Multimodal Assessment of Cannabinoid Target Engagement in Adults With Obsessive-Compulsive Disorder

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04880278

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to test how a medication called nabilone (Cesamet) affects neurocognitive processes involved in obsessive-compulsive disorder (OCD), including threat response, processing of fear signals, and habitual behavior. OCD is a disabling illness that affects around 2% of the population and involves recurrent intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that lead to distress and/or impaired functioning. Nabilone is a synthetic form of delta-9-tetrahydrocannabinol (THC, the primary psychoactive component of the cannabis plant). It acts on the brain's endocannabinoid system, which has been hypothesized to play a role in OCD symptoms. Nabilone is approved by the FDA for the treatment of chemotherapy-induced nausea and vomiting. It is not FDA-approved for treating OCD.

In this study, 60 adults with OCD will receive a single dose of either nabilone or placebo. Participants will then complete a series of assessments including neuroimaging, psychophysiology (e.g., skin conductance recording), computerized behavioral tasks, and self-report measures. The information gained from this study could contribute to the development of new treatments for people with OCD and related disorders.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder	Drug: Nabilone Drug: Placebo	Phase 1/Phase 2

Detailed Description

The total time required for each participant is 4 visits, as outlined below:

Visit 1: Screening, Questionnaires, and Orientation: During this visit potential participants will learn about the study procedures, sign the informed consent documents, complete diagnostic evaluations and medical screening with study staff. Participants will also complete a series of forms that ask about demographic information, OCD symptoms, use of drugs and alcohol, and other aspects of physical and mental health.

Visit 2: Behavioral Tests: During this visit participants will complete several computer tasks. Study staff will measure reaction time and obtain psychophysiological information (e.g., skin conductance recordings). The tasks that the participant completes will involve viewing images within a virtual environment. An aversive stimulus (e.g., loud burst of noise, animated snake) may follow one image most of the time, while other images may never be followed by a noise or a snake. The participant will need to try to predict whether the aversive cue will occur or not based on which image is shown, and will be asked to repeatedly rate on a scale how likely they think it is that a noise/snake will occur after each image.

Visit 3: Behavioral Tests with Drug or Placebo and MRI scan: For safety reasons, participants will be asked not to take any drugs for at least 24 hours before this visit. They will also be asked not to use marijuana/cannabis for at least 2 weeks before participating. Participants will be required to test negative on a urine drug screen and breathalyzer before continuing with this visit; women must also have a negative pregnancy test. Participants will need to complete a field sobriety test at the end of this visit and will be asked not to drive or operate machinery for the following 24 hours; participants not traveling to the clinic by subway or taxi should arrange to have a friend or family member pick them up.

Two hours before beginning the Visit 3 tasks, participants will be asked to swallow a capsule containing either nabilone or placebo (sugar pill). Nabilone is a Food & Drug Administration (FDA) approved medication, and the dose (1mg, one time) is unlikely to have any effects that last beyond the duration of the study visit. About every 30 minutes after taking the pill, the participant will fill out some questionnaires asking about how they are feeling at the moment. At the end of the session, they will also be asked to guess whether they received nabilone or placebo.

Participants will then complete a task that is similar to the one on the previous day (Visit 2), but will be completed in the MRI scanner. During the MRI scan, participants will view the same images as on the previous day (Visit 2), and may experience the same aversive stimulus as during Visit 2. They will again be asked to rate how much they expect to experience the aversive stimulus after each image and to self-report their level of anxiety on a scale from 0 to 100. Finally, they will be asked to relax with their eyes open while viewing a white fixation cross on a back background.

Participants will complete an additional task outside of the MRI scanner. Participants will be repeatedly asked to view and choose between different images (e.g., spaceships), which lead to a different set of images. They must select one image from this second set, with some choices leading to a small monetary reward.

Visit 4: Behavioral Tests and MRI scan: This visit will be very similar to Visit 3, except that participants will not receive any study medication. Participants will complete the same type of task inside the MRI scanner, while the study staff measures reaction time, psychophysiological response, and brain activation. Participants will view the same images as in Visits 2 and 3, and may experience the same aversive stimulus. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and to report their level of anxiety on a scale from 0 to 100. Participants will again be asked to relax with their eyes open while viewing a white fixation cross on a black background. Finally, outside of the scanner, participants will complete another decision-making task similar to the one they completed the day before.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Multimodal Assessment of Cannabinoid Target Engagement in Adults With Obsessive-Compulsive Disorder

Actual Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nabilone In a randomized, double-blind, placebo-controlled design, we will administer a one-time oral dose of nabilone (1mg) or placebo approximately two hours prior to fMRI scanning and task performance in 60 adults with OCD.	Drug: Nabilone Half of the participants (30 individuals) will receive nabilone 1mg. Nabilone will be placed in opaque capsules with dextrose filler and administered by mouth only once (around 120 minutes prior to fMRI scanning). Other Names: Cesamet (brand name)
Placebo Comparator: Placebo In a randomized, double-blind, placebo-controlled design, we will administer a one-time oral dose of nabilone (1mg) or placebo approximately two hours prior to fMRI scanning and task performance in 60 adults with OCD.	Drug: Placebo Half of the participants (30 individuals) will receive placebo capsules that are opaque and contain only dextrose. Placebo capsules will be administered by mouth only once (around 120 minutes prior to fMRI scanning).

