Sublingual Cannabidiol for Anxiety

This is an open-label to double-blind study evaluating the effects of cannabidiol (CBD) for the treatment of anxiety in adults. Participants will use a sublingual (under-the-tongue) solution of whole plant-derived CBD or placebo three times daily for four weeks in addition to their normal treatment regimen. Participants' clinical state will be assessed weekly during the treatment period. In addition, cognitive function and measures of quality of life, sleep, and general health will be assessed at baseline and the post-treatment final visit.

Study Overview

• Status: Completed
• Conditions: Anxiety
• Intervention / Treatment: Drug: Full-Spectrum Cannabidiol; Drug: Single-Compound Cannabidiol; Drug: Placebo

Detailed Description

Cannabis has been used for medicinal purposes across many cultures for a range of disorders for thousands of years. The plant is comprised of a variety of components, such as phytocannabinoids, which include (among others) the major intoxicating constituent of cannabis, delta-9 tetrahydrocannabinol (THC), and cannabidiol (CBD), a major non-intoxicating constituent of cannabis. 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. 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 cannabis, a gap exists in the scientific literature regarding the effects of CBD on anxiety.

This investigation is composed of two stages. Stage 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 CBD solution 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. Stage 1 of the study was completed in early 2020.

Stage 2 of the study is a double-blind clinical trial of this solution in patients with anxiety. This double-blind trial began after the open-label trial was 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 full-spectrum CBD solution, single-compound CBD solution, or placebo solution 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 stage 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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478-9106
      • McLean Hospital Brain Imaging Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 or older
• Native English speaker or acquired English prior to age 5
• Provides informed consent
• Endorses moderate or severe anxiety at the screening visit

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
• History of head injury or loss of consciousness >5 minutes
• Current use of cannabis or cannabinoid products >1x/month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Full-Spectrum Cannabidiol; 1 ml of full-spectrum sublingual cannabidiol solution (10 mg/ml CBD) administered three times per day (TID) for four weeks.	Drug: Full-Spectrum Cannabidiol; Full-Spectrum Cannabidiol; total daily dose of 30 mg.
Experimental: Single-Compound Cannabidiol; 1 ml of single-compound sublingual cannabidiol solution (10 mg/ml CBD) administered three times per day (TID) for four weeks.	Drug: Single-Compound Cannabidiol; Single-Compound Cannabidiol; total daily dose of 30 mg.
Placebo Comparator: Placebo; 1 ml of placebo solution administered three times per day (TID) for four weeks.	Drug: Placebo; Placebo solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Self-Reported Anxiety as Assessed by the Beck Anxiety Inventory (BAI)	The BAI is a 21-item self-report measure used to rate subjective, somatic, and panic-related symptoms of anxiety on a scale of 0 to 3, with total scores ranging from 0 to 63 (higher scores indicating more anxiety).	4 Weeks
Change From Baseline in Anxiety Assessed by the Overall Anxiety Severity and Impairment Scale (OASIS)	The OASIS is a brief 5-item measure used to evaluate the functional impairment cause by anxiety that will be given on a weekly basis; the frequency and intensity of anxiety, as well as the degree of avoidance and interference with work and social function are rated on a scale of 0 to 4; total scores range from 0 to 20 (higher scores indicating more anxiety).	4 Weeks
Change From Baseline in Self-Reported Anxiety Assessed by the State-Trait Anxiety Inventory (STAI)	This self-report measure is comprised of two 20-item scales (STAI-State and STAI-Trait), with a range of four possible responses from 1 to 4 (higher scores indicating more anxiety), and differentiates between the more temporary condition of "state" anxiety and the more general quality of "trait" anxiety. Total scores on each scale range from 20-80, with higher scores indicating more anxiety.	4 Weeks
Change From Baseline in Anxiety Measured by the Hamilton Anxiety Scale (HAM-A)	This observer-rated 14-item scale is administered in the form of an interview, and allows information from multiple sources to influence ratings (i.e. subject report, examiner's observation), and has been shown to be reliable index of clinical state. A range of 5 possible responses (0-4, not present-very severe) are possible for each item, with a total score range of 0-56 with higher scores indicating more anxiety.	4 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Depressive Symptoms Assessed by the Beck Depression Inventory (BDI)	The BDI is a 21 item-self-report measure that can be used to assess the severity of depression. Each item on the BDI relates to a symptom of depression and is rated by the subject using a 0-3 scale (higher scores indicating increased severity), with a total score range of 0-63.	4 Weeks
Change From Baseline in Sleep Quality Assessed by the Pittsburgh Sleep Quality Index (PSQI)	The PSQI contains 19 self-rated questions that assess sleep quality and disturbance over the previous 1-month period. The 19 items yield seven component scores such as sleep latency, sleep duration, and daytime dysfunction, which are then summed to generate a global score ranging from 0-21 (higher scores indicating lower sleep quality).	4 Weeks
Patient's Global Impression of Change (PGIC) Scale Score at Week 4	The PGIC is a single-question, 7-point scale depicting a patient's rating of overall improvement since baseline from "very much worse" (score=1) to "very much improved" (score=7). Higher scores indicate greater improvement.	Week 4

Collaborators and Investigators

• Sponsor: Staci Gruber, Ph.D.
• Investigators: Principal Investigator: Staci Gruber, PhD., McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: September 4, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimated): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 2015P000959

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No