Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder (THC-BD)

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).

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder; Healthy Controls; Delta-9-Tetrahydroncannabinol
• Intervention / Treatment: Drug: 4 mg Delta-9-THC; Drug: 2 mg Delta-9-THC; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Biological Studies Unit, VA Connecticut Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active 4 mg inhaled 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.	Drug: 4 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.
Experimental: Active 2 mg inhaled 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.	Drug: 2 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.
Placebo Comparator: Placebo; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): September 29, 2017
• Study Completion (Actual): September 29, 2017

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 2000020272

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No