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Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study

Summary

This study examines how antidepressant medications (like SSRIs) affect the experience of classic psychedelics such as psilocybin and LSD. Researchers found that people taking these antidepressants experienced less intense emotional and mystical effects from psychedelics, but surprisingly, both groups showed similar improvements in mood and well-being several weeks later. This raises important questions about whether patients need to stop their antidepressants before using psychedelics therapeutically.

Background

There is growing evidence for therapeutic effects of psychedelics, but uncertainty remains about how these drugs interact with serotonergic antidepressants (SRIs). Current clinical practice requires patients to discontinue SRIs for at least 2 weeks before psychedelic-assisted therapy due to safety concerns and reports suggesting SRIs may reduce subjective psychedelic effects.

Objective

To compare acute psychedelic subjective effects and subsequent changes in well-being and depressive symptoms between individuals not on psychiatric medication (SRI−) and those undergoing SRI treatment (SRI+) using prospective survey data.

Results

SRI− participants experienced significantly more intense subjective effects including 18.2% higher mystical experiences, 50.9% higher challenging experiences, and 31.9% higher emotional breakthroughs compared to SRI+ participants. However, both groups showed similar improvements in well-being and depressive symptoms at 4-week follow-up, with no significant differences in drug-induced visual effects between groups.

Conclusion

While individuals on SRIs display reduced subjective psychedelic effects in emotional domains, they experience comparable long-term improvements in depressive symptoms and well-being. These exploratory findings suggest the need for controlled research to optimize psychedelic-assisted therapy implementation, potentially reconsidering the requirement to discontinue SRIs prior to treatment.
  • Published in:Journal of Psychopharmacology,
  • Study Type:Prospective Observational Survey Study,
  • Source: PMID: 38281075, DOI: 10.1177/02698811231224217
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