Expectations affect the course of many medical conditions, impacting key measures, including long-term mortality1 and surgical outcomes.2 Expectations account for a substantial proportion of the overall therapeutic effect of some pharmacological treatments; for example, up to 50% of the effectiveness of pain therapeutics may be expectation driven.3 Expectations can also be tempered by previous unsuccessful treatments and unfavorable encounters, diminishing therapeutic outcomes.3
Expectations are particularly important in relation to psychedelic drugs and 3,4-methylenedioxymethamphetmine (MDMA) because they may paradoxically serve both as potential confounding factors and as critical mediating factors in the mechanism of antidepressant action. The role of pretreatment expectations in relation to psychedelic treatment effectiveness and the potentially unique ability of these treatments to alter future expectations has profound clinical consequences that deserve special consideration when evaluating the place of psychedelic medications and MDMA in the treatment of mental (and other chronic) disorders. This discussion goes beyond the clinical trial limitations related to functional unblinding and a priori patient expectations associated with psychedelic agents reported elsewhere.4 Rather, we focus on the more complex role expectations may play in relation to the mechanisms underlying psychedelic treatments’ putative effectiveness in treating psychiatric disorders. We offer a call to action for investigators to thoughtfully integrate longitudinal assessments of expectations into future studies. We believe that this information would not only provide a better understanding of how expectations are associated with treatment outcomes at various stages during treatment, but also afford insight into how these treatment effects could be successfully amplified in clinical settings. .....more
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