Healthy ParticipantsPhase 4NCT02472847
Cannabinoid Control of Fear Extinction Neural Circuits in Humans
A Phase 4 study testing Dronabinol in people with Healthy Participants, run by University of Illinois Chicago.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- Dronabinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- No sites listed yet
- Study dates
- May 2012to Jul 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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.
About this study
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.
Read the 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.
- Conditions
- Healthy Participants
- Being tested
- Dronabinol, Placebo
- Keywords
- Marinol, Dronabinol, Fear extinction, Healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DronabinolDrug
Also called Marinol
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.
PlaceboDrug
Also called Sugar Pill
Placebo is administered only once by the oral route and contains only dextrose in opaque capsules. Half of the participants will receive placebo.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Dronabinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1, 2, 3, & 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2015 (estimated)
- Study startMay 2012
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, K. Luan Phan, MD, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472847
- Sponsor's protocol ID
- 2012-0242
- Other IDs
- R21MH093917
- Status last verified
- Jul 2015
- First submitted
- 12 Jun 2015
- Last updated
- 25 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabinoid Control of Fear Extinction Neural Circuits in Humans
- ClinicalTrials.gov ID
- NCT02472847
- Acronym / sponsor ID
- 2012-0242
- Conditions
- Healthy Participants
- Keywords
- Marinol, Dronabinol, Fear extinction, Healthy volunteers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
- Study start
- May 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 16 Jun 2015 (estimated)
- Results
- Posted 25 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIn 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 | Active comparator | Drug: DronabinolIn 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 |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DronabinolAlso: MarinolDronabinol (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. | Drug | Dronabinol |
| PlaceboAlso: Sugar PillPlacebo is administered only once by the oral route and contains only dextrose in opaque capsules. Half of the participants will receive placebo. | Drug | Placebo |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dronabinol in people with Healthy Participants, run by University of Illinois Chicago.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD Signal Measured by Functional Magnetic Resonance Imaging (fMRI) (time frame: Day 1, 2, 3, & 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2015.