Effects of SERT Inhibition on the Subjective Response to LSD in Healthy Subjects
Sponsored by University Hospital, Basel, Switzerland
About This Study
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. SSRIs like paroxetine are first-line treatments for depression and anxiety disorders. Paroxetine acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to LSD.
Conditions Studied
Interventions
- •Paroxetine
- •Lysergic Acid Diethylamide
- •Placebo
Eligibility
View full eligibility criteria
Inclusion Criteria: * Understanding of the German language. * Understanding the procedures and the risks that are associated with the study. * Participants must be willing to adhere to the protocol and sign the consent form. * Participants must be willing to refrain from taking illicit psychoactive substances during the study. * Participants must be willing to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions. * Participants must be willing not to drive a traffic vehicle or to operate machines within 48h after substance administration. * Willing to use double-barrier birth control throughout study participation. * Body mass index between 18-29 kg/m2. Exclusion Criteria: * Chronic or acute medical condition, including a history of seizures. * Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders). * Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain. * Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg); QT-time\>450 ms (men) or \>470 ms (women). * Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months. * History of acute glaucoma. * Pregnant or nursing women. * Participation in another clinical trial (currently or within the last 30 days). * Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known pharmacokinetic or pharmacodynamic interactions with paroxetine). * Tobacco smoking (\>10 cigarettes/day). * Consumption of alcoholic drinks (\>20 drinks/week).