Effect of Ketanserin After LSD Administration (L-Ket)

• ClinicalTrials.gov Identifier: NCT04558294
• Recruitment Status: Completed
• First Posted: September 22, 2020
• Last Update Posted: October 21, 2021
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Lysergic Acid Diethylamide; Drug: Ketanserin Placebo; Drug: Ketanserin	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment

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

• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effect of Ketanserin After LSD Administration on the Acute Response to LSD in Healthy Subjects
• Actual Study Start Date: October 16, 2020
• Actual Primary Completion Date: August 28, 2021
• Actual Study Completion Date: September 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 100 μg LSD + Ketanserin placebo	Drug: Lysergic Acid Diethylamide; A moderate dose of 100 μg LSD will be administered.; Other Name: LSD; Drug: Ketanserin Placebo; Mannitol capsules instead of capsules containing Ketanserin.
Experimental: 100 μg LSD + Ketanserin (40mg)	Drug: Lysergic Acid Diethylamide; A moderate dose of 100 μg LSD will be administered.; Other Name: LSD; Drug: Ketanserin; A dose of 40 mg Ketanserin will be administered.

Outcome Measures

Primary Outcome Measures :

1. Duration of subjective response [ Time Frame: 12 months ]
   Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS will be used: "any effect", "good effect", "bad effect", "fear", "stimulated", "nausea", "tiredness", "alteration of hearing", "alteration of vision", "synesthesia", "alteration in sense of time", "the boundaries between myself and my surroundings seemed to blur", "talkative", "open", "trust" and "my focus is directed: outward/inward". Subjects will mark the scale with vertical lines.
2. Extent of subjective response [ Time Frame: 12 months ]
   Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS will be used: "any effect", "good effect", "bad effect", "fear", "stimulated", "nausea", "tiredness", "alteration of hearing", "alteration of vision", "synesthesia", "alteration in sense of time", "the boundaries between myself and my surroundings seemed to blur", "talkative", "open", "trust" and "my focus is directed: outward/inward". Subjects will mark the scale with vertical lines.
3. Plasma concentrations of LSD [ Time Frame: 12 months ]
   LSD plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale).
4. Plasma concentrations of Ketanserin [ Time Frame: 12 months ]
   LSD plasma concentrations will be measured repeatedly over time using Liquid chromatography-mass spectrometry (LC-MS)/MS techniques (nanogram per milliliter scale).

Secondary Outcome Measures :

1. 5 dimensions of altered state of consciousness (5D-ASC) profile total score [ Time Frame: 12 months ]
   Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.
2. Adjective mood rating scale (AMRS) [ Time Frame: 12 months ]
   The adjective mood rating scale (AMRS or EWL60S) is a 60-item 4-point Likert scale ("not at all", "somewhat", "rather", "strongly") that allows repeated assessment of mood in 6 dimensions: activation, inactivation, well-being, anxiety/depressed mood, extroversion and introversion, and emotional excitability.The AMRS consists of subscales measuring "activation", "positive mood", "extroversion", "introversion", "inactivation", and "emotional excitability".
3. States of consciousness questionnaire (SCQ) [ Time Frame: 12 months ]
   This 100-item questionnaire is rated on a 6-point scale (0=none, not at all; 1=so slight cannot decide; 2=slight; 3=moderate; 4=strong (equivalent in degree to any previous strong experience or expectation of this description); 5=extreme (more than ever before in my life and stronger than 4)). Forty-three items embedded into this questionnaire comprise the Mystical Experience Questionnaire (MEQ). The 43 items provide scale scores for each of seven domains of mystical experiences: internal unity (pure awareness, a merging with ultimate reality), external unity (unity of all things, all things are alive, all is one), sense of sacredness (reverence, sacred), noetic quality (encounter with ultimate reality, more real than everyday reality), transcendence of time and space, deeply felt positive mood (joy, peace, love), paradoxicality/ineffability (claim of difficulty in describing the experience in words).
4. Blood pressure [ Time Frame: 12 months ]
   Repeatedly measured using blood pressure / pulse apparatus (mmHg scale).
5. Heart rate [ Time Frame: 12 months ]
   Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale).
6. Body temperature [ Time Frame: 12 months ]
   Repeatedly measured using ear thermometer (degree Celsius scale).
7. Pupil diameter [ Time Frame: 12 months ]
   Repeatedly measured using pupil distance meter (millimeter scale).
8. Elliot Humility Scale (EHS) [ Time Frame: 12 months ]
   Assesses the personality trait humility through 13 items on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree".
9. Jankowski Humility Scale (JHS) [ Time Frame: 12 months ]
   Assesses the personality trait humility through 18 items on a 5-point Likert scale ranging from "not at all" to "strongly".
10. Arnett Inventory of Sensation Seeking (AISS-d) [ Time Frame: 12 months ]
    Assesses the personality trait of sensation seeking, which is is defined as a need for novel and intense stimulation. It uses 20 items using 4-point scales (1 = "describes me very well" to 4 = "does not describe me at all").
11. Freiburger Persönlichkeitsinventar (FPI) [ Time Frame: 12 months ]
    The FPI-R version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").
12. Saarbrücker Persönlichkeitsfragebogen (SPF) [ Time Frame: 12 months ]
    The SPF defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.
13. Defense Style Questionnaire (DSQ-40) [ Time Frame: 12 months ]
    The DSQ-40 can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

Switzerland

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

• Principal Investigator: Matthias E Liechti, Dr., MD; University Hospital, Basel, Switzerland

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT04558294
• Other Study ID Numbers: BASEC 2020-00614
• First Posted: September 22, 2020
• Last Update Posted: October 21, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ketanserin; Lysergic Acid Diethylamide; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists; Antihypertensive Agents; Platelet Aggregation Inhibitors