Effect of Ketanserin After LSD Administration (L-Ket)

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Ketanserin; Drug: Ketanserin Placebo; Drug: Lysergic Acid Diethylamide

Study type: Interventional

Funder types: Other

Identifiers

NCT04558294

BASEC 2020-00614

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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24 participants in 2 patient groups

100 μg LSD + Ketanserin placebo

Experimental group

Treatment:

Drug: Lysergic Acid Diethylamide

Drug: Ketanserin Placebo

100 μg LSD + Ketanserin (40mg)

Experimental group

Treatment:

Drug: Lysergic Acid Diethylamide

Drug: Ketanserin