Psilodyne PBC

This new study assessed the feasibility of psilocybin-assisted psychotherapy (PAP/PAT) in a complex population with treatment-resistant depression (TRD), including major depressive and bipolar II disorders, baseline suicidality, and significant comorbidity. Participants received one, two, or three sessions of PAP with psilocybin (25mg), accompanied by preparation and integration psychotherapy sessions. Immediate treatment showed greater reductions in depression severity (MADRS) compared to the waitlist period, with a large effect size (g = 1.07, p < 0.01). **Repeated doses were associated with further reductions in depression severity.** Adverse events were transient, and the study demonstrated feasibility, preliminary antidepressant efficacy, safety, and tolerability in this population.

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The benefits of psychedelics for mental health may result from changes to the regulation of emotions and cognitive processing, suggested by research correlating ratings of psychological insight and flexibility with reduced depression. To understand the mechanisms of psychological changes, this study examined how psilocybin affects brain connectivity with the amygdala. The amygdala is a subcortical region involved in processing emotional significance and regulating arousal in response to stimuli, including physical threats and challenges to beliefs. Hyperactivation of the amygdala is implicated in the pathophysiology of stress and anxiety-related internalising disorders. Empirical investigations of amygdala response under psychedelics have primarily focused on emotional stimuli. Reduced response to fearful stimuli associated with reduced amygdala activity has been found in healthy adults under the acute effects of psilocybin, and has been linked to increased positive and decreased negative affect lasting up to one month. In contrast, one-day post-psilocybin treatment increased responses to emotional stimuli, which were associated with increased amygdala activity in subjects with treatment-resistant depression and correlated with reduced depressive symptoms. These acute and post-acute psychedelic activation differences were related to improved outcomes, suggesting the behavioural significance of amygdala activation may be contextualised by connectivity with other brain regions.

TL;DR Psilocybin might help you stop drinking even if you aren’t necessarily an “alcoholic.” This study involved 160 individuals who reported a psychedelic experience and a concomitant drinking habit but did not necessarily have an alcohol used disorder(AUD). It examined the effect of a naturalistic psychedelic experience on alcohol use and related measures. Researchers found that a naturalistic psychedelic experience could be associated with a reduction in alcohol use and dependency. Such positive health outcomes can be associated with the intensity of the mystical experience as well as an increase in psychological flexibility. Results: The mean number of drinking days per week and AUDIT scores significantly decreased after the psychedelic experience (P < .001). Subjects who quit or reduced drinking had a more severe AUD (P < .01) and lower psychological flexibility (P = .003) before the psychedelic session. Alcohol use reduction was significantly associated with the intensity of the mystical experience (P = .03). Psychological flexibility increased more in participants who reduced their alcohol use (P < .001), and the change in psychological flexibility was one of the predictors of alcohol use improvement (P = .003). Conclusion: Our findings suggest that a naturalistic psychedelic experience could be associated with a reduction in alcohol use and dependency. Such positive health outcomes can be associated with the intensity of the mystical experience as well as an increase in psychological flexibility.

On Wednesday, JAMA Psychiatry published results from a small nonrandomized study in which people with type two bipolar disorder received psilocybin-assisted therapy to treat depressive symptoms. The study followed fifteen participants who received three sessions of therapy before receiving psilocybin, and who spent three to six weeks before psilocybin administration tapering off their antidepressants and other medications prescribed for mental health issues. They were also asked a series of questions about their mental health in a standard psychological rating scale called MADRS. Next, they received a single 25 mg dose of psilocybin and had a therapy integration session the following day, then two more sessions over the next two weeks. For the following twelve weeks, researchers followed up with participants to readminister the MADRS psychological rating scale six more times. Three weeks after the psilocybin session, all participants showed lower MADRS scores. The MADRS scale ranges from 0 to 60; most participants in the study initially scored in the 25-40 range, demonstrating what’s considered moderate to severe depression. One week after treatment, their MADRS scores showed an average reduction of 24 points. By week 12 of the study, 12 of the 15 participants met criteria for being “in remission” from depressive symptoms. “There was an association between 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 researchers wrote.