Cannabinol Use in Patients With Insomnia Disorder

Phase 1

Completed

• Conditions: Insomnia Disorder
• Interventions: Drug: 30 mg Cannabinol (CBN); Drug: 300 mg Cannabinol (CBN); Drug: Placebo

• Registration Number: NCT05344170
• Lead Sponsor: Woolcock Institute of Medical Research

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-12
• Study First Submitted QC: 2022-04-19
• Study First Posted: 2022-04-25
• Study Start: 2022-08-24
• Status Verified: 2023-05
• Primary Completion: 2023-08-29
• Study Completion: 2023-09-05
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Between 25 - 65 years of age
2. Insomnia Severity Index (ISI) score ≥ 15 at eligibility screening
3. Insomnia disorder (symptoms occurring at least 3 times per week and present for longer than 3 months) as determined by the study physician
4. Ability to take oral medication
5. Provision of signed and dated informed consent form
6. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

1. Medical condition or medication that is the cause of the insomnia disorder as determined by the study physician
2. Known hypersensitivity to cannabis or cannabinoid products (including if this becomes evident during the trial)
3. 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)
4. Sleep apnoea (defined as Apnoea Hypopnea Index [AHI] > 15 and Oxygen Desaturation Index [ODI]>10) as confirmed by polysomnography at screening
5. Sleep-related movement disorder as determined by the study physician
6. Delayed or advanced sleep phase syndrome (based on actigraphy and sleep diary) as confirmed during screening
7. Any medical condition that produces an abnormal EEG (i.e., epilepsy, brain injury)
8. Clinically relevant cardiovascular abnormalities as determined by the study physician and a 12-lead electrocardiogram (ECG) at screening
9. Shift work or trans meridian travel (two time zones) within the last month
10. History of major psychiatric disorder in the past 12 months at the study physician's discretion, except clinically managed mild depression and/or anxiety
11. History of suicide attempt or current suicide ideation (score greater than 1 on Q9 of the Patient Health Questionnaire [PHQ-9])
12. 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
13. History of drug or alcohol dependency or abuse within approximately the past 2 years
14. 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
15. 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
16. 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
17. Inability to refrain from alcohol consumption 24 hours prior to each overnight sleep study
18. Individuals with nicotine dependence (i.e., daily smokers)
19. Medical conditions that result in frequent need to get out of bed (e.g., sleep walking, nocturia)
20. Psychological or behavioural treatment for insomnia disorder, including cognitive behavioural therapy for insomnia, within 3 months before screening (excluding sleep hygiene advice)
21. Occupational or judicially ordered drug screening
22. Has held an unrestricted driving license < 1 year
23. Cannot speak English fluently

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
30 mg Cannabinol (CBN)	30 mg Cannabinol (CBN)	Single fixed dose administered 2 hours prior to habitual sleep onset.
300 mg Cannabinol (CBN)	300 mg Cannabinol (CBN)	Single fixed dose administered 2 hours prior to habitual sleep onset.
Placebo	Placebo	Single fixed dose administered 2 hours prior to habitual sleep onset.

Primary Outcome Measures

Name	Time	Method
Wake After Sleep Onset (WASO)	Night 1	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.

Secondary Outcome Measures

Name	Time	Method
Sleep Onset Latency (SOL)	Night 1	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.
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.	Night 1	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.
Traditional sleep staging	Night 1	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.

Trial Locations

Locations (1)

Woolcock Institute of Medical Research; 🇦🇺 Glebe, New South Wales, Australia