Recruiting

Phase 1

Phase 2

Psilocybin with PimavanserinPsilocybin Efficacy With or Without Pimavanserin Pretreatment

Sponsor:

Johns Hopkins University

Code:

NCT07610135

Conditions

Mood (Psychological Function)

Well Being

Mood

Healthy

Eligibility Criteria

Sex: All

Age: 21 - 65

Healthy Volunteers: Accepted

Interventions

Psilocybin

Pimavanserin

Inactive Placebo

Study Details

Brief summary:

Twenty healthy adults (≥21 years old) will be enrolled to evaluate the efficacy of a single oral dose of psilocybin (25 mg) administered with or without pretreatment using oral pimavanserin (34 mg) or placebo. Outcome assessments will occur at 1 week and 1 month following psilocybin administration.

The purpose of this study is to clarify the receptor-level mechanisms underlying psilocybin's effects on mood and well-being, along with the associated neurophysiologic signatures. These mechanisms will be examined using psychometric scales, autonomic and fMRI-based neurophysiologic markers, and integrated pharmacokinetic/pharmacodynamic modeling.

Conditions

Mood (Psychological Function)

Well Being

Mood

Healthy

Study ID

NCT07610135

Start date

Sep 30, 2026

Status verified date

Aug, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Jun, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 21 - 65

Healthy Volunteers: Accepted

Inclusion Criteria:

Age 21 to 65 years old
Provision of written informed consent
Fluency in English
At least high school level of education
Right-handed
Agree to abstain from any psychoactive drugs on the day prior to and the day of the drug administration session as demonstrated by a negative toxicology report.
Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
Agree not to take any PRN medications on the mornings of drug sessions
Agree that for one week before the drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
Female participants of childbearing potential must agree to use a highly effective method of contraception throughout the study.
Highly effective methods are defined as those that, when used consistently and correctly (alone or in combination), are associated with a failure rate of less than 1% per year.
Condoms alone are not considered highly effective.
Abstinence is not considered a highly effective method. However, at the investigator's discretion, abstinence may be accepted if, based on the investigator's judgment and knowledge of the participant's usual and preferred lifestyle, it can be reasonably expected to result in 100% effectiveness.

Exclusion Criteria:

Non-English speakers and those with language or hearing impairments
Left-handedness (assessed by the Edinburgh Handedness Inventory)
Any lifetime history of psychedelic use, including serotonergic compounds (e.g., psilocybin, LSD, mescaline, DMT, 5-MeO-DMT) and nontraditional psychedelics (e.g., MDMA, ketamine, ibogaine)
History of psychiatric diagnosis in adulthood (≥18 years), including, but not limited to, major depressive disorder, bipolar disorder I and II, psychotic disorders, and substance use disorder.
Current use of neuropsychiatric medications, including but not limited to typical/atypical antidepressants, antipsychotics, and stimulants.
Lifetime history of substance use disorder
Current (within past six months) substance use disorder of moderate or greater severity
Clinically significant suicidal ideation (with strong intent or means) within the past 6 months or lifetime history of suicide attempt, current suicidal ideation, or otherwise judged by a study clinician to be more than low risk for suicidality
Current use/positive toxicology for illicit drugs at screening and prior to drug administration session (includes illicit, non-prescribed, or prohibited substances such as amphetamines, barbiturates, buprenorphine, benzodiazepines, cocaine, MDMA, methadone, opioids, phencyclidine (PCP), and tetrahydrocannabinol (THC))
Nicotine user consuming the equivalent of ≥ 10 cigarettes/day
Altered gastrointestinal anatomy \[history of surgeries that promote a general intestinal malabsorption (e.g., jejunoileal bypass, jejunocolic bypass, roux-en-Y gastric bypass, vertical banded gastroplasty, gastric band, gastric stapling, sleeve gastrectomy, biliopancreatic diversion with partial gastrectomy, distal gastric bypass, duodenal switch)\]
Weight < 40kg
Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder
MRI contraindications (e.g., claustrophobia incompatible with MRI scanning, medical device or implant incompatible with MRI, prior history as a metal worker and/or certain metallic objects in the body). Must complete MRI screening form and be approved by MRI technologist before each scan.
Unable or unwilling to perform study procedures, or inappropriate for further study participation as determined by the PI and/or study clinicians

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Psilocybin + Pimavanserin

Two oral pretreatment doses of pimavanserin (34 mg each) followed by a single oral dose of psilocybin (25 mg)

placebo comparator: Psilocybin + Placebo

Two oral pretreatment doses of inactive placebo followed by a single oral dose of psilocybin (25 mg)

Interventions

Psilocybin

Psilocybin, 25 mg, oral, single dose

Pimavanserin

Pimavanserin, 34 mg, oral, two doses

Inactive Placebo

Inactive placebo, oral, two doses

Primary outcome measure

Persisting Effects Questionnaire (PEQ) score [ Time Frame: Day 7, Day 30 ]

Central Contacts and Locations

Central contacts

Arozo Azimi

410-550-0007 aazimi2@jh.edu

Mazen A. Atiq, MD

matiq3@jh.edu

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research

Recruiting

Baltimore, Maryland, United States, 21224

Contacts

Arozo Azimi

410-550-0007 aazimi2@jh.edu

Mazen A Atiq, MD

matiq3@jh.edu

Principal Investigator:

David B. Yaden, PhD

More Information

Sponsor

Johns Hopkins University

Last update posted

Aug 31, 2026

Last verified

Aug, 2026

Keywords

Psilocybin
Randomized Controlled Trial
Tryptamine
Pimavanserin
Indoles
Indole Alkaloid

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-19. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-08-31.