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| Name | Class |
|---|---|
| The Emmes Company, LLC | INDUSTRY |
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One hundred participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.
The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo in otherwise medically-healthy participants, assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.
Major depressive disorder (MDD) has become a health crisis of epidemic proportions in the modern world. One in six individuals in the United States will experience an episode of major depression in his or her lifetime, and it is estimated that major depression will rank second after cardiac disease as a cause of international medical morbidity by the year 2020. Depression is associated with greater disability than are most other chronic illnesses and is a risk factor for mortality. Additionally, depression predicts the later development of a number of medical conditions, including cardiac and cerebrovascular disease, hypertension, diabetes, obesity, metabolic syndrome, dementia, and cancer. Unfortunately, most patients with depression do not experience a complete resolution of symptoms with antidepressant treatment. Partial-but incomplete-response to antidepressants is associated with an increased risk of full symptomatic relapse (even when on therapy) and a worse long-term disease course. Combined with the high prevalence and significant disability associated with MDD, the fact that currently available treatments are not fully adequate highlights the tremendous need to identify novel treatment strategies.
Data suggest that psilocybin may have behavioral effects relevant to the treatment of depression and recent studies also suggest that psilocybin may possess antidepressant properties. To further assess the effects of psilocybin on MDD signs and symptoms, this trial will enroll 100 participants, ages 21 to 65, who meet criteria for MDD. Participants will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.
To enhance participant safety, a Set and Setting (SaS) protocol will be utilized similar to the protocol that has been used in all modern studies of psilocybin. The SaS protocol for this study includes: 1) a period of preparation with session Facilitators prior to dosing; 2) administration of study medications in an aesthetically pleasing room under the supervision of two Facilitators who are present throughout the session; and 3) three post-dose integration sessions during which participants are encouraged to discuss their intervention experience with the Facilitators. The SaS protocol will be identical for those randomized to psilocybin or active placebo.
The primary objective of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo (niacin), assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Psilocybin | Experimental | Participants will receive a single 25 mg dose of psilocybin along with the Set and Setting (SaS) protocol. Psilocybin is administered orally as a capsule and taken with water. |
|
| Niacin | Active Comparator | Participants will receive a single 100 mg dose of niacin along with the Set and Setting (SaS) protocol. Niacin is administered orally as a capsule and taken with water. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Psilocybin | Drug | The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Central Rater Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Post-dose Day 43 | The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score range of 0-60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint. | Baseline; Day 43 post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Central Rater MADRS Score From Baseline to Post-dose Day 8 | The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles Raison, MD | Usona Institute | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94121 | United States | ||
| Pacific Neuroscience Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24550805 | Background | Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, Chialvo DR, Nutt D. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci. 2014 Feb 3;8:20. doi: 10.3389/fnhum.2014.00020. eCollection 2014. | |
| 14761703 | Background |
| Label | URL |
|---|---|
| World Health Organization Overview of Depression | View source |
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Eligible participants completed baseline assessments and preparation sessions. Participants taking antidepressants entered a supervised medication taper. Three participants were discontinued during the preparation phase prior to randomization (1 voluntary withdrawal, 2 withdrawn by investigator decision). Randomization occurred on the day of dosing.
Participants were recruited at 11 US sites. Individuals were screened by telephone and then in person to confirm eligibility. Of 1,529 individuals who completed prescreening, 347 provided informed consent (enrolled) and 104 were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Psilocybin | Single oral dose of 25 mg psilocybin administered as a capsule in a supervised clinical setting in conjunction with the Set and Setting (SaS) protocol. Participants were supervised by two trained facilitators throughout the dosing session and assessed for readiness prior to release. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 5, 2021 | Mar 12, 2026 |
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| Niacin | Drug | The active placebo is encapsulated using a HPMC capsule and contains 100 mg of pharmaceutical grade niacin. |
|
|
