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Feasibility pilot was completed
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The overarching goal of this study is to characterize the acute cognitive and psychophysiological effects of the main psychoactive constituent of cannabis, 9-delta-tetrahydrocannabinol (THC) in individuals with euthymic bipolar disorder (BD), and to begin probing the mechanisms that may underlie its effects in this illness.
This study is expected to contribute to a better characterization of specific effects of THC in individuals with BD compared to healthy controls (HC).
To compare the dose related acute effects of inhaled THC, administered through a vaporizer over approximately 20 minutes, between HC and euthymic BD individuals (referred to as eBD) on a range of subjective and objective parameters as described below:
Primary Aims:
Secondary Aims:
Exploratory aims:
•Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active 4 mg inhaled THC | Experimental | Subject will have 1/3 chance of receiving 4 mg THC administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. |
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| Active 2 mg inhaled THC | Experimental | Subject will have 1/3 chance of receiving 2 mg THC administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. |
|
| Placebo | Placebo Comparator | Subject will have 1/3 chance of receiving the inhaled placebo condition administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. The placebo condition will include no active cannabinoids. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 4 mg Delta-9-THC | Drug | Subject will have 1/3 chance of receiving 4 mg THC administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Verbal memory | Verbal memory will be measured by a modified computer version of the Rey Auditory Verbal Learning Test (RAVLT) and/or the CogState battery, administered while EEG data is collected. | baseline and +35 mins after drug administration |
| Change in Executive functioning | Executive functioning will be measured by the CogState battery and/or Trails Making Test-Part B. | baseline and +35 mins after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Attention | Attention will be measured by the Continuous Performance Test-Identical Pairs (CPT-IP). | baseline and +35 mins after drug administration |
| Working memory | Working memory will be tested by the Wechsler Memory Scale-3 Letter-Number Sequencing. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood serum hormonal levels • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. | As an exploratory aim, serum prolactin (ng/mL), serum ACTH (pg/ml), and serum cortisol (μg/dL) levels will be measured to provide an objective measure of THC effects on the hypothalamic pituitary adrenal (HPA) axis. | baseline, +20 mins after drug administration, +30 mins after drug administration, +60 mins after drug administration, +90 mins after drug administration, +150 mins after drug administration, +210 mins after drug administration |
Inclusion Criteria for individuals with Bipolar Disorder (BD)
Inclusion Criteria for Healthy Control (HC) individuals:
General exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mohini Ranganathan, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biological Studies Unit, VA Connecticut Healthcare System | West Haven | Connecticut | 06516 | United States |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D013759 | Dronabinol |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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The study is a double-blind, randomized, placebo-controlled, crossover laboratory evaluation of the acute subjective, cognitive and psychophysiological effects of 2 mg and 4 mg inhaled THC in Healthy Control individuals and individuals with euthymic Bipolar Disorder.
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| Placebo | Drug | Subject will have 1/3 chance of receiving the inhaled placebo condition administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. The placebo condition will include no active cannabinoids. |
|
| 2 mg Delta-9-THC | Drug | Subject will have 1/3 chance of receiving 2 mg THC administered through a vaporizer, over approximately 20 minutes, followed by approximately 45 minutes of neuropsychological and physiological testing. |
|
| baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration |
| Mood | Mood will be measured by the Profile of Mood States (POMS). | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration |
| Psychotic-type experiences | Psychotic-type experiences will be measured by the Psychotomimetic States Inventory (PSI) and/or the Clinician Administered Dissociative Symptoms Scale (CADSS). | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration |
| Anxiety symptoms | Anxiety symptoms will be measured by the Visual Analog Scale for Anxiety (VAS-A). | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration |
| Impulsivity | Impulsivity will be measured by the Balloon Analogue Risk Task (BART). | baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration |
| Blood serum THC and metabolite levels (ng/ml) | Blood levels of THC and both its active and inactive metabolites will be assayed to explore the gender related differences in the metabolism of THC. | baseline, +20 mins after drug administration, +30 mins after drug administration, +60 mins after drug administration, +90 mins after drug administration, +150 mins after drug administration, +210 mins after drug administration |
| Blood pressure | Blood pressure (mmHg) will be assessed as part of the medical monitoring of the subjects | baseline, -60 mins before drug administration, +2, +4, +6, +8,+10, +20, +30, +35, +40, +45, +50, +60, +90, +150, +210 mins after drug administration. |
| Pulse | Pulse (beats per min) will be assessed as part of the medical monitoring of the subjects | baseline, -60 mins before drug administration, +2, +4, +6, +8,+10, +20, +30, +35, +40, +45, +50, +60, +90, +150, +210 mins after drug administration. |
| Genetics | Blood samples for DNA extraction will be collected to examine whether any of the genes implicated in cognition in the response to cannabinoids (e.g., COMT, CNR1, FAAH, BDNF) modify the effects of THC. | Only on 1st test day |