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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 100 μg LSD + Ketanserin placebo | Experimental |
| |
| 100 μg LSD + Ketanserin (40mg) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lysergic Acid Diethylamide | Drug | A moderate dose of 100 μg LSD will be administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Duration of subjective response | 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. | 12 months |
| Extent of subjective response | 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. | 12 months |
| Plasma concentrations of LSD | LSD plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale). | 12 months |
| Plasma concentrations of Ketanserin | LSD plasma concentrations will be measured repeatedly over time using Liquid chromatography-mass spectrometry (LC-MS)/MS techniques (nanogram per milliliter scale). | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 5 dimensions of altered state of consciousness (5D-ASC) profile total score | 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. | 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, Dr., MD | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology & Toxicology, University Hospital Basel | Basel | 4031 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36342343 | Derived | Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, Eckert A, Liechti ME. Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants. Int J Neuropsychopharmacol. 2023 Feb 14;26(2):97-106. doi: 10.1093/ijnp/pyac075. |
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| ID | Term |
|---|---|
| D008238 | Lysergic Acid Diethylamide |
| D007650 | Ketanserin |
| ID | Term |
|---|---|
| D008237 | Lysergic Acid |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
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Double-blind, placebo-controlled, random-order 2-period cross-over design with 2 treatment conditions:
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| Ketanserin Placebo | Drug | Mannitol capsules instead of capsules containing Ketanserin. |
|
| Ketanserin | Drug | A dose of 40 mg Ketanserin will be administered. |
|
| Adjective mood rating scale (AMRS) | 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". | 12 months |
| States of consciousness questionnaire (SCQ) | 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). | 12 months |
| Blood pressure | Repeatedly measured using blood pressure / pulse apparatus (mmHg scale). | 12 months |
| Heart rate | Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale). | 12 months |
| Body temperature | Repeatedly measured using ear thermometer (degree Celsius scale). | 12 months |
| Pupil diameter | Repeatedly measured using pupil distance meter (millimeter scale). | 12 months |
| Elliot Humility Scale (EHS) | Assesses the personality trait humility through 13 items on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree". | 12 months |
| Jankowski Humility Scale (JHS) | Assesses the personality trait humility through 18 items on a 5-point Likert scale ranging from "not at all" to "strongly". | 12 months |
| Arnett Inventory of Sensation Seeking (AISS-d) | 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"). | 12 months |
| Freiburger Persönlichkeitsinventar (FPI) | 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 months |
| Saarbrücker Persönlichkeitsfragebogen (SPF) | 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. | 12 months |
| Defense Style Questionnaire (DSQ-40) | 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". | 12 months |
| D006571 |
| Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D052999 | Quinazolinones |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |