A Pilot Trial of Nabilone for the Treatment of Obesity

Impact of Chronic Nabilone Self-administration on Body Weight, Metabolic Markers, Gut Microbiota, and Neural Circuitry in Human Obesity

Obesity is a serious health problem which increases the likelihood of developing other life-changing medical conditions. Despite increasing knowledge about the neural and metabolic basis of obesity, the development of effective anti-obesity treatment strategies has been a challenge. Evidence shows an association between cannabis consumption and body weight. However, to date, no human trials have assessed the potential of cannabis-like compounds to reduce body weight in individuals who are obese. This pilot trial aims to determine the safety and feasibility of administering nabilone (a cannabinoid drug similar to the active component of cannabis) to patients who are obese. Our secondary aims are to determine if nabilone is effective in reducing weight in this population, and to probe potential mechanisms of the weight-loss-promoting effects of nabilone, such as neural reactivity to food stimuli, changes in gut bacteria, and changes in metabolic biomarkers.

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Nabilone

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Center for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Obese adults (BMI > 30.0 kg/m2).
• For the optional imaging component of the study, a maximum weight (315 lbs) and a maximum girth in line with capacity of the machine (60 cm horizontal and 45 cm vertical; therefore, circumference of scanner is 166.6 cm)
• For women of reproductive potential (WORP) and men whose sexual partners are WORP: use of adequate methods of contraception (effective barrier methods such as male condoms, female condoms, cervical caps, diaphragms, or contraceptive sponges; and highly effective methods of contraception such as oral hormonal contraceptives, intrauterine devices (IUDs), vasectomy, or tubal ligation)
• AST/ALT, bilirubin, and kidney function tests within normal limits at screening.

Exclusion Criteria:

• Unstable gastrointestinal, respiratory, endocrinological, cardiovascular or cerebrovascular diseases that would prevent participation in the trial at QI (or its delegate) discretion,
• Unstable major psychiatric disorder(s) (i.e. Axis I Disorders) that would prevent participation in the trial at QI (or its delegate) discretion,
• Current substance use disorders (DSM-V) (excluding tobacco and caffeine),
• History of, or current neurological illnesses, that would prevent participation in the trial,
• Current use or use during the previous month of antipsychotic medications,
• Learning disability, amnesia or other conditions that impede memory and attention,
• Visual impairments that prevent participation in the study,
• Personal or family history of schizophrenia, or psychosis (or psychosis-related) disorders,
• Antibiotic use in the last 4 weeks,
• Previous bariatric surgery,
• Current use or use in the past month of other weight-loss pharmaceuticals,
• Cannabis use in last 6 months,
• Known sensitivity to cannabis or other cannabinoid agents,
• Pregnancy or lactation (females), and

• For the optional imaging component of the study:

  • Presence of metal implants or objects unsafe for MRI such as cardiac pacemakers, metal fragments in the eye, and aneurysm clips in your brain
  • Piercings or jewelry that are unable to be removed
  • Tattoos inked with metal dyes

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Six placebo capsules taken orally twice daily
Experimental: Low-Dose Nabilone; pms-nabilone titrated to 2 mg daily	Drug: Nabilone; Titrated to two 0.5 mg capsules and four placebo capsules taken orally twice daily (Low-Dose) OR Titrated to six 0.5 mg capsules taken orally twice daily (High-Dose)
Experimental: High-Dose Nabilone; pms-nabilone titrated to 6 mg daily	Drug: Nabilone; Titrated to two 0.5 mg capsules and four placebo capsules taken orally twice daily (Low-Dose) OR Titrated to six 0.5 mg capsules taken orally twice daily (High-Dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of SAEs per treatment arm	Number of SAEs collected to assess nabilone safety	12 weeks of treatment
Number of dropouts per treatment arm	Number of dropouts collected to assess feasibility of study design and intervention	12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Change in body weight	Baseline, then weekly for 12 weeks of treatment
Abdominal fat	Change in abdominal fat, as measured by abdominal MRI	One scan at baseline and one scan at Week 12
Blood glucose levels	Change in metabolic biomarker (blood levels of glucose)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood insulin levels	Change in metabolic biomarker (blood levels of insulin)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood triglyceride levels	Change in metabolic biomarker (blood triglyceride levels)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood cholesterol levels	Change in metabolic biomarker (blood levels of HDL and LDL)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood leptin levels	Change in hunger-related hormones (blood levels of leptin)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood ghrelin levels	Change in hunger-related hormones (blood levels of ghrelin)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Blood PYY levels	Change in hunger-related hormones (blood levels of PYY)	Blood drawn at baseline, Week 5, Week 9, and Week 12
Gut microbiota	Stool samples collected for quantification of gut microbiome composition	Baseline, Week 12
Neural reactivity to food vs. control stimuli	Task-based fMRI to determine differences in neural reactivity to food vs. control pictures	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Bernard Le Foll, MD, PhD, Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: March 4, 2021
• First Submitted That Met QC Criteria: March 12, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Nabilone
• Other Study ID Numbers: 084/2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No