Role of CBD in Regulating Meal Time Anxiety in Anorexia Nervosa

• ClinicalTrials.gov Identifier: NCT04878627
• Recruitment Status: Recruiting
• First Posted: May 7, 2021
• Last Update Posted: February 8, 2023
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Guido Frank, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa	Drug: Cannabidiol; Drug: Placebo	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Placebo-controlled, randomized, double-blind study
• Masking: Double (Participant, Investigator)
• Masking Description: The PI and research coordinator administering the medication will be blinded to the randomization schedule. The research subject will be blinded to what medication she receives.
• Primary Purpose: Treatment
• Official Title: The Role of Cannabidiol in Regulating Meal Time Anxiety in Anorexia Nervous: Safety, Tolerability and Pharmacokinetics
• Actual Study Start Date: January 20, 2022
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cannabidiol (CBD); 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; patients receive cannabidiol at various doses for 3 weeks; Other Name: Epidiolex
Placebo Comparator: Placebo; 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; patients receive placebo for 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Committee of Clinical Investigations UKU-Side Effect Scale Week 1 [ Time Frame: After completion of Week 1 of treatment ]
   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.
2. Committee of Clinical Investigations UKU-Side Effect Scale Week 2 [ Time Frame: After completion of Week 2 of treatment ]
   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.
3. Committee of Clinical Investigations UKU-Side Effect Scale Week 3 [ Time Frame: After completion of Week 3 of treatment ]
   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.
4. Blood tests for cannabinol (CBD) metabolites Week 1 [ Time Frame: After Completion of Week 1 of treatment ]
   Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values.
5. Blood tests for cannabinol (CBD) metabolites Week 2 [ Time Frame: After completion of Week 2 of treatment ]
   Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values.
6. Blood tests for cannabinol (CBD) metabolites Week 3 [ Time Frame: After completion of Week 3 of treatment ]
   Blood levels for CBD, 6-OH-CBD, 7COOH-CBD, THC. The results will be compared to standard laboratory values.
7. Change from baseline scores of Eating Disorder Examination Questionnaire (EDE-Q) over the course of treatment [ Time Frame: Weekly for the duration of the project (three weeks) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female individuals will be enrolled. Gender eligibility is based on biological sex of participants.
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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)
2. Have a duration of illness ≥ 6 months
3. Be medically stable as assessed by a comprehensive medical and behavioral evaluation conducted by a study physician

Exclusion Criteria:

1. Psychotic illness/other mental illness requiring inpatient hospitalization
2. Current dependence on drugs or alcohol
3. Physical conditions (e.g., diabetes mellitus, pregnancy) known to influence eating or weight or liver disease which may affect pharmacokinetics of the study drug
4. Use of other psychoactive medications
5. Significant changes in medication in past month
6. Expression of acute suicidality
7. Previous hypersensitivity reaction to Epidiolex or any of its constituents

Contacts and Locations

Contacts

Contact: Megan E Shott, BS; 858-246-5272; mshott@health.ucsd.edu

Locations

United States, California

University of California San Diego; Recruiting

San Diego, California, United States, 92121

Contact: Megan E Shott, BS 858-246-5272 mshott@health.ucsd.edu

Contact: Guido Frank, MD gfrank@health.ucsd.edu

Principal Investigator: Guido Frank, MD

Sponsors and Collaborators

University of California, San Diego

Investigators

• Principal Investigator: Guido K Frank, MD; University of California, San Diego

More Information

Publications:

Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K. Comorbidity of anxiety disorders with anorexia and bulimia nervosa. Am J Psychiatry. 2004 Dec;161(12):2215-21. doi: 10.1176/appi.ajp.161.12.2215.

Ando T, Tamura N, Mera T, Morita C, Takei M, Nakamoto C, Koide M, Hotta M, Naruo T, Kawai K, Nakahara T, Yamaguchi C, Nagata T, Ookuma K, Okamoto Y, Yamanaka T, Kiriike N, Ichimaru Y, Ishikawa T, Komaki G; Japanese Genetic Research Group For Eating Disorders. Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population. Mol Genet Genomic Med. 2014 Jul;2(4):313-8. doi: 10.1002/mgg3.69. Epub 2014 Feb 24.

Tambaro S, Bortolato M. Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives. Recent Pat CNS Drug Discov. 2012 Apr 1;7(1):25-40. doi: 10.2174/157488912798842269.

Rong C, Lee Y, Carmona NE, Cha DS, Ragguett RM, Rosenblat JD, Mansur RB, Ho RC, McIntyre RS. Cannabidiol in medical marijuana: Research vistas and potential opportunities. Pharmacol Res. 2017 Jul;121:213-218. doi: 10.1016/j.phrs.2017.05.005. Epub 2017 May 10.

Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52. doi: 10.1038/sj.bjp.0704327.

• Responsible Party: Guido Frank, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT04878627
• Other Study ID Numbers: 191570
• First Posted: May 7, 2021
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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.: Yes

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders; Cannabidiol; Anticonvulsants