Lucas Kosobuski, PharmD, Welia Health - Mora, MN
Background: Modern psychedelic medication or entheogen research began in 1938 after the synthesis of lysergic acid diethylamide (LSD) by the Swiss chemist Albert Hofmann. Research and use of psychedelic compounds for the treatment of a variety of mental health disorders peaked during the 1950s and 60s with a multiplicity of compounds being found to be either promising or life-changing treatments for patients. Papers of the era, written by such authors as Kurland, Grof, Kast, Abramson, Bender, O’Reilly, Ludwig, Geert-Jörgensen and colleagues asserted psychedelics as treatments for ailments such as cancer induced pain, alcohol/substance use disorders, and refractory depression/anxiety, as well as aiding patients in coming to terms with mortality. Research into these compounds was halted via a combination of the 1970 Controlled Substances Act making psychedelics Schedule 1 substances and growing stigma surrounding these medications. In recent decades, there has been a renaissance in psychedelic research with rediscovery of information known to our 1950s and 60s counterparts and revelations of these medications as possible treatment options for mental health patients. The 2023 meta-analysis by Bahji and colleagues adds to this rediscovery by analyzing the safety and efficacy of LSD, psilocybin, 3,4-methylenedioxymethamphetamine (MDMA), and ayahuasca in adults suffering from anxiety, depression, and posttraumatic stress disorder (PTSD).
Objective: The objective of Bahji and colleagues was to analyze the efficacy and safety of LSD, MDMA, psilocybin, and ayahuasca in treating adults suffering from PTSD, depression, and anxiety.
Study Design: Bahji and colleagues’ systematic review and meta-analysis analyzed articles published after the year 2000 that included adult patients afflicted with depression, anxiety, or PTSD who were treated with LSD, MDMA, psilocybin, or ayahuasca and included a control group given a placebo or active placebo. Articles were selected if they met the previous criteria and had, at minimum, one efficacy measurement.
Results: In total, 3584 articles were identified, with 18 included in the final analysis. All 18 studies were noted to be at high risk for bias due to poor blinding caused by participants being able to easily discern their treatment group. MDMA and psilocybin were found to significantly reduce depression symptoms (95% CI, -1.39 to 0.03, and -2.73 to -1.11, respectively). Palhano-Fontes and colleagues found ayahuasca to be an effective antidepressant, but this article was excluded from the analysis due to being the only one of its kind. Overall, LSD did not have a significant effect on depression (95% CI, -5.05 to 1.15), but a study by Gasser and colleagues found LSD to be effective for treating depression in cancer patients. Overall, psychedelics were found to be effective for anxiety (95% CI, -4.13 to -0.76). However, when individual medications were analyzed, psilocybin was the only one to significantly reduce anxiety (95% CI, -2.16 to -0.51). Of the articles analyzed by Bahji and colleagues, those articles that specifically analyzed adults suffering from PTSD, the only medication utilized was MDMA and MDMA was found to significantly improve PTSD symptoms (95% CI, -1.28 to -0.62). Psychedelics overall were found to be safe and tolerable, with overall dropout rates being similar to comparison groups (RR = 0.88; 95% CI, 0.96-1.04). The most common adverse medication reactions noted were anxiety, nausea, vomiting, headaches, transient blood pressure increases, and fatigue. Of note, one article by Goodwin and colleagues found suicidal ideation to worsen in some participants three weeks after treatment with psilocybin.
Conclusions/Key Points: Based on the findings of Bahji and colleagues, psychedelic medications overall had a positive impact in managing participants' mental health. Of note, MDMA and psilocybin were found to have the most significant positive impact on depression. With MDMA having less significant impacts on anxiety and psilocybin having less significant impacts on PTSD. Additionally, these medications were found to be tolerable in most participants, but, as with all medications for mental health, monitoring for suicidal ideation needs to be done. This meta-analysis adds to the rediscovery and growing literature supporting the use of psychedelic medications in mental health patients. However, continued research and re-investigation of older research are needed. As noted by Bahji and colleagues, the studies analyzed had a high risk for bias and further studies with robust blinding/controls are needed to find the place in treatment for psychedelic medications.
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