Extrapharmacological and Contextual Factors in Psychedelic Research: A Scoping Review

Abstract

This scoping review is part of a three-paper dissertation examining the role of social and contextual factors in psychedelic-assisted therapy (PAT). While most psychedelic research has focused on pharmacological mechanisms and immediate “set and setting” influences, less attention has been given to broader extrapharmacological factors such as social support, cultural identity, and systemic conditions. These extended factors may significantly shape therapeutic outcomes, particularly for populations who experience structural marginalization. The purpose of this review is to systematically map how contextual and environmental influences have been examined in psychedelic clinical and naturalistic studies. Guided by Ecological Systems Theory (EST), the review will categorize findings across nested levels of influence (microsystem, mesosystem, exosystem, macrosystem, and chronosystem). Specific attention will be paid to how social support is conceptualized and measured, as well as how identity variables and social determinants of health are represented. The review will address the following questions: What extrapharmacological factors, as defined by EST, have been studied in psychedelic research? Which factors are most frequently reported, and in what contexts (clinical vs. naturalistic)? How does social support influence outcomes, particularly for vulnerable populations (e.g., LGBTQ+ individuals and veterans)? What gaps exist in the literature related to identity and systemic influences? Expected outcomes include (a) a comprehensive synthesis of existing evidence on extrapharmacological factors, (b) identification of key gaps in how social and contextual influences are studied, and (c) recommendations for integrating EST and social determinants of health frameworks into future psychedelic research. Findings will inform both clinical trial design and community-based practices, contributing to a more equitable and contextually grounded model of psychedelic therapy. Although this preregistration is being posted after the search and screening process has begun, it documents the planned methodology and analytic framework to increase transparency. Any methodological refinements that emerge during data extraction or synthesis will be added as amendments.

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