Clinical trial NCT04603781: CBD Oil for Reducing Emotional Impact of COVID-19
Official title: Use of CBD Oil for Reducing the Negative Emotional Impact of COVID-19: A Randomized Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Anxiety Depression
Alcohol Abuse
Substance Abuse
Anger
Sleep Disturbance
Stress Reaction
Keywords: CBD Oil
CBD Isolate
COVID-19
stress symptoms
RCT
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: Way West Wellness
name: SunFlora.Inc
First posted: 2020-10-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 4-arm double-blind placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: Our purpose is to conduct a 4-arm placebo-controlled clinical trial to investigate the relative clinical efficacy of 300 mg. of pure hemp-derived CBD isolate, 300 mg. of full spectrum CBD oil, 300 mg. of broad- spectrum CBD Oil, or Placebo oil among adults presenting with COVID-19 -induced stress reactions including one or more of the following: anxiety, depression, anger, substance use, or sleep disturbance.

Detailed description: Background and Significance of the Proposed Project

The COVID-19 pandemic has hit us like a ton of bricks creating unimaginable levels of unanticipated death, financial hardship, and dramatic changes in nearly every facet of our life including school, work, shopping, social and family life. Sadly, the physical, mental, economic, and health burden of COVID-19 disproportionately affects the poor, the elderly, and people of color.

The stress induced by these changes as well as the lack of control we have over them increases risk for new onset of mental health problems such as anxiety, depression, substance abuse, sleep disturbance, and family violence as well as exacerbation of symptoms among those with pre-existing psychiatric conditions. Although many people will successfully manage the increased stress from COVID-19 on their own or with the support from family and friends, others may need extra help to cope. Consequently, there is an urgent need for developing cost-effective strategies for managing the stress-induced psychological consequences of COVID-19.

There's been considerable excitement in the press over the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems. Delta-9-tetrahydrocannabinol (delta-9 THC) is still illegal in most states because of its psychoactive abuse potential. In contrast, cannabidiol (CBD) does not convert to THC in the body and has negligible side effects relative to main-stream psychiatric drugs (benzodiazepines and antidepressants) commonly prescribed for the treatment of stress-related disorders such as anxiety, depression, and insomnia. Mounting evidence from studies with rodents suggests that CBD may confer significant promising health-related benefits including anti-inflammatory, pain-relieving, anti-cancer, memory enhancement, and facilitation of fear extinction (see White for a recent review).

The biggest success story for CBD use in humans to date comes from placebo-controlled randomized clinical trials demonstrating a 50% or more reduction in previously intractable seizures in children suffering from Dravet syndrome and Lennox-Gastaut syndrome. Moreover, several controlled clinical trials have shown promising findings in reducing psychotic symptoms among patients with schizophrenia and among young adults displaying THC-induced psychosis.

Preliminary Evidence that CBD may offer promise in the treatment of stress-related disorders has started to emerge. A small pilot trial with 24 patients presenting with social anxiety disorder found that relative to placebo, a single dose of 100 mg of CBD oil led to lower levels of anxiety, cognitive impairment, and discomfort in their actual speech performance as well as their anxiety before the speech. An uncontrolled case series of 11 PTSD patients receiving 8 weeks of CBD, reported a 28% reduction in PTSD symptom scores. In a small 4-week placebo-controlled study of 37 young Japanese adults with social anxiety disorder, Masataka found a significant advantage of CBD over placebo in reducing subjects' scores on two widely used measures of social anxiety symptoms.

Why Compare CBD-Isolate with Broad-Spectrum and Full-Spectrum CBD? CBD isolate is the purest form of CBD. It is made by extracting it from its natural environment - either hemp which is legal and recognized as generally safe in all states because of its low THC content (less than .3%), or the marijuana plant which has high levels of THC (up to 30%) and remains a Schedule 1 controlled substance under the Controlled Substances Act of 1970.

Unlike hemp-derived CBD Isolate, hemp-derived full-spectrum CBD contains all the hundreds of phytochemicals naturally found in the cannabis plant, including CBD, trace cannabinoids including Cannabinol (CBN), Cannabichromene (CBC), Cannabigerol (CBDA) and Cannabidivarin (CBDV), and more than 200 different terpenes, essential oils, and negligible THC content (less than 0.3%).

Research demonstrating the wide-ranging therapeutic effects of CBD oil including anti-emetic, anti-inflammatory, anxiolytic, and anti-psychotic effects were based on studies using pure doses of CBD Isolate. However, more recently it has been shown that the therapeutic effects of purified CBD display a bell-shaped dose-response curve suggesting a limited dose range, with no beneficial effects achieved at either lower or higher doses. This narrow therapeutic window presents a challenge for using CBD isolate clinically.

Based on recent research with rodents and humans, administration of a full spectrum cannabis extract containing mostly CBD but also containing other minor phytocannabinoids and non-cannabinoids exerted a synergistic effect with CBD that was both more effective than CBD Isolate without the unwanted bell-shaped dose-response curve. This finding has been named the entourage effect. However, to date, there are no human trials for any physical or mental health problem comparing the gold standard CBD isolate with a full-spectrum CBD formulation, despite the fact that both forms of CBD are widely available without a prescription in stores all across the United States. The proposed project will provide important data to determine whether a full-spectrum CBD formulation offers any advantages over CBD isolate in reducing COVID-19 stress-induced symptoms.

