Uncovering psychological mechanisms mediating the effects of drugs: some issues and comments using the example of psychedelic drugs

Abstract

Researchers have begun efforts to uncover the psychological mechanisms by which psychedelic drugs may have beneficial effects on long-term outcomes in some circumstances. The approaches several recent publications on the topic have taken to analyze such mechanisms have some pitfalls and limitations. Based on the rich literature on mechanisms and mediation analysis in psychological science, I comment on five particular issues: (1) Separating mediating and moderating factors, (2) problems inherent in using cross-sectional data, (3) statistical methods in mediation analysis, (4) assumptions and limitations inherent in traditional mediation analysis, and (5) criteria beyond mediation to establish a mechanism. Suggested practices for future research on the psychological mechanisms through which drugs have their effects are presented.

The Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ): A theory-based approach to psychedelic drugs’ effects on psychological flexibility

“…Like most extra-pharmacological conceptions of acute and longerterm psychedelic drug effects (Carhart-Harris and Nutt, 2017), the present theorized model (Figure 1) postulates a mediation effect: Context factors determine the acute drug response, which in turn predicts longer-term outcomes. While the present cross-sectional and retrospective data collection method does not technically allow for the identification of mediation effects (for an in-depth discussion of mediation analysis in psychedelic research, see Kangaslampi, 2020), the SEM summarized in Figure 3 is consistent with the mediation assumption and may provide preliminary evidence that ACE and AVE are potential mediators between different motives for using psychedelics and longer-term changes in psychological flexibility. In line with the view that learning acceptance requires a willingness to confront and engage with personally meaningful negative emotions, ACE was strongly positively associated with therapeutic intentions.…”

Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

“…As pointed out previously ( Baier et al, 2020 ; Kangaslampi, 2020 ), the nascent field of mechanistic studies in psychedelic research suffers from several methodological limitations, including the lack of appropriate testing of putative causal relationships. By implementing sequential mediation analyses on variables that were measured across successive time points, the current study was able to inform on causal relations in the treatment process.…”

Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca

“…Future studies are also needed to clarify the impact of acute and post-acute mediators (e.g. therapeutic changes occurring 1 week after a psychedelic session) of effects on final outcomes (Kangaslampi, 2020). This study utilized a novel measure to index flexibility/reappraisal, clarity, and spiritual-type experiences during ceremony (AEI: Weiss et al, 2020Weiss et al, , 2021; planned validation in a forthcoming article) as well as a well-established measure of mystical experience (MEQ-30; Barrett et al, 2015).…”

“…Future studies are also needed to clarify the impact of acute and post-acute mediators (e.g. therapeutic changes occurring 1 week after a psychedelic session) of effects on final outcomes (Kangaslampi, 2020).…”