Alcohol Use DisorderPhase 2NCT05421065
Psilocybin-Assisted vs Ketamine-Assisted Psychotherapy for Alcohol Use Disorder
A Phase 2 study testing Psilocybin and Ketamine in people with Alcohol Use Disorder, run by Peggy C Nopoulos at 1 site in United States.
Trial summary
This pilot study will collect preliminary data that measures the effects of psilocybin-assisted psychotherapy vs ketamine-assisted psychotherapy on patients struggling with alcohol use. Read more about this study
- Who is it for?
- Ages 25 to 65 years, men only
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Psilocybin and Ketamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2024to Sep 2026
- Phase
- Phase 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 25 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 25-65 years old
- Male
- English fluency
- Meets criteria for DSM-V moderate or severe AUD.
- Have at least 4 heavy drinking days (5 or more standard drinks in a day) in the past 30 days.
- No history of a of cerebrovascular accident, asthma, or significant alcohol withdrawal history
Show all 18Show fewer
- No seizure disorder, coronary artery disease, heart failure, uncontrolled hypertension, insulin-dependent diabetes
- No current substance use disorder other than AUD
- Negative drug screen (other than THC) on drug administration day
- No prescription medications classified as UGT1A9 inhibitors, UGT1A10 inhibitors, aldehyde or alcohol dehydrogenase inhibitors.
- At least a high-school level of education or equivalent (e.g. GED).
- Lived at current residence for at least 3 months.
- Family member/friend for pick-up, overnight post-drug session monitoring.
- No hallucinogen or ketamine use in past 1 year
- No self-reported, personal, or familial history of specific psychotic disorders/episodes as subjects who take psilocybin may experience a worsening and/or persistent psychotic state. Therefore, these subjects are excluded due to an abundance of caution since even a family history may create a vulnerability to psychosis.
- No serious traumatic brain injury (TBI) in the past 2 years.
- No known allergies to rescue medication (diazepam)
- Weight between 110 and 330 lbs
Who cannot join
- Drug/medication assessment that yields: nonprescription medication use, nutritional supplement, or herbal supplement (except when approved by the study investigators), medically unstable, current medication use that has significant potential to interact with study drug (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants, or benzodiazepines).
- Psychiatric assessment that yields:1) history of severe suicide attempt, 2) current suicidality 3) first degree relative with schizophrenia or schizoaffective disorder, 4) comorbid substance use including cocaine, psychostimulant, or opioid use disorder within past 12 months and/or any use within past 30 days, 5) history of co-occurring psychotic episode/diagnosis including schizophrenia, schizoaffective disorder, schizophreniform, substance-induced psychosis, delusional disorder, or psychosis not otherwise specified, 6) high risk of adverse emotional or behavioral reaction based on the medical monitor's clinical evaluation that may also yield evidence of serious current stressors, a lack of meaningful social support, antisocial behavior, and/or serious personality disorders amongst other conditions.
- Medical assessment that yields: serious ECG abnormalities (evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045]), serious abnormalities of complete blood count or chemistries, medical conditions that would preclude safe participation (significantly impaired liver function).
- MRI contraindication (pacemaker, etc.)
Trial locations and contacts
1 site in 1 country.
About this study
This pilot study will collect preliminary data that measures the effects of psilocybin-assisted psychotherapy vs ketamine-assisted psychotherapy on patients struggling with alcohol use.
Read the detailed description
This pilot study will be a double blind, randomized, active-comparator controlled trial with two study arms. Subjects randomized to Arm 1 (n=10) will receive individual psychotherapy sessions plus a 25mg dose of psilocybin, while Arm 2 subjects (n=10) will receive individual psychotherapy sessions and a 200mg dose of ketamine. Psychotherapy sessions will involve integrative psychotherapy modalities.
At baseline, subjects will be consented, randomized into one of the two arms, complete psychiatric and medical evaluations, and will undergo an MRI scan. The first two therapy sessions (week 1 and week 2) will be used to learn about the participant's life story, engage the patient, and evoke their reasons for wanting to change their pattern of alcohol use. At week 3, participants will undergo a psilocybin-assisted therapy session or a ketamine-assisted therapy session. The last 2 psychotherapy sessions will be focused on integration of their experiences in the drug administration session and will include a second MRI scan and more assessments. Therefore, each arm receives 4 psychotherapy sessions, and the primary difference between the groups is which drug participants receive. After the psychotherapy sessions are completed at the end of week 4, subjects will be followed weekly for 4 weeks. At the last follow-up (week 8), they will undergo a third MRI scan and a final assessment. At the conclusion of the study, those randomized to the ketamine group will be offered a psilocybin-assisted therapy session, and two follow-up/integration sessions in an open-label extension. The open-label extension will also include an additional 4 weeks of follow-up.
- Conditions
- Alcohol Use Disorder
- Being tested
- Psilocybin, Ketamine
- Keywords
- psilocybin, ketamine
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
1 oral dose
KetamineDrug
1 oral dose
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin Group (Arm 1) | Experimental | Not described Receives: Drug: Psilocybin |
| Ketamine Group (Arm 2) | Active comparator | Not described Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timeline Follow-Back for Alcohol to assess change
quantifies daily alcohol use
Measured: weekly, over the course of 8 weeks
Secondary outcomes (2)
T1rho
Measures biological changes in the brain
Measured: three times (before intervention, immediately after intervention, and 4 weeks-post intervention)
Resting state fMRI
Measures biological changes in the brain
Measured: three times (before intervention, immediately after intervention, and 4 weeks-post intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study start2 Feb 2024
- Primary completion30 Aug 2025
- Study completionSep 2026 (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 Alcohol Use DisorderStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peggy C Nopoulos
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Peggy C Nopoulos, University of Iowa
- Investigators
- Peggy C Nopoulos, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05421065
- Sponsor's protocol ID
- 202205036
- Status last verified
- Nov 2025
- First submitted
- 12 Jun 2022
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.
