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

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ClinicalTrials.gov Identifier: NCT03206463
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
Mohini Ranganathan, Yale University

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).


Condition or disease Intervention/treatment Phase
Delta-9-Tetrahydroncannabinol Bipolar Disorder Healthy Controls Drug: 4 mg Delta-9-THC Drug: Placebo Drug: 2 mg Delta-9-THC Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Cognitive and Psychophysiological Effects of Delta-9-Tetrahydrocannabinol in Bipolar Disorder
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder
Drug Information available for: Dronabinol

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.




Primary Outcome Measures :
  1. Change in Verbal memory [ Time Frame: 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.

  2. Change in Executive functioning [ Time Frame: baseline and +35 mins after drug administration ]
    Executive functioning will be measured by the CogState battery and/or Trails Making Test-Part B.


Secondary Outcome Measures :
  1. Attention [ Time Frame: baseline and +35 mins after drug administration ]
    Attention will be measured by the Continuous Performance Test-Identical Pairs (CPT-IP).

  2. Working memory [ Time Frame: 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.

  3. Mood [ Time Frame: 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).

  4. Psychotic-type experiences [ Time Frame: 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).

  5. Anxiety symptoms [ Time Frame: 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).

  6. Impulsivity [ Time Frame: 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 Outcome Measures:
  1. Blood serum hormonal levels • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. • Serum prolactin, serum ACTH, serum cortisol and serum endocannabinoid levels. [ Time Frame: 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.

  2. Blood serum THC and metabolite levels (ng/ml) [ Time Frame: 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.

  3. Blood pressure [ Time Frame: 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

  4. Pulse [ Time Frame: 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

  5. Genetics [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03206463


Locations
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United States, Connecticut
Biological Studies Unit, VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Mohini Ranganathan, MD Yale University

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Responsible Party: Mohini Ranganathan, Assistant Professor of Psychiatry, Yale University
ClinicalTrials.gov Identifier: NCT03206463     History of Changes
Other Study ID Numbers: 2000020272
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: July 10, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Disease
Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Dronabinol
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists