Impact of CBD-Rich Oil on Aversive Memory Reconsolidation

Anxiety and Fear Clinical Trial

Official title:

Impact of Cannabidiol-Rich Hemp Extract Oil on Reconsolidation Disruption of Naturalistic Interoceptive Aversive Memory in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04726475
• Other study ID #: 2020-07-0141
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2022
• Est. completion date: January 2024

Study information

• Verified date: January 2022
• Source: University of Texas at Austin
• Contact: Michael J. Telch, PhD
• Phone: 5125604100
• Email: telch[@]austin.utexas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria include:

1. Ages 18-65

2. Fluent in English

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

Exclusion criteria include:

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

Related Conditions & MeSH terms

• Anxiety and Fear

Intervention

Behavioral:
• 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.

Dietary Supplement:
• Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil
300mg CBD-rich hemp-derived formulation in MCT coconut oil.
• Placebo Oil
3ml oral dose of MCT coconut oil.

Locations

Country	Name	City	State
United States	University of Texas	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas at Austin

Country where clinical trial is conducted

United States, 

References & Publications (3)

Murkar A, Kent P, Cayer C, James J, Durst T, Merali Z. Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of ?9-Tetrahydrocannabinol on Fear Memory Reconsolidation. Front Behav Neurosci. 2019 Aug 1;13:174. doi: 10.3389/fnbeh.2019.00174. eCollection 2019. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Two-week follow-up
Secondary	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.	Two-week follow-up
Secondary	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.	Two-week

External Links

•   Eligibility survey link