Back to results

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

Primary Purpose

Schizophrenia Spectrum Disorders, Cannabis Use

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cannabidiol (CBD)

Placebo

About this trial

This is an interventional treatment trial for Schizophrenia Spectrum Disorders focused on measuring schizophrenia, cannabis, cannabidiol, psychosis

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Semel Institute for Neuroscience and Human Behavior
Sheppard Pratt Health System
Maryland Psychiatric Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol (CBD)

Placebo

Arm Description

Participants receive CBD daily for 12 weeks.

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

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Change in BPRS positive symptoms

The average of four BPRS key positive symptom items (conceptual disorganization, suspiciousness, unusual thought content, and hallucinatory behavior) will be analyzed as an index of antipsychotic effects of CBD. Possible values range from 1 to 7, with larger values reflecting more severe positive symptoms.

Change in BPRS "Anxiety/Depression" subscale

This subscale will be analyzed separately to obtain an index of the anxiolytic effects of CBD. Possible values range from 1 to 7, with larger values reflecting more anxiety/depression.

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

The STAI-State provides another probe for potential anxiolytic effects of CBD. The participant rates 20 items about how they feel right now and a scale from 1 (not at all) to 4 (very much so). The total score is derived by adding all values and ranges from 20 to 80, with larger values indicating greater anxiety.

Change in MCCB Processing Speed subscale

The 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 MCCB Attention/Vigilance subscale

The 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 MCCB Working Memory subscale

The 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 MCCB Verbal Learning subscale

The 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 MCCB Visual Learning subscale

The 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 MCCB Reasoning/Problem solving subscale

The 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 MCCB Social Cognition subscale

The 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 The UCSD Performance-Based Skills Assessment (UPSA)

Measures ability to perform real-life tasks by standardized role-play. Scores reflect percent correct, i.e. range from 0-100, with larger scores reflecting better performance.

Change in Serum concentrations of THC

Index of recent cannabis use.

Change in Self-reported days of cannabis use

The reference period is the last three weeks. Thus, possible values range from 0 to 21.

Change in Cannabis Use Disorders Identification Test-Revised (CUDIT-R)

The CUDIT-R is an 8-item questionnaire probing cannabis use frequency, amount, loss of control, and adverse consequences in the last 6 months. Each item is rated on a scale from 0 to 4. The total score is derived by summing all answers and ranges from 0 to 32, with larger values representing greater use severity.

Change in Specific Levels of Functioning scale (SLOF)

An index of real-world, everyday functioning, derived by summing 30 item scores (1-5). Higher scores reflect better functioning.

Change in Behavior And Symptom Identification Scale (BASIS) - revised

A self-report questionnaire to assess mental health treatment outcomes. Only the first 24 items (probing daily life functioning, social behavior, and mood) are included, each scored on a scale from 0 to 4. The total score is derived by summing individual item scores are re-poling some items, with larger values representing worse outcome.

Change in Serum concentrations of CBD

To confirm bioavailability of the study drug.

Change in Serum concentrations of anandamide

Anandamide is an endocannabinoid that has been reported to be down-regulated by cannabis use and up-regulated by CBD.

Full Information

NCT ID

NCT03883360

First Posted

March 14, 2019

Last Updated

April 14, 2021

Sponsor

University of Maryland, Baltimore

Collaborators

Sheppard Pratt Health System, University of California, Los Angeles

1. Study Identification

Unique Protocol Identification Number

NCT03883360

Brief Title

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

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Withdrawn

Why Stopped

not funded

Study Start Date

January 2050 (Anticipated)

Primary Completion Date

February 2050 (Anticipated)

Study Completion Date

March 2050 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

Collaborators

Sheppard Pratt Health System, University of California, Los Angeles

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia Spectrum Disorders, Cannabis Use

Keywords

schizophrenia, cannabis, cannabidiol, psychosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

A matched placebo is employed. Only the biostatistician performing the randomization and the pharmacists will know the treatment assignment.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cannabidiol (CBD)

Arm Type

Experimental

Arm Description

Participants receive CBD daily for 12 weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Cannabidiol (CBD)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Brief Psychiatric Rating Scale (BPRS) total score

Description

Time Frame

Baseline and 12 weeks

Title

Change in MATRICS Consensus Cognitive Battery (MCCB) composite score

Description

Time Frame

Baseline and 12 weeks

Title

Change in Serum concentrations of THCCOOH

Description

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.

Time Frame

Baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Change in BPRS positive symptoms

Description

Time Frame

Baseline and 12 weeks

Title

Change in BPRS "Anxiety/Depression" subscale

Description

This subscale will be analyzed separately to obtain an index of the anxiolytic effects of CBD. Possible values range from 1 to 7, with larger values reflecting more anxiety/depression.

Time Frame

Baseline and 12 weeks

Title

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

Description

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Processing Speed subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Attention/Vigilance subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Working Memory subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Verbal Learning subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Visual Learning subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Reasoning/Problem solving subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in MCCB Social Cognition subscale

Description

The score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Higher scores reflect better performance.

Time Frame

Baseline and 12 weeks

Title

Change in The UCSD Performance-Based Skills Assessment (UPSA)

Description

Measures ability to perform real-life tasks by standardized role-play. Scores reflect percent correct, i.e. range from 0-100, with larger scores reflecting better performance.

Time Frame

Baseline and 12 weeks

Title

Change in Serum concentrations of THC

Description

Index of recent cannabis use.

Time Frame

Baseline and 12 weeks

Title

Change in Self-reported days of cannabis use

Description

The reference period is the last three weeks. Thus, possible values range from 0 to 21.

Time Frame

Baseline and 12 weeks

Title

Change in Cannabis Use Disorders Identification Test-Revised (CUDIT-R)

Description

Time Frame

Baseline and 12 weeks

Title

Change in Specific Levels of Functioning scale (SLOF)

Description

An index of real-world, everyday functioning, derived by summing 30 item scores (1-5). Higher scores reflect better functioning.

Time Frame

Baseline and 12 weeks

Title

Change in Behavior And Symptom Identification Scale (BASIS) - revised

Description

Time Frame

Baseline and 12 weeks

Title

Change in Serum concentrations of CBD

Description

To confirm bioavailability of the study drug.

Time Frame

Baseline and 12 weeks

Title

Change in Serum concentrations of anandamide

Description

Anandamide is an endocannabinoid that has been reported to be down-regulated by cannabis use and up-regulated by CBD.

Time Frame

Baseline and 12 weeks

Other Pre-specified Outcome Measures:

Title

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

Description

The 16-item Negative Symptom Assessment (NSA-16) is a validated and widely used scale capturing different facets of negative symptoms. Each item is scored on a scale of 1 to 6, and the total score is derived by adding individual item scores. Larger values represent worse symptoms.

Time Frame

Baseline and 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Semel Institute for Neuroscience and Human Behavior

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Sheppard Pratt Health System

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21204

Country

United States

Facility Name

Maryland Psychiatric Research Center

City

Catonsville

State/Province

Maryland

ZIP/Postal Code

21228

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs