Evaluating the risk of psilocybin for the treatment of bipolar depression: A review of the research literature and published case studies

Gard, David E.; Pleet, Mollie; Bradley, Ellen; Penn, Andrew; Gallenstein, Matthew L.; Riley, Lauren S.; DellaCrosse, Meghan; Michalak, Erin E.; Woolley, Joshua

doi:10.1016/j.jadr.2021.100240

Cited by 20 publications

(30 citation statements)

References 57 publications

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“…Conversely, reward hypersensitivity and elevated approach motivation is related to a subgroup of hypo/manic symptoms characterized by excessive approach motivation and psychomotor hyperactivation in the context of bipolar disorder (192). This reward hypohypersensitivity divergence maps onto the contra-indication of psychedelic therapy in bipolar type 1 disorders (BPAD I) (226,227) and caution will be required in the treatment of the depressive phase of BPAD II (228). We await with interest the results of an open label safety and efficacy psilocybin (25 mg) therapy study in depressed participants with BPAD II and the future integration of dimensional approaches, such as rewardrelated reactivity assessments (Table 3).…”

Section: Depressionmentioning

confidence: 99%

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

et al. 2021

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Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

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Section: Depressionmentioning

confidence: 99%

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

et al. 2021

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“…Belser and colleagues [46] highlight the value of qualitative approaches in emergent psychedelic research as hypothesis generating, in contrast to hypothesis testing in quantitative analysis. Here, thematic analysis [52] provided a flexible approach to explore and conceptualize variation among individuals' experiences in the context of this understudied population in psychedelic science [32,43]. Despite challenging dosing experiences and undesired impacts, our findings suggest that increased emotion processing may be an important change process related to reductions in depressive symptoms, as well as to enabling formation of helpful new perspectives for individuals with BD.…”

Section: Discussionmentioning

confidence: 93%

“…One major reason for exclusion is the belief among clinicians and researchers that the serotonergic action of psilocin could precipitate Treatment Emergent Affective Switching (TEAS) or some other adverse experiences [32] similar to antidepressant monotherapy for this population [10,11,33,34]. TEAS characterizes what is typically a switch from a depressive episode to hypo/mania [33,34].…”

Section: Recent Resurgence In Psychedelic Researchmentioning

confidence: 99%

“…At present, information on psilocybin use among people with BD is limited to case reports. In a review of published case reports, 17 individuals were found with a clear description of emergent BD symptoms after psychedelic use (i.e., psilocybin, ayahuasca, LSD, DMT) [32]. Across the cases, emergent manic symptoms or adverse reactions were associated with factors such as poly-substance use, repeated drug consumption, and large doses.…”

Section: Recent Resurgence In Psychedelic Researchmentioning

confidence: 99%

“…She was stabilized using lithium and aripiprazole, and later lamotrigine [42]. The authors concluded that development of mania following psychedelic use can occur, but the rates are likely low given the widespread use of these compounds and the paucity of cases that did not involve polysubstance use or other clear instigating circumstances [32]. Given the variability and other limitations inherent to case studies, in addition to family history exclusionary criteria, more research is needed to further understand the risks for this population.…”

Section: Recent Resurgence In Psychedelic Researchmentioning

confidence: 99%

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“A sense of the bigger picture:” A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use

et al. 2022

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Objectives People with bipolar disorder (BD) spend more time depressed than manic/hypomanic, and depression is associated with greater impairments in psychosocial functioning and quality of life than mania/hypomania. Emerging evidence suggests psilocybin, the psychoactive compound in “magic mushrooms,” is a promising treatment for unipolar depression. Clinical trials of psilocybin therapy have excluded people with BD as a precaution against possible adverse effects (e.g., mania). Our study centered the experiences of adults living with BD who consumed psilocybin-containing mushrooms, and aimed to (1) understand its subjective impacts on BD symptoms, (2) deepen understanding of Phase I survey results, and (3) elucidate specific contextual factors associated with adverse reactions in naturalistic settings. Methods Following an international survey (Phase I), follow-up interviews were conducted with 15 respondents (Phase II) to further understand psilocybin use among adults with BD. As part of a larger mixed-methods explanatory sequential design study, reflexive thematic analysis was used to elaborate findings. Results Three major themes containing sub-themes were developed. (1) Mental Health Improvements: (1.1) decreased impact and severity of depression, (1.2) increased emotion processing, (1.3) development of new perspectives, and (1.4) greater relaxation and sleep. (2) Undesired Mental Health Impacts: (2.1) changes in sleep, (2.2) increased mania severity, (2.3) hospitalization, and (2.4) distressing sensory experiences. (3) Salient Contextual Factors for psilocybin use included: (3.1) poly-substance use and psilocybin dose, (3.2) solo versus social experiences, and (3.3) pre-psilocybin sleep deprivation. Conclusion Our findings demonstrate both benefits and risks of psilocybin use in this population. Carefully designed clinical trials focused on safety and preliminary efficacy are warranted.

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Toward Risk-Benefit Assessments in Psychedelic- and MDMA-Assisted Therapies

Bradberry

Gukasyan

2022

JAMA Psychiatry

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Evaluating the risk of psilocybin for the treatment of bipolar depression: A review of the research literature and published case studies

Cited by 20 publications

References 57 publications

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

“A sense of the bigger picture:” A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use

Toward Risk-Benefit Assessments in Psychedelic- and MDMA-Assisted Therapies

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