Bipolar DisorderEarly Phase 1NCT04231643
Effects of Cannabis on Cognition and Endocannabinoid Levels in Bipolar Disorder Patients and Healthy Volunteers
A Early Phase 1 study testing Dronabinol and Epidiolex in people with Bipolar Disorder, run by University of California, San Diego at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Dronabinol and Epidiolex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2021to 28 Nov 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- A previous adverse reaction to cannabinoids will be cause for exclusion as will a historical diagnosis of cannabis use disorder.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Medical Center
San Diego, California, 92103
About this study
Official title: A Randomized, Controlled Trial of Cannabis in Bipolar Disorder Patients and Healthy Volunteers Evaluating Cognition and Endocannabinoid Levels
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
- Being tested
- Dronabinol, Epidiolex, Placebos
- Keywords
- cannabidiol, THC
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DronabinolDrug
one-time oral administration of 5 mg dronabinol
EpidiolexDrug
one-time oral administration of 600 mg Epidiolex
PlacebosDrug
one-time oral administration of placebo
| Study group | Role | What they receive |
|---|---|---|
| Bipolar Disorder | Experimental | adults with bipolar disorder Receives: Drug: Dronabinol; Drug: Epidiolex; Drug: Placebos |
| Healthy Volunteers | Active comparator | adults with no psychiatric disease Receives: Drug: Dronabinol; Drug: Epidiolex; Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Score on Iowa Gambling Task
This is an experimental measure and not a scale with specific anchor points. Lower scores reflect increased risk-taking
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: one day
cerebrospinal fluid levels of anandamide
Reflects increased availability of the endogenous cannabinoid anandamide in the brain
Measured: one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start1 Sep 2021
- Primary completion28 Nov 2023
- Study completion28 Nov 2023
Why it stopped: Budgetary limitations prevented us from completing our planned sample size.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, William Perry, University of California, San Diego
- Investigators
- William Perry, PhD, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04231643
- Sponsor's protocol ID
- 180356
- Other IDs
- R01DA043535
- Status last verified
- May 2024
- First submitted
- 8 Jan 2020
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Trial of Cannabis in Bipolar Disorder Patients and Healthy Volunteers Evaluating Cognition and Endocannabinoid Levels
- ClinicalTrials.gov ID
- NCT04231643
- Acronym / sponsor ID
- 180356
- Conditions
- Bipolar Disorder
- Keywords
- cannabidiol, THC
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Budgetary limitations prevented us from completing our planned sample size.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 28 Nov 2023 (actual)
- Study completion
- 28 Nov 2023 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bipolar Disorder | Experimental | Drug: Dronabinol, Drug: Epidiolex, Drug: Placebosadults with bipolar disorder |
| Healthy Volunteers | Active comparator | Drug: Dronabinol, Drug: Epidiolex, Drug: Placebosadults with no psychiatric disease |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dronabinolone-time oral administration of 5 mg dronabinol | Drug | Bipolar Disorder, Healthy Volunteers |
| Epidiolexone-time oral administration of 600 mg Epidiolex | Drug | Bipolar Disorder, Healthy Volunteers |
| Placebosone-time oral administration of placebo | Drug | Bipolar Disorder, Healthy Volunteers |
Primary outcome
Score on Iowa Gambling Task
Time frame: one day
This is an experimental measure and not a scale with specific anchor points. Lower scores reflect increased risk-taking
Score on Progressive Ratio Test
Time frame: one day
This is an experimental measure and not a scale with specific anchor points. Higher scores indicate increased willingness to work for a reward
Scores on Probabilistic Learning Task
Time frame: one day
This is an experimental measure and not a scale with specific anchor points. Measures decision-making strategies such as win-stay, lose-shift.
Scores on Continuous Performance Task
Time frame: one day
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
Percent Prepulse Inhibition (PPI)
Time frame: one day
This is a physiological measure and not a scale with specific anchor points. Higher percent PPI reflects better sensorimotor gating
motor activity in the human Behavioral Pattern Monitor
Time frame: one day
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.
object interactions in the human Behavioral Pattern Monitor
Time frame: one day
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.
cerebrospinal fluid levels of anandamide
Time frame: one day
Reflects increased availability of the endogenous cannabinoid anandamide in the brain
Results and safety
The study was stopped early (reason given: Budgetary limitations prevented us from completing our planned sample size.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Perry, PhD principal investigator
UCSD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Dronabinol and Epidiolex in people with Bipolar Disorder, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Budgetary limitations prevented us from completing our planned sample size.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Score on Iowa Gambling Task (time frame: one day). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.