Sublingual Cannabidiol for Anxiety

Cannabis has been used for medicinal purposes across many cultures for a range of disorders
dating as far back as 2700 B.C. The plant is comprised of a variety of components, including
phytocannabinoids that act on CB1 and CB2 receptors. Numerous phytocannabinoids are present
in cannabis, including the major psychoactive constituent of cannabis, delta-9
tetrahydrocannabinol (THC), which acts as a CB1 receptor agonist. Another phytocannabinoid,
cannabidiol (CBD), is a major non-psychoactive constituent of cannabis and is only a partial
agonist at CB1 receptors. Increasing evidence indicates that CBD in particular may have
significant medicinal properties and benefits; experimental studies in both animals and
humans have demonstrated that CBD can act as an anticonvulsant, antipsychotic, and muscle
relaxant. CBD is often found in higher levels in products dispensed as medical marijuana
relative to strains used primarily for recreational use. Several studies have demonstrated
that CBD produces acute anxiolytic effects in animals and humans, although thus far no
clinical trials of CBD have been conducted in patients with anxiety. As a growing number of
states are legalizing medical marijuana, a gap exists in the scientific literature regarding
the effects of CBD on anxiety.

This investigation is composed of two phases. Phase 1 is comprised of a four-week, open label
clinical trial of a high-CBD containing compound in individuals with anxiety. Participants
will be pre-screened by phone in order to evaluate their eligibility for the study. If
approved, participants will come to the hospital for a baseline/screening visit, and will
complete a structured clinical interview, clinical and quality of life questionnaires, and
cognitive assessments. Enrolled participants will be given tincture to use for the duration
of the study; participants will be instructed to self-administer 1 milliliter (ml) of the
tincture under the tongue three times per day for four weeks. Throughout the treatment
period, participants will return to the hospital on a weekly basis to complete questionnaires
about their mood and quality of life. Participants will also return to the hospital for a
final visit after four weeks of treatment to complete additional questionnaires and cognitive
assessments.

Phase 2 of the study is a double-blind clinical trial of this tincture in patients with
anxiety. This double-blind trial will begin after the open-label trial has been completed. In
the same manner as the open-label trial, participants will be pre-screened by phone, and
approved participants will come to the hospital for a baseline/screening visit to complete a
structured clinical interview, questionnaires, and cognitive assessments. Eligible
participants will also have the option to complete an hour-long MRI scan at the baseline and
final visits. Enrolled participants will receive either CBD tincture or placebo tincture to
self-administer throughout the four week treatment period, as described above. Participants
will return to the hospital weekly during the treatment period to complete questionnaires
about their mood and quality of life. Participants in this phase of the study will also
return for a final visit after four weeks of treatment to complete additional questionnaires,
cognitive assessments, and an optional hour-long MRI scan.

Inclusion Criteria:

- 18 or older

- Native English speaker or acquired English prior to age 5

- Provides informed consent

Exclusion Criteria:

- Non-native English speakers

- Estimated IQ < 75

- Pregnancy

- Presence of serious medical illness, including liver or kidney disease, neurological
disorder, or certain psychiatric disorders