The Role of 5-HT2A Receptor in the Perception of Self and Personal Meaning in Healthy Volunteers

Study Overview
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Brief Summary
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Aim of the present study is to investigate the neuronal correlates of self and of personal meaning as well as the role of the serotonin (5-HT) 2A receptor system in these processes using functional magnetic resonance imaging (fMRI) and psychometric and cognitive measures.

Detailed Description
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The present study aims at identifying the contribution of the 5-HT2A receptor system to the formation of self and personal meaning in normal and altered states of consciousness. Specifically, the effect of the 5-HT2/1/6/7 receptor agonist lysergic acid diethylamide (LSD) on self-consciousness, perception and the making of meaning will be assessed in 25 healthy subjects using a randomized, placebo-controlled, double blind, cross-over design. Furthermore, the contribution of the 5-HT2A receptor to these functions shall be assessed by pretreatment with the specific 5-HT2A antagonist ketanserin.

Official Title
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The Role of 5-HT2A Receptor on Perception of the Self and Perception of Meaning in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Placebo
* Drug: LSD
* Drug: Ketanserin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers at the age of 20-40 Willing and capable to give informed consent for study participation as documented by signature after the nature of the study has been thoroughly explained Willing to refrain from drinking alcohol the day before testing session, from drinking alcohol and caffeinated drinks at the testing days and from consuming psychoactive substances 2 weeks before testing days and for the duration of the study Able and willing to comply with all study requirements MRI-compatible body shape and size (Body mass index [BMI] 17-30) Right-handedness Exclusion Criteria: Poor knowledge of the German language Previous significant adverse response to a hallucinogenic drug Participation in another study where pharmaceutical compounds are given within the 30 days preceding and during the present study Self or first-degree relatives with present or antecedent psychiatric disorders Present or antecedent alcohol/drug dependence or present alcohol/drug abuse History of head trauma, fainting, seizures, or electroconvulsive therapy Recent cardiac or brain surgery Current use of medication known to affect brain function (e.g. benzodiazepines, antihistamines, aspirin, beta blockers, theophylline, acetazolamide, etc.) Concomitant therapy with potent inhibitors of cytochrome P-450 isoenzyme 3A4 (HIV protease inhibitors, macrolide antibiotics, acylderivative anti-infective agents) Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine) Presence of psychiatric disorder Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardial infarction within the past 6 months, coronary spastic angina) Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease) Liver or renal disease Pregnant or breastfeeding women (a urine pregnancy test will be done before each session for all women capable of bearing children) Inability to lie still for about 60 minutes (e.g. because of sneezing, itching, tremor, pain) Metal parts in the body (piercings, brain aneurysm clip, implanted neural stimulator/cardiac pacemaker/defibrillator/Swan Ganz catheter/insulin pump, cochlear implant); metal shrapnel or bullet, ocular foreign body (e.g. metal shavings); current or previous job in metalworking industry Claustrophobia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo, LSD, Ketanserin/LSD<br>Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but three treatment conditions in the same subject | Drug: Placebo<br>* Capsules containing mannitol looking identical to LSD per os<br>Drug: LSD<br>* 100µg per os, single dose<br>* Other names: Lysergic acid diethylamide;Drug: Ketanserin<br>* 40mg per os, single dose looking identical to LSD per os<br>* Other names: Sufrexal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI brain activity (BOLD signal) |  | two MRI acquisitions separated by a break of 160 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| associations between personality traits, subjective experiences, and mood changes and the changes in BOLD signal |  | 14 hours | 
| repeated assessment of subjective effects with validated questionnaires |  | 14 hours |