Ketanserin is a selective and reversible antagonist of the serotonin, dopamine and adrenergic receptors. It is prescribed as an anti-hypertensive medicine in some countries, especially as an adjunct to chemotherapy, usually in 10 mg, 20 mg and 40 mg tablets.

In a recent, double-blind, clinical-trial (involving healthy human subjects) conducted by the University of Zurich, ketanserin was found to reliably and consistently block the effects of LSD in humans. Patients were separated into one treatment group (which received LSD) and two control groups (one which received placebo, and one which received LSD plus ketanserin). Researchers conducted behavioral studies on the patients and fMRI scans measuring their brain activity. The control groups which took placebo were behaviorally and physiologically identical to those who received LSD and ketanserin. The ketanserin was well tolerated, with no adverse incidents or side effects documented in the control group, and is commonly used in human clinical trials to block the effects of psychedelics. The ketanserin also did not have any psychoactive or sedating effects when used to counteract LSD, and the behavioural effects on the control group were no different than the placebo control.

In a separate series of studies conducted by the same research team (led by Franz Vollenweider), the ability of ketanserin was compared to other serotonergic antagonists (such as busprione) to block the effects of psilocybin in human volunteers. As reported in a Scientific American article, “they did not report visual hallucinations and other common effects, according to a study published in April 2016 in European Neuropsychopharmacology. […] Vollenweider previously found that a blood pressure drug, ketanserin, blocks the serotonin 2A receptor and prevents virtually all psilocybin effects.” Comparatively, buspirone “had no impact on other psychedelic symptoms such as the anxious sense of ego dissolution or the fear of going insane that some people experience, nor did it prevent decreased alertness during the trip.” As reported by the authors of the original study, “psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects.”

Based on this evidence, ketanserin may be an effective treatment for overdoses on drugs of the serotonin, dopamine, or adrenergic agonist class (including stimulants, psychedelics, etc), and may be useful in the emergency treatment of psychedelics, such as those seen in hospitalizations due to 25I-NBOMe, DOI, DOB and others. It may be a highly effective harm reduction tool, being well-established as a safe treatment and being widely approved in human clinical trials involving healthy volunteers. It may pose a less harmful and more efficient treatment than benzodiazepenes, which only indirectly counteract the effects of a psychedelic overdose by sedating the patient. Whereas benzodiazepenes work primarily by acting on the GABA receptors, which in turn can cause downregulation of the serotonin receptors as a secondary effect, ketanserin directly counteracts the psychedelic by blocking the serotonin receptors which psychedelics bind to, in the same way that naloxone (a selective opioid antagonist) blocks the effect of an opioid agonist when used in the treatment of an overdose.