- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02472847
Cannabinoid Control of Fear Extinction Neural Circuits in Humans
July 28, 2015 updated by: K. Luan Phan, MD, University of Illinois at Chicago
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The inability to suppress inappropriate fear responses is the hallmark of anxiety disorders, such as posttraumatic stress disorder (PTSD), panic, and phobia disorders.
Extinction of fear occurs during exposure therapy; however, this is temporary and fear often re-emerges with the passage of time (spontaneous recovery), undermining the maintenance of therapeutic gains.
Enhancing the neural and neurochemical substrates involved in retention of extinction memory will be critical to solving this challenge.
Animal studies have shown that activation of the cannabinoid system within the amgydala, hippocampus, and ventromedial prefrontal cortex (AMYG, HPC, vmPFC, respectively), brain structures critical to fear expression and extinction learning, enhances fear extinction and its retention.
Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats.
However, this phenomenon has not been, but should be, investigated in humans.
This proof-of-concept project specifically aims to assess the effects of THC on the recall of extinction learning and underlying neural circuit activation (HPC, vmPFC) when tested 24 hours and 1 week after extinction training, and to determine if the maintenance of extinction retention (1 week later) is mediated by the enhancement of vmPFC-HPC activation by THC observed during a recall test 24 hours after extinction learning.
In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will couple a standard Pavlovian fear extinction paradigm in fMRI and simultaneous skin conductance recordings with an acute pharmacological challenge with oral, synthetic THC prior to extinction learning in healthy adult volunteers (n=80) and test extinction retention and maintenance of extinction learning at 24 hours and 1 week later, as well as fear renewal.
This proof-of-concept study provides the most translational, impactful, informative, and critical test and first step towards the development of cannabinoid modulators as an adjunctive strategy to exposure-based therapies to augment extinction retention and prevent the return of fear memories in patients with PTSD and other anxiety disorders.
Study Type
Interventional
Enrollment (Actual)
85
Phase
- Phase 4
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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.
|
Placebo is administered only once by the oral route and contains only dextrose in opaque capsules.
Half of the participants will receive placebo.
Other Names:
|
Active Comparator: Dronabinol
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
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BOLD Signal Measured by Functional Magnetic Resonance Imaging (fMRI)
Time Frame: Day 1, 2, 3, & 9
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2012
Primary Completion (Actual)
July 1, 2014
Study Completion (Actual)
July 1, 2014
Study Registration Dates
First Submitted
June 12, 2015
First Submitted That Met QC Criteria
June 12, 2015
First Posted (Estimate)
June 16, 2015
Study Record Updates
Last Update Posted (Estimate)
August 25, 2015
Last Update Submitted That Met QC Criteria
July 28, 2015
Last Verified
July 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Psychotropic Drugs
- Hallucinogens
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Dronabinol
Other Study ID Numbers
- 2012-0242
- R21MH093917 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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