Clinical trial NCT03883360: Effects of Cannabidiol on Psychiatric Symptoms, Cognition, and Cannabis Consumption in Cannabis Users With Recent-Onset Psychosis
Official title: Effects of Cannabidiol on Psychiatric Symptoms, Cognition, and Cannabis Consumption in Cannabis Users With Recent-Onset Psychosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Schizophrenia Spectrum Disorders
Cannabis Use
Keywords: schizophrenia
cannabis
cannabidiol
psychosis
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Sheppard Pratt Health System
name: University of California, Los Angeles
First posted: 2019-03-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 1:1 to either the cannabidiol group or the placebo group.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Cancer.
* 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.

Primary outcomes:
measure: Change in Brief Psychiatric Rating Scale (BPRS) total score
timeFrame: Baseline and 12 weeks
measure: Change in MATRICS Consensus Cognitive Battery (MCCB) composite score
timeFrame: Baseline and 12 weeks
measure: Change in Serum concentrations of THCCOOH
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in BPRS positive symptoms
timeFrame: Baseline and 12 weeks
measure: Change in BPRS "Anxiety/Depression" subscale
timeFrame: Baseline and 12 weeks
measure: Change in State-Trait Anxiety Inventory (STAI) - State version
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Processing Speed subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Attention/Vigilance subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Working Memory subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Verbal Learning subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Visual Learning subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Reasoning/Problem solving subscale
timeFrame: Baseline and 12 weeks
measure: Change in MCCB Social Cognition subscale
timeFrame: Baseline and 12 weeks
measure: Change in The UCSD Performance-Based Skills Assessment (UPSA)
timeFrame: Baseline and 12 weeks
measure: Change in Serum concentrations of THC
timeFrame: Baseline and 12 weeks
measure: Change in Self-reported days of cannabis use
timeFrame: Baseline and 12 weeks
measure: Change in Cannabis Use Disorders Identification Test-Revised (CUDIT-R)
timeFrame: Baseline and 12 weeks
measure: Change in Specific Levels of Functioning scale (SLOF)
timeFrame: Baseline and 12 weeks
measure: Change in Behavior And Symptom Identification Scale (BASIS) - revised
timeFrame: Baseline and 12 weeks
measure: Change in Serum concentrations of CBD
timeFrame: Baseline and 12 weeks
measure: Change in Serum concentrations of anandamide
timeFrame: Baseline and 12 weeks
Other outcomes:
measure: Change in Negative Symptom Assessment (NSA-16) - exploratory
timeFrame: Baseline and 12 weeks
Locations:
city: Los Angeles
country: United States
facility: Semel Institute for Neuroscience and Human Behavior
state: California
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: Catonsville
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
Study officials:
References: