As interest in psychedelic-assisted therapies (PATs) grows, so does the need for clearer safety guidelines. Psychedelic treatments using substances like psilocybin, LSD, and MDMA are being explored for mental health issues like depression and PTSD, showing promising results. The FDA has granted breakthrough therapy status to some, but its recent rejection of MDMA for PTSD due to safety concerns highlights the need for standardized assessments of adverse events (AEs) in these therapies.

While research has largely focused on their benefits, assessing the risks and AEs related to these therapies has not been as thorough. A new framework published in the Journal of Psychopharmacology seeks to change that, introducing a comprehensive approach for identifying, monitoring, and reporting potential negative effects specific to psychedelic therapies.

The Need For Tailored Adverse Event Reporting

Psychedelic-assisted therapies are different from traditional treatments because they combine the effects of powerful psychedelic substances with psychotherapy. This combination can lead to unique experiences such as intense visual effects, spiritual insights, and deep psychological changes that standard safety assessments often overlook. Current guidelines for reporting side effects in clinical trials, like those in the Medical Dictionary for Regulatory Activities, may not fully capture these unique effects. 

Author Roman Palitsky and his team have created a new framework to address this gap. It outlines 54 potential adverse events specific to psychedelic therapies, covering physical, mental, and spiritual impacts. “Psychedelic therapies require specialized guidelines because they blend strong pharmacological effects with psychotherapy,” said Palitsky. This new approach aims to provide a more detailed understanding of the risks, which can help researchers and clinicians better protect patients.

Challenges Of Identifying Adverse Events

A key issue in assessing side effects in psychedelic therapy is underreporting. Patients may avoid mentioning negative experiences, especially if they support the push to decriminalize psychedelics. Therapists may also overlook or misinterpret adverse events due to their own expectations about the treatment’s benefits.

The framework suggests using self-reports, clinician observations and feedback from those close to the patient to better assess side effects. It distinguishes between normal discomfort, like facing tough emotions and genuine adverse events, such as lasting anxiety or depression. In some cases, these issues can lead to severe outcomes, as seen in some psilocybin trials.

New Areas of Focus for Safety Assessments

The framework introduces several new categories for tracking adverse events specific to psychedelic therapies: Psychospiritual Issues, which involve negative impacts on spiritual beliefs or existential well-being; Interpersonal Issues, such as changes in social behavior due to psychedelics' effects on brain systems; Behavioral Changes, like disrupted sleep or increased substance use and Cultural and Epistemic Harms, which address potential conflicts with a patient's cultural or religious beliefs. These categories highlight the unique risks of combining psychedelics and psychotherapy, offering a more detailed approach to patient safety.

Importance of Long-Term Monitoring

The framework emphasizes the need for extended follow-up, as many adverse effects may not become apparent until weeks or even months after the therapy session. This long-term monitoring is critical because the changes induced by psychedelics can have lasting effects on a person's worldview, relationships and overall well-being.

“Changes brought about by psychedelic experiences can take time to fully emerge, making long-term follow-up essential for accurate assessment,” the authors suggest. They recommend assessing adverse events for at least six months after treatment, allowing researchers to capture any delayed effects that might otherwise go unnoticed.

Moving Towards Safer Psychedelic Therapies

This new framework is a significant advancement in psychedelic research, offering a structured approach to track side effects more effectively. By identifying a wider range of risks, it helps clinicians make informed decisions and improve patient safety. Future studies will need to validate and refine the framework to ensure it captures all potential adverse events.

In summary, Palitsky’s framework provides a comprehensive method to standardize safety reporting in psychedelic therapies, playing a key role in making these treatments safer and more reliable as they move toward mainstream use.

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