Role of CBD in Regulating Meal Time Anxiety in Anorexia Nervosa

Study Overview
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Brief Summary
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No studies of cannabidiol (CBD) have focused on Anorexia Nervosa (AN). Dose, side effects, tolerability, acceptability of pure CBD in AN must be established. The current study is an important first step in the investigation of CBD for AN. Cannabis products have been recently legalized in many states, and CBD in particular has been shown to reduce anxiety. Therefore, CBD may represent a promising new treatment for AN. The endocannabinoid system is involved in the regulation of functions relevant to eating disorders. Furthermore, data suggest that eating disorders are associated with alterations of the endocannabinoid system. Prior attempts to target the endocannabinoid system in AN have focused on CB1 receptor agonists that can increase anxiety. Moreover, CBD may be particularly beneficial in decreasing anxiety in AN via its action at serotonin receptors. Lastly, the impact of CBD on eating behavior and weight in AN must be determined. The current study seeks to explore these hypotheses using the aims in the following section.

Official Title
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The Role of Cannabidiol in Regulating Meal Time Anxiety in Anorexia Nervous: Safety, Tolerability and Pharmacokinetics

Conditions
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Anorexia Nervosa

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must currently meet DSM-5 criteria for AN-R and AN Spectrum Disorders (i.e., Atypical AN) based on the Structured Clinical Interview for the DSM-5 (SCID-5-RV) Have a duration of illness ≥ 6 months Be medically stable as assessed by a comprehensive medical and behavioral evaluation conducted by a study physician Exclusion Criteria: Psychotic illness/other mental illness requiring inpatient hospitalization Current dependence on drugs or alcohol Physical conditions (e.g., diabetes mellitus, pregnancy) known to influence eating or weight or liver disease which may affect pharmacokinetics of the study drug Use of other psychoactive medications Significant changes in medication in past month Expression of acute suicidality Previous hypersensitivity reaction to Epidiolex or any of its constituents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-controlled, randomized, double-blind study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol (CBD)<br>Days 1 to 7: Patients will receive CBD 2.5 mg/kg in divided doses BID for 7 days. Days 8 to 14: Patients will receive an increase dose of 7.5 mg/kg of CBD in divided doses. Days 15 to 21: Patients will receive an increased dose of 12.5 mg/kg CBD, in divided doses. If patients experience dose limiting side-effects, they ill be maintained on the lowest tolerated dose. | Drug: Cannabidiol<br>* patients receive cannabidiol at various doses for 3 weeks<br>* Other names: Epidiolex;|
| Placebo Comparator: Placebo<br>Days 1 to 7: Patients will receive placebo in divided doses BID for 7 days. Days 8 to 14: Patients will continue to receive placebo in divided doses. Days 15 to 21: Patients will receive continue to receive placebo in divided doses. | Drug: Placebo<br>* patients receive placebo for 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Committee of Clinical Investigations UKU-Side Effect Scale Week 1 | The Committee of Clinical Investigations (UKU) scale is used to rate psychiatric (e.g., depression, failing memory, concentration difficulty), neurological (e.g., rigidity, tremor, epileptic seizure), and autonomic (e.g., nausea, diarrhea, tachycardia) side effects, plus others. Higher scores indicate more side effects. | After completion of Week 1 of treatment | 
| Committee of Clinical Investigations UKU-Side Effect Scale Week 2 | The Committee of Clinical Investigations (UKU) scale is used to rate psychiatric (e.g., depression, failing memory, concentration difficulty), neurological (e.g., rigidity, tremor, epileptic seizure), and autonomic (e.g., nausea, diarrhea, tachycardia) side effects, plus others. Higher scores indicate more side effects. | After completion of Week 2 of treatment | 
| Committee of Clinical Investigations UKU-Side Effect Scale Week 3 | The Committee of Clinical Investigations (UKU) scale is used to rate psychiatric (e.g., depression, failing memory, concentration difficulty), neurological (e.g., rigidity, tremor, epileptic seizure), and autonomic (e.g., nausea, diarrhea, tachycardia) side effects, plus others. Higher scores indicate more side effects. | After completion of Week 3 of treatment | 
| Blood tests for cannabinol (CBD) metabolites Week 1 | Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values. | After Completion of Week 1 of treatment | 
| Blood tests for cannabinol (CBD) metabolites Week 2 | Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values. | After completion of Week 2 of treatment | 
| Blood tests for cannabinol (CBD) metabolites Week 3 | Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values. | After completion of Week 3 of treatment | 
| Change from baseline scores of Eating Disorder Examination Questionnaire (EDE-Q) over the course of treatment | Assesses the change from baseline in BMI, Eating Restraint, Eating Concern, Shape Concern, Weight Concern over the course of treatment. Each of those subscales is rated between 0 and 5. Subscales are calculated based on the average scores for the respective subscale. Higher scores indicate poorer outcome. | Weekly for the duration of the project (three weeks) |