Effects of Cannabis on Cognition and Endocannabinoid Levels in Bipolar Disorder Patients and Healthy Volunteers

NCT ID: NCT04231643

Last Updated: 2024-05-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2023-11-28

Brief Summary

Cannabis use is associated with younger age at onset of bipolar disorder, poor outcome, and more frequent manic episodes, but the effects of cannabis on cognition are less clear. Contrary to reports among non-psychiatric patients, cannabis may improve cognition among people with bipolar disorder. Nevertheless, no study to date has systematically tested the acute effects of cannabis on cognition in bipolar disorder. Therefore, the investigators propose to determine the effects of oral cannabinoid administration on cognitive domains relevant to bipolar disorder, e.g., arousal, decision making, cognitive control, inhibition, and temporal perception (sense of timing). In addition, the investigators will evaluate different doses of the two major components of cannabis, cannabidiol and ∆9-tetrahydrocannabinol, and compare them to placebo on these neurocognitive measures. The investigators will also test the effects of acute exposure to cannabinoids on cerebrospinal levels of anandamide and homovanillic acid - markers of endocannabinoid and dopamine activity in the brain, respectively. These studies will provide information that effectively bridges the fields of addiction and general psychiatry, informing treatment development for co-morbid substance abuse and psychiatric disorders.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Bipolar Disorder

adults with bipolar disorder

Group Type: EXPERIMENTAL

Dronabinol

Intervention Type: DRUG

one-time oral administration of 5 mg dronabinol

Epidiolex

Intervention Type: DRUG

one-time oral administration of 600 mg Epidiolex

Placebos

Intervention Type: DRUG

one-time oral administration of placebo

Healthy Volunteers

adults with no psychiatric disease

Group Type: ACTIVE_COMPARATOR

Dronabinol

Intervention Type: DRUG

one-time oral administration of 5 mg dronabinol

Epidiolex

Intervention Type: DRUG

one-time oral administration of 600 mg Epidiolex

Placebos

Intervention Type: DRUG

one-time oral administration of placebo

Interventions

Dronabinol

one-time oral administration of 5 mg dronabinol

Intervention Type: DRUG

Epidiolex

one-time oral administration of 600 mg Epidiolex

Intervention Type: DRUG

Placebos

one-time oral administration of placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. For subjects in BD group, DSM-5 criteria for Bipolar Disorder as determined by the Structured Clinical Interview for DSM-5 (SCID).

2. Young Mania Rating Scale (YMRS) < 12.

3. Infrequent cannabis use as defined by a history of cannabis use and current use no more than 4 times per month.

4. Willing to abstain from cannabis use for at least two days prior to the experimental visit.

Exclusion Criteria

1. Hamilton Depression Rating Scale (HDRS) score > 10.

2. Suicidality. Exposure to cannabis does not lead to depression but it may be associated with suicidal thoughts and attempts. Therefore, the Center for Epidemiological Studies-Depression Scale (CES-D) subscale measuring suicidal ideation ("I wished I were dead". "I wanted to hurt myself") will be completed. Should any of these items be answered affirmatively, e.g., the subject has endorsed these items for at least 1-2 days in the last week, the subject will not be enrolled in the study.

3. The Substance Abuse Module of the Diagnostic Interview Schedule for DSM-5 will be administered to exclude individuals with current substance use disorders.

4. Clinically significant or unstable medical condition. Subjects will undergo a medical evaluation (H&P, toxicology screening, and for females of childbearing potential, pregnancy testing (utilizing a human chorionic gonadotropin (hCG) urine test). Individuals with significant cardiovascular disease (e.g., angina, myocardial infarction or stroke), hepatic or renal disease, uncontrolled hypertension, and chronic pulmonary disease (e.g., asthma, COPD), will be excluded. With respect to cardiovascular and pulmonary status, a clinician will screen participants with a tool developed for this purpose (Appendix 3 Cardiopulmonary Screen). Hepatic and renal disease will be evaluated with liver and renal function laboratory tests. Females who are pregnant or lactating will be excluded.

5. Infections - evidence of skin infection at lumbar puncture site.

6. To avoid confounding of cognitive testing, a neurological disorder such as seizures, stroke, Parkinson's disease, dementia, or a history of head injury with loss of consciousness for at least 15 minutes will be excluded.

7. Unwilling to refrain from driving or operate heavy machinery for four hours after consuming study medication. This criterion is consistent with current expert recommendations on driving following the use of cannabis.

8. Additionally, because the hBPM paradigm requires participants to be ambulatory, those who cannot ambulate independently (e.g., require a wheelchair) or those who have a motor disease (e.g., multiple sclerosis, cerebral palsy) will be excluded.

9. A previous adverse reaction to cannabinoids will be cause for exclusion as will a historical diagnosis of cannabis use disorder.

10. Positive result on Draeger 5000 test indicating recent cannabis use.

11. Unwillingness to prevent pregnancy during the cannabinoid administration portion of the study (using birth control in female participants of child-bearing age) Acceptable methods of birth control are: oral contraceptive pills, diaphragm, condom, progestin implant, intrauterine contraceptive device, sterilization, etc.

12. Any active opportunistic infection or malignant condition requiring acute treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

William Perry

Professor in Residence of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Perry, PhD

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

UC San Diego Medical Center

San Diego, California, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DA043535

Identifier Type: NIH

Identifier Source: secondary_id

View Link

180356

Identifier Type: -

Identifier Source: org_study_id