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Addressing blinding in classic psychedelic studies with innovative active placebos

Summary

This research paper discusses how scientists can better test whether psychedelic drugs actually work by improving the way they conduct clinical trials. A major problem is that psychedelic drugs produce obvious effects that make it easy for patients and researchers to figure out who received the real drug versus a fake one. The authors recommend using different types of drugs as placebos that produce similar effects without being therapeutic themselves, such as certain existing medications. By using these better-designed placebos along with other strategies, future research can more definitively prove whether psychedelics truly help treat depression, chronic pain, and other conditions.

Background

Classic psychedelics have shown promise in treating various neuropsychiatric disorders, but weak blinding integrity in clinical trials limits the interpretability of therapeutic effects. The use of inert placebos in psychedelic studies is problematic because the acute perceptual effects are easily distinguishable, leading to functional unblinding and confounding results.

Objective

To describe drawbacks of current placebo conditions in classic psychedelic studies, propose criteria for suitable active placebos, and review pharmacological interventions that may meet these criteria to improve blinding integrity in future trials.

Results

The paper identifies five key criteria for ideal active placebos: acute psychoactive effects, acute physiological effects, matching onset and duration, safety profile, and lack of therapeutic effects in target disease. Several agents are proposed as potential active placebos including salvinorin A and dextromethorphan for moderate-to-high doses, THC for long-acting psychedelics, and stimulants for microdosing studies.

Conclusion

Future classic psychedelic research should employ thoughtfully selected active placebos and ancillary blinding strategies to accurately assess safety and efficacy. Agents like salvinorin A, dextromethorphan, and THC show promise as alternatives to currently used placebos, though each has specific advantages and limitations depending on the psychedelic and dosing regimen under investigation.
  • Published in:International Journal of Neuropsychopharmacology,
  • Study Type:Review,
  • Source: PMID: 40183712, DOI: 10.1093/ijnp/pyaf023
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