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

NCT04880278 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 7809K23MH125315
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder

Keywords

Nabilone; Fear Extinction; Threat Response; Goal-directed vs. Habitual Behavior; fMRI

Outcome Measures

Primary Outcomes (5)

• Brain Measure 1

  Functional magnetic resonance imaging (fMRI) BOLD percent signal change within regions of interest (e.g., amygdala; ventromedial prefrontal cortex; hippocampus) during task performance

  5 years

• Brain Measure 2

  Difference in fMRI resting state functional connectivity

  5 years

• Skin conductance response (SCR)

  Change in SCR (peak amplitude from 0.5-4.5 sec following stimulus presentation minus average 2 second baseline prior to stimulus presentation).

  5 years

• Electromyography (EMG)

  Change in orbicularis oculi EMG response (peak-to-peak value in the 21-150ms after stimulus presentation)

  5 years

• Expectancy Ratings

  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).

  5 years

Secondary Outcomes (10)

• Two-step task performance

  5 years

• Subjective Units of Distress

  5 years

• 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.

• 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.

• Visual Analog Scales (VAS)

  Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.

Study Arms (2)

Nabilone

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Nabilone DRUG

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).

Also known as: Cesamet (brand name)

Nabilone

Placebo DRUG

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).

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

nabilone

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Officials

• Reilly Kayser, MD

  Columbia University/New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 10, 2021
• Study Start: March 1, 2022
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)