| Set and Setting (SaS) Protocol | Other | The SaS Protocol prescribes 6-8 hours of preparatory meetings with two facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two facilitators, and 4 hours of post-dose integration sessions with facilitators. During the dosing session participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
|
| Baseline; Day 8 post-dose |
| Change in On-site Rater Administered Sheehan Disability Scale (SDS) Score From Baseline to Post-dose Day 43 | The SDS consists of three self-rated items designed to measure the extent to which three major domains in the patient's life are impaired by psychiatric symptoms, including depression. The SDS Mean score is calculated as the mean of three items (work/school, social life, family life/home responsibilities), each scored 0 to 10. Mean score range: 0 to 10. Higher scores indicate greater functional impairment. | Baseline; Day 43 post-dose |
| Sustained Depressive Symptom Response Defined as a ≥ 50% Reduction From Baseline Central Rater MADRS Score at All Post-dose Assessments | Sustained depressive symptom response defined as ≥50% reduction from Baseline central-rater MADRS total score at all of the following post-dose assessments: Day 8, Day 15, Day 29, and Day 43. Participants who did not meet the criterion at all four timepoints were classified as non-responders. MADRS total score range: 0 to 60; higher scores indicate more severe depression. | Day 8, 15, 29, and 43 post-dose |
| Sustained Depressive Symptom Remission Defined as a Central Rater Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score ≤ 10 at All Post-dose Assessments | Sustained depressive symptom remission defined as a central-rater MADRS total score ≤ 10 at all of the following post-dose assessments: Day 8, Day 15, Day 29, and Day 43. Participants missing a MADRS assessment at any post-dose timepoint were excluded from this analysis. MADRS total score range: 0 to 60; higher scores indicate more severe depression. | Day 8, 15, 29, and 43 post-dose |
| Santa Monica |
| California |
| 91404 |
| United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| Segal Trials | Lauderhill | Florida | 33319 | United States |
| Emory University | Atlanta | Georgia | 30322 | United States |
| Great Lakes Clinical Trials | Chicago | Illinois | 60640 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21229 | United States |
| Hassman Research Institute | Berlin | New Jersey | 08009 | United States |
| New York University School of Medicine | New York | New York | 10016 | United States |
| Cedar Clinical Research | Draper | Utah | 84020 | United States |
| University of Wisconsin - Madison | Madison | Wisconsin | 53706 | United States |
| Nichols DE. Hallucinogens. Pharmacol Ther. 2004 Feb;101(2):131-81. doi: 10.1016/j.pharmthera.2003.11.002. |
| 12813115 | Background | Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095. |
| 26063472 | Background | Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Aug 22;386(9995):743-800. doi: 10.1016/S0140-6736(15)60692-4. Epub 2015 Jun 7. |
| 10024062 | Background | Wulsin LR, Vaillant GE, Wells VE. A systematic review of the mortality of depression. Psychosom Med. 1999 Jan-Feb;61(1):6-17. doi: 10.1097/00006842-199901000-00003. |
| 12893101 | Background | Joynt KE, Whellan DJ, O'Connor CM. Depression and cardiovascular disease: mechanisms of interaction. Biol Psychiatry. 2003 Aug 1;54(3):248-61. doi: 10.1016/s0006-3223(03)00568-7. |
| 15023483 | Background | Thomas AJ, Kalaria RN, O'Brien JT. Depression and vascular disease: what is the relationship? J Affect Disord. 2004 Apr;79(1-3):81-95. doi: 10.1016/S0165-0327(02)00349-X. |
| 10826464 | Background | Davidson K, Jonas BS, Dixon KE, Markovitz JH. Do depression symptoms predict early hypertension incidence in young adults in the CARDIA study? Coronary Artery Risk Development in Young Adults. Arch Intern Med. 2000 May 22;160(10):1495-500. doi: 10.1001/archinte.160.10.1495. |
| 10772396 | Background | Jonas BS, Lando JF. Negative affect as a prospective risk factor for hypertension. Psychosom Med. 2000 Mar-Apr;62(2):188-96. doi: 10.1097/00006842-200003000-00006. |
| 8886555 | Background | Eaton WW, Armenian H, Gallo J, Pratt L, Ford DE. Depression and risk for onset of type II diabetes. A prospective population-based study. Diabetes Care. 1996 Oct;19(10):1097-102. doi: 10.2337/diacare.19.10.1097. |
| 10388970 | Background | Kawakami N, Takatsuka N, Shimizu H, Ishibashi H. Depressive symptoms and occurrence of type 2 diabetes among Japanese men. Diabetes Care. 1999 Jul;22(7):1071-6. doi: 10.2337/diacare.22.7.1071. |
| 9705031 | Background | Barefoot JC, Heitmann BL, Helms MJ, Williams RB, Surwit RS, Siegler IC. Symptoms of depression and changes in body weight from adolescence to mid-life. Int J Obes Relat Metab Disord. 1998 Jul;22(7):688-94. doi: 10.1038/sj.ijo.0800647. |
| 11331685 | Background | Pine DS, Goldstein RB, Wolk S, Weissman MM. The association between childhood depression and adulthood body mass index. Pediatrics. 2001 May;107(5):1049-56. doi: 10.1542/peds.107.5.1049. |
| 12489070 | Background | Raikkonen K, Matthews KA, Kuller LH. The relationship between psychological risk attributes and the metabolic syndrome in healthy women: antecedent or consequence? Metabolism. 2002 Dec;51(12):1573-7. doi: 10.1053/meta.2002.36301. |
| 11990888 | Background | Jorm AF. History of depression as a risk factor for dementia: an updated review. Aust N Z J Psychiatry. 2001 Dec;35(6):776-81. doi: 10.1046/j.1440-1614.2001.00967.x. |
| 12893103 | Background | Spiegel D, Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry. 2003 Aug 1;54(3):269-82. doi: 10.1016/s0006-3223(03)00566-3. |
