Effects of Cannabidiol on Psychiatric Symptoms, Cognition, and Cannabis Consumption in Cannabis Users With Recent-Onset Psychosis
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- Change in Brief Psychiatric Rating Scale (BPRS) total score
研究概览
简要总结
A large proportion of people with a schizophrenia-spectrum disorder, especially in the early stages of the disease, regularly consume cannabis. Cannabis use is associated with poor prognostic outcome; however, there are no effective interventions targeted at reducing cannabis use or its deleterious effects in this population. The present trial is designed to test whether cannabidiol (CBD), a cannabinoid whose effects are in many ways antagonistic to those of Δ9-tetrahydrocannabinol (THC), can reduce psychiatric symptoms, cognitive deficits, and cannabis use in people with recent-onset psychosis who regularly consume cannabis.
详细描述
This is a double-blind, randomized, placebo-controlled trial, evaluating the effects of a 12-week treatment course with CBD on psychiatric symptoms, cognition, and cannabis consumption in regular cannabis users with recent-onset psychosis. The study will be conducted at the Maryland Psychiatric Research Center (University of Maryland School of Medicine) and associated Early Intervention Programs in Baltimore, at the Sheppard Pratt Health System in Baltimore, and at the Psychosis Clinic of the University of California Los Angeles.
The daily dose of CBD is 600 mg (p.o.), administered as adjunct medication. Any non-exclusionary antipsychotic, antidepressant, anxiolytic, or other medication prescribed prior to the trial will be continued. Participants may, but do not have to be taking conventional antipsychotic medication.
The study will include 84 regular cannabis users with a schizophrenia-spectrum disorder who experienced their first psychotic episode within the last 5 years (90). Participants will be randomized 1:1 to either the CBD or the placebo group.
Outcome measures include psychiatric symptoms, cognition, global functioning, and drug use, and will be assessed at baseline, and every 3 or 6 weeks thereafter (depending on the measure), until the end of treatment at 12 weeks. Outcome will be assessed again at a 3-month follow-up.
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)
盲法说明
A matched placebo is employed. Only the biostatistician performing the randomization and the pharmacists will know the treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, and other specified or unspecified schizophrenia spectrum and other psychotic disorder.
- •Experienced a first psychotic episode within the last 5 years.
- •Self-reported cannabis use at least twice/week for at least the last 4 weeks.
- •THCCOOH serum levels of ≥ 5 ng/mL.
- •Total score ≥45 on the 18-item version of the Brief Psychiatric Rating Scale.
- •Able to give written informed consent.
- •Normal or corrected to normal vision.
- •If medicated, no change in psychiatric medication within the preceding 4 weeks, with no foreseeable changes.
排除标准
- •DSM-5 diagnosis of Substance Use Disorder other that cannabis or nicotine within the last year (recreational use is not exclusionary).
- •Currently undergoing active treatment for Cannabis Use Disorder other than low-level (once/week or less) psychosocial intervention.
- •Uncontrolled hypertension (resting systolic BP above 150 or diastolic above 95 mm Hg).
- •Cardiovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, severe arrhythmias, or EKG abnormalities (Wolf-Parkinson-White syndrome, Complete left bundle branch block, PR interval <120 ms or >200 ms, Prolonged QT interval (corrected) >500 ms, Cardiac arrhythmias as defined by PACs >3 per min or PVCs >1 per min).
- •History of or current neurological illness, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome.
- •Intellectual disability.
- •Pregnant or lactating.
- •Diabetes.
- •Significant kidney or liver impairment.
- •Any chronic or severe infectious disease, including HIV and hepatitis.
- •Use of any barbiturates, diazepam, diltiazem, verapamil, protease inhibitors, any anticonvulsant medications (including valproate/valproic acid, lamotrigine, carbamazepine, and clobazam), glipizide, glyburide, warfarin, and cyclophosphamide/ ifosfamide, due to potential interaction with CBD at the metabolic level.
- •Suicidal ideation currently or within last 6 months (score of >/= 3 on the Columbia Suicide Severity Rating Scale).
- •Less than the lower limit of normal hemoglobin and hematocrit at screening.
- •Elevated transaminase levels >3 times the ULN, accompanied by elevations in bilirubin >2 times the ULN.
研究组 & 干预措施
Cannabidiol (CBD)
Participants receive CBD daily for 12 weeks.
干预措施: Cannabidiol (CBD) (Drug)
Placebo
Participants receive vehicle not containing any drug daily for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Brief Psychiatric Rating Scale (BPRS) total score
时间窗: Baseline and 12 weeks
The BPRS consists of 18 items assessing a broad range of psychiatric symptoms, including positive, negative, and affective symptoms. Each item is scored 1-7. Total scores are the sum of all items and range from 18 to 126, with larger values reflecting worse symptoms. The BPRS total score has been used widely in clinical studies of psychosis and has demonstrated reliability in assessing psychopathology across diverse psychosis populations.
Change in MATRICS Consensus Cognitive Battery (MCCB) composite score
时间窗: Baseline and 12 weeks
The MCCB is an FDA-approved assessment tool for trials of cognition-enhancing treatments in people with schizophrenia. The MCCB is comprised of the following domains: 1) Speed of Processing; 2) Attention/Vigilance; 3) Working Memory; 4) Verbal Learning; 5) Visual Learning; 6) Reasoning and Problem Solving; and 7) Social Cognition. The composite score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.
Change in Serum concentrations of THCCOOH
时间窗: Baseline and 12 weeks
THCCOOH is a THC metabolite and is used to quantify cannabis consumption. It has a long half-life (5-6 days) and thus provides a summary index of cannabis use within the last 1-2 weeks.
次要结局
- Change in The UCSD Performance-Based Skills Assessment (UPSA)(Baseline and 12 weeks)
- Change in Serum concentrations of THC(Baseline and 12 weeks)
- Change in State-Trait Anxiety Inventory (STAI) - State version(Baseline and 12 weeks)
- Change in Specific Levels of Functioning scale (SLOF)(Baseline and 12 weeks)
- Change in Self-reported days of cannabis use(Baseline and 12 weeks)
- Change in MCCB Attention/Vigilance subscale(Baseline and 12 weeks)
- Change in MCCB Verbal Learning subscale(Baseline and 12 weeks)
- Change in MCCB Reasoning/Problem solving subscale(Baseline and 12 weeks)
- Change in BPRS positive symptoms(Baseline and 12 weeks)
- Change in BPRS "Anxiety/Depression" subscale(Baseline and 12 weeks)
- Change in MCCB Working Memory subscale(Baseline and 12 weeks)
- Change in MCCB Visual Learning subscale(Baseline and 12 weeks)
- Change in MCCB Social Cognition subscale(Baseline and 12 weeks)
- Change in Behavior And Symptom Identification Scale (BASIS) - revised(Baseline and 12 weeks)
- Change in Serum concentrations of CBD(Baseline and 12 weeks)
- Change in MCCB Processing Speed subscale(Baseline and 12 weeks)
- Change in Cannabis Use Disorders Identification Test-Revised (CUDIT-R)(Baseline and 12 weeks)
- Change in Serum concentrations of anandamide(Baseline and 12 weeks)
研究者
Britta Hahn
Associate Professor
University of Maryland, Baltimore