Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Wolff, Max; Evens, Ricarda; Mertens, Lea J.; Koslowski, Michael; Betzler, Felix; Gründer, Gerhard; Jungaberle, Henrik

doi:10.3389/fpsyt.2020.00005

Cited by 118 publications

(128 citation statements)

References 102 publications

(159 reference statements)

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“…Indeed, observational study has identified a positive correlation between acutely challenging psychedelic experiences and long-term well-being, and at least one model of psychedelic efficacy proposes that overcoming difficult experiences through acceptance is of therapeutic benefit overall. [34,35] Interestingly, this model is consistent with stress inoculation effects seen in pre-clinical studies of anxious responding. [36,37] As the deliberate induction of challenging experiences through increases in environmental stressors or other manipulations are ethically impermissible in psychedelic clinical trials, this study proposes use of rodent models as an important means by which to potentially help resolve this issue.…”

Section: Introductionsupporting

confidence: 79%

Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release

Jones

Zahid

Grady

et al. 2020

Preprint

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Psilocybin has shown positive preliminary signals in small-scale clinical trials for psychiatric disorders that exhibit maladaptive stress responses as a major component of their presentation. However, there are relatively few assessments of whether an acute administration of psilocybin exhibits reproducible effects in rodent models useful for the study of stress-associated psychiatric disorders. Here, we measured the responses of male C57BL/6J mice to this compound in a battery of relevant behavioral tests. These tests included the open-field test, forced swim test, sucrose preference test, and novelty suppressed feeding test. Furthermore, these tests were presented in either the absence or presence of chronic corticosterone administration, as a chemically induced model of ongoing stress burden. Our results indicate that the effects of psilocybin within these tests are dependent on the chronic hormonal stress burden of the mice: psilocybin alone promotes anxiolytic and hedonic responses, but promotes anxiogenic and anhedonic responses when pre-treated with chronic corticosterone. This identified interaction between stress hormone burden and psilocybin behavioral effects in mice suggests the possibility of further developing rodent behavioral models that can assess additional context-dependent effects of psychedelic administration that are deemed clinically-relevant, but are otherwise difficult to control for, in human studies.

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Section: Introductionsupporting

confidence: 79%

Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release

Jones

Zahid

Grady

et al. 2020

Preprint

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“…As such, moving from experiential avoidance to acceptance may play a key role in therapeutic outcomes associated with psychedelics. Therefore, we suggest that integrating psychedelics and psychotherapeutic interventions that specifically target experiential avoidance may help to enhance and prolong ( 93 ) the effectiveness of psychedelic therapy [for discussions, see ( 87 , 94 , 95 )]. Experiential avoidance is a primary target of ACT ( 26 ), an evidence-based psychotherapeutic intervention for a range of mental health problems [for a meta-analysis, see ( 96 )].…”

Section: Discussionmentioning

confidence: 99%

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

Zeifman

Wagner²,

Watts

et al. 2020

Front. Psychiatry

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Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy's (ACT's) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.

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“…Psychotherapeutic models putting the psychedelic experience in a psychotherapeutic framework are now starting to be developed e. g., [149,150]. Whether the subjective experience has a therapeutic value in itself or should be regarded as an epiphenomenon of therapeutic neurobiological changes is still not agreed upon as the existing evidence is currently correlational in nature.…”

Section: The Subjective Psychedelic Experiencementioning

confidence: 99%

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Mertens

Preller

2021

Pharmacopsychiatry

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Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders.In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression.While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.

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Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Cited by 118 publications

References 102 publications

Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release

Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

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