NCT05964647

Effect of Ketanserin, Olanzapine, and Lorazepam After LSD Administration on the Acute Response to LSD in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The main objective of this study is to determine whether administration of ketanserin (40 mg), olanzapine (10 mg), and lorazepam (2 mg) after administration of LSD (150 µg) attenuates and shortens the subjective LSD response (any drug effect) compared to administration of LSD (150 µg) alone

Detailed description

LSD is investigated as treatment for various psychiatric (e.g., depression and anxiety) but also somatic disorders (e.g., cluster headache). In Switzerland, compassionate use of psychedelics including LSD is possible based on single authorizations of the federal office of public health in treatment-resistant patients. Additionally, current social and political changes demonstrate a shift of how psychedelics are seen and how they might be used in therapy in the future. Despite the good safety profile of LSD, a broader use might increase the number of adverse psychological reactions to LSD. For such occasions, health professionals should have a tool to not only psychologically but also pharmacologically interfere and end states of acute psychedelic-induced distress. In clinical practice, the gamma-butyric acid (GABA) agonistic acting benzodiazepine lorazepam or the atypical neuroleptic olanzapine with affinity to the 5-HT2A, 5-HT2C and dopamine D1-4 receptors are primarily used for the treatment of drug-induced psychotic symptoms. However, the ability of these drugs to block these effects after LSD intake remains to be investigated. The primary goal of the present study is therefore to investigate whether ketanserin, olanzapine and lorazepam administration after LSD administration might attenuate and shorten the LSD response compared to administration of LSD alone. Additionally, the present study examines changes in quality of the LSD experience after administration of ketanserin, olanzapine or lorazepam and effects on sensorimotor gating and sleep. The study provides insight into the receptor mechanisms involved in alterations of consciousness and specifically the relevance of ongoing 5-HT2A receptor stimulation in the mediation of the psychedelic response to LSD and psychotic symptoms.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	LSD (150 µg) + ketanserin (40 mg)	Drug: LSD (150 µg) per os, single dose Other: Ketanserin (40 mg) per os, single dose
DRUG	LSD (150 µg) + olanzapine (10 mg)	Drug: LSD (150 µg) per os, single dose Other: Olanzapine (10 mg) per os, single dose
DRUG	LSD (150 µg) + lorazepam (2 mg)	Drug: LSD (150 µg) per os, single dose Other: Lorazepam (2 mg) per os, single dose
DRUG	LSD (150 µg) + placebo	Drug: LSD (150 µg) per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)
DRUG	Placebo + placebo	Drug: Placebo (Capsules containing mannitol looking identical to the other drugs) Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

Timeline

• Start date: 2024-02-01
• Primary completion: 2025-06-30
• Completion: 2025-06-30
• First posted: 2023-07-28
• Last updated: 2025-11-17

Locations

1 site across 1 country: Switzerland