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.

This month, we'll focus on several key topics that could be useful for clinical practice. We'll look at the long-term effects of LSD- and psilocybin-assisted therapy. We’ll also discuss the highly anticipated brain imaging study that gave us the best picture of the tripping brain to date.

Unexpected Durability of Therapeutic Effects

One of the significant advantages of psychedelic-assisted therapy over traditional medications is the potential for long-lasting therapeutic effects after only a few sessions. Traditional treatments for conditions like anxiety and depression often require continuous, sometimes lifelong, administration. Psychedelics, however, might offer sustained relief from symptoms with just a handful of dosages, raising important questions about their long-term efficacy and safety.

A recent study conducted at the University of Basel provides compelling evidence of the long-term benefits of psychedelic therapy. This rigorous follow-up study involved 39 participants and investigated the effects of LSD-assisted therapy on anxiety over an extended period, up to 94 weeks post-treatment. 

The findings were promising: participants reported sustained reductions in anxiety and depression, with 33% achieving remission from anxiety and 49% from depression. Additionally, personality traits such as neuroticism decreased, while extraversion increased, indicating positive, lasting changes attributed to the psychedelic experience.

These findings are consistent with earlier studies but add a new layer of understanding. For instance, a systematic review published in 2020 synthesized results from 34 studies on the long-term effects of classical psychedelics. This review highlighted enduring changes in personality, emotional well-being, and mental health, linked to profound experiences of connectedness and emotional breakthroughs during psychedelic sessions. 

Similarly, another long-term follow-up study on psilocybin-assisted therapy for cancer-related distress reported sustained reductions in anxiety and depression, with participants attributing significant positive life changes to their psychedelic experiences.

The recent LSD study employed a robust methodology, including a double-blind, placebo-controlled, crossover design, which strengthens the validity of its findings. Participants received two sessions of either oral LSD (200 μg) or placebo, with follow-ups occurring on average 81 weeks after the last treatment. The results showed significant reductions in anxiety and depression scores compared to baseline, and participants reported the experience as one of the most meaningful in their lives, highlighting the profound impact of the therapy.

Real-World Experiences in Canada

In the context of Canada’s Section 56 exemption, which allows for the legal use of psilocybin-assisted psychotherapy, a recent observational study sheds light on the practical applications and effects of this therapeutic approach. This prospective longitudinal survey included eight participants, all with cancer diagnoses, who were granted exemptions to legally receive psilocybin therapy. The study provides valuable insights into the real-world implications and challenges of psychedelic therapy, reflecting practices closer to how many clinicians currently work with these substances.

Participants in the study, with an average age of 52, showed significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks post-treatment. These findings are encouraging, demonstrating that even a short duration after treatment can yield considerable benefits. Most participants found the sessions to be highly meaningful, despite being challenging, which is consistent with the transformative potential often reported in psychedelic therapy.

However, it is essential to note that the study also highlighted some challenges. One participant reported a substantial decrease in well-being following the psilocybin session, underscoring the variability of individual responses to psychedelic therapy. This points to the necessity of careful screening, preparation, and follow-up to mitigate potential negative outcomes. Unlike the longer-term study on LSD we just discussed, this study’s two-week follow-up period may not fully capture the enduring effects or possible adverse reactions that could emerge over time.

The Canadian Section 56 exemption provides a legal framework for accessing psilocybin, but it comes with its own set of challenges. Patients must navigate the application process and, in many cases, bear the costs of obtaining and administering the substance. 

Out of Sync Brain on Psilocybin

A recent brain imaging study provides critical insights into the profound changes that psilocybin induces in brain connectivity. This study involved 24 healthy adults who underwent brain imaging before, during, and up to three weeks after taking a high dose of psilocybin (25 mg) or an active placebo (methylphenidate; Ritalin), with some participants returning for follow-up sessions six to twelve months later. The findings revealed that psilocybin caused over threefold greater acute changes in functional brain networks than methylphenidate, particularly affecting the default mode network (DMN), which is integral to our sense of self.

For clinicians and practitioners, these results underscore the significant impact of psilocybin on brain function, offering a potential mechanism for its therapeutic effects. The study found that psilocybin led to a persistent decrease in connectivity between the anterior hippocampus and cortex, especially the DMN, lasting for weeks but normalizing after six months. 

This desynchronization of brain networks might explain psilocybin's ability to promote neuroplasticity and its antidepressant effects. To help explain this to patients, an analogy could be likening the brain to an orchestra: psilocybin temporarily disrupts the synchronized playing of the musicians (neurons), creating a new harmony that can lead to lasting changes in performance (mental state).

The study's use of precision functional mapping (PFM) allowed for detailed tracking of individual-specific brain changes. This method involves dense, repeated resting-state fMRI scans to observe how brain connectivity evolves over time. The observed desynchronization primarily affected the DMN, which is known to support self-referential thinking and daydreaming. This network is crucial for maintaining a stable sense of identity and temporal continuity. The disruptions in the DMN align with the subjective experiences reported during psilocybin sessions, such as ego dissolution and altered perceptions of space and time.

Interestingly, the study also found that engaging in a perceptual task during the psilocybin session reduced these disruptions, suggesting a potential strategy for grounding individuals during psychedelic therapy. This insight could be highly relevant for practitioners looking to optimize the therapeutic context for psilocybin administration.

Moreover, the persistent decrease in connectivity between the anterior hippocampus and the DMN observed in the study suggests a possible neuroanatomical basis for psilocybin's enduring therapeutic effects. The anterior hippocampus is involved in memory and emotional processing, and its altered connectivity with the DMN might contribute to psilocybin's ability to facilitate emotional breakthroughs and cognitive flexibility. These changes could underlie the reported improvements in mood and reductions in depressive symptoms following psilocybin therapy.

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July 2024 in Psychedelic Research

The studies reviewed this month provide compelling evidence of the long-lasting and profound effects of psychedelic-assisted therapy. The research on LSD underscores the potential for these substances to offer durable therapeutic benefits after just a few sessions, challenging the traditional continuous medication model. The insights from the Canadian real-world study highlight both the promise and the practical challenges of integrating psychedelic therapy into clinical practice, underlining the importance of careful patient selection and follow-up. Meanwhile, the brain imaging study offers a detailed view of how psilocybin alters brain connectivity, providing a potential mechanism for its therapeutic effects and reinforcing the importance of context in psychedelic therapy.

For clinicians and practitioners, these findings are not just academic; they have practical implications for how psychedelic therapies can be implemented and optimized. As the legal landscape evolves and more pathways for access open, staying informed about the latest research will be crucial for providing the best care to patients. The potential for psychedelics to transform mental health treatment is immense, and ongoing research will continue to illuminate how these powerful substances can be harnessed safely and effectively.