Investigating the Effects of Nabilone on Endocannabinoid Metabolism

Healthy Clinical Trial

— NABI  

Official title:

Investigating the Effects of Nabilone on Endocannabinoid Metabolism in the Human Brain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05885685
• Other study ID #: 098-2017
• Secondary ID: CAMHPET-CTA-109
• Status: Recruiting
• Phase: Phase 4
• Start date: October 31, 2023
• Est. completion date: October 2026

Study information

• Verified date: February 2024
• Source: Centre for Addiction and Mental Health
• Contact: Raesham Mahmood, BSc
• Phone: 416-535-8501
• Email: Raesham.Mahmood[@]camh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn about the effects of a cannabis-like substance, nabilone, on the levels of endocannabinoid enzyme fatty acid amide hydrolase (FAAH) in brain of healthy individuals. Using magnetic resonance imagine (MRI) and positron emission tomography (PET), the main questions we aim to answer are: 1) Does nabilone decrease levels of FAAH in the brain? and 2) Are changes in levels of FAAH associated with clinical response to nabilone? Participants will complete:

• An in-person interview (~4 hours)

• Two brain imaging scanning sessions (~11 hours)

• A one week 2 mg titrated dose of nabilone

• Virtual check-ins (up to ~1.5 hours)

Description:

There is limited data regarding the effect of exogenous cannabinoids, such as tetrahydrocannabinol (THC), on the endogenous cannabinoid system (eCS). Specifically, we do not know whether brain levels of fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid anandamide, is affected by sub-chronic THC exposure.

Our primary objective is to use positron emission tomography (PET) imaging of the FAAH probe [11C]CURB to test the hypothesis that exposure to nabilone, a synthetic THC analogue, will reduce FAAH levels in the brain. Our secondary objective is to investigate whether reductions in FAAH levels are related to clinical response to nabilone.

Participant eligibility will be assessed through a series of questionnaires and assessments on medical, family, psychiatric and alcohol and drug use history. Individuals will also be required to provide blood and urine samples which we will test for recent drug use and pregnancy in female participants. Thirty healthy participants will complete one magnetic resonance imaging scan and two PET scans with [11C]CURB: one at baseline prior to nabilone administration and one approximately 4 weeks apart following a one week, 2 mg titrated dose of nabilone. Venous and arterial blood draws will be done during PET scans to measure FAAH genotype and plasma radiometabolites, respectively. Mood assessments will also be administered at these visits. During the nabilone dosing period, we will meet virtually with participants to check-in and monitor their tolerance and compliance.

Understanding whether recent nabilone exposure affects FAAH levels in brain may help to explain variability in clinical response to THC, the main psychoactive component in cannabis. This information can help guide therapeutic use of cannabis and cannabinoid derivatives, and aid in the development of evidence-based medicine targeting the eCS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged 19-65 years old. For safety reasons, we will ask participants to provide photo ID showing birthdate, in order to verify age.

• The ability to tolerate complete dosing regimen of nabilone (2mg titrated, 1 week course)

• Able to sign and date informed consent form.

• Willing and able to complete study as described in protocol

Exclusion Criteria:

• Serious, unstable medical condition including but not limited to cerebrovascular, renal, hepatic and coronary heart disease;

• Coagulation/Blood Disorders or use of anticoagulant medication

• Past or current neurological illness or head trauma;

• Lifetime diagnosis of DSM-5 Axis I psychiatric conditions including mood, anxiety, eating, somatoform and/or psychotic disorders and substance abuse and/or dependence;

• Suicidality or history of suicide attempts;

• Family history of psychotic disorders (first degree relative with a psychotic disorder);

• Current use (~30 days) of drugs of abuse that may affect the CNS, including cannabis;

• Tobacco dependence (Fagerstrom Test for Nicotine Dependence >4);

• Pregnancy or breastfeeding;

• Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning;

• Claustrophobia;

• Known sensitivity to marijuana or other cannabinoid agents;

• Are on medications known to interact with nabilone such as: diazepam, sodium secobarbital, alcohol, codeine, any medications that affect mental and/or psychomotor function;

• Positive during drug screening for drugs of abuse;

• Exposure to radiation <20 mSv in the last 12 months and a number of PET scans that, including the number of PET scans under this protocol, will bring the total to more than 8 PET scans/lifetime, exceeding permissible limit for subjects participating in research set by Brain Health Imaging Centre Guideline;

• Participant has any other problem that, in the investigators opinion, would preclude participation in the trial;

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Nabilone Oral Capsule
Each oral capsule contains a 0.25 mg dose of nabilone. Participants begin by taking 1 capsule at night then 1 capsule in the morning and 1 at night for the next 2 days. On the 4th day, the dose is doubled. On the 6th day, the dose is doubled again.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[11C]CURB binding in the brain	Change in levels of [11C]CURB binding in the brain as indicated by the lambda k3 value from baseline to post-nabilone	4 weeks
Secondary	[11C]CURB decreases related to mood related assessments	Changes in mood related assessment Profile of Mood States (POMS) scores from baseline to post-nabilone. Negative subscales include tension (9 items, range 0-36), depression (15 items, range 0-60), fatigue (7 items, 0-28), confusion (7 items, range 0-28), and anger (12 items, range 0-48). Positive subscale includes vigor (8 items, range 0-32).	4 weeks
Secondary	[11C]CURB decreases related to drug-related effects	Changes in drug-related assessment Addiction Research Center Inventory (ARCI) scores from baseline to post-nabilone (81 items, range 0-81) with higher score indicating greater drug-related effects.	4 weeks
Secondary	[11C]CURB decreases related to drug-related effects	Changes in drug-related assessment Visual Analogue Scales (VAS) score from beginning of nabilone administration period to end of nabilone administration period. Score can range from a minimum of 0 (no pain) to a maximum of 10 (pain as bad as it could possibly be).	1 week
Secondary	[11C]CURB related to blood measurements of endocannabinoids	Changes in blood measurements of endocannabinoids such as anandamide post-nabilone administration from baseline to post-nabilone.	4 weeks