| 11480881 | Background | Greden JF. The burden of disease for treatment-resistant depression. J Clin Psychiatry. 2001;62 Suppl 16:26-31. |
| 9707379 | Background | Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Paulus MP, Kunovac JL, Leon AC, Mueller TI, Rice JA, Keller MB. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998 Aug;55(8):694-700. doi: 10.1001/archpsyc.55.8.694. |
| 9862607 | Background | Miller IW, Keitner GI, Schatzberg AF, Klein DN, Thase ME, Rush AJ, Markowitz JC, Schlager DS, Kornstein SG, Davis SM, Harrison WM, Keller MB. The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine. J Clin Psychiatry. 1998 Nov;59(11):608-19. doi: 10.4088/jcp.v59n1108. |
| 10885162 | Background | Simon GE. Long-term prognosis of depression in primary care. Bull World Health Organ. 2000;78(4):439-45. |
| 27210031 | Background | Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17. |
| 27909165 | Background | Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513. |
| 27909164 | Background | Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512. |
| 37651119 | Derived | Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530. |
| 33993135 | Derived | Penn A, Dorsen CG, Hope S, Rosa WE. Psychedelic-Assisted Therapy: Emerging Treatments in Mental Health Disorders. Am J Nurs. 2021 Jun 1;121(6):34-40. doi: 10.1097/01.NAJ.0000753464.35523.29. |
| 33902087 | Derived | Greenway KT, Garel N, Goyette N, Turecki G, Richard-Devantoy S. Adjunctive music improves the tolerability of intravenous ketamine for bipolar depression. Int Clin Psychopharmacol. 2021 Jul 1;36(4):218-220. doi: 10.1097/YIC.0000000000000363. |
| Niacin |
Single oral dose of 100 mg niacin administered as a capsule, used as an active comparator to maintain blinding through flushing effects. Administered in conjunction with the identical Set and Setting (SaS) protocol and supervised conditions as the psilocybin group. |
| COMPLETED |
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| NOT COMPLETED |
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|
All randomized participants (intent to treat population, N=104). Participants are grouped by randomized treatment assignment. One participant randomized to receive psilocybin incorrectly received niacin. This participant is included in the psilocybin group for baseline measures and outcome measures and in the niacin group for assessment of adverse events.
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| ID | Title | Description |
|---|---|---|
| BG000 | Psilocybin | Single oral dose of 25 mg psilocybin administered as a capsule in a supervised clinical setting in conjunction with the Set and Setting (SaS) protocol. Participants were supervised by two trained facilitators throughout the dosing session and assessed for readiness prior to release. |
| BG001 | Niacin | Single oral dose of 100 mg niacin administered as a capsule, used as an active comparator to maintain blinding through flushing effects. Administered in conjunction with the identical Set and Setting (SaS) protocol and supervised conditions as the psilocybin group. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Baseline Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score range of 0-60. Higher scores indicate more severe depression. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Treatment-Resistant Depression Status | Treatment-resistant depression defined based on Massachusetts General Hospital Antidepressant Treatment History Questionnaire as meeting the following criteria: 1) participant report of receiving treatment with at least 2 antidepressant medications (or one antidepressant with at least one augmenting agent) for this current depressive episode for at least 8 weeks, 2) dose of medication is equal to or greater than minimally adequate dose, and 3) response to these medications is <50% improvement. | Count of Participants | Participants |
| |||||||||||||||
| Baseline Sheehan Disability Scale (SDS) Total Score | The SDS consists of three self-rated items designed to measure the extent to which three major domains in the patient's life are impaired by psychiatric symptoms, including depression. The SDS Mean score is calculated as the mean of three items (work/school, social life, family life/home responsibilities), each scored 0 to 10. Mean score range: 0 to 10. Higher scores indicate greater functional impairment. | Mean | Standard Deviation | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Central Rater Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Post-dose Day 43 | The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score range of 0-60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint. | All 104 randomized participants analyzed by randomized treatment assignment using a mixed-effect model for repeated measures under missing-at-random assumption. Number analyzed reflects the intent-to-treat analysis population, not observed cases at each timepoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 43 post-dose |
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| Secondary | Change in Central Rater MADRS Score From Baseline to Post-dose Day 8 | The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint. | All 104 randomized participants analyzed by randomized treatment assignment using a mixed-effect model for repeated measures under missing-at-random assumption. Number analyzed reflects the intent-to-treat analysis population, not observed cases at each timepoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 8 post-dose |
