Impact of CBD-Rich Oil on Aversive Memory Reconsolidation

NCT ID: NCT04726475

Last Updated: 2022-01-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-31
• Study Completion Date: 2024-01-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CBD-WR

• 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.

Group Type: EXPERIMENTAL

Interoceptive Aversive Memory Reactivation

Intervention Type: BEHAVIORAL

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 Oil

Intervention Type: DIETARY_SUPPLEMENT

300mg CBD-rich hemp-derived formulation in MCT coconut oil.

PBO-WR

• 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.

Group Type: PLACEBO_COMPARATOR

Interoceptive Aversive Memory Reactivation

Intervention Type: BEHAVIORAL

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.

Placebo Oil

Intervention Type: DIETARY_SUPPLEMENT

3ml oral dose of MCT coconut oil.

CBD-OR

• 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.

Group Type: ACTIVE_COMPARATOR

Interoceptive Aversive Memory Reactivation

Intervention Type: BEHAVIORAL

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 Oil

Intervention Type: DIETARY_SUPPLEMENT

300mg CBD-rich hemp-derived formulation in MCT coconut oil.

Interventions

Interoceptive Aversive Memory Reactivation

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.

Intervention Type: BEHAVIORAL

Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil

300mg CBD-rich hemp-derived formulation in MCT coconut oil.

Intervention Type: DIETARY_SUPPLEMENT

Placebo Oil

3ml oral dose of MCT coconut oil.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Ages 18-65

2. Fluent in English

3. Willingness to refrain from all non-study cannabis use during the study period.

Exclusion Criteria

1. Insufficient phobicity (<50 on CO2 challenge);

2. Presence of significant suicidality;

3. History of psychosis;

4. Currently receiving exposure-based treatment;

5. Current substance use disorder;

6. Unstable psychiatric medication for a psychological condition;

7. Medical conditions contraindicating CO2 inhalation (e.g., cardiac arrhythmia, cardiac failure, asthma, lung fibrosis, high blood pressure, epilepsy, or stroke);

8. 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);

9. History of an adverse reaction to CBD oil or other CBD products,

10. Coconut allergy (coconut oil is the carrier oil for CBD-rich extract)

(l) Regular cannabis use

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas at Austin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael J. Telch, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas at Austin

Locations

University of Texas

Austin, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michael J. Telch, PhD

Role: CONTACT

telch@austin.utexas.edu

5125604100

Eric D. Zaizar, B.A.

Role: CONTACT

eric.zaizar@utexas.edu

8303704044

Facility Contacts

Michael J. Telch, PhD

Role: primary

telch@austin.utexas.edu

512-560-4100

Eric D Zaizar, B.A.

Role: backup

eric.zaizar@utexas.edu

8303704044

References

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.

Reference Type: BACKGROUND

PMID: 28729064 (View on PubMed)

Murkar 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.

Reference Type: BACKGROUND

PMID: 31417379 (View on PubMed)

Telch 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.

Reference Type: BACKGROUND

PMID: 23117637 (View on PubMed)

Zaizar 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.

Reference Type: DERIVED

PMID: 35811050 (View on PubMed)

Related Links

http://telchpsy.co1.qualtrics.com/jfe/form/SV_b9PjqSIzDtzXdNc

Eligibility survey link

Other Identifiers

2020-07-0141

Identifier Type: -

Identifier Source: org_study_id