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

Bipolar Disorder Clinical Trial

Official title:

A Randomized, Controlled Trial of Cannabis in Bipolar Disorder Patients and Healthy Volunteers Evaluating Cognition and Endocannabinoid Levels

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04231643
• Other study ID #: 180356
• Secondary ID: R01DA043535
• Status: Terminated
• Phase: Early Phase 1
• Start date: September 1, 2021
• Est. completion date: November 28, 2023

Study information

• Verified date: May 2024
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: November 28, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Dronabinol
one-time oral administration of 5 mg dronabinol
• Epidiolex
one-time oral administration of 600 mg Epidiolex
• Placebos
one-time oral administration of placebo

Locations

Country	Name	City	State
United States	UC San Diego Medical Center	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	cerebrospinal fluid levels of anandamide	Reflects increased availability of the endogenous cannabinoid anandamide in the brain	one day