Psilocybin Treatment in Obsessive-Compulsive Disorder: a Preliminary Efficacy Study and Exploratory Investigation of Neural Correlates.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Changes in severity of OCD symptoms, measured by Acute Yale-Brown Obsessive-Compulsive Scale (A-YBOCS)
研究概览
简要总结
This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate psilocybin's purported therapeutic effects on OCD.
详细描述
Aim 1: To investigate the effects of psilocybin on OCD symptomatology. OCD symptom severity will be assessed before treatment and 24 and 48 hours after treatment, one week after treatment, two weeks, one month, and three months after treatment. Hypothesis: We hypothesize that 0.25mg/kg of psilocybin will lead to greater symptom improvement than niacin (as the active-placebo-control agent) at the primary endpoint of 48 hours post-dosing and at all other assessment points.
Aim 2: To explore the relationship between the psilocybin-induced brain connectivity changes and symptom change in OCD. Resting-state brain connectivity will be assessed before and 48 hours after treatment. Hypothesis: We hypothesize that (i) psilocybin will normalize abnormal fronto-striatal functional connectivity in patients with OCD; and (ii) normalization of these abnormalities will correlate with improvement in symptomatology after psilocybin treatment.
This study will pilot a single-center, randomized, active-placebo-controlled, double-blind design to examine the clinical and neural effects on OCD, of either 0.25mg/kg of psilocybin or active placebo-control agent (niacin 250mg), given along with non-drug preparatory and follow-up support appointments to 30 study participants. The duration of the randomized study phase is from consent until two weeks after drug administration. Participants will be followed for 12 weeks (3 months) post-study drug administration.
Eligible participants will be admitted as an inpatient for at least 3 nights / 4 days surrounding the initial drug administration (or more, at the option of the subject and the investigator). Participants will be randomized into active medication and active-placebo-control groups, and will be blinded as to their study condition. This admission 2 nights prior to the drug administration will allow the participant to adjust to sleeping on the unit and allow them to settle in to the research unit routine. A return for an fMRI scan (48 hours after the administration session) will be scheduled. The participants who received active-placebo-control will be offered the option to receive open-label psilocybin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary DSM-5 diagnosis of OCD
- •Y-BOCS score of 19 or greater
- •Failure of at least one trial of standard care treatment (medication and/or psychotherapy [CBT/ERP]) for OCD
- •English proficiency and fluency, and ability to understand the consent process and provide written informed consent
- •Willingness to sign a medical release for direct communication between research staff and external provider(s) about the participant's treatment and medical histories
- •Non-consumption of SSRIs for at least 8 weeks at the time of randomization
- •Willingness to refrain from psychiatric medications (e.g., antidepressants, first- and second-generation antipsychotics, mood stabilizers) during the study period, as well as certain other medications (e.g., anti-seizure medications, cardiovascular medications, and aldomet specifically) during the day of dosing
- •Willingness to abstain from THC-containing products for study duration. A negative urinary drug screen is also required at baseline and the day of dosing.