PubMed 33146667Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015 Mar;29(3):289-99. doi: 10.1177/0269881114565144. Epub 2015 Jan 13.
PubMed 25586396Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20. doi: 10.1177/0269881108093587. Epub 2008 Jul 1.
PubMed 18593734
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin-Assisted vs Ketamine-Assisted Psychotherapy for Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT05421065
- Acronym / sponsor ID
- 202205036
- Conditions
- Alcohol Use Disorder
- Keywords
- psilocybin, ketamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peggy C NopoulosUniversity, hospital or other
- Study start
- 2 Feb 2024 (actual)
- Primary completion
- 30 Aug 2025 (actual)
- Study completion
- Sep 2026 (estimated)
- First posted
- 16 Jun 2022 (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.
This pilot study will collect preliminary data that measures the effects of psilocybin-assisted psychotherapy vs ketamine-assisted psychotherapy on patients struggling with alcohol use.
Detailed description
This pilot study will be a double blind, randomized, active-comparator controlled trial with two study arms. Subjects randomized to Arm 1 (n=10) will receive individual psychotherapy sessions plus a 25mg dose of psilocybin, while Arm 2 subjects (n=10) will receive individual psychotherapy sessions and a 200mg dose of ketamine. Psychotherapy sessions will involve integrative psychotherapy modalities.
At baseline, subjects will be consented, randomized into one of the two arms, complete psychiatric and medical evaluations, and will undergo an MRI scan. The first two therapy sessions (week 1 and week 2) will be used to learn about the participant's life story, engage the patient, and evoke their reasons for wanting to change their pattern of alcohol use. At week 3, participants will undergo a psilocybin-assisted therapy session or a ketamine-assisted therapy session. The last 2 psychotherapy sessions will be focused on integration of their experiences in the drug administration session and will include a second MRI scan and more assessments. Therefore, each arm receives 4 psychotherapy sessions, and the primary difference between the groups is which drug participants receive. After the psychotherapy sessions are completed at the end of week 4, subjects will be followed weekly for 4 weeks. At the last follow-up (week 8), they will undergo a third MRI scan and a final assessment. At the conclusion of the study, those randomized to the ketamine group will be offered a psilocybin-assisted therapy session, and two follow-up/integration sessions in an open-label extension. The open-label extension will also include an additional 4 weeks of follow-up.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin Group (Arm 1) | Experimental | Drug: Psilocybin |
| Ketamine Group (Arm 2) | Active comparator | Drug: Ketamine |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 25-65 years old
- Male
- English fluency
- Meets criteria for DSM-V moderate or severe AUD.
- Have at least 4 heavy drinking days (5 or more standard drinks in a day) in the past 30 days.
Key exclusion criteria (4 listed)
- Drug/medication assessment that yields: nonprescription medication use, nutritional supplement, or herbal supplement (except when approved by the study investigators), medically unstable, current medication use that has significant potential to interact with study drug (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants, or benzodiazepines).
- Psychiatric assessment that yields:1) history of severe suicide attempt, 2) current suicidality 3) first degree relative with schizophrenia or schizoaffective disorder, 4) comorbid substance use including cocaine, psychostimulant, or opioid use disorder within past 12 months and/or any use within past 30 days, 5) history of co-occurring psychotic episode/diagnosis including schizophrenia, schizoaffective disorder, schizophreniform, substance-induced psychosis, delusional disorder, or psychosis not otherwise specified, 6) high risk of adverse emotional or behavioral reaction based on the medical monitor's clinical evaluation that may also yield evidence of serious current stressors, a lack of meaningful social support, antisocial behavior, and/or serious personality disorders amongst other conditions.
- Medical assessment that yields: serious ECG abnormalities (evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045]), serious abnormalities of complete blood count or chemistries, medical conditions that would preclude safe participation (significantly impaired liver function).
- MRI contraindication (pacemaker, etc.)
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 |
|---|---|---|
| Psilocybin1 oral dose | Drug | Psilocybin Group (Arm 1) |
| Ketamine1 oral dose | Drug | Ketamine Group (Arm 2) |
Primary outcome
Timeline Follow-Back for Alcohol to assess change
Time frame: weekly, over the course of 8 weeks
quantifies daily alcohol use
2 secondary outcomes
T1rho
Time frame: three times (before intervention, immediately after intervention, and 4 weeks-post intervention)
Resting state fMRI
Time frame: three times (before intervention, immediately after intervention, and 4 weeks-post intervention)
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 17 Nov 2025.
- Background: PubMed 33146667Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.
- Background: PubMed 25586396Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015 Mar;29(3):289-99. doi: 10.1177/0269881114565144. Epub 2015 Jan 13.
- Background: PubMed 18593734Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20. doi: 10.1177/0269881108093587. Epub 2008 Jul 1.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Peggy C Nopoulos, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin and Ketamine in people with Alcohol Use Disorder, run by Peggy C Nopoulos 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 18 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 17 Nov 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timeline Follow-Back for Alcohol to assess change (time frame: weekly, over the course of 8 weeks). 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 NCT05421065, 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 17 Nov 2025.