Clinical trial NCT05344170: Cannabinol Use in Patients With Insomnia Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Insomnia Disorder
Keywords: 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
Lead sponsor: Woolcock Institute of Medical Research
Sponsor class: OTHER
Collaborators: name: University of Sydney
First posted: 2022-04-25
Enrollment: 20
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single site allocation: Randomised Intervention model: Crossover Masking: Double-blind (participant, investigator) Primary purpose: Pilot
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Wake After Sleep Onset (WASO)
timeFrame: Night 1
Secondary outcomes:
measure: Traditional sleep staging
timeFrame: Night 1
measure: Sleep Onset Latency (SOL)
timeFrame: Night 1
measure: Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.
timeFrame: Night 1
Other outcomes:
measure: Sleep Spindles During Non-Rapid Eye Movement (NREM) Sleep (Tertiary outcome)
timeFrame: Night 1
measure: Electroencephalogram (EEG) Arousal Index (Tertiary outcome)
timeFrame: Night 1
measure: Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep (Tertiary outcome)
timeFrame: Night 1
measure: Next day post-wake subjective sleep evaluation (LSEQ) (Tertiary outcome)
timeFrame: Morning after drug administration
measure: Next day post-wake subjective sleep evaluation (RCSQ) (Tertiary outcome)
timeFrame: Morning after drug administration
measure: Standard Deviation of Lateral Position (SDLP) During Next-day Post-Wake Simulated Drive (Safety outcome)
timeFrame: Morning after drug administration
measure: Speed During Next-day Post-Wake Simulated Drive (Safety outcome)
timeFrame: Morning after drug administration
measure: Distance Headway During Next-day Post-Wake Simulated Drive (Safety outcome)
timeFrame: Morning after drug administration
measure: Subjective Mood Evaluation (Safety outcome)
timeFrame: Immediately after and morning after drug administration
measure: Subjective Drug Effects (Safety outcome)
timeFrame: Immediately after and morning after drug administration
measure: Postural sway (Safety outcome)
timeFrame: Immediately after and morning after drug administration
measure: Behavioural Alertness and Reaction Time (Safety outcome)
timeFrame: Morning after drug administration
measure: Overnight Declarative Memory Consolidation (Safety outcome)
timeFrame: Morning after drug administration
measure: Overnight Procedural Memory Consolidation (Safety outcome)
timeFrame: Morning after drug administration
measure: Resting Wake Electroencephalography (EEG) Power After Sleep (Post-Wake Effects) (Safety Outcome)
timeFrame: Morning after drug administration
measure: Subjective sleepiness after sleep
timeFrame: Morning after drug administration
measure: Resting Wake Electroencephalography (EEG) Power Before Sleep (Acute Effects)(Exploratory outcome)
timeFrame: Immediately after drug administration
measure: Subjective sleepiness after sleep (acute effects) (Exploratory outcome)
timeFrame: Immediately after drug administration
measure: Plasma cannabinoid concentrations (Exploratory outcome)
timeFrame: Immediately after and morning after drug administration
measure: Urinary cannabinoid concentrations (Exploratory outcome)
timeFrame: Immediately after and morning after drug administration
measure: Salivary cannabinoid concentrations (Exploratory outcome)
timeFrame: Immediately after and morning after drug administration
Locations:
city: Glebe
country: Australia
facility: Woolcock Institute of Medical Research
state: New South Wales
Study officials:
affiliation: Woolcock Institute of Medical Research
name: Camilla Hoyos, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Woolcock Institute of Medical Research
name: Brendon Yee, MBChB, FRACP, FCCP, PhD
role: PRINCIPAL_INVESTIGATOR
References: