Major Depressive DisorderPhase 2NCT06230757
Psilocybin for Treatment-Resistant Depression
A Phase 2 study testing Psilocybin 25mg in people with Major Depressive Disorder and Anhedonia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Major Depressive Disorder, Anhedonia, Treatment Resistant Depression
- What is being tested?
- Psilocybin 25mg
- 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
- 8 Jul 2024to 8 May 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 21 years of age at Screening
- Diagnosis of Major Depressive Disorder (MDD)
- Score of at least 12 (symptomatic depression) on administration of the Montgomery Asberg Depression Rating Scale (MADRS)
- Score of at least a 3 on question 8 on the MADRS evaluating loss of interest and ability to feel at both Screening and Baseline Visit 1
- The participant's Major depressive disorder meets the criteria for being treatment-resistant, defined as not experiencing a 50% improvement to two or more antidepressant treatments for adequate duration (6 weeks minimum) within the current episode, as determined by the Antidepressant Treatment Response Questionnaire (Desseilles et al., 2011; Posternak et al., 2004)
- Sufficiently competent in English Language
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- Currently under the care of a psychiatric practitioner (MD, DO, NP, PA) OR under the consistent care of a clinician within the UCHealth/CUMedicine health system (for example, primary care provider, neurologist, therapist). Participants engaged in additional psychosocial treatments beyond seeing a psychiatric practitioner or regular therapist will be evaluated on a case by case basis.
- Right-handed
- Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study. A person of childbearing potential is anyone born female who has experienced menarche and who has not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months of amenorrhea in a person over age 45 in the absence of other biological, physiological, or pharmacological causes.
- Have an identified support person and agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing
- Written informed consent obtained from participant and ability for subject to comply with the requirements of the study.
- Ability to abstain from caffeine and nicotine for 2 hours prior to fMRI scan visits
Who cannot join
- Unstable medical conditions or serious abnormalities of complete blood count, chemistries, or EKG that in the opinion of the study physician would preclude safe participation in the trial. Some examples include:
- Congestive heart failure
- Clinically significant arrhythmias (e.g. ventricular fibrillation, torsades) or clinically significant EKG abnormality (i.e. QTC interval > 450)
- Recent acute myocardial infarction or evidence of ischemia
- Malignant hypertension
- Congenital long QT syndrome
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- Acute renal failure
- Severe hepatic impairment
- Respiratory failure
- Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) Blood Pressure >140/90 mmHg.
- High resting heart rate defined as Screening, Baseline, and Medication Session (prior to dosing) heart of rate of >90 BPM
- Significant CNS pathology as determined by self-report and confirmed by a history and physical examination and review of medical records. Current and historical psychiatric disorders will be determined by the MINI. Specific examples include:
- Primary or secondary cerebral neoplasm
- Epilepsy
- History of stroke
- Cerebral aneurysm
- Dementia
- Delirium
- Current or lifetime primary psychotic disorder, bipolar affective disorder, affective disorder with psychotic features. Some examples include: i. Schizophrenia spectrum disorders j. Schizoaffective disorder k. Bipolar I or Bipolar II disorder l. History of mania m. Major depressive disorder with psychotic features
- Family history of first-degree relative with psychotic or serious bipolar spectrum illnesses. Examples include first-degree relative with:
- Schizophrenia spectrum disorders
- Schizoaffective disorder
- Bipolar I disorder with psychotic features
- High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation. Examples include:
- Agitation
- Violent behavior
- Active SUDs evaluated by the MINI and defined as: DSM-5 criteria for moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine) within the past year
- Extensive use of serotonergic hallucinogens (e.g. LSD, psilocybin) defined as:
- Any use in the last 6 months
- >25 lifetime uses
- History of hallucinogen persisting perception disorder (HPPD)
- Women who are pregnant, as indicated by a positive urine pregnancy test at Screening. Women who intend to become pregnant during the study or who are currently nursing.
- History of severe suicide attempt requiring hospitalization in the past year
- Have any suicidal ideation or thoughts, in the opinion of the study physician or PI, that presents a serious risk of imminent suicidal or self-injurious behavior
- Use of drugs or dietary supplements that per the discretion of the study team, have a mechanism of action that would interfere with procedures of study or have an adverse interaction with the study drug. Examples include direct agonists/antagonists of serotonin receptors such as those listed below. Selective Serotonin Re-uptake Inhibitors and Serotonin Norepinephrine Re-uptake Inhibitors are allowed at the discretion of the PI. Individuals need to be off all non-allowed drugs for a period of 5 half-lives prior to the baseline visit.
- Antipsychotics
- Trazodone
- Nefazodone
- Cyproheptadine
- Mirtazapine
- Flibanserin
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- Lithium
- Efavirenz
- Serotonergic dietary supplements including St. John's Wort, L-tryptophan and 5-Hydroxytryptophan (5-HTP)
- Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin based on investigator's clinical evaluation
- Have an allergy or intolerance to any of the materials contained in either drug product
- Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP).
- Note: Prescribed benzodiazepine medications and non-benzodiazepine sleeping medications will be allowed to continue through the study period for participants who have been on a stable dose of such a medicine for at least 6 weeks prior to Screening, as determined during review of concomitant medications.
- Note: Participants using cannabis, including legal cannabis, for any purposes and who do not screen positive for a moderate to severe substance use disorder must agree to refrain from use beginning at Screening and through to the end of the study.
- Note: Participants using prescribed psychostimulants (amphetamines and Ritalin), must agree to refrain from use for five half-lives of the drug as confirmed with a negative Baseline drug test, and through to the end of the study.
- Have any psychological or physical symptom, medication or other relevant finding prior to baseline visit based on the clinical judgment of the PI or relevant clinical study staff that would make a participant unsuitable for the study.
- Claustrophobia
- Lack of internet access
- Weight over 300 pounds
- Metal in body unsafe for MRI or conditions that would make MRI unsafe for participants (e.g. aneurysm clip, cardiac pacemaker, etc.).
- Known contraindication to the drugs clonidine, diazepam, or olanzapine including:
- Hypersensitivity or allergy to clonidine, diazepam, or olanzapine
- Myasthenia gravis
- Severe respiratory insufficiency
- Severe hepatic insufficiency
- Acute narrow-angle glaucoma 23. History of valvular heart disease 24. Inability of the study team to obtain proper medical/psychiatric information (e.g. records from a current or previous clinician), that per the PI, would prevent an adequate assessment of the patient's eligibility and ability to safely participate in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Effects of Psilocybin With Psychological Support on Anhedonia in Treatment-resistant Depression: a Randomized Controlled Pilot Trial
The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.
- Being tested
- Psilocybin 25mg, Placebo (active placebo)
- Medical subject headings
- Depressive Disorder, Major, Anhedonia, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin 25mgDrug
25mg psilocybin capsule
Placebo (active placebo)Drug
Also called Ultra Low Dose Psilocybin
1mg psilocybin capsule
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | Participants receive Psilocybin 25mg capsule orally, administered with psychological support, on dosing day. Receives: Drug: Psilocybin 25mg |
| Active Placebo | Placebo comparator | Participants receive Psilocybin 1mg capsule (identical to the Psilocybin 25mg capsule) orally, administered with psychological support, on dosing day. Receives: Drug: Placebo (active placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).
The DARS is a 17-item scale that captures multiple domains of anhedonia found in depression. Scores range from 0 to 68 with lower scores indicating greater anhedonia and 68 indicating no anhedonia.
Measured: One week post-dosing
Secondary outcomes (6)
Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).
The DARS is a 17-item scale that captures multiple domains of anhedonia found in depression. Scores range from 0 to 68 with lower scores indicating greater anhedonia and 68 indicating no anhedonia.
Measured: Eight weeks post-dosing
Change from baseline in self-reported anhedonia scores on the Snaith-Hamilton Pleasure Scale (SHAPS).
The SHAPS is a 14-item scale that assesses the pleasure component of hedonic experience across multiple domains. Scores range from 0 to 14 with 0 indicating no anhedonia and high scores indicating greater anhedonia.
Measured: One week and eight weeks post-dosing
Change from baseline in response bias for the high reward condition on the Probabilistic Reward Task (PRT)
The PRT is a behavioral task that assesses the capacity to develop a response bias towards more highly rewarded stimuli, in which individuals with MDD demonstrate reduced bias towards highly rewarded stimuli.
Measured: One and eight weeks post-dosing
Change from baseline in nucleus accumbens neural activation during expectation of reward versus expectation of non-reward during the Monetary Incentive Delay Task (MID).
The MID is used in conjunction with fMRI to assess neural activity during reward processing and reliably induces neural activation in brain regions related to reward.
Measured: One week post-dosing
Change from baseline in depression scores of the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS).
The MADRS is a standard 10-item clinician-rated scale that assesses severity of depression in anti-depressant trials. Scores range form 0-60, with scores of 0-6 indicating no depression, 7-19 indicating mild depression, 20-34 indicating moderate depression and 35 or greater indicating severe depression.
Measured: One and eight weeks post-dosing
Change from baseline in depression scores as measured by self-report on the Quick Inventory of Depressive Symptomatology (QIDS-SR-16).
The QIDS-SR-16 is a widely used 16-item self-report scale of depressive symptoms. Scores range form 0-27, with scores of 0-5 indicating no depression, 6-10 indicating mild depression, 11-15 indicating moderate depression, 16-20 indicating severe depression, and 21-27 indicating very severe depression.
Measured: One, four, and eight weeks post-dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2024
- Study start8 Jul 2024
- Primary completion8 May 2026
- Study completion8 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew M Novick, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06230757
- Sponsor's protocol ID
- 22-1681
- Status last verified
- May 2026
- First submitted
- 19 Jan 2024
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Psilocybin With Psychological Support on Anhedonia in Treatment-resistant Depression: a Randomized Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT06230757
- Acronym / sponsor ID
- 22-1681
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 8 Jul 2024 (actual)
- Primary completion
- 8 May 2026 (actual)
- Study completion
- 8 May 2026 (actual)
- First posted
- 30 Jan 2024 (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.
The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: Psilocybin 25mgParticipants receive Psilocybin 25mg capsule orally, administered with psychological support, on dosing day. |
| Active Placebo | Placebo comparator | Drug: Placebo (active placebo)Participants receive Psilocybin 1mg capsule (identical to the Psilocybin 25mg capsule) orally, administered with psychological support, on dosing day. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adults ≥ 21 years of age at Screening
- Diagnosis of Major Depressive Disorder (MDD)
- Score of at least 12 (symptomatic depression) on administration of the Montgomery Asberg Depression Rating Scale (MADRS)
- Score of at least a 3 on question 8 on the MADRS evaluating loss of interest and ability to feel at both Screening and Baseline Visit 1
- The participant's Major depressive disorder meets the criteria for being treatment-resistant, defined as not experiencing a 50% improvement to two or more antidepressant treatments for adequate duration (6 weeks minimum) within the current episode, as determined by the Antidepressant Treatment Response Questionnaire (Desseilles et al., 2011; Posternak et al., 2004)
Key exclusion criteria (63 listed)
- Unstable medical conditions or serious abnormalities of complete blood count, chemistries, or EKG that in the opinion of the study physician would preclude safe participation in the trial. Some examples include:
- Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) Blood Pressure >140/90 mmHg.
- High resting heart rate defined as Screening, Baseline, and Medication Session (prior to dosing) heart of rate of >90 BPM
- Significant CNS pathology as determined by self-report and confirmed by a history and physical examination and review of medical records. Current and historical psychiatric disorders will be determined by the MINI. Specific examples include:
- Family history of first-degree relative with psychotic or serious bipolar spectrum illnesses. Examples include first-degree relative with:
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 |
|---|---|---|
| Psilocybin 25mg25mg psilocybin capsule | Drug | Psilocybin |
| Placebo (active placebo)Also: Ultra Low Dose Psilocybin1mg psilocybin capsule | Drug | Active Placebo |
Primary outcome
Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).
Time frame: One week post-dosing
The DARS is a 17-item scale that captures multiple domains of anhedonia found in depression. Scores range from 0 to 68 with lower scores indicating greater anhedonia and 68 indicating no anhedonia.
6 secondary outcomes
Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS).
Time frame: Eight weeks post-dosing
Change from baseline in self-reported anhedonia scores on the Snaith-Hamilton Pleasure Scale (SHAPS).
Time frame: One week and eight weeks post-dosing
Change from baseline in response bias for the high reward condition on the Probabilistic Reward Task (PRT)
Time frame: One and eight weeks post-dosing
Change from baseline in nucleus accumbens neural activation during expectation of reward versus expectation of non-reward during the Monetary Incentive Delay Task (MID).
Time frame: One week post-dosing
Change from baseline in depression scores of the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS).
Time frame: One and eight weeks post-dosing
Change from baseline in depression scores as measured by self-report on the Quick Inventory of Depressive Symptomatology (QIDS-SR-16).
Time frame: One, four, and eight weeks post-dosing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- 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.
Andrew M Novick, MD, PhD principal investigator
University of Colorado, Denver
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 25mg in people with Major Depressive Disorder and Anhedonia, run by University of Colorado, Denver 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 12 inclusion and 63 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: finished, as of the sponsor's last update on 22 May 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change from baseline in self-reported anhedonia scores on the Dimensional Anhedonia Rating Scale (DARS). (time frame: One week post-dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2026.