Effects of Cannabidiol on Psychiatric Symptoms, Cognition, and Cannabis Consumption in Cannabis Users With Recent-Onset Psychosis

NCT03883360 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HP-00082213
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Schizophrenia Spectrum Disorders; Cannabis Use

Keywords

schizophrenia; cannabis; cannabidiol; psychosis

Outcome Measures

Primary Outcomes (3)

• Change in Brief Psychiatric Rating Scale (BPRS) total score

  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.

  Baseline and 12 weeks

• Change in MATRICS Consensus Cognitive Battery (MCCB) composite score

  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.

  Baseline and 12 weeks

• Change in Serum concentrations of THCCOOH

  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.

  Baseline and 12 weeks

Secondary Outcomes (18)

• Change in BPRS positive symptoms

  Baseline and 12 weeks

• Change in BPRS "Anxiety/Depression" subscale

  Baseline and 12 weeks

• Change in State-Trait Anxiety Inventory (STAI) - State version

  Baseline and 12 weeks

• Change in MCCB Processing Speed subscale

  Baseline and 12 weeks

• Change in MCCB Attention/Vigilance subscale

  Baseline and 12 weeks

Other Outcomes (1)

• Change in Negative Symptom Assessment (NSA-16) - exploratory

  Baseline and 12 weeks

Study Arms (2)

Cannabidiol (CBD)

EXPERIMENTAL

Participants receive CBD daily for 12 weeks.

Drug: Cannabidiol (CBD)

Placebo

PLACEBO COMPARATOR

Participants receive vehicle not containing any drug daily for 12 weeks.

Drug: Placebo

Interventions

Cannabidiol (CBD) DRUG

Participants receive a single dose of CBD (600 mg p.o.) per day for 12 weeks.

Cannabidiol (CBD)

Placebo DRUG

Participants receive a single daily dose of the oil vehicle used to dissolve CBD but without any active ingredient, in the same amount as the CBD group, for 12 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Sheppard Pratt Health System: collaborator
• University of California, Los Angeles: collaborator

Study Sites (3)

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90095, United States

Location

Sheppard Pratt Health System

Baltimore, Maryland, 21204, United States

Location

Maryland Psychiatric Research Center

Catonsville, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Schizophrenia; Marijuana Abuse; Psychotic Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A matched placebo is employed. Only the biostatistician performing the randomization and the pharmacists will know the treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants will be randomized 1:1 to either the cannabidiol group or the placebo group.

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 20, 2019
• Study Start (Estimated): January 1, 2050
• Primary Completion (Estimated): February 1, 2050
• Study Completion (Estimated): March 1, 2050
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)