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:
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.
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.
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.