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

The Role of 5-HT2A Receptor on Perception of the Self and Perception of 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.

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.

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