Clinical trial NCT03206463: Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder
Official title: Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Delta-9-Tetrahydroncannabinol
Bipolar Disorder
Healthy Controls
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Verbal memory
timeFrame: baseline and +35 mins after drug administration
measure: Change in Executive functioning
timeFrame: baseline and +35 mins after drug administration
Secondary outcomes:
measure: Attention
timeFrame: baseline and +35 mins after drug administration
measure: Working memory
timeFrame: baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration
measure: Mood
timeFrame: baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration
measure: Psychotic-type experiences
timeFrame: baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration
measure: Anxiety symptoms
timeFrame: baseline and +20 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration
measure: Impulsivity
timeFrame: baseline, +35 mins after drug administration, +90 mins after drug administration and +210 mins after drug administration
Other outcomes:
measure: Blood serum hormonal levels • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels.
timeFrame: 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
measure: Blood serum THC and metabolite levels (ng/ml)
timeFrame: 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
measure: Blood pressure
timeFrame: 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.
measure: Pulse
timeFrame: 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.
measure: Genetics
timeFrame: Only on 1st test day
Locations:
city: West Haven
country: United States
facility: Biological Studies Unit, VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University
name: Mohini Ranganathan, MD
role: PRINCIPAL_INVESTIGATOR
References: