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

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