A single dose of psilocybin, when combined with supportive psychotherapy, might help to significantly reduce depression symptoms in individuals with bipolar II disorder, according to new research published in JAMA Network Open. This reduction in depression was both substantial and sustained over a 12-week period.
Psilocybin, a naturally occurring psychedelic compound, is best known for its use in certain types of mushrooms, often referred to as “magic mushrooms.” In recent years, psilocybin has gained attention in the medical community for its potential therapeutic benefits, especially in treating various mental health conditions.
Psilocybin-assisted psychotherapy involves administering psilocybin in a controlled setting, under the guidance of trained therapists. This approach is believed to facilitate deeper psychological insights and emotional processing, which can lead to significant improvements in mental health conditions like depression.
Previous studies have shown promising results for psilocybin in treating major depressive disorder. However, its effects on bipolar II disorder—a condition marked by recurring episodes of depression and hypomania—remained unexplored. Given the limited treatment options and the severity of depressive episodes in bipolar II disorder, researchers were motivated to investigate whether psilocybin could offer a new, effective treatment pathway.
The study involved 15 participants, aged 18 to 65, diagnosed with bipolar II disorder. These individuals had not responded adequately to at least two prior pharmacologic treatments for their current depressive episode. The trial, conducted over 12 weeks, involved a single 25-milligram dose of synthetic psilocybin administered under controlled conditions at the Sheppard Pratt Health System.
Prior to the dosing, participants underwent a period of preparation that included stopping other antidepressants and mood stabilizers and engaging in sessions with a trained therapist to build rapport and prepare for the psilocybin experience. On the day of dosing, the participants spent 8 to 9 hours in a specially designed, calming environment under the supervision of a therapist and assistant. Following the dosing, participants attended follow-up sessions for integration and assessment.
The study’s primary finding was a significant reduction in depression severity, measured using the Montgomery-Åsberg Depression Rating Scale. Three weeks after psilocybin administration, participants showed a remarkable 76.3% reduction in depression symptoms from their baseline levels. This improvement remained consistent throughout the 12-week study period.
In terms of secondary outcomes, there were significant reductions in self-reported depression symptoms, and quality of life scores improved notably. No significant changes were observed in mania symptoms or suicidal ideation. Furthermore, the intensity of the psychedelic experience correlated with the degree of antidepressant effects, suggesting that a stronger psychedelic experience might predict a better clinical outcome.
The safety of the treatment was a critical aspect of the study. Notably, no significant adverse events were linked to the psilocybin dosing, with only minor events like headaches reported in a few participants. Importantly, there were no instances of increased mania, psychosis, or suicidal behavior, which are potential concerns in treatments involving psychedelics, especially in individuals with mood disorders.
In a prior study using self-reported survey data, it was observed that although most individuals with bipolar disorder felt that their recreational experiences with psilocybin were beneficial for their mental well-being, about one-third (32.2%) reported adverse effects. These included the emergence or worsening of manic symptoms, and in some cases, the need for emergency medical attention. This contrast in findings suggests that the outcomes of psilocybin use might vary significantly between controlled, therapeutic settings and unguided use.
“Individuals in this study displayed strong and persistent antidepressant effects, with no signal of worsening mood instability or increased suicidality,” the researchers wrote. However, they cautioned that “as a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings.”
While the results are promising, the study’s design and scope come with several limitations. Being an open-label study without a control group, it’s hard to definitively attribute the improvements solely to psilocybin, as factors like the placebo effect or the intensive therapeutic support could have contributed.
The small sample size and the short duration of follow-up limit the ability to generalize these findings to a larger population or understand the long-term effects. Additionally, the study only included patients in a depressive phase of bipolar II disorder, so the results cannot be applied to those in a hypomanic or mixed phase.
Looking ahead, the researchers suggest conducting randomized controlled trials with larger groups and longer follow-up periods to confirm these findings. It’s also crucial to investigate whether psilocybin treatment could impact the risk of substance use disorders, a concern in the bipolar population. While these initial results are encouraging, much more research is needed before psilocybin could become a mainstream treatment option for bipolar II disorder.
The study, “Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Controlled Trial“, was authored by Scott T. Aaronson, Andrew van der Vaart, Tammy Miller, Jeffrey LaPratt, Kimberly Swartz,Audrey Shoultz, Margo Lauterbach, Harold A. Sackeim, and Trisha Suppes.
