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


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.

Full Title of Study: “The Role of 5-HT2A Receptor on Perception of the Self and Perception of Meaning in Healthy Volunteers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 2016

Detailed Description

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.


  • Drug: Placebo
    • Capsules containing mannitol looking identical to LSD per os
  • Drug: LSD
    • 100µg per os, single dose
  • Drug: Ketanserin
    • 40mg per os, single dose looking identical to LSD per os

Arms, Groups and Cohorts

  • Experimental: Placebo, LSD, Ketanserin/LSD
    • 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

Clinical Trial Outcome Measures

Primary Measures

  • fMRI brain activity (BOLD signal)
    • Time Frame: two MRI acquisitions separated by a break of 160 minutes

Secondary Measures

  • associations between personality traits, subjective experiences, and mood changes and the changes in BOLD signal
    • Time Frame: 14 hours
  • repeated assessment of subjective effects with validated questionnaires
    • Time Frame: 14 hours

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Psychiatric University Hospital, Zurich
  • Provider of Information About this Clinical Study
    • Principal Investigator: Franz X. Vollenweider, Prof. Dr. med. – Psychiatric University Hospital, Zurich
  • Overall Official(s)
    • Franz X. Vollenweider, Prof. Dr., Principal Investigator, Center for Psychiatric Research, Department of Psychiatry, Psychotherapy and Psychosomatic, Psychiatric Hospital, University of Zurich

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