Stay up to date on the latest research in psychedelic medicine

Every month, around 100 new studies on psychedelics are published, adding to what we know about these substances. To help clinicians and practitioners stay up-to-date with the most important findings, the Psychedelic Provider Network has teamed up with Blossom to review the latest studies.

August 2024 Research Summary

Every month, around 100 new studies on psychedelics are published, adding to what we know about these substances. To help clinicians and practitioners stay up-to-date with the most important findings, the Psychedelic Provider Network has teamed up with Blossom to review the latest studies from August 2024. 

This month, we'll focus on several key topics that could be useful for clinical practice. We'll look at the evidence for the effectiveness of the number of psilocybin doses. We’ll also discuss the prevalence and causes of false beliefs resulting from psychedelic therapy. Finally, we’re covering the gut-brain axis and its relationship to psychedelics.

Dosing Strategies for Psilocybin in Depression Treatment

What is the optimal dosing schedule for psychedelic-assisted therapies? Between costs, efficacy and the need for optimizing patient outcomes, there is often a difficult balancing ongoing. A recent systematic review and meta-analysis has shed light on the efficacy of single-dose versus two-dose psilocybin administration in treating major depressive disorder (MDD) and treatment-resistant depression (TRD). This comprehensive study covered 12 clinical trials and exactly 600 patients.

The review found that psilocybin is highly effective in reducing depressive symptoms in both MDD and TRD patients, regardless of whether a single dose or two doses were administered. While two-dose treatments showed a trend towards more pronounced and lasting effects, the difference was not statistically significant. This finding underscores the potent therapeutic potential of psilocybin, even with a single administration.

However, it's crucial to contextualize these findings within the broader landscape of psychedelic research and therapy. A significant portion of the data (over one-third) comes from a single trial by Compass Pathways, which utilized a relatively minimal therapy protocol alongside a single psilocybin dose. This contrasts with many other studies that have employed two doses, and with established protocols in MDMA-assisted therapy, where three doses are standard practice.

Furthermore, when considering these results, it's important to note the evolving understanding of dosing strategies in psychedelic therapy. For instance, ketamine treatment for depression, with or without psychotherapy, typically involves multiple sessions - often half a dozen or more. This multi-session approach allows for cumulative effects and ongoing integration of the experience.

Navigating the Risks of Psychedelic-Induced Beliefs

Psychological insights are often a vital part of the healing process regardless of the number of sessions. But what if not all insights gained during a psychedelic trip are to be trusted? A recent review examines the complex relationship between psychedelics, insights, and the formation of potentially false beliefs. The study proposes that psychedelics increase both the quantity and subjective intensity of insights. While many of these insights can be therapeutically beneficial, some may lead to false or maladaptive beliefs.

This phenomenon, termed False Insights and Beliefs Under Psychedelics (FIBUS; reminding us of the REBUS framework), occurs through several mechanisms. These include decreased precision weighting of existing beliefs, increased precision weighting of novel, dopamine-modulated insights, and enhanced feelings of familiarity, regardless of accuracy. During psychedelic experiences, the brain's usual constraints on perception and cognition are relaxed, allowing for new interpretations of sensory data and the generation of novel ideas. While this process can lead to valuable therapeutic breakthroughs, it also opens the door to potentially misleading or false insights.

The danger of false insights lies in their potential to become deeply entrenched. The intense, emotionally charged nature of psychedelic experiences can imbue these insights with a profound sense of truth and significance, making them resistant to later revision. This is particularly concerning in clinical settings, where false beliefs could potentially exacerbate existing mental health issues or create new ones. The study suggests that the subjective feeling of insight is not necessarily indicative of a genuine breakthrough, and that psychedelic-occasioned insights may be particularly difficult to revise due to the strong noetic feelings accompanying them.

Exploring the Gut-Brain Axis in Psychedelic Therapy

The last two decades have witnessed a remarkable resurgence in psychedelic research, with most studies focusing on behavioral outcomes and neurological changes in individuals benefiting from psychedelic therapies. Concurrently, another field of research has been flourishing, centered on the gut microbiome and its profound implications for human health. The Microbiome-Gut-Brain Axis (MGB) has emerged as a crucial pathway influencing brain function and behavior, highlighting the intricate bidirectional communication between our digestive system and central nervous system. 

As these two fields converge, a recent review has shed light on an often-overlooked aspect of psychedelic therapy: the potential role of the gut microbiome in mediating the effects of these compounds on behavior and mental health. This timely research comes as gut-brain axis studies are gaining significant momentum in the broader fields of neuroscience and psychiatry, offering new perspectives on how psychedelics may exert their therapeutic effects and potentially revolutionizing our understanding of their mechanisms of action.

The review argues that the current understanding of psychedelic mechanisms, which primarily focuses on serotonin 2A receptor agonism in the brain, is incomplete. It proposes that a more comprehensive model should incorporate the gut microbiome and its bidirectional interactions with the brain. This perspective is particularly intriguing when we consider that the majority of serotonin receptors in the human body are actually located in the gut, not the brain. This fact alone suggests that psychedelics may have significant effects on gut function and, by extension, on the microbiome that resides there.

The authors present evidence suggesting that psychedelics may directly affect the composition of the gut microbiota. While research in this area is still in its infancy, preliminary studies and anecdotal reports indicate that psychedelics can induce changes in gut microbial populations. Conversely, the gut microbiome may play a role in modulating responses to psychedelics, potentially influencing their metabolism, bioavailability, and ultimately, their psychological effects. This two-way interaction opens up new avenues for understanding the variability in individual responses to psychedelic therapies.

For clinicians and practitioners working with psychedelics, these findings present both opportunities and challenges. On the one hand, they suggest the potential for developing more personalized approaches to psychedelic therapy based on individual microbiome profiles. This could lead to more targeted and effective treatments, potentially allowing practitioners to predict and optimize therapeutic outcomes. On the other hand, the complexity of these interactions underscores the need for a more holistic approach to psychedelic therapy, one that considers not just brain chemistry, but also gut health and the broader ecosystem of the body.

However, it's important to note that this research is still in its early stages, and there are currently no specific, evidence-based recommendations for practitioners to alter their approaches based on gut health considerations. The findings primarily serve to highlight the need for further research and to encourage a more comprehensive understanding of psychedelic mechanisms.

---

August 2024 in Psychedelic Research

This month's studies give us a broad look at psychedelic therapy, showing both its challenges and its promise. We learned that one dose of psilocybin is just as effective as two doses, but that in the broader landscape of psychedelic-assisted therapy two or more doses is more common. We also saw how important it is for therapists to help patients make sense of their experiences, especially when it comes to spotting false insights. The new research on how the gut and brain work together during psychedelic therapy opens up exciting possibilities for more personalized treatments. 

For those working with patients, these findings show why looking at the whole person is crucial - their brain, gut, beliefs, and unique needs. As we learn more about psychedelic medicine, staying up-to-date with this wide range of research will help provide the best care. Psychedelics have enormous potential to change how we treat mental health, and ongoing studies will help us understand how to use these powerful substances safely and effectively.