Specific Aims and Hypotheses:

1. Compare the efficacy of a 4-week daily regimen of hemp-derived CBD isolate (300 mg/day), broad-spectrum CBD oil, full spectrum CBD oil (300 mg/day), or placebo oil in reducing patient-rated symptoms of stress, anxiety, depression, and sleep disturbance. It is predicted that patients receiving and of the three active CBD oil formulations (pure isolate, broad-spectrum, or full spectrum CBD oil) will show significantly greater reduction in emotional distress and sleep disturbance relative to those receiving placebo oil. It is also predicted that broad-spectrum and full-spectrum CBD oil will outperform CBD isolate in reducing COVID-19 stress-induced symptoms of stress, anxiety, depression, anger, and sleep disturbance.
2. Examine predictors of patients' clinical response to the 4 treatments. It is expected that the superiority of broad-spectrum and full-spectrum CBD oil relative to CBD isolate or placebo will be more pronounced for patients showing more severe COVID-19 stress-induced symptoms at baseline.
3. Examine the perceived acceptability and side effects profile of 4 weeks of daily CBD/Placebo oil ingestion. It is expected that each of the three CBD formulations (CBD isolate, Broad-spectrum or Full spectrum CBD oil) will show minimal side effects that will not exceed the level of side effects for those ingesting placebo oil with the possible exception of somnolence.

Eligibility criteria: INCLUSION CRITERIA:

* Displays elevated symptom scores on one or more of the following established assessment instruments for depression (PROMIS-Depression), anxiety (PROMIS-Anxiety), Anger (PROMIS-Anger), sleep disturbance (PROMIS-Sleep); or Alcohol/Substance (PROMIS-Alcohol; PROMIS- Substance Use)
* Age between 18 to 70;
* Fluent in English;
* Has home access to the Internet;
* Willingness to provide signed informed consent;
* Willingness to refrain from all non-study CBD products during the 6-week study period;
* Willing to complete a brief pre-study 7-day online symptom monitoring log;
* Currently residing in the United States

EXCLUSION CRITERIA:

* History of a suicide attempt within the past 6 months
* Any medical problem that would preclude participating in the study including liver disease
* Current use of warfarin or other prescribed blood thinners,
* Currently taking seizure medications such as valproate, lamotrigine, or clobazam;
* Currently taking thyroid medications such as levothyroxine;
* Currently taking heart rhythm medications such as amiodarone;
* Currently taking anti-hypertension medications;
* Pregnant or planning to become pregnant within the next 6 weeks.
* History of adverse reaction to CBD oil or other CBD products.
* Allergic to coconut oil.

Primary outcomes:
measure: PROMIS Emotional Distress Index
timeFrame: Week 0-Baseline
measure: PROMIS Emotional Distress Index
timeFrame: Week 1-Treatment
measure: PROMIS Emotional Distress Index
timeFrame: Week 2-Treatment
measure: PROMIS Emotional Distress Index
timeFrame: Week 3-Treatment
measure: PROMIS Emotional Distress Index
timeFrame: Week 4-Treatment
measure: PROMIS Emotional Distress Index
timeFrame: Week 5-Follow-up
Secondary outcomes:
measure: PROMIS Depression Scale
timeFrame: Week 0-Baseline
measure: PROMIS Depression Scale
timeFrame: Week 1-Treatment
measure: PROMIS Depression Scale
timeFrame: Week 2-Treatment
measure: PROMIS Depression Scale
timeFrame: Week 3-Treatment
measure: PROMIS Depression Scale
timeFrame: Week 4-Treatment
measure: PROMIS Depression Scale
timeFrame: Week 5-Follow-up
measure: PROMIS Anxiety Scale
timeFrame: Week 0- Baseline
measure: PROMIS Anxiety Scale
timeFrame: Week 1-Treatment
measure: PROMIS Anxiety Scale
timeFrame: Week 2-Treatment
measure: PROMIS Anxiety Scale
timeFrame: Week 3-Treatment
measure: PROMIS Anxiety Scale
timeFrame: Week 4-Treatment
measure: PROMIS Anxiety Scale
timeFrame: Week 5-Follow-up
measure: PROMIS Anger Scale
timeFrame: Week 0- Baseline
measure: PROMIS Anger Scale
timeFrame: Week 1- Treatment
measure: PROMIS Anger Scale
timeFrame: Week 2- Treatment
measure: PROMIS Anger Scale
timeFrame: Week 3- Treatment
measure: PROMIS Anger Scale
timeFrame: Week 4- Treatment
measure: PROMIS Anger Scale
timeFrame: Week 5- Follow-up
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 0- Baseline
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 1- Treatment
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 2- Treatment
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 3- Treatment
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 4- Treatment
measure: PROMIS Alcohol Negative Consequences Scale
timeFrame: Week 5- Follow-up
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 0- Baseline
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 1- Treatment
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 2- Treatment
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 3- Treatment
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 4- Treatment
measure: PROMIS Sleep Disturbance Scale
timeFrame: Week 5- Follow-up
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 0- Baseline
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 1- Treatment
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 2- Treatment
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 3- Treatment
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 4- Treatment
measure: COVID-19 Coping Self-Efficacy
timeFrame: Week 5- Follow-up
measure: Sheehan Disability Scale
timeFrame: Week 0- Baseline
measure: Sheehan Disability Scale
timeFrame: Week 5- Follow-up
Other outcomes:
Locations:
city: Austin
country: United States
facility: University of Texas at Austin, Laboratory for the Study of Anxiety Disorders
state: Texas
Study officials:
affiliation: University of Texas at Austin
name: Michael J Telch, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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