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

NCT04231643 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: 180356R01DA043535
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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

Keywords

cannabidiol; THC

Outcome Measures

Primary Outcomes (8)

• Score on Iowa Gambling Task

  This is an experimental measure and not a scale with specific anchor points. Lower scores reflect increased risk-taking

  one day

• Score on Progressive Ratio Test

  This is an experimental measure and not a scale with specific anchor points. Higher scores indicate increased willingness to work for a reward

  one day

• Scores on Probabilistic Learning Task

  This is an experimental measure and not a scale with specific anchor points. Measures decision-making strategies such as win-stay, lose-shift.

  one day

• Scores on Continuous Performance Task

  This is an experimental measure and not a scale with specific anchor points. Higher scores reflect better attention and ability to discriminate important information from unimportant information

  one day

• Percent Prepulse Inhibition (PPI)

  This is a physiological measure and not a scale with specific anchor points. Higher percent PPI reflects better sensorimotor gating

  one day

• motor activity in the human Behavioral Pattern Monitor

  This is an experimental measure and not a scale with specific anchor points. Subjects' behavior in an open field (a room filled with novel objects) is quantified over a 15-minute period via amount of motor activity as measured by a wearable accelerometer. Increased motor activity reflects increased tendency to engage in exploratory behavior.

  one day

• object interactions in the human Behavioral Pattern Monitor

  This is an experimental measure and not a scale with specific anchor points. Subjects' behavior in an open field (a room filled with novel objects) is quantified over a 15-minute period via video ratings that quantify number of interactions with novel objects. Increased object interactions reflects increased novelty-seeking behavior.

  one day

• cerebrospinal fluid levels of anandamide

  Reflects increased availability of the endogenous cannabinoid anandamide in the brain

  one day

Study Arms (2)

Bipolar Disorder

EXPERIMENTAL

adults with bipolar disorder

Drug: Dronabinol; Drug: Epidiolex; Drug: Placebos

Healthy Volunteers

ACTIVE COMPARATOR

adults with no psychiatric disease

Drug: Dronabinol; Drug: Epidiolex; Drug: Placebos

Interventions

Dronabinol DRUG

one-time oral administration of 5 mg dronabinol

Bipolar Disorder; Healthy Volunteers

Epidiolex DRUG

one-time oral administration of 600 mg Epidiolex

Bipolar Disorder; Healthy Volunteers

Placebos DRUG

one-time oral administration of placebo

Bipolar Disorder; Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Participants will be asked about which gender they identify with
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For subjects in BD group, DSM-5 criteria for Bipolar Disorder as determined by the Structured Clinical Interview for DSM-5 (SCID).
• Young Mania Rating Scale (YMRS) \< 12.
• Infrequent cannabis use as defined by a history of cannabis use and current use no more than 4 times per month.
• Willing to abstain from cannabis use for at least two days prior to the experimental visit.

You may not qualify if:

• Hamilton Depression Rating Scale (HDRS) score \> 10.
• 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.
• The Substance Abuse Module of the Diagnostic Interview Schedule for DSM-5 will be administered to exclude individuals with current substance use disorders.
• 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.
• Infections - evidence of skin infection at lumbar puncture site.
• 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.
• 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.
• 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.
• Positive result on Draeger 5000 test indicating recent cannabis use.
• 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.
• Any active opportunistic infection or malignant condition requiring acute treatment.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UC San Diego Medical Center

San Diego, California, 92103, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Dronabinol; Cannabidiol

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• William Perry, PhD

  UCSD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Residence of Psychiatry

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 18, 2020
• Study Start: September 1, 2021
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: May 10, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)