Results of a new clinical trial published by the American Medical Association “suggest efficacy and safety” of psilocybin-assisted psychotherapy for treatment of bipolar II disorder, a mental health condition often associated with debilitating and difficult-to-treat depressive episodes.
“The 15 participants in this trial had well-documented treatment-resistant BDII depression of marked severity and a lengthy duration of the current depressive episode,” authors wrote. After seven psychotherapy sessions, one involving a single dose of psilocybin, the paper says, study subjects “displayed strong and persistent antidepressant effects, with no signal of worsening mood instability or increased suicidality.”
In the nonrandomized controlled study, which was conducted at Sheppard Pratt Hospital in Baltimore, “12 patients met both response and remission criteria” at the end of a 12-week study period, the trial found, meaning that measures of the diagnosis had dropped by more than half and fell below a minimum threshold.
Patients’ self-reported quality of life scores “demonstrated similar improvements,” the study, which was funded by the biotechnology company COMPASS Pathways that develops psychedelic treatments, found. In terms of safety, metrics of suicidal ideation and mania “did not change significantly at posttreatment compared to baseline.”
The nine-author study, published on Wednesday in the journal JAMA Psychiatry, involved administering a single, 25-milligram dose of psilocybin. Patients with bipolar II disorder (BDII) met with therapists seven times—during three pre-treatment sessions, once during an “8-hour dosing day” and at three post-treatment integration sessions.
“In this study, most participants remitted rapidly (ie, within 1 week of dosing), and in most participants, remission persisted for the 12-week study duration,” the report says. “The 3 participants who restarted medication due to lack of benefit or relapse following improvement generally had poorer response throughout the trial.”
“In a sample of patients with treatment-resistant cyclical mood disorder, achieving persistent remission over a 3-month period is notable, especially given the single dosing of psilocybin,” it continues. “Further follow-up is warranted.”
Intensity of the psychedelic experience may be one area worth studying further, researchers indicated. They found that “there was an association between the general intensity of the psychedelic experience and clinical benefit. In particular, individuals in whom psilocybin administration had little subjective impact showed little clinical benefit.”
“The necessity of a distinct psychedelic experience for response remains a point of debate within the field,” the study says, “and the findings of this study suggest that the degree of psychedelic experience is predictive of longer-term antidepressant effects.”
Despite the promising results of the trial, authors were careful to warn against reading the findings as an endorsement of casual or unsupported psilocybin use.
“As a first open-label foray into this underserved and treatment-resistant population,” they wrote, “care should be taken not to overinterpret the findings. Administration of a psychedelic agent under carefully controlled and supportive conditions may yield distinct effects compared to self-report surveys on recreational use of psychedelics by people with BD.”
Notably, the trial excluded patients with a history of bipolar I, schizophrenia, psychosis, delusions or borderline personality disorder, among other conditions, or any substance use disorder within the past year.
All 15 participants were also “fully withdrawn from all antidepressant and mood stabilizing medications at least 2 weeks prior to dosing,” the study says. Nine did not recommence medications for the duration of the study period, while six people restarted at least one medication. A few others had mixed results, including one who “remitted at week 3, relapsed at week 6, dropped out of the study, and restarted medication and was coded as a nonresponder for weeks 9 and 12” and one who restarted medication “at week 2, before the primary outcome visit at week 3, and was considered a nonresponder throughout the study.”
Authors said follow-up studies are needed to better gauge the longer-term potential impacts of the treatment and noted that their trial’s “small sample size also limits results.”
They added that their findings “cannot be extrapolated” to patients with bipolar I disorder or to patients with bipolar II “in a mixed or hypomanic phase of their illness.”
The new JAMA study is the latest in a growing body of research demonstrating the potential of psilocybin and other entheogens to treat a range of mental health conditions, including PTSD, treatment-resistant depression, anxiety, substance use disorders and others.
A recently published survey of more than 1,200 patients in Canada, for example, suggested use of psilocybin can help ease psychological distress in people who had adverse experiences as children. Researchers said the psychedelic appeared to offer “particularly strong benefits to those with more severe childhood adversity.”
In September, meanwhile, researchers at Johns Hopkins University, Ohio State University and Unlimited Sciences published findings showing an association between psilocybin use and “persisting reductions” in depression, anxiety and alcohol misuse—as well as increases in emotional regulation, spiritual wellbeing and extraversion.
Those results were “highly consistent with a growing body of clinical trial, behavioral pharmacology, and epidemiological data on psilocybin,” authors of that study said. “Overall, these data provide an important window into the current resurgence of public interest in classic psychedelics and the outcomes of contemporaneous increases in naturalistic psilocybin use.”
A separate study from the American Medical Association (AMA) came out in August showing that people with major depression experienced “clinically significant sustained reduction” in their symptoms after just one dose of psilocybin.
As for other entheogens, a peer-reviewed study published in the journal Nature recently found that treatment with MDMA reduced symptoms in patients with moderate to severe PTSD—results that position the substance for approval by the Food and Drug Administration (FDA) as soon as next year.
Another study published in August found that administering a small dose of MDMA along with psilocybin or LSD appears to reduce feelings of discomfort like guilt and fear that are sometimes side effects of consuming so-called magic mushrooms or LSD alone.
A first-of-its-kind analysis released in June, meanwhile, offered novel insights into the mechanisms through which psychedelic-assisted therapy appears to help people struggling with alcoholism.
At the federal level, the National Institute on Drug Abuse (NIDA) recently started soliciting proposals for a series of research initiatives meant to explore how psychedelics could be used to treat drug addiction, with plans to provide $1.5 million in funding to support relevant studies. (Full Story)