Anxiety and FearPhase 1/2NCT04726475
Impact of CBD-Rich Oil on Aversive Memory Reconsolidation
A Phase 1/2 study testing Interoceptive Aversive Memory Reactivation and Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil in people with Anxiety and Fear, run by University of Texas at Austin at 1 site in United States.
Trial summary
The purpose of this study is to test whether cannabidiol (CBD) rich hemp extract oil can interfere with the reconsolidation (storage) of pathological fear memory in humans. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anxiety and Fear
- What is being tested?
- Interoceptive Aversive Memory Reactivation and Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2022to Jan 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-65
- Fluent in English
- Willingness to refrain from all non-study cannabis use during the study period.
Who cannot join
- Insufficient phobicity (<50 on CO2 challenge);
- Presence of significant suicidality;
- History of psychosis;
- Currently receiving exposure-based treatment;
- Current substance use disorder;
- Unstable psychiatric medication for a psychological condition;
Show all 11Show fewer
- Medical conditions contraindicating CO2 inhalation (e.g., cardiac arrhythmia, cardiac failure, asthma, lung fibrosis, high blood pressure, epilepsy, or stroke);
- Any medical problems (e.g., liver or renal abnormalities) or medication use that would preclude ingesting CBD oil, including but not limited to currently taking blood thinners (e.g., Warfarin and some anti-epileptic medications);
- History of an adverse reaction to CBD oil or other CBD products,
- Coconut allergy (coconut oil is the carrier oil for CBD-rich extract)
- Regular cannabis use
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Texas
Austin, Texas, 78712
Michael J. Telch, PhD, 512-560-4100, telch@austin.utexas.edu
Eric D Zaizar, B.A., 8303704044, eric.zaizar@utexas.edu
About this study
Official title: Impact of Cannabidiol-Rich Hemp Extract Oil on Reconsolidation Disruption of Naturalistic Interoceptive Aversive Memory in Humans
The purpose of this study is to test whether cannabidiol (CBD) rich hemp extract oil can interfere with the reconsolidation (storage) of pathological fear memory in humans.
Read the detailed description
Preclinical experiments demonstrate that isolated cannabidiol (CBD), the non-psychotomimetic constituent of the Cannabis sativa plant, disrupts reconsolidation of aversive memories conditioned in the laboratory when administered within the memory reconsolidation window (< 6 hrs. post-retrieval) by indirectly activating cannabinoid type-1 (CB1) receptors in the dorsal anterior cingulate cortex (dACC). Furthermore, background material (e.g., terpenoids) naturally present in the cannabis plant may also disrupt aversive memory reconsolidation both alone and in concert with CBD. Based on these preclinical findings, we aim to test whether administration of 300mg CBD-rich hemp extract oil following fear reactivation of an aversive interoceptive threat memory can disrupt reconsolidation of naturalistic aversive memories in humans. More specifically, naturalistic interoceptive aversive memories, a form of transdiagnostic fear memory that contributes to the pathogenesis of fear-related disorders such as panic disorder, posttraumatic stress disorder (PTSD), and illness anxiety disorder.
For this proof-of-concept double-blind trial, volunteers (n=96) reporting elevated fears of somatic sensations will be stratified on biological sex and baseline levels of interoceptive fear and randomized to one of three intervention arms: (a). CBD-rich oil administered within the reconsolidation window, (b). Placebo oil administered within the reconsolidation window, or (c). CBD-rich oil administered outside of the reconsolidation window. Change in emotional reactivity to a 35% CO2 challenge from baseline to two-week follow-up will serve as our primary outcome.
Study findings may contribute towards the development of a novel ultra-brief transdiagnostic intervention guided by reconsolidation theory for individuals prone to fear-related psychiatric disorders.
- Conditions
- Anxiety and Fear
- Being tested
- Interoceptive Aversive Memory Reactivation, Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil, Placebo Oil
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interoceptive Aversive Memory ReactivationBehavioural
In order to reactivate interoceptive aversive memory, participants will be asked to breathe a medical grade 35% CO2/65% O2 gas mixture which produces somatic perturbations. The 35% CO2 challenge is a widely used and safe symptom induction technique that has been utilized in our laboratory in several experiments. Participants will be informed that breathing the gas is safe, but that it will likely cause changes in their physical sensations. Participants will specifically be asked to breathe the gas mixture normally with their mouth open through an oxygen mask for 10 seconds.
Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract OilDietary supplement
300mg CBD-rich hemp-derived formulation in MCT coconut oil.
Placebo OilDietary supplement
3ml oral dose of MCT coconut oil.
| Study group | Role | What they receive |
|---|---|---|
| CBD-WR | Experimental | * 300 mg CBD-rich hemp extract oil administered within the reconsolidation window.
* The timing of CBD-rich oil administration is based on preclinical studies demonstrating that CBD's disruptive effects on reconsolidation procedurally depend on timing pharmacological administration to be within the memory reconsolidation window (< 6 hrs. post-retrieval).
* Thus, immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single 300mg CBD-rich oral dose of a hemp-derived oil formulation. Receives: Behavioral: Interoceptive Aversive Memory Reactivation; Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil |
| PBO-WR | Placebo comparator | * Placebo administered within the reconsolidation window.
* Immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single dose of an MCT coconut oil placebo solution. Receives: Behavioral: Interoceptive Aversive Memory Reactivation; Dietary Supplement: Placebo Oil |
| CBD-OR | Active comparator | * CBD-rich hemp extract oil administered outside of the reconsolidation window.
* Participants will be asked to take a single 300mg oral dose of CBD-rich oil approximately 24 hrs after the initial 35% CO2 interoceptive memory reactivation challenge.
* Thus, CBD will be administered well beyond the critical period for memory reconsolidation. The inclusion of this third arm provides a more robust test of the specific reconsolidation theory-based study hypotheses and aids in controlling for any nonspecific possible anxiolytic effects of CBD. Receives: Behavioral: Interoceptive Aversive Memory Reactivation; Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
CO2 Emotional Reactivity
Self-reported peak-distress (range: 0-100), defined as the highest level of distress experienced at any point during the 35% CO2 challenge completed at the two-week follow-up assessment, adjusting for baseline rating (immediately after the 35% CO2 challenge, but before receiving either immediate CBD/placebo or delayed CBD).
Measured: Two-week follow-up
Secondary outcomes (2)
CO2 Emotional Distress Recovery Trajectory
Participants will be asked to rate their current distress level (range: 0-100) every minute for five consecutive minutes after the CO2 inhalation (recovery phase). Change in CO2 emotional distress recovery trajectory from baseline to the two-week follow will serve as a secondary continuous index of emotional reactivity to somatic cues.
Measured: Two-week follow-up
Short Scale Anxiety Sensitivity Index (SASSI)
The 5-item SSASI is a self-report instrument designed to measure the transdiagnostic construct of anxiety sensitivity, defined as a fear of anxiety and arousal-related sensations. Change on the SSASI from baseline to the two-week follow-up will serve as a secondary outcome measure.
Measured: Two-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2021
- Study startJan 2022 (estimated)
- Primary completionJan 2024 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Anxiety and FearStudies of the same condition, open and under way.
- More trials run by University of Texas at AustinThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael J. Telch, PhD, Principal investigator, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04726475
- Sponsor's protocol ID
- 2020-07-0141
- Status last verified
- Jan 2022
- First submitted
- 22 Jan 2021
- Last updated
- 19 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stern CAJ, de Carvalho CR, Bertoglio LJ, Takahashi RN. Effects of Cannabinoid Drugs on Aversive or Rewarding Drug-Associated Memory Extinction and Reconsolidation. Neuroscience. 2018 Feb 1;370:62-80. doi: 10.1016/j.neuroscience.2017.07.018. Epub 2017 Jul 17.
PubMed 28729064Murkar A, Kent P, Cayer C, James J, Durst T, Merali Z. Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Delta9-Tetrahydrocannabinol on Fear Memory Reconsolidation. Front Behav Neurosci. 2019 Aug 1;13:174. doi: 10.3389/fnbeh.2019.00174. eCollection 2019.