- •A negative urinary pregnancy screen at study entry and day of dosing if of childbearing potential, and willingness to use adequate birth control for study duration
- •Having a contact person who is willing and able to be reached by the study team in the event of an emergency/crisis, and who is able to transport the participant home at the end of the inpatient stay/dosing week
- •Willingness to commit to all study procedures and visits, including inpatient stay, assessments and self-reports, neuroimaging, and being medically cleared to be discharged and transported home at the end of the dosing week
排除标准
- •Personal or immediate family history of schizophrenia spectrum and other psychotic disorders, bipolar I or II disorder, or major depressive disorder with psychotic features
- •Active suicidal intent
- •Unremitted Tourette syndrome
- •Autism spectrum disorder
- •OCPD or BPD
- •Current substance use disorder (except mild alcohol use disorder)
- •Unstable neurological or medical condition(s) that may render study procedures unsafe, including poorly managed diabetes, hypertension, or cardiovascular conditions, or history of seizure(s) or chronic/severe headaches
- •Any history of head injury with loss of consciousness for more than 30 minutes
- •Any contraindications to undergoing an MRI scan, including having metal implants or metal fragments in the body
- •Any use of psychedelic substances within the prior 12 months
研究组 & 干预措施
Psilocybin
Psilocybin (0.25mg/kg)
干预措施: Psilocybin (0.25mg/kg) (Drug)
Niacin
Niacin (250mg)
干预措施: Niacin (250mg) (Drug)
结局指标
主要结局
Changes in severity of OCD symptoms, measured by Acute Yale-Brown Obsessive-Compulsive Scale (A-YBOCS)
时间窗: Baseline, 24 hours post-drug, 48 hours post-drug
A clinician-administered measure of specific participant OCD symptoms over prior 24 hours. The most prominent obsessions and compulsions that were previously identified by the checklist are rated by the symptom severity scale. The symptom severity scale consists of 11 items (3 items are not included in the total score) and uses a 0 to 4 severity scale. Total A-YBOCS scores range from 0 to 40, with higher scores indicating greater severity of OCD symptoms.
Changes in severity of OCD symptoms, measured by Visual Analog Scale (VAS) for OCD symptoms
时间窗: Baseline, 24 hours post-drug, 48 hours post-drug
A self-report measure of severity of and distress related to OCD symptoms over the past 24 hours. Consists of 5 items assessing compulsive urges, obsessions, anxiety, mood, and discomfort, each on a 0-100 VAS, with higher scores on each item indicating greater severity.
Changes in severity of OCD symptoms, which will be measured by The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The Primary Outcome Measure will be collected at baseline and 48 hours, assessing change from baseline at 48 hours.
时间窗: Baseline, 48 hours post-drug, weeks: 1, 2, 4, 12 post-drug
Assesses severity and types of OCD symptoms over the past seven days. Consists of two parts: 1- symptom checklist, 2- symptom severity scale. The most prominent obsessions and compulsions are identified by the checklist and then rated by the symptom severity scale. The symptom severity scale consists of 11 items (3 items are not included in the total score) and uses a 0 to 4 severity scale. Total Y-BOCS scores range from 0 to 40, with higher scores indicating greater severity of OCD symptoms.
Changes in suicidality, measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Since Last Visit version
时间窗: Up to 12 weeks post-drug
A clinician-administered measure of suicidality since the last visit. Consists of 5 items assessing suicidal ideation and 6 items assessing suicidal and non-suicidal self-injurious behaviors. Higher scores on either scale indicate more severe suicidal ideation and suicidal or non-suicidal behaviors since the last study visit.
次要结局
- Changes in beliefs of mind-body dualism, which will be measured by The Mind-Body Dualism Scale (MBDS).(Baseline & 2 weeks post-drug)
- Changes in alcohol consumption, which will be measured by The Alcohol Use Disorders Identification Test (AUDIT).(Baseline & 12 weeks post-drug)
- Changes in dysfunctional beliefs, which will be measured by The Obsessive Beliefs Questionnaire (OBQ-44).(Baseline & 2 weeks post-drug)
- Changes in OCD symptoms, which will be measured by The Obsessive-Compulsive Inventory - Revised (OCI-R).(Baseline & 2 weeks post-drug)
- Changes in OCD dimensions, which will be measured by The Obsessive-Compulsive Trait Core Dimensions Questionnaire (OC-TCDQ).(Baseline & 2 weeks post-drug)
- 5-Dimension - Altered States of Consciousness (5D-ASC)(Day of drug administration)
- Changes of the effects of Psilocybin, which will be measured by The Persisting Effects Questionnaire (PEQ).(2 days post-drug, weeks: 4 & 12 post-drug)
- Change in moral relativism and idealism, which will be measured by The Ethical Positions Questionnaire (EPQ).(Baseline & 2 weeks post-drug)
- Changes in drug-related problems, which will be measured by The Drug Use Disorders Identification Test (DUDIT).(Baseline & 12 weeks post-drug)
- Changes in depression symptoms, which will be measured by The Montgomery-Asberg Depression Scale (MADRS).(Baseline, 2 days post-drug, weeks: 1, 2, 4, 12, post-drug)
- Changes in depression symptoms, which will be measured by the Beck Depression Inventory (BDI).(Baseline, 1 day post-drug, weeks: 2 & 12 post-drug)
- Changes in experiential aspects of psilocybin, which will be measured by The Mystical Experience Questionnaire (MEQ).(Day of drug administration, weeks: 2 & 12 post-drug)
- Challenging Experience Questionnaire (CEQ)(Day of drug administration)
- Changes in opinion towards pro-environmental behavior, which will be measured by The Pro-Environmental Behavior Scale (PEBS).(Baseline & 2 weeks post-drug)
- Changes in brain connectivity, which will be measured with functional Magnetic Imaging Resonance (fMRI).(Baseline & 48 hours post-drug)
- Changes in anxiety, which will be measured by State-Trait Anxiety Inventory (STAI).(Baseline, 2 days post-drug, weeks: 1, 2, 4, 12 post-drug)
- Changes in meaning of life, which will be measured by The Schedule for Meaning in Life Evaluation (SMiLE).(Baseline, weeks: 1 & 12 post-drug)
- Changes in different dimensions of emotional experience, which will be measured by The Positive and Negative Affect Schedule Expanded Form (PANAS-X).(Baseline, 2 days post-drug, weeks: 1, 2, 4, 12 post-drug)
- Changes in anthropomorphism, which will be measured by The Individual Differences in Anthropomorphism Questionnaire (IDAQ).(Baseline & 2 weeks post-drug)
- Change in interpersonal connectedness, which will be measured by The Inclusion of Others in Self Scale (IOS).(Baseline & 2 weeks post-drug)
- Changes in urgent care and emergency room use, which will be measured by The Utilization of Facility and Emergent Care (UFEC).(Baseline & 12 weeks post-drug)
- Changes in readiness to change, which will be measured by The University of Rhode Island Change Assessment (URICA).(Baseline, 48 hours post-drug, weeks: 4, 8, 12 post-drug)
- Changes in quality of life, which will be measured by The Quality of Life Enjoyment & Satisfaction Questionnaire (Q-LESQ-SF).(Baseline, weeks: 2 & 12 post-drug)
- Changes in connection to nature, which will be measured by The Nature Relatedness Scale (NRS).(Baseline & 2 weeks post-drug)
- Changes in tobacco use, motivation to quit, and dependence, which will be measured by The Self-reported Nicotine Use (SRNU).(Baseline & 12 weeks post-drug)
- Changes in OCD symptoms, which will be measured by The Padua Inventory of OCD symptoms.(Baseline & 12 weeks post-drug)
- Changes in action identification, measured by the Behavior Identification Form (BIF)(Baseline & 1 week post-drug)
- Changes in reactions to research participation, measured by the Reactions to Research Participation Questionnaire (RRPQ)(48 hours post-drug and 12 weeks post-drug)
- Changes in sleep quality, which will be measured by The Pittsburgh Sleep Quality Index (PSQI).(Baseline, 48 hours post-drug, weeks: 4 & 12 post-drug)
- Changes in functional impairment, which will be measured by The Sheehan Disability Scale (SDS).(Baseline & 12 weeks post-drug)
- Changes in symptom severity and treatment response, which will be measured by The Clinical Global Impressions (CGI).(Baseline & 12 weeks post-drug)
- Changes in optimism and pessimism, which will be measured by The Life Orientation Test Revised (LOT-R).(Baseline & 12 weeks post-drug)
研究者
Benjamin Kelmendi, MD
Associate Research Scientist
Yale University