Clinical trial NCT04231643: Effects of Cannabis on Cognition and Endocannabinoid Levels in Bipolar Disorder Patients and Healthy Volunteers
Official title: A Randomized, Controlled Trial of Cannabis in Bipolar Disorder Patients and Healthy Volunteers Evaluating Cognition and Endocannabinoid Levels
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Bipolar Disorder
Keywords: cannabidiol
THC
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2020-01-18
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Score on Iowa Gambling Task
timeFrame: one day
measure: Score on Progressive Ratio Test
timeFrame: one day
measure: Scores on Probabilistic Learning Task
timeFrame: one day
measure: Scores on Continuous Performance Task
timeFrame: one day
measure: Percent Prepulse Inhibition (PPI)
timeFrame: one day
measure: motor activity in the human Behavioral Pattern Monitor
timeFrame: one day
measure: object interactions in the human Behavioral Pattern Monitor
timeFrame: one day
measure: cerebrospinal fluid levels of anandamide
timeFrame: one day
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UC San Diego Medical Center
state: California
Study officials:
affiliation: UCSD
name: William Perry, PhD
role: PRINCIPAL_INVESTIGATOR
References: