Effects of blocking the 5‑HT2A serotonin receptor on thinking and memory
Investigating the Neuropsychological Effects of 5-HT2a Antagonism
This research will test whether a single 10 mg dose of pimavanserin (a 5‑HT2A serotonin blocker) changes memory, thinking, and learning in healthy adults aged 18–45.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 18 Years to 45 Years |
| Sex | All |
| Sponsor | University of Oxford Academic / other |
| Locations | 1 site (Oxford) |
| Trial ID | NCT07022366 on ClinicalTrials.gov |
What this trial studies
Pimavanserin, a selective 5‑HT2A receptor antagonist licensed for Parkinson's disease psychosis, will be given as a 10 mg dose or placebo to healthy volunteers aged 18–45. Participants will complete a battery of cognitive and neuropsychological tasks measuring memory, learning, and cognitive flexibility before and after dosing. The trial is placebo-controlled and designed to characterize how blocking 5‑HT2A receptors alters cognitive processes in humans. Findings are intended to inform how 5‑HT2A modulation might contribute to antidepressant mechanisms and guide future treatment development.
Who should consider this trial
Good fit: Healthy adults aged 18–45 with good vision and hearing, BMI 18–35, fluent in English, not currently receiving treatment for mental health conditions, and willing to avoid alcohol before visits.
Not a fit: People with current or past serious psychiatric disorders, those taking psychotropic or stimulant medications, heavy drinkers, older adults, or those unable to attend in-person visits are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, results could guide development of new antidepressant treatments that target the 5‑HT2A receptor and improve cognitive symptoms.
How similar studies have performed: Several antidepressant drugs act as 5‑HT2A antagonists and animal and human work links 5‑HT2A modulation to cognition, but using pimavanserin specifically in healthy volunteers for cognitive effects is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Willing and able to give informed consent for participation in the research * Aged 18-45 years * Good vision and hearing * Body mass index (BMI) within the range of 18-35kg/m2 (This is to ensure an appropriate pharmacokinetic profile for pimavanserin is achieved by all participants) * Sufficiently fluent in English to understand tasks * Willing to avoid drinking any alcohol the day before the research visit Exclusion Criteria: * Currently receiving or seeking treatment for any mental health condition * Any past or current history of severe and/or serious psychiatric disorder, including but not limited to schizophrenia, psychosis, bipolar affective disorder, severe major depressive disorder, obsessive compulsive disorder (covered in SCID-5 assessment in screening procedures) * ADHD requiring treatment with stimulant or other centrally-acting drugs * Regular alcohol consumption of more than 21 units per week * A head injury causing concussion or unconsciousness in the past 6 months * Pregnancy / intention to become pregnant during the study or breastfeeding * Any use of recreational drugs in the last three months * Participation in any other drug study in the last three months * Participation in any other study with the same tasks in the last year * History of cardiac disease or cardiac arrhythmias * Prolonged QTc interval on baseline ECG * Current usage of other drugs known to prolong QT interval including Class 1A or 3 antiarrhythmics, e.g. certain antibiotics (getifloxacin, moxifloxacin) * Current use of drugs that inhibit CYP3A4 (eg Clarithromycin. Diltiazem. Erythromycin. Fluconazole). Participants will be asked to avoid grapefruit juice in the week before the study. * Current use of psychoactive medication that in the opinion of the Chief Investigator may interfere with the study measures * History of, or current medical condition(s) which, in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, severe hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, severe neurological problems (e.g. Parkinson's disease; blackouts requiring hospitalisation); * Any physical (including visual and auditory), cognitive or language impairment that would make complying with the study protocol challenging * Excessive caffeine consumption, i.e., consumption higher than 8 cups of standard caffeinated drinks (tea, instant coffee) or higher than 6 cups of stronger coffee or other drinks containing methylxanthines such as coca cola or Red Bull per day; * Smoking \>10 cigarettes per day; or equivalent nicotine consumption * Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the chief investigator. * Inability to ingest up to 95mg of lactose Additional Exclusion Criteria for Participants in the Sleep Study Cohort: * Unable to undergo cardiac monitoring * Unable to wear the sleep patch device for full monitoring period * Implanted neurostimulator
Where this trial is running
Oxford
- Department of Psychiatry, University of Oxford — Oxford, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Susannah Murphy, PhD
- Email: susannah.murphy@psych.ox.ac.uk
- Phone: +441865618313
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.