Mood (Psychological Function)Phase 1/2PRISMaticNCT07610135
Psilocybin Efficacy With or Without Pimavanserin Pretreatment
A Phase 1/2 study testing Psilocybin and Pimavanserin in people with Mood (Psychological Function) and Well Being, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Mood (Psychological Function), Well Being, Mood
- What is being tested?
- Psilocybin and Pimavanserin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2026to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mazen A. Atiq, MD contact
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Center for Psychedelic and Consciousness Research
Baltimore, Maryland, 21224
Arozo Azimi, 410-550-0007, aazimi2@jh.edu
Mazen A Atiq, MD, matiq3@jh.edu
About this study
Official title: PRISMatic: A Phase 1b Randomized, Double-Armed, Parallel-Group, Placebo-Controlled Trial of Psilocybin Efficacy With or Without Pimavanserin Pretreatment
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
- Being tested
- Psilocybin, Pimavanserin, Inactive Placebo
- Keywords
- Psilocybin, Randomized Controlled Trial, Tryptamine, Pimavanserin, Indoles, Indole Alkaloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Psilocybin, 25 mg, oral, single dose
PimavanserinDrug
Also called Nuplazid
Pimavanserin, 34 mg, oral, two doses
Inactive PlaceboDrug
Inactive placebo, oral, two doses
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin + Pimavanserin | Experimental | Two oral pretreatment doses of pimavanserin (34 mg each) followed by a single oral dose of psilocybin (25 mg) Receives: Drug: Psilocybin; Drug: Pimavanserin |
| Psilocybin + Placebo | Placebo comparator | Two oral pretreatment doses of inactive placebo followed by a single oral dose of psilocybin (25 mg) Receives: Drug: Psilocybin; Drug: Inactive Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Persisting Effects Questionnaire (PEQ) score
Persisting effects will be assessed using the single item well-being item from the Persisting Effects Questionnaire (PEQ) at 1-week (primary inferential contrast) and 1-month post-dosing. The PEQ is an instrument designed to measure participants' retrospective attributions regarding the longer-term impact of the psilocybin experience, including effects on mood, behavior, and overall well-being. The item is rated on a 7-point Likert scale (-3 = decreased very much; -2 = decreased moderately; -1 = decreased slightly; 0 = no change; 1 = increased slightly; 2 = increased moderately; 3 = increased very much). Score range -3 to 3.
Measured: Day 7, Day 30
Secondary outcomes (2)
Amygdala Response to Stimuli in the Emotion Recognition Test
Blood oxygenation level-dependent (BOLD) percent signal change in response to stimuli in the emotion recognition task will be measured in the left and right amygdala.
Measured: Day -1 (baseline), Day 7, Day 30
Pharmacokinetics (PK) of Psilocybin metabolites
PK parameter (AUC 0-6h) for unconjugated psilocin in plasma.
Measured: 0-6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study start30 Oct 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mood (Psychological Function)Studies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David B. Yaden, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07610135
- Sponsor's protocol ID
- IRB00526000
- Acronym
- PRISMatic
- Status last verified
- Sep 2026
- First submitted
- 20 May 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barrett FS, Doss MK, Sepeda ND, Pekar JJ, Griffiths RR. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep. 2020 Feb 10;10(1):2214. doi: 10.1038/s41598-020-59282-y.
PubMed 32042038Atiq MA, Baker MR, Voort JLV, Vargas MV, Choi DS. Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties. Psychopharmacology (Berl). 2025 Jul;242(7):1481-1506. doi: 10.1007/s00213-024-06599-5. Epub 2024 May 14.
PubMed 38743110Yaden DB, Griffiths RR. The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacol Transl Sci. 2020 Dec 10;4(2):568-572. doi: 10.1021/acsptsci.0c00194. eCollection 2021 Apr 9.
PubMed 33861219
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRISMatic: A Phase 1b Randomized, Double-Armed, Parallel-Group, Placebo-Controlled Trial of Psilocybin Efficacy With or Without Pimavanserin Pretreatment
- ClinicalTrials.gov ID
- NCT07610135
- Acronym / sponsor ID
- PRISMatic / IRB00526000
- Conditions
- Mood (Psychological Function), Well Being, Mood, Healthy
- Keywords
- Psilocybin, Randomized Controlled Trial, Tryptamine, Pimavanserin, Indoles, Indole Alkaloid
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 30 Oct 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 27 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin + Pimavanserin | Experimental | Drug: Psilocybin, Drug: PimavanserinTwo oral pretreatment doses of pimavanserin (34 mg each) followed by a single oral dose of psilocybin (25 mg) |
| Psilocybin + Placebo | Placebo comparator | Drug: Psilocybin, Drug: Inactive PlaceboTwo oral pretreatment doses of inactive placebo followed by a single oral dose of psilocybin (25 mg) |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age 21 to 65 years old
- Provision of written informed consent
- Fluency in English
- At least high school level of education
- Right-handed
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinPsilocybin, 25 mg, oral, single dose | Drug | Psilocybin + Pimavanserin, Psilocybin + Placebo |
| PimavanserinAlso: NuplazidPimavanserin, 34 mg, oral, two doses | Drug | Psilocybin + Pimavanserin |
| Inactive PlaceboInactive placebo, oral, two doses | Drug | Psilocybin + Placebo |
Primary outcome
Persisting Effects Questionnaire (PEQ) score
Time frame: Day 7, Day 30
Persisting effects will be assessed using the single item well-being item from the Persisting Effects Questionnaire (PEQ) at 1-week (primary inferential contrast) and 1-month post-dosing. The PEQ is an instrument designed to measure participants' retrospective attributions regarding the longer-term impact of the psilocybin experience, including effects on mood, behavior, and overall well-being. The item is rated on a 7-point Likert scale (-3 = decreased very much; -2 = decreased moderately; -1 = decreased slightly; 0 = no change; 1 = increased slightly; 2 = increased moderately; 3 = increased very much). Score range -3 to 3.
2 secondary outcomes
Amygdala Response to Stimuli in the Emotion Recognition Test
Time frame: Day -1 (baseline), Day 7, Day 30
Pharmacokinetics (PK) of Psilocybin metabolites
Time frame: 0-6 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Background: PubMed 32042038Barrett FS, Doss MK, Sepeda ND, Pekar JJ, Griffiths RR. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep. 2020 Feb 10;10(1):2214. doi: 10.1038/s41598-020-59282-y.
- Background: PubMed 38743110Atiq MA, Baker MR, Voort JLV, Vargas MV, Choi DS. Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties. Psychopharmacology (Berl). 2025 Jul;242(7):1481-1506. doi: 10.1007/s00213-024-06599-5. Epub 2024 May 14.
- Background: PubMed 33861219Yaden DB, Griffiths RR. The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacol Transl Sci. 2020 Dec 10;4(2):568-572. doi: 10.1021/acsptsci.0c00194. eCollection 2021 Apr 9.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mazen A. Atiq, MD contact
David B. Yaden, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Psilocybin and Pimavanserin in people with Mood (Psychological Function) and Well Being, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Arozo Azimi (410-550-0007, aazimi2@jh.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persisting Effects Questionnaire (PEQ) score (time frame: Day 7, Day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07610135, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026; AzTrials last refreshed its copy on 1 Nov 2026.