Effects of blocking the 5‑HT2A serotonin receptor on thinking and memory
Official title: Investigating the Neuropsychological Effects of 5-HT2a Antagonism
Run by University of Oxford · NCT07022366 · Data updated 2026-11-12
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
| Study type | Interventional |
|---|---|
| Ages | 18 Years to 45 Years |
| Sex | All |
| Enrollment | 80 (estimated) |
| Sponsor | University of Oxford Academic / other |
| Locations | 1 site (Oxford) |
| Status | Recruiting |
| Started | February 10, 2025 |
| Main results expected | June 2026 |
| Study ends | September 2026 |
| Registry record updated | April 29, 2026 |
| Trial ID | NCT07022366 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a 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.
✕Probably 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.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
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.
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 gone: 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.
Who can join: the full rules
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 it's running
-
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
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
Newborn SMA Screening Service Evaluation
This project tests newborn SMA screening to see if it works well and is acceptable to families in the UK.
-
Prucalopride for low mood: testing a 5-HT4 receptor activator for cognition and sleep
This study tests whether prucalopride, a 5-HT4 receptor drug, can improve thinking and sleep in adults with low mood or major depressive disorder compared to a placebo.
-
Robotic-assisted tPA injection for retinal vein occlusion
This trial tests whether robot-assisted delivery of a clot-dissolving drug (tPA) into a blocked retinal vein can restore blood flow in people with central retinal vein occlusion.
-
Understanding heart artery disease using biomarkers and imaging in Oxford
Researchers in Oxford are testing how biomarkers and advanced imaging can help explain why some heart artery plaques are unstable and how this affects heart damage after a heart attack.
-
VTA real-time biofeedback with 7-Tesla MRI in depression
This study tests whether people with major depressive disorder can learn to modulate their brain's reward center (the VTA) using real-time feedback during 7-Tesla MRI sessions, to see if it changes mood and motivation.
-
Gut leakage in dengue: is the intestinal barrier affected during infection?
Researchers are studying whether dengue infection disrupts the gut barrier and if that contributes to severe disease in adults with dengue who are in hospital.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.