Arm

Intervention/Treatment

Active Comparator: Nabilone

In a randomized, double-blind, placebo-controlled design, we will administer a one-time oral dose of nabilone (1mg) or placebo approximately two hours prior to fMRI scanning and task performance in 60 adults with OCD.

Drug: Nabilone

Half of the participants (30 individuals) will receive nabilone 1mg. Nabilone will be placed in opaque capsules with dextrose filler and administered by mouth only once (around 120 minutes prior to fMRI scanning).

Other Names:

Cesamet (brand name)

Placebo Comparator: Placebo

Drug: Placebo

Half of the participants (30 individuals) will receive placebo capsules that are opaque and contain only dextrose. Placebo capsules will be administered by mouth only once (around 120 minutes prior to fMRI scanning).

Outcome Measures

Primary Outcome Measures

Brain Measure 1 [5 years]
Functional magnetic resonance imaging (fMRI) BOLD percent signal change within regions of interest (e.g., amygdala; ventromedial prefrontal cortex; hippocampus) during task performance
Brain Measure 2 [5 years]
Difference in fMRI resting state functional connectivity
Skin conductance response (SCR) [5 years]
Change in SCR (peak amplitude from 0.5-4.5 sec following stimulus presentation minus average 2 second baseline prior to stimulus presentation).
Electromyography (EMG) [5 years]
Change in orbicularis oculi EMG response (peak-to-peak value in the 21-150ms after stimulus presentation)
Expectancy Ratings [5 years]
To assess the expected likelihood that an aversive cue (e.g. noise burst or animated snake) will occur or not based on which image was shown, participants will repeatedly rate their expectancy of the aversive cue using a button box on a scale from 1 to 3 (1 = certain that the aversive cue will be presented; 2 = certain that the aversive cue will not be presented; 3 = uncertain whether the aversive cue will be presented).

Secondary Outcome Measures

Two-step task performance [5 years]
Computational modeling will be applied to examine the balance between model-free vs. model-based behavior based on the relative frequency of outcomes selected at each stage of the task (i.e., Choice 1 vs. Choice 2).
Subjective Units of Distress [5 years]
Subjective Units of Distress (SUDS): Self-reported fear/anxiety on a scale from 0-100; taken at three time points throughout the tasks: before the task begins, in the middle of the task, and at the end of the task.
Yale-Brown Obsessive-Compulsive Challenge Scale [Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Measure of self-reported obsessions and compulsions over short timeframes (e.g., minutes to hours).
Spielberger State/Trait Anxiety Inventory (STAI) [Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Self-report measure of trait anxiety and of current anxiety symptoms
Visual Analog Scales (VAS) [Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Measures self-report of current OCD and anxiety symptoms on a visual scale of 1-10
Nabilone Side Effects Checklist [Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Self-report checklist of potential nabilone side effects on a scale of 1-4 (absent, mild, moderate, severe)
Drug Effects Questionnaire (DEQ) [Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 90, 120, 150, 180, and 240 minutes afterwards, as well as at 8 hours and 24 hours afterwards.]
Self-report measure of intoxicating effects on a scale of 1-4
End of Session Questionnaire (ESQ) [5 years]
A brief questionnaire that asks participants about their experiences during the experimental session
Heart rate [Heart rate will be collected at the following intervals during Visit 3: Immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Heart rate in beats per minute
Blood pressure [Blood pressure will be collected at the following intervals during Visit 3: Immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.]
Blood pressure (systolic blood pressure/diastolic blood pressure; units: mmHg)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 21-55 years of age
Physically healthy and, if female, not pregnant
Able to tolerate all study procedures
Able to provide written informed consent to participate
Right-handed
Primary diagnosis of OCD
Not taking psychotropic medications or other substances likely to interact with nabilone

Exclusion Criteria:

History of any significant medical condition that may increase the risk of participation
Females who are pregnant or nursing
Current or lifetime history of psychiatric disorders other than OCD that may increase the risk of participation (e.g. lifetime psychosis or bipolar disorder)
Current substance use disorder
Positive urine toxicology or alcohol breathalyzer
Any history of adverse reaction to a cannabinoid
History of receiving cognitive behavior or exposure-based psychotherapy in the past 3 months
History of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
History of claustrophobia or unable to tolerate confined spaces like an MRI