Bipolar Disorder, Delta-9-Tetrahydroncannabinol, Healthy Controls
Conditions
Brief summary
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).
Detailed description
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: * Verbal memory, 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. * Executive functioning measured by the CogState battery and/or Trails Making Test-Part B. Secondary Aims: * Attention, measured by the Continuous Performance Test-Identical Pairs (CPT-IP). * Working memory, measured by the Wechsler Memory Scale-3 Letter-Number Sequencing. * Mood, measured by the Profile of Mood States (POMS). * Psychotic-type experiences, measured by the Psychotomimetic States Inventory (PSI) and/or the Clinician Administered Dissociative Symptoms Scale (CADSS). * Anxiety symptoms, measured by the Visual Analog Scale for Anxiety (VAS-A). * Impulsivity, measured by the Balloon Analogue Risk Task (BART). Exploratory aims: •Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels.
Interventions
DRUG4 mg Delta-9-THC
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.
DRUGPlacebo
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.
DRUG2 mg Delta-9-THC
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.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
for individuals with Bipolar Disorder (BD) 1. Men and women aged 18-55 years (extremes included). 2. Able to provide informed consent in English. 3. A diagnosis of BD type I or BD type II and good physical health. 4. Current euthymic state for at least 4 weeks. Inclusion Criteria for Healthy Control (HC) individuals: 1. Men and women aged approximately 18-55 years (extremes included). 2. Able to provide informed consent in English. 3. No psychiatric diagnoses and in good physical health. General
Exclusion criteria
1. Cannabis naïve 2. Unwillingness to remain alcohol-free, cannabis-free for at least 1 week (in infrequent cannabis users) prior to each test day. 3. Evidence of a hearing deficit. 4. IQ less than 80. 5. Positive pregnancy test, lactation, and refusal to practice birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Verbal memory | baseline and +35 mins after drug administration | 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. |
| Change in Executive functioning | baseline and +35 mins after drug administration | Executive functioning will be measured by the CogState battery and/or Trails Making Test-Part B. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Working memory | baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration | Working memory will be tested by the Wechsler Memory Scale-3 Letter-Number Sequencing. |
| Attention | baseline and +35 mins after drug administration | Attention will be measured by the Continuous Performance Test-Identical Pairs (CPT-IP). |
| Mood | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration | Mood will be measured by the Profile of Mood States (POMS). |
| Psychotic-type experiences | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration | Psychotic-type experiences will be measured by the Psychotomimetic States Inventory (PSI) and/or the Clinician Administered Dissociative Symptoms Scale (CADSS). |
| Anxiety symptoms | baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration | Anxiety symptoms will be measured by the Visual Analog Scale for Anxiety (VAS-A). |
| Impulsivity | baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration | Impulsivity will be measured by the Balloon Analogue Risk Task (BART). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pulse | 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 (beats per min) will be assessed as part of the medical monitoring of the subjects |
| Genetics | Only on 1st test day | 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. |
| Blood serum THC and metabolite levels (ng/ml) | 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 levels of THC and both its active and inactive metabolites will be assayed to explore the gender related differences in the metabolism of THC. |
| Blood serum hormonal levels • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. | 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 | 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. |
| Blood pressure | 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. | Blood pressure (mmHg) will be assessed as part of the medical monitoring of the subjects |
Countries
United States
Outcome results
None listed