Clinical trial NCT04558294: Effect of Ketanserin After LSD Administration
Official title: Effect of Ketanserin After LSD Administration on the Acute Response to LSD in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 24
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, placebo-controlled, random-order 2-period cross-over design with 2 treatment conditions:

1. 100 μg LSD + ketanserin (40 mg)
2. 100 μg LSD + placebo
Primary purpose: BASIC_SCIENCE

Brief summary: LSD (lysergic acid diethylamide) is a serotonergic (5-HT) hallucinogen widely used for recreational and/or ethnomedical purposes. LSD is thought to induce its prototypical psychedelic effects primarily via stimulation of the 5-HT2A receptor. This study investigates whether an LSD experience can be attenuated and shortened using 5-HT2A receptor antagonist ketanserin administration after LSD once the psychedelic effects have established.

Detailed description: LSD is a so-called "classic" or serotonergic hallucinogen or psychedelic.The effects of LSD have been frequently investigated in the past in both healthy participants and patients. In these studies, LSD produced acute transient alterations in waking consciousness including visual perceptual alterations, audio-visual synesthesia, derealization and depersonalization. Moreover, several of these studies described robust and sustained effects of LSD in patients suffering from addiction, anxiety and depression.

Its psychedelic effects are mainly attributed to its potent partial 5-HT2A receptor agonism. Consistently, administration the 5-HT2A receptor antagonist ketanserin (40 mg) prior to the administration of LSD (100 μg) almost completely prevented the acute effects of LSD in another study of our research group (NCT03321136). The present study hypothesis is that ketanserin (40 mg) administered 1h after LSD shortens and reduces the acute subjective effects of LSD (100 μg) compared to LSD alone (100 μg) followed by placebo in healthy humans. Such a finding would confirm a primarily competitive antagonism of ketanserin and LSD at the 5-HT2A receptor in vivo and indicate that LSD produces its psychedelic effects only when present at the receptor.

Eligibility criteria: Inclusion Criteria:

1. Age between 25 and 65 years old
2. Sufficient understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study
6. Abstaining from xanthine-based liquids and foods from the evenings prior to the study sessions to the end of the study days
7. Willing not to operate heavy machinery within 48 hours after substance administration
8. Willing to use double-barrier birth control throughout study participation
9. Body mass index between 18-29 kg/m2

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
5. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
6. Pregnancy or current breastfeeding
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medication that may interfere with the effects of the study medication
9. Tobacco smoking (\>10 cigarettes/day)
10. Consumption of alcoholic beverages (\>20 drinks/week)

Primary outcomes:
measure: Duration of subjective response
timeFrame: 12 months
measure: Extent of subjective response
timeFrame: 12 months
measure: Plasma concentrations of LSD
timeFrame: 12 months
measure: Plasma concentrations of Ketanserin
timeFrame: 12 months
Secondary outcomes:
measure: 5 dimensions of altered state of consciousness (5D-ASC) profile total score
timeFrame: 12 months
measure: Adjective mood rating scale (AMRS)
timeFrame: 12 months
measure: States of consciousness questionnaire (SCQ)
timeFrame: 12 months
measure: Blood pressure
timeFrame: 12 months
measure: Heart rate
timeFrame: 12 months
measure: Body temperature
timeFrame: 12 months
measure: Pupil diameter
timeFrame: 12 months
measure: Elliot Humility Scale (EHS)
timeFrame: 12 months
measure: Jankowski Humility Scale (JHS)
timeFrame: 12 months
measure: Arnett Inventory of Sensation Seeking (AISS-d)
timeFrame: 12 months
measure: Freiburger Persönlichkeitsinventar (FPI)
timeFrame: 12 months
measure: Saarbrücker Persönlichkeitsfragebogen (SPF)
timeFrame: 12 months
measure: Defense Style Questionnaire (DSQ-40)
timeFrame: 12 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Clinical Pharmacology & Toxicology, University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, Dr., MD
role: PRINCIPAL_INVESTIGATOR
References: