Impact of CBD-Rich Oil on Aversive Memory Reconsolidation

The University of Texas System (UT)

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Anxiety and Fear

Treatments: Behavioral: Interoceptive Aversive Memory Reactivation; Dietary Supplement: Placebo Oil; Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil

Study type: Interventional

Funder types: Other

Identifiers

NCT04726475

2020-07-0141

Details and patient eligibility

About

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.

Full 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.

Enrollment: 96 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 3 patient groups, including a placebo group

CBD-WR

Experimental group

Description:

* 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.

Treatment:

Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil

Behavioral: Interoceptive Aversive Memory Reactivation

PBO-WR

Placebo Comparator group

Description:

* 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.

Treatment:

Dietary Supplement: Placebo Oil

Behavioral: Interoceptive Aversive Memory Reactivation

CBD-OR

Active Comparator group

Description:

* 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.

Treatment:

Dietary Supplement: Cannabidiol (CBD)-Rich Broad Spectrum Hemp Extract Oil

Behavioral: Interoceptive Aversive Memory Reactivation