Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder

Conditions
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Delta-9-Tetrahydroncannabinol, Bipolar Disorder, Healthy Controls

Intervention / Treatment
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* Drug: 4 mg Delta-9-THC
* Drug: Placebo
* Drug: 2 mg Delta-9-THC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for individuals with Bipolar Disorder (BD) Men and women aged 18-55 years (extremes included). Able to provide informed consent in English. A diagnosis of BD type I or BD type II and good physical health. Current euthymic state for at least 4 weeks. Inclusion Criteria for Healthy Control (HC) individuals: Men and women aged approximately 18-55 years (extremes included). Able to provide informed consent in English. No psychiatric diagnoses and in good physical health. General exclusion criteria: Cannabis naïve Unwillingness to remain alcohol-free, cannabis-free for at least 1 week (in infrequent cannabis users) prior to each test day. Evidence of a hearing deficit. IQ less than 80. Positive pregnancy test, lactation, and refusal to practice birth control.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active 4 mg inhaled THC<br>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. | Drug: 4 mg Delta-9-THC<br>* 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.<br>|
| Experimental: Active 2 mg inhaled THC<br>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. | Drug: 2 mg Delta-9-THC<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 |