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Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants

Summary

Researchers tested whether ketanserin, a drug that blocks serotonin receptors, could stop or reverse an LSD experience once it had already started. In a controlled study with healthy volunteers, ketanserin given one hour after LSD administration cut the duration of the LSD experience from 8.5 hours down to 3.5 hours and eliminated visual and auditory hallucinations. This finding suggests ketanserin could be useful as an emergency medication in psychedelic-assisted therapy to help patients who have negative reactions to LSD.

Background

Lysergic acid diethylamide (LSD) is being investigated in psychedelic-assisted therapy and produces its acute effects through stimulation of the serotonin 5-HT2A receptor. While the 5-HT2A antagonist ketanserin can prevent LSD effects when administered before LSD, it is unclear whether ketanserin can reverse LSD effects when administered after they have already begun.

Objective

This study investigated whether ketanserin (40 mg) administered 1 hour after LSD (100 μg) could reverse or shorten the acute subjective and autonomic effects of LSD in healthy participants.

Results

Ketanserin significantly reduced the duration of LSD’s subjective effects from 8.5 hours to 3.5 hours, reversing visual and auditory alterations, ego dissolution, and other psychedelic effects. Ketanserin also reduced cardiovascular effects and pupil dilation associated with LSD but did not affect brain-derived neurotrophic factor elevations or LSD pharmacokinetics.

Conclusion

Ketanserin effectively reverses the acute response to LSD when administered after effects have developed, supporting LSD’s primary action through 5-HT2A receptor stimulation. This finding suggests ketanserin could be useful as a planned intervention or rescue option in LSD-assisted therapy to shorten the acute experience and improve safety and flexibility.
  • Published in:International Journal of Neuropsychopharmacology,
  • Study Type:Clinical Trial,
  • Source: PMID: 36342343, DOI: 10.1093/ijnp/pyac075
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