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| Secondary | Change in On-site Rater Administered Sheehan Disability Scale (SDS) Score From Baseline to Post-dose Day 43 | The SDS consists of three self-rated items designed to measure the extent to which three major domains in the patient's life are impaired by psychiatric symptoms, including depression. The SDS Mean score is calculated as the mean of three items (work/school, social life, family life/home responsibilities), each scored 0 to 10. Mean score range: 0 to 10. Higher scores indicate greater functional impairment. | All 104 randomized participants analyzed by randomized treatment assignment using a mixed-effect model for repeated measures under missing-at-random assumption. Number analyzed reflects the intent-to-treat analysis population, not observed cases at each timepoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; Day 43 post-dose |
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| Secondary | Sustained Depressive Symptom Response Defined as a ≥ 50% Reduction From Baseline Central Rater MADRS Score at All Post-dose Assessments | Sustained depressive symptom response defined as ≥50% reduction from Baseline central-rater MADRS total score at all of the following post-dose assessments: Day 8, Day 15, Day 29, and Day 43. Participants who did not meet the criterion at all four timepoints were classified as non-responders. MADRS total score range: 0 to 60; higher scores indicate more severe depression. | All randomized participants with observed central-rater MADRS assessments at Baseline, Day 8, Day 15, Day 29, and Day 43. Participants missing a MADRS assessment at any post-dose timepoint were excluded from this analysis. | Posted | Count of Participants | Participants | Day 8, 15, 29, and 43 post-dose |
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| Secondary | Sustained Depressive Symptom Remission Defined as a Central Rater Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score ≤ 10 at All Post-dose Assessments | Sustained depressive symptom remission defined as a central-rater MADRS total score ≤ 10 at all of the following post-dose assessments: Day 8, Day 15, Day 29, and Day 43. Participants missing a MADRS assessment at any post-dose timepoint were excluded from this analysis. MADRS total score range: 0 to 60; higher scores indicate more severe depression. | All randomized participants with observed central-rater MADRS assessments at Baseline, Day 8, Day 15, Day 29, and Day 43. Participants missing a MADRS assessment at any post-dose timepoint were excluded from this analysis. | Posted | Count of Participants | Participants | Day 8, 15, 29, and 43 post-dose |
|
The maximum study duration was 12 weeks (enrollment through Day 43 post-dose). Adverse events were collected at all study visits from the time of signed informed consent through the end-of-study visit (Day 43).
All randomized participants who received the study intervention, analyzed by actual treatment received. One participant randomized to psilocybin received niacin. Adverse events (AEs) were graded for severity, seriousness, and relationship to study product by site principal investigator. Reported events are treatment emergent AEs, defined as any AE not present prior to treatment or any event already present that worsened in intensity or frequency following study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Psilocybin | Single oral dose of 25 mg psilocybin administered as a capsule in a supervised clinical setting in conjunction with the Set and Setting (SaS) protocol. Participants were supervised by two trained facilitators throughout the dosing session and assessed for readiness prior to release. | 0 | 50 | 0 | 50 | 43 | 50 |
| EG001 | Niacin | Single oral dose of 100 mg niacin administered as a capsule, used as an active comparator to maintain blinding through flushing effects. Administered in conjunction with the identical Set and Setting (SaS) protocol and supervised conditions as the psilocybin group. | 0 | 54 | 0 | 54 | 32 | 54 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA V25.0 | Systematic Assessment | Solicited adverse event |
|
| Nausea | Gastrointestinal disorders | MedDRA V25.0 | Systematic Assessment | Solicited adverse event |
|
| Illusion | Psychiatric disorders | MedDRA V25.0 | Systematic Assessment | Solicited adverse event |
|
| Dizziness | Nervous system disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA V25.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA V25.0 | Non-systematic Assessment |
| |
| Antidepressant discontinuation syndrome | General disorders | MedDRA V25.0 | Non-systematic Assessment |
|
Per Protocol Section 13.17 (Publication Policy), principal investigators are required to submit all manuscripts or abstracts to the Sponsor prior to submission for publication or presentation. The Sponsor may review to protect proprietary information and provide comments. No specific embargo period is defined. All data analysis must be performed on the official Sponsor database with the analysis plan agreed upon with the Sponsor statistician.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sofiya Hupalo | Usona Institute | 608-210-5955 | sofiya.hupalo@usonainstitute.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 9, 2022 | Mar 12, 2026 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
Not provided
Not provided
| ID | Term |
|---|---|
| D011562 | Psilocybin |
| D009525 | Niacin |
| D009536 | Niacinamide |
| C513473 | SET protein, human |
| D002985 | Clinical Protocols |
| ID | Term |
|---|---|
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013812 | Therapeutics |
| D016020 | Epidemiologic Study Characteristics |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| No |
|
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