Cannabinol Use in Patients With Insomnia Disorder

Study Overview
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Brief Summary
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This study aims to investigate the acute effects of cannabinol (CBN) 30 mg and 300 mg, versus placebo, on sleep architecture and next-day functioning in adults aged 25-65 years with chronic insomnia disorder.

Detailed Description
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This is a randomised, double-blind, placebo-controlled, three-arm, crossover, single-centre, proof-of-concept study in twenty participants with chronic insomnia disorder (as per clinician diagnosis and Insomnia Severity Index [ISI] Score ≥15). Across three overnight treatment sessions, participants will receive single dose oral liquid 30 mg cannabinol (CBN), 300 mg CBN, and matched placebo. Participants will undergo overnight sleep assessment using in-laboratory polysomnography (PSG) to examine CBN-related changes to sleep parameters; and various objective and subjective measures of sleep and next-day neurobehavioral function. Each treatment session will be separated by the two-week washout period.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Single-dose, Crossover, Pilot Study Investigating the Effects of Cannabinol (CBN) 30 mg and 300 mg on Sleep Architecture and Next-day Function in Insomnia Disorder

Conditions
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Insomnia Disorder

Intervention / Treatment
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* Drug: 30 mg Cannabinol (CBN)
* Drug: 300 mg Cannabinol (CBN)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 25 - 65 years of age Insomnia Severity Index (ISI) score ≥ 15 at eligibility screening Insomnia disorder (symptoms occurring at least 3 times per week and present for longer than 3 months) as determined by the study physician Ability to take oral medication Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Exclusion Criteria: Medical condition or medication that is the cause of the insomnia disorder as determined by the study physician Known hypersensitivity to cannabis or cannabinoid products (including if this becomes evident during the trial) Reported use of cannabis or cannabinoid products within the past 3 months as confirmed by at least one negative urine drug screen (UDS) (or at the study physician's discretion) Sleep apnoea (defined as Apnoea Hypopnea Index [AHI] > 15 and Oxygen Desaturation Index [ODI]>10) as confirmed by polysomnography at screening Sleep-related movement disorder as determined by the study physician Delayed or advanced sleep phase syndrome (based on actigraphy and sleep diary) as confirmed during screening Any medical condition that produces an abnormal EEG (i.e., epilepsy, brain injury) Clinically relevant cardiovascular abnormalities as determined by the study physician and a 12-lead electrocardiogram (ECG) at screening Shift work or trans meridian travel (two time zones) within the last month History of major psychiatric disorder in the past 12 months at the study physician's discretion, except clinically managed mild depression and/or anxiety History of suicide attempt or current suicide ideation (score greater than 1 on Q9 of the Patient Health Questionnaire [PHQ-9]) Pregnancy or lactating. Female participants are required to complete a urine pregnancy test at screening and treatment sessions and all participants are instructed to use a reliable form of contraception throughout the study duration History of drug or alcohol dependency or abuse within approximately the past 2 years Use of CNS-active drugs (cannabis, amphetamines, cocaine, antidepressants, opioids, benzodiazepines) in the past 3 months as confirmed by a positive urine drug test at screening or at the study physician's discretion Use of medications that may have a clinically significant impact upon the metabolism and excretion of cannabinoids as determined by the study physician (e.g., CYP450 enzyme inducers/inhibitors Excessive caffeine use that in the opinion of the study physician contributes to the participant's insomnia disorder, or the inability to abstain from caffeine use 24 hours prior to each overnight sleep study Inability to refrain from alcohol consumption 24 hours prior to each overnight sleep study Individuals with nicotine dependence (i.e., daily smokers) Medical conditions that result in frequent need to get out of bed (e.g., sleep walking, nocturia) Psychological or behavioural treatment for insomnia disorder, including cognitive behavioural therapy for insomnia, within 3 months before screening (excluding sleep hygiene advice) Occupational or judicially ordered drug screening Has held an unrestricted driving license < 1 year Cannot speak English fluently

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Interventional Model Description: Single site allocation: Randomised Intervention model: Crossover Masking: Double-blind (participant, investigator) Primary purpose: Pilot
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 mg Cannabinol (CBN)<br>Single fixed dose administered 2 hours prior to habitual sleep onset. | Drug: 30 mg Cannabinol (CBN)<br>* Participants will receive a 2 mL oral dose of 'ECS 310' (1.5%), an oral formulation of CBN (15 mg/mL) suspended in medium chain triglycerides (MCT) oil.<br>* Other names: ECS 310 (1.5%);|
| Experimental: 300 mg Cannabinol (CBN)<br>Single fixed dose administered 2 hours prior to habitual sleep onset. | Drug: 300 mg Cannabinol (CBN)<br>* Participants will receive a 2 mL oral dose of 'ECS 310' (15%), an oral formulation of CBN (150 mg/mL) suspended in medium chain triglycerides (MCT) oil.<br>* Other names: ECS 310 (15%);|
| Placebo Comparator: Placebo<br>Single fixed dose administered 2 hours prior to habitual sleep onset. | Drug: Placebo<br>* Participants will receive a 2 mL oral dose of placebo. Placebo contains the same excipient, medium chain triglycerides (MCT) oil, as the investigational products but does not contain cannabinoids.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake After Sleep Onset (WASO) | WASO measured in minutes using in-laboratory overnight polysomnography, from the first epoch after lights out until the last epoch, scored as any stage of sleep by an experienced polysomnographic technician in accordance with American Academy of Sleep Medicine (AASM) 2020 Sleep Scoring criteria (Version 2.6). Comparisons between each CBN dose versus placebo. | Night 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Traditional sleep staging | Proportion of the sleep opportunity scored at the 5 stages (wake, and N1, N2, N3, and REM sleep) between lights out and lights on, measured using overnight in-laboratory polysomnography, scored by a polysomnography technician in accordance with AASM Sleep Scoring criteria. Comparisons between each CBN dose versus placebo. | Night 1 | 
| Sleep Onset Latency (SOL) | SOL measured in minutes using in-laboratory polysomnography, calculated from the time of lights out to the first sleep epoch as scored by a polysomnographic technician in accordance with AASM Sleep Scoring criteria. Comparisons between each CBN dose versus placebo. | Night 1 | 
| Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep. | Spectral power of delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed. Comparisons between each CBN dose versus placebo. | Night 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cannabinol, CBN, cannabinoid, medicinal cannabis, primary insomnia, chronic insomnia disorder, sleep architecture, wake after sleep onset, polysomnography, next-day function, randomised controlled trial, placebo-controlled, crossover, double-blinded