PubMed 31417379Telch MJ, Rosenfield D, Lee HJ, Pai A. Emotional reactivity to a single inhalation of 35% carbon dioxide and its association with later symptoms of posttraumatic stress disorder and anxiety in soldiers deployed to Iraq. Arch Gen Psychiatry. 2012 Nov;69(11):1161-8. doi: 10.1001/archgenpsychiatry.2012.8.
PubMed 23117637Zaizar ED, Papini S, O'Connor P, Telch MJ. Impact of cannabidiol-rich hemp extract oil on reconsolidation disruption of naturalistic interoceptive aversive memory in humans: Protocol for a randomized clinical trial. Contemp Clin Trials. 2022 Aug;119:106847. doi: 10.1016/j.cct.2022.106847. Epub 2022 Jul 8.
PubMed 35811050
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Cannabidiol-Rich Hemp Extract Oil on Reconsolidation Disruption of Naturalistic Interoceptive Aversive Memory in Humans
- ClinicalTrials.gov ID
- NCT04726475
- Acronym / sponsor ID
- 2020-07-0141
- Conditions
- Anxiety and Fear
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Study start
- Jan 2022 (estimated)
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 27 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test whether cannabidiol (CBD) rich hemp extract oil can interfere with the reconsolidation (storage) of pathological fear memory in humans.
Detailed description
Preclinical experiments demonstrate that isolated cannabidiol (CBD), the non-psychotomimetic constituent of the Cannabis sativa plant, disrupts reconsolidation of aversive memories conditioned in the laboratory when administered within the memory reconsolidation window (< 6 hrs. post-retrieval) by indirectly activating cannabinoid type-1 (CB1) receptors in the dorsal anterior cingulate cortex (dACC). Furthermore, background material (e.g., terpenoids) naturally present in the cannabis plant may also disrupt aversive memory reconsolidation both alone and in concert with CBD. Based on these preclinical findings, we aim to test whether administration of 300mg CBD-rich hemp extract oil following fear reactivation of an aversive interoceptive threat memory can disrupt reconsolidation of naturalistic aversive memories in humans. More specifically, naturalistic interoceptive aversive memories, a form of transdiagnostic fear memory that contributes to the pathogenesis of fear-related disorders such as panic disorder, posttraumatic stress disorder (PTSD), and illness anxiety disorder.
For this proof-of-concept double-blind trial, volunteers (n=96) reporting elevated fears of somatic sensations will be stratified on biological sex and baseline levels of interoceptive fear and randomized to one of three intervention arms: (a). CBD-rich oil administered within the reconsolidation window, (b). Placebo oil administered within the reconsolidation window, or (c). CBD-rich oil administered outside of the reconsolidation window. Change in emotional reactivity to a 35% CO2 challenge from baseline to two-week follow-up will serve as our primary outcome.
Study findings may contribute towards the development of a novel ultra-brief transdiagnostic intervention guided by reconsolidation theory for individuals prone to fear-related psychiatric disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CBD-WR | Experimental | Behavioral: Interoceptive Aversive Memory Reactivation, Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil* 300 mg CBD-rich hemp extract oil administered within the reconsolidation window. * The timing of CBD-rich oil administration is based on preclinical studies demonstrating that CBD's disruptive effects on reconsolidation procedurally depend on timing pharmacological administration to be within the memory reconsolidation window (< 6 hrs. post-retrieval). * Thus, immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single 300mg CBD-rich oral dose of a hemp-derived oil formulation. |
| PBO-WR | Placebo comparator | Behavioral: Interoceptive Aversive Memory Reactivation, Dietary Supplement: Placebo Oil* Placebo administered within the reconsolidation window. * Immediately after the 35% CO2 interoceptive memory reactivation procedure and associated measures (see measures), participants will be asked to take a single dose of an MCT coconut oil placebo solution. |
| CBD-OR | Active comparator | Behavioral: Interoceptive Aversive Memory Reactivation, Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil* CBD-rich hemp extract oil administered outside of the reconsolidation window. * Participants will be asked to take a single 300mg oral dose of CBD-rich oil approximately 24 hrs after the initial 35% CO2 interoceptive memory reactivation challenge. * Thus, CBD will be administered well beyond the critical period for memory reconsolidation. The inclusion of this third arm provides a more robust test of the specific reconsolidation theory-based study hypotheses and aids in controlling for any nonspecific possible anxiolytic effects of CBD. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages 18-65
- Fluent in English
- Willingness to refrain from all non-study cannabis use during the study period.
Key exclusion criteria (11 listed)
- Insufficient phobicity (<50 on CO2 challenge);
- Presence of significant suicidality;
- History of psychosis;
- Currently receiving exposure-based treatment;
- Current substance use disorder;
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 |
|---|---|---|
| Interoceptive Aversive Memory ReactivationIn order to reactivate interoceptive aversive memory, participants will be asked to breathe a medical grade 35% CO2/65% O2 gas mixture which produces somatic perturbations. The 35% CO2 challenge is a widely used and safe symptom induction technique that has been utilized in our laboratory in several experiments. Participants will be informed that breathing the gas is safe, but that it will likely cause changes in their physical sensations. Participants will specifically be asked to breathe the gas mixture normally with their mouth open through an oxygen mask for 10 seconds. | Behavioural | CBD-OR, CBD-WR, PBO-WR |
| Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil300mg CBD-rich hemp-derived formulation in MCT coconut oil. | Dietary supplement | CBD-OR, CBD-WR |
| Placebo Oil3ml oral dose of MCT coconut oil. | Dietary supplement | PBO-WR |
Primary outcome
CO2 Emotional Reactivity
Time frame: Two-week follow-up
Self-reported peak-distress (range: 0-100), defined as the highest level of distress experienced at any point during the 35% CO2 challenge completed at the two-week follow-up assessment, adjusting for baseline rating (immediately after the 35% CO2 challenge, but before receiving either immediate CBD/placebo or delayed CBD).
2 secondary outcomes
CO2 Emotional Distress Recovery Trajectory
Time frame: Two-week follow-up
Short Scale Anxiety Sensitivity Index (SASSI)
Time frame: Two-week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Background: PubMed 28729064Stern CAJ, de Carvalho CR, Bertoglio LJ, Takahashi RN. Effects of Cannabinoid Drugs on Aversive or Rewarding Drug-Associated Memory Extinction and Reconsolidation. Neuroscience. 2018 Feb 1;370:62-80. doi: 10.1016/j.neuroscience.2017.07.018. Epub 2017 Jul 17.
- Background: PubMed 31417379Murkar A, Kent P, Cayer C, James J, Durst T, Merali Z. Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Delta9-Tetrahydrocannabinol on Fear Memory Reconsolidation. Front Behav Neurosci. 2019 Aug 1;13:174. doi: 10.3389/fnbeh.2019.00174. eCollection 2019.
- Background: PubMed 23117637Telch MJ, Rosenfield D, Lee HJ, Pai A. Emotional reactivity to a single inhalation of 35% carbon dioxide and its association with later symptoms of posttraumatic stress disorder and anxiety in soldiers deployed to Iraq. Arch Gen Psychiatry. 2012 Nov;69(11):1161-8. doi: 10.1001/archgenpsychiatry.2012.8.
- Derived from this study: PubMed 35811050Zaizar ED, Papini S, O'Connor P, Telch MJ. Impact of cannabidiol-rich hemp extract oil on reconsolidation disruption of naturalistic interoceptive aversive memory in humans: Protocol for a randomized clinical trial. Contemp Clin Trials. 2022 Aug;119:106847. doi: 10.1016/j.cct.2022.106847. Epub 2022 Jul 8.
- Eligibility survey linkLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Michael J. Telch, PhD principal investigator
University of Texas at Austin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Interoceptive Aversive Memory Reactivation and Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil in people with Anxiety and Fear, run by University of Texas at Austin at 1 site in United States.
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 3 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael J. Telch, PhD (5125604100, telch@austin.utexas.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CO2 Emotional Reactivity (time frame: Two-week follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04726475, which also lists 4 linked publications.
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 19 Jan 2022.