This study will examine the doses, safety, and test the preliminary efficacy of hemp-derived CBD product for improving anxiety symptoms and sleep disturbances among individuals with anxiety. A 4-week, randomized, double-blind, placebo-controlled trial will be conducted to determine the safety, tolerability, preliminary efficacy, and acceptability of 50 to 150 mg/day of CBD. The treatment period will consist of a two-week titration period followed by a 2- week maintenance period. In addition, the study seeks to examine whether changes in sleep disturbances precede changes in anxiety symptoms.
Approximately one-third (33.1%) of Americans will experience an anxiety disorder at some point in their lifetime. Anxiety disorders are primarily treated with antidepressants or benzodiazepines, but unfortunately, many patients report a partial response or cannot tolerate the side effects of these medications, which include risk for abuse, cognitive impairment, and even death. The therapeutic potential of various compounds derived from the Cannabis sativa plant has generated considerable interest, particularly for managing neuropsychiatric disorders that have limited treatment options. Among these compounds, tetrahydrocannabinol (THC) and cannabidiol (CBD), have received significant attention. CBD has shown a unique pharmacological profile that lacks the potential for abuse associated with THC. Animal and small-scale human studies have demonstrated CBD's anxiolytic, antidepressant, panicolytic, and anticompulsive actions, however more research is needed to investigate the mechanisms of action and determine whether these products represent a safe and effective option for the treatment of anxiety. This study will examine the safety and test the preliminary efficacy of hemp-derived CBD product for improving anxiety symptoms and sleep disturbances among individuals with anxiety. A 4-week, randomized, double-blind, placebo-controlled trial will be conducted to determine the safety, tolerability, efficacy, and acceptability of 50 to 150 mg/day of CBD. The treatment period will consist of a two-week titration period followed by a 2- week maintenance period. Standardized questionnaires, blood, and urine exams will be used to comprehensively monitor adverse drug events. Clinical measurements will be performed to assess changes in anxiety and sleep quality. This study will also examine whether changes in sleep disturbances precede changes in anxiety symptoms. Participants will complete a comprehensive evaluation for the assessment of relevant medical history, and concomitant medication use. This study will provide information about the dosing and safety profile of a CBD hemp-based product and its major metabolites following single and multiple doses of a CBD extract among individuals with anxiety. In addition, the study will provide preliminary evidence of the independent and concomitant effects of CBD on anxiety symptoms and sleep patterns among individuals with anxiety and finally will assess the feasibility and acceptability of study procedures, including dosing, adherence to the study protocols, and the assessment of anxiety symptoms and sleep disturbances measurements over time.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
30
Participants will be given the study drug in a titrated method of 50-150mgs per day for 4 weeks
Partcipants will be given placebo substance to be taken with titrated instructions that mimic IP dispensing method daily for 4 weeks
University of Florida
Gainesville, Florida, United States
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.
Time frame: From enrollment to the end of titration phase at 2 weeks (Day 1 to Day 14).
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.
Time frame: From week 2 to the end of maintenance phase at 4 weeks (Day 15 to Day 28)
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).
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84)
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.
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84).
Percentage of severity of depression symptoms based on the Patient Health Questionnaire-9
The Patient Health Questionnaire-9 is a 9-item scale useful for the assessment of the presence and severity of depressive symptom, and a possible depressive disorder. Each of the nine items reflects a DSM-5 symptom of depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively.
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84).
Percentage of participants reporting suicidal ideation and behavior based on the Columbia Suicide Severity Rating Scale
The Columbia Suicide Severity Rating Scale (C-SSRS) is a 6-item scale that assesses suicidal ideation and behavior by helping to identify specific behaviors that may be indicative of an individual's intent to kill oneself. Four constructs are measured, including: severity of ideation, intensity of ideation, behavior and lethality.
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84).
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.
Time frame: From enrollment to the end of treatment at 4 weeks
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.
Time frame: From enrollment to the end of treatment at 4 weeks
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.
Time frame: From enrollment to the end of treatment at 4 weeks.
Change in sleep quality and disturbances based on the Pittsburgh Sleep Quality Index (PSQI):
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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.
Time frame: From enrollment to the end of treatment at 4 weeks.
Changes in insomnia symptoms based on the Insomnia Severity Index.
This study will provide preliminary evidence of the independent and concomitant effects of CBD on improving sleep based on the following self-report assessments. Changes in insomnia symptoms will be estimated using the Insomnia Severity Index (ISI). This 7-item scale assesses the severity of sleep-onset and sleep maintenance difficulties (both nocturnal and early morning awakenings), satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28. A higher score suggests more severe insomnia.
Time frame: From enrollment to the end of treatment at 4 weeks.
Average of acceptability to study procedures score based on feasibility and acceptability study forms
This study will collect data on the acceptability of the study procedures which examine adherence to the study protocols, including acceptability of study procedures (e.g., adjustment of daily activities to participate in the study and levels of engagement) using standardized forms designed by the research team and based on prior studies. The form is a 7-point 15 item scale that will be conducted during six in-person and two phone assessments.
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84).
Percentage of participants reporting levels of adherence to study procedures based on feasibility and acceptability study forms
This study will collect weekly data on the feasibility and acceptability (F\&A) form of the study procedures which examine levels (low, middle and high) of adherence to the study protocols, including missing doses and adherence to procedures (e.g., completion of lab and questionnaire assessments, adherence to recommended doses) using a 15-item standardized form designed by the research team and based on prior studies. Patients will be asked to return unused medications every other week when the new product is dispensed. The research team will check the returned medications against the usage recorded. Any discrepancies will be discussed with the patient and documented accordingly within the patient's source documents.
Time frame: From enrollment to the end of the study period at 12 weeks (Day 1 to Day 84).