Use of CBD in the Treatment of Anxiety

Average CBD dose (mgs) used in the titration phase as reported in participant forms.

This trial will inform the dosing of a CBD hemp-based product and its major metabolites following single and multiple doses of a CBD extract (from 50 to 150 mg/day of CBD) among individuals with anxiety. The treatment period will consist of a two-week titration period followed by a 2- week maintenance period. Standardized questionnaires will be used to examine adherence to dosing protocol and potential changes due to side effects. During the titration phase, participants will be instructed to use an initial dosing of 50 mg/day in the morning progressively increasing 50 mg CBD/day before bedtime as tolerated by the individual participant, up to 150 mg/day by day 14. If a patient experiences mild side effects at doses at or higher than 50 mg daily, the investigators will monitor and may consider temporarily or permanently reducing the dose for the remainder of the study to the doses tolerated. Participants will report the daily doses used on a weekly basis in a dosing sheet.

Average CBD dose (mgs) used in the maintenance phase as indicated and reported in participant forms.

This trial will inform the dosing of a CBD hemp-based product and its major metabolites following single and multiple doses of a CBD extract (50 to 150 mg/day of CBD) among individuals with anxiety. The treatment period will consist of a two-week titration period followed by a 2- week maintenance period. Standardized questionnaires will be used to examine adherence to dosing protocol and potential changes due to side effects. During the maintenance phase, participants will stay at the optimal tolerated dose (between 50-150 mg) for two additional weeks. If a patient experiences mild side effects at doses at or higher than 50 mg daily, the investigators will monitor and may consider temporarily or permanently reducing the dose for the remainder of the study to the doses tolerated. Participants will report the daily doses used on a weekly basis in a dosing sheet.

Percentage of Severity of treatment-related adverse events based on the side effects/adverse events checklist, laboratory test, and self-report of unexpected ADE

The safety and tolerability will be determined in eight-assessments conducted during a 12-week period, and based on the side effects/adverse events checklist, laboratory tests, and self-reports of unexpected adverse drug events (ADEs). The type of treatment-related adverse events based will be characterized based on those assessments. The side effects/adverse events will be categorized as: no ADEs, mild (i.e., no intervention required; no impact on activities of daily living), moderate (minimal, local, or non-invasive intervention indicated; moderate impact on activities of daily living) or severe (i.e., significant symptoms requiring invasive intervention; subject seeks medical attention, needs major assistance).

Percentage of patients reporting Drug-Induced Liver Injury based on liver chemistries

In this study, patients are going to be followed for 84 days after treatment initiation, with serum liver chemistries assessments at baseline, and in four subsequent visits (visits 3, 5, 6 and 8), with the last serum liver chemistries 49 days after the last doses. The result is reported as the number of participants that had a clinically significant clinically significant elevation in serum liver chemistries (i.e., Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) or alkaline phosphatase (ALP) \>2 times ULN, Total serum bilirubin \>2.5 mg/dL with elevated AST, ALT or ALP; or International normalized ratio (INR) \>1.5 with elevated AST, ALT or ALP.

Change in anxiety symptoms scores based on the Hamilton Anxiety Rating Scale.

This study will provide preliminary evidence of the independent and concomitant effects of CBD on anxiety symptoms among individuals with moderate to severe anxiety. Anxiety symptoms will be assessed over the 12-week period using the Hamilton Anxiety Rating Scale (HAM-A). This scale consists of 14 symptom-defined elements, and caters for both psychological (e.g., fears, anhedonia) and somatic (e.g., tachycardia, chest tightness) symptoms. Each item is scored on a basic numeric scoring of 0 (not present) to 4 (severe). HAM-A score ranges are: mild anxiety = 8-14; moderate = 15-23; severe 24 or more. Scores below 8 were considered to represent no/minimal anxiety. For this study the HAM-A test will be conducted during eight assessments in the 12-week study period.

Change in perceived severity of anxiety symptoms and functionality based on the Clinical Global Impression.

This study will assess the change in perceived severity of anxiety symptoms and functionality based on the Clinical Global Impression (CGI). The CGI is a 3-item scale that assesses the patient's functioning prior to and after initiating medication in trials which is an important part of the study process. Its 3 items assess, 1) Severity of Illness (CGI-S), 2) Global Improvement (CGI-I), and 3) Efficacy Index (CGI-E, which is a measure of treatment effect and side effects specific to drugs that were administered). For this study the CGI test will be conducted during eight assessments in the 12-week study period.

Change in generalized anxiety symptoms and severity based on the Generalized Anxiety Disorder 7 scale

This study will provide preliminary evidence of the independent and concomitant effects of CBD on generalized anxiety symptoms among individuals with moderate to severe anxiety using the Generalized Anxiety Disorder 7 (GAD 7). This 7-items scale with strong criterion validity is useful for identifying probable cases of GAD and assessing its severity. Increasing scores on the GAD-7 are strongly associated with multiple domains o symptoms will be assessed over the 12-week study period.

Change in sleep quality and disturbances based on the Pittsburgh Sleep Quality Index (PSQI):

This study will provide preliminary evidence of the independent and concomitant effects of CBD on improving sleep based on the Pittsburgh Sleep Quality Index (PSQI). This 19-item scale assesses sleep quality and disturbances over a 1-week time interval. The items generate seven "component" scores, including: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.