Abstract

Depression is a major public health problem that affects approximately 4.4% of the global population. Since conventional pharmacotherapies and psychotherapies are only partially effective, as demonstrated by the number of patients failing to achieve remission, alternative treatments are needed. Mindfulness meditation (MM) and psilocybin represent two promising novel treatments that might even have complementary therapeutic effects when combined. Since the current literature is limited to theoretical and empirical underpinnings of either treatment alone, the present review aimed to identify possible complementary effects that may be relevant to the treatment of depression. To that end, the individual effects of MM and psilocybin, and their underlying working mechanisms, were compared on a non-exhaustive selection of six prominent psychological and biological processes that are well known to show impairments in patients suffering from major depression disorder, that is mood, executive functioning, social skills, neuroplasticity, core neural networks, and neuroendocrine and neuroimmunological levels. Based on predefined search strings used in two online databases (PubMed and Google Scholar) 1129 articles were identified. After screening title and abstract for relevance related to the question, 82 articles were retained and 11 were added after reference list search, resulting in 93 articles included in the review. Findings show that MM and psilocybin exert similar effects on mood, social skills, and neuroplasticity; different effects were found on executive functioning, neural core networks, and neuroendocrine and neuroimmune system markers. Potential mechanisms of MM’s effects are enhanced affective self-regulation through mental strategies, optimization of stress reactivity, and structural and functional adjustments of prefrontal and limbic areas; psilocybin’s effects might be established via attenuation of cognitive associations through deep personal insights, cognitive disinhibition, and global neural network disintegration. It is suggested that, when used in combination, MM and psilocybin could exert complementary effects by potentiating or prolonging mutual positive effects, for example, MM potentially facilitating psilocybin-induced peak experiences. Future placebo-controlled double-blind randomized trials focusing on psilocybin-assisted mindfulness-based therapy will provide knowledge about whether the proposed combination of therapies maximizes their efficacy in the treatment of depression or depressive symptomatology.

Highlights

  • Depression or major depressive disorder (MDD) is a common mood disorder and major cause of disability worldwide

  • Findings showed that Mindfulness meditation (MM) and psilocybin exerted similar effects on mood, social skills, and neuroplasticity; different effects were found on executive functioning, neural core networks, and neuroendocrine and neuroimmune system markers

  • The effects on mood were “dose”-dependent, with more MM practice or higher psilocybin doses leading to more pronounced mood effects; effects on neuroplasticity were already visible after a single dose of psilocybin, while more MM practice sessions were needed before effects were visible

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Summary

Introduction

Depression or major depressive disorder (MDD) is a common mood disorder and major cause of disability worldwide. Typical symptoms include depressed mood, anhedonia, fatigue, feelings of worthlessness or guilt, changes in appetite, weight, and sleep, psychomotor retardation or agitation, executive deficits, and suicidal ideation [2]. These are thought to originate from a complex interplay of psychological and biological factors [3]. Psychological factors that underlie the pathology of MDD comprise deficiencies on an emotional, cognitive, and social level [3]. The aforementioned combination of these three psychological processes further promotes cognitive rigidity, as evident from underperformance in executive functioning tests measuring for example taskswitching, working memory (WM), attention, and inhibitory control [4, 6,7,8]. To exemplify, depressed patients take more time to adapt to new rules in the Wisconsin Card Sorting Test and show attentional and memory deficits predominantly in the context of positive affective stimuli [9, 10]

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