In recent years, psychedelics such as psilocybin, LSD, and DMT have gained attention for their potential therapeutic effects on mental health disorders like depression, anxiety, and PTSD. However, as their medical use expands, so too does the need for a thorough understanding of their safety and limitations. A new systematic review published in JAMA Psychiatry explored how adverse events (AEs) are associated with psychedelics, focusing on their nature, frequency, and severity.
What are adverse events in psychedelic therapy?
In clinical settings, adverse events (AEs) refer to any undesirable effects that occur after the administration of a drug. These events are divided into two categories: serious adverse events (SAEs) and non-serious adverse events (NSAEs). SAEs include life-threatening symptoms such as psychosis, seizures, or suicidal thoughts, while NSAEs are milder reactions like headaches, nausea, or anxiety. Although both types of AEs require monitoring, SAEs are more concerning, as they can severely impact a patient’s mental or physical health.
In clinical research, AEs are closely tracked through systematic assessments and follow-ups to ensure that participants are not at risk. Yet, despite this diligent monitoring, concerns persist about underreporting or incomplete detection of AEs, as pointed out in the recent JAMA Psychiatry review. This concern is particularly relevant as psychedelics become more widely used in therapeutic settings, highlighting the need for better pharmacovigilance to fully understand the risk profiles of these substances.
Findings from the study: how safe are psychedelics?
The study conducted a meta-analysis of 114 studies involving over 3,500 participants, aiming to assess the safety of psychedelics like psilocybin, LSD, and DMT in clinical settings. Encouragingly, no SAEs were reported among healthy participants. However, for those with preexisting mental health conditions, approximately 4% experienced serious side effects such as worsening depression, suicidal thoughts, or psychotic episodes1. This finding emphasizes the importance of exercising caution when using psychedelics in vulnerable populations.
In terms of non-serious adverse events (NSAEs), the study found that while mild issues like nausea, headaches, and anxiety were relatively rare, they were not unheard of. These reactions were comparable across different psychedelics, including LSD and psilocybin. For example, nausea and headaches were reported more frequently in studies involving psilocybin, as demonstrated in a separate meta-analysis of clinical trials treating depression and anxiety with psilocybin, published earlier this year 2. Despite these mild effects, both LSD and psilocybin were generally well-tolerated in controlled environments.
How Common Are Adverse Events?
The overall incidence of AEs in psychedelic-assisted therapy appears to be low. The review highlighted that, across all studies, serious side effects were rare, occurring only in those with preexisting mental health conditions. Among healthy individuals, no SAEs were reported, and NSAEs were infrequent and typically mild.
Another study focused on magic mushroom-related emergency medical treatment (EMT) incidents found that the rate of such incidents was extremely low, with only 0.2% of users seeking medical attention after using psilocybin-containing mushrooms recreationally3. This equates to about 1 in 1,800 people needing medical intervention after ingestion, a figure that reflects the relative safety of psilocybin in non-clinical settings when compared to other recreational substances.
Who is most at risk for serious side effects?
Those with preexisting mental health conditions, particularly mood disorders like depression or psychosis, are at higher risk for experiencing SAEs during psychedelic use. The JAMA Psychiatry meta-analysis reported that about 4% of participants with neuropsychiatric disorders experienced worsening symptoms, including depression and suicidal behavior.
In recreational settings, younger individuals were more likely to seek EMT after using psychedelics, with adverse events such as panic, paranoia, and fainting being the most commonly reported symptoms. This age-related vulnerability may be due to lower risk aversion and emotional regulation in younger users.
How safe are psychedelics for people without mental health conditions?
For healthy individuals, psychedelics appear to be relatively safe when used in controlled environments. The review found no instances of SAEs among healthy participants, suggesting that the risk of serious mental or physical health issues is low for those without preexisting conditions. However, common NSAEs like headaches, nausea, and anxiety were still observed in some studies.
A second study on the acute effects of psilocybin found that while mild side effects like dizziness and elevated blood pressure were more common, they were generally short-lived, resolving within 24 to 48 hours. This tolerability suggests that psychedelics may be safe for broader populations, although further research is needed to fully understand long-term effects.
Why is monitoring important?
Given the rarity but potential severity of SAEs in vulnerable populations, consistent and thorough monitoring of psychedelic use in clinical settings is essential. Current research highlights the gaps in AE reporting, with only a small percentage of recent studies using systematic methods to track these events. This underreporting could obscure our understanding of the full spectrum of risks associated with psychedelics, particularly in therapeutic contexts.
Improving pharmacovigilance—continuous safety monitoring of drug use—could help researchers better predict and manage adverse reactions. This is especially important as psychedelic-assisted therapy continues to expand, with ongoing studies exploring its application for a wide range of mental health disorders. Monitoring is also crucial for the development of safety guidelines, which can ensure that psychedelic treatments are administered with minimal risk.
The future of psychedelic therapy
As psychedelics gain traction in the medical field, understanding their safety profile is crucial for ensuring patient well-being. The recent meta-analysis suggests that psychedelics are generally safe for healthy individuals, with few serious adverse events reported. However, for those with preexisting mental health conditions, caution is advised, as SAEs like worsening depression or psychotic episodes are more common.
To ensure the safe use of psychedelics in therapeutic settings, ongoing monitoring and improved reporting of AEs are essential. This will help medical professionals better understand and mitigate risks, paving the way for more effective and safer psychedelic therapies in the future.
References
- Hinkle, Jared T, et al. “Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis.” JAMA Psychiatry, 2024, jamanetwork.com/journals/jamapsychiatry/article-abstract/2822968, https://doi.org/10.1001/jamapsychiatry.2024.2546. ↩︎
- Yerubandi, Akhila, Jennifer E. Thomas, N. M. Mahmudul Alam Bhuiya, Catherine Harrington, Lorenzo V. Zapata, and Joshua Caballero. “Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis.” JAMA Network Open 7, no. 4 (2024). https://doi.org/10.1001/jamanetworkopen.2024.5960. ↩︎
- Kopra, Emma I., Jason A. Ferris, Adam R. Winstock, Allan H. Young, and James J. Rucker. “Adverse Experiences Resulting in Emergency Medical Treatment Seeking following the Use of Magic Mushrooms.” Journal of Psychopharmacology (Oxford, England) 36, no. 8 (2022): 965-973. https://doi.org/10.1177/02698811221084063 ↩︎
