Skip to main content
OpenTrials
Completed

NCT Number: NCT05344170

Cannabinol Use in Patients With Insomnia Disorder

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Insomnia Disorder Dyssomnias Mental Disorders Nervous System Diseases Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

25 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Woolcock Institute of Medical Research

Glebe, New South Wales, 2095, Australia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

30 mg Cannabinol (CBN)

Drug

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.

Other names: ECS 310 (1.5%)

300 mg Cannabinol (CBN)

Drug

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.

Other names: ECS 310 (15%)

Placebo

Drug

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.

Primary outcomes

  1. Wake After Sleep Onset (WASO)

    Time frame: 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 outcomes

  1. Traditional sleep staging

    Time frame: 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.

  2. Sleep Onset Latency (SOL)

    Time frame: 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.

  3. Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.

    Time frame: 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.

Other outcomes

  1. Sleep Spindles During Non-Rapid Eye Movement (NREM) Sleep (Tertiary outcome)

    Time frame: Night 1

    Sleep spindle and slow oscillation events in NREM sleep from in-laboratory overnight polysomnography. A sleep spindle and slow oscillation detection algorithm will be applied to electroencephalography (EEG) signals from polysomnography after artefacts are detected and removed. Comparisons between each CBN dose versus placebo.

  2. Electroencephalogram (EEG) Arousal Index (Tertiary outcome)

    Time frame: Night 1

    Number of cortical arousals captured via the electroencephalogram per hour of sleep scored by the polysomnographic technician on the polysomnogram in accordance with AASM Sleep Scoring criteria. Comparisons between each CBN dose versus placebo.

  3. Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep (Tertiary outcome)

    Time frame: 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.

  4. Next day post-wake subjective sleep evaluation (LSEQ) (Tertiary outcome)

    Time frame: Morning after drug administration

    LSEQ score. LSEQ scores range from 0-100, with higher scores indicating better subjective experience. Assessed within 1 h after wake (comparison between each CBN dose versus placebo).

  5. Next day post-wake subjective sleep evaluation (RCSQ) (Tertiary outcome)

    Time frame: Morning after drug administration

    RCSQ score. RCSQ scores range from 0-100, with higher scores indicating better subjective experience. Assessed within 1 h after wake (comparison between each CBN dose versus placebo).

  6. Standard Deviation of Lateral Position (SDLP) During Next-day Post-Wake Simulated Drive (Safety outcome)

    Time frame: Morning after drug administration

    SDLP ("weaving") is measured across the 'standard', 'car following', and 'divided attention' sub-sections of a ~30 minute simulated driving task. Assessed within 2 h after wake (comparison between each CBN dose versus placebo).

  7. Speed During Next-day Post-Wake Simulated