models. Barriers such as regulatory challenges, stigma, and a lack of familiarity with psychedelic treatments were also highlighted.

Broader Perspectives on Implementing Psychedelic Research and Practice

Establishing psychedelic research programs faces unique challenges, from regulatory hurdles to stigma surrounding Schedule I substances. A recent perspective article for U.S. academic medical centers highlighted the importance of cultivating institutional support, securing funding, and navigating complex regulations. Researchers are advised to engage regulatory bodies like the FDA and DEA early, create secure and welcoming study spaces, and foster interdisciplinary collaboration. Despite these obstacles, strategic planning and persistence have enabled many institutions to launch programs, advancing the field of psychedelic science successfully.

Australia’s 2023 decision to approve psilocybin for treatment-resistant depression and MDMA for PTSD offers a global blueprint for integrating psychedelics into psychiatric care. The approval, spearheaded by Mind Medicine Australia (MMA), limited prescribing rights to trained psychiatrists under strict protocols. This cautious approach ensures high safety standards while addressing the urgent need for alternative treatments. Early data from Australia’s real-world applications could accelerate similar approvals worldwide, providing valuable insights into the practical implementation of psychedelic therapies.

What you can find on Blossom

Last month, we added 14 studies to the database of over 2200 research publications. Our link overview provides links to an additional 129 studies.

If you enjoy Blossom, please subscribe to our weekly psychedelic research newsletter. Join us with any level of membership to browse the website without limits.