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

Bipolar Disorder Clinical Trial

— THC-BD  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03206463
• Other study ID #: 2000020272
• Status: Terminated
• Phase: Phase 1
• Start date: August 1, 2017
• Est. completion date: September 29, 2017

Study information

• Verified date: January 2022
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: September 29, 2017
• Est. primary completion date: September 29, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bipolar Disorder
• Delta-9-Tetrahydroncannabinol
• Healthy Controls

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Biological Studies Unit, VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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.
Other	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.
Other	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
Primary	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
Primary	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	Attention	Attention will be measured by the Continuous Performance Test-Identical Pairs (CPT-IP).	baseline and +35 mins after drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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