Background: Psychedelic-Assisted Therapy (PAT) refers to the psychotherapeutic use of psychedelics - such as psilocybin, LSD and ayahuasca - in the treatment of psychiatric disorders. Throughout the recent 20 years or so, there has been a renewed scientific interest in psychedelics’ therapeutic potentials for treating a wide range of disorders, including cancer-related distress, anxiety, OCD, eating disorders and depression. Particularly, PAT has yielded impressive results in treating major depressive (MDD) and treatment-resistant depressive (TRD) populations, which indicates its promising potential as a novel, effective means of psychological treatment. To this date, most studies have focused on identifying biochemical and neurological causal mechanisms involved in PAT, whereas the psychological mechanisms of action have received less attention.

Aim: This paper aims to review available theoretical and empirical literature on the psychological and phenomenological mechanisms of action involved in psychotherapeutic treatment of MDD and TRD with psychedelics.

Method: In the present integrative review, a systematic search of relevant literature is conducted across the databases PsycInfo, Embase and PubMed. Given the broad scope of the research question, the review seeks to identify methodologically diverse studies with the aim of providing a holistic picture of the psychological mechanisms of PAT. Thus, the review includes empirical studies characterized by quantitative and qualitative methodologies, as well as theoretical studies, which aim to explain the putative therapeutic mechanisms of PAT for depression.
The process of article selection was based on empirically informed inclusion- and exclusion criteria, which emphasized contemporary, peer reviewed, empirical and theoretical studies on the psychological mechanisms of PAT published since 2017. Data from the included articles are extracted and analyzed with regards to relevant sample characteristics as well as primary results, and these are synthesized and categorized in general themes.

Results: A total of 11 studies were included in the data analysis. The results revealed several general themes of psychological mechanisms of action. Overall, psychedelics appear to induce acute, psychological insights, which promotes increased self-acceptance as well as a reduction of avoidance-related strategies for regulating emotionally distressing thoughts and emotions. This process might be explained by psychedelics’ potential for creating a temporary disintegration of the neurological hierarchical organization, which in turn allows for the revision of pathologically relevant beliefs and behaviors, characterized by depressive self-rumination and negative attitudes about the self.
With regards to the meaning of mystical-type experiences for the antidepressant effects of psychedelics, the review yielded mixed results. Future studies should test the validity of this construct as a putative antidepressant mechanism of PAT through the application of more well-controlled scientifical designs.

Discussion: The findings are discussed and compared internally as well as with existing literature on the putative mechanisms of PAT. Furthermore, strengths and limitations of the included studies are discussed. Limitations include small sample sizes as well as a lack of control groups, which limits the generalization of the findings. Lastly, practical implications of the identified results are discussed with regards to the therapists’ role in PAT as well as a general discussion on the differences between psychedelics and standard antidepressant pharmacological interventions for depression.