Cannabinoid Control of Fear Extinction Neural Circuits in Humans

NCT02472847 | Completed Phase 4 Results

• 2 other identifiers: 2012-0242R21MH093917
• Study Type: interventional
• Target: 85
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of the current proposal is to investigate the effects of a cannabinoid drug on the memory of extinguished fear in humans and the brain circuitry important for the recall of extinction learning. The investigators findings will translate previous discoveries from animal studies to humans and increase their understanding of the neurobiological mechanisms supporting retention of extinction memory. This proof-of-concept study is a critical translational first step towards the development of cannabinoid modulators as an adjunctive strategy to exposure-based therapies to augment extinction learning and prevent the return of fear memories in patients with post-traumatic stress and other anxiety disorders.

Conditions

Healthy Participants

Keywords

Marinol; Dronabinol; Fear extinction; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• BOLD Signal Measured by Functional Magnetic Resonance Imaging (fMRI)

  Mean BOLD hippocampal signal during extinction learning and retention task in brain responsebetween the placebo (PBO) and the dronabinol (THC) group. Target areas are analyzed from fMRI scans. The scans were completed on days 1, 2, 3, and 9. Participants were randomized to the PBO and THC condition and received either placebo or dronabinol on day 2, 2 hours prior to extinction learning. Data from days 1, 2, 3, \& 9 was combined and a single value was averaged for each group.

  Day 1, 2, 3, & 9

Study Arms (2)

Placebo

PLACEBO COMPARATOR

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will couple a standard Pavlovian fear extinction paradigm in fMRI with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo 2 hours prior to extinction learning in healthy adult volunteers and test extinction retention and maintenance 24 hours and 1 week later, respectively, after extinction learning.

Drug: Placebo

Dronabinol

ACTIVE COMPARATOR

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will couple a standard Pavlovian fear extinction paradigm in fMRI with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo 2 hours prior to extinction learning in healthy adult volunteers and test extinction retention and maintenance 24 hours and 1 week later, respectively, after extinction learning

Drug: Dronabinol

Interventions

Dronabinol DRUG

Dronabinol (7.5mg) is administered only once by the oral route and is placed in opaque capsules with dextrose filler. Half of the participants will receive dronabinol.

Also known as: Marinol

Dronabinol

Placebo DRUG

Placebo is administered only once by the oral route and contains only dextrose in opaque capsules. Half of the participants will receive placebo.

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• age 21-45
• right-handed
• free of lifetime diagnosis of Axis I psychiatric disorder
• must be able to given informed consent
• must be medically and neurologically healthy.

You may not qualify if:

• any current medical condition requiring psychoactive/psychotropic medication or medication that would interact with dronabinol or interfere with study procedures
• current or past allergic or adverse reaction or known sensitivity to cannabinoid-like substance (Dronabinol /Marijuana/Cannabis/THC, cannabinoid oil, sesame oil, gelatin, glycerin, and titanium dioxide.)
• any current or past Axis I psychiatric disorder, including alcohol/substance abuse or dependence disorder
• less than a high school education
• lack of fluency in English
• night shift work
• currently pregnant or planning pregnancy or lactating (women)
• unwilling/unable to sign informed consent document
• inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia), as determined by self-report and a preliminary session in a mock scanner
• left-handed
• presence of ferrous-containing metals within the body (e.g., aneurysm clips,shrapnel/retained particles)
• under 21 or over 45 years of age
• anticipation of a required drug test in the 4 weeks following the study. No vulnerable participant populations will be included in this study
• participation in an experiment involving shocks in the last 6 months.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• National Institute of Mental Health (NIMH): collaborator
• National Institutes of Health (NIH): collaborator

MeSH Terms

Interventions

Dronabinol; Sugars

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Dr. K. Luan Phan
• Organization: University of Illinois at Chicago

klphan@psych.uic.edu

312-355-5954

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 12, 2015
• First Posted: June 16, 2015
• Study Start: May 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 25, 2015
• Results First Posted: August 25, 2015

Record last verified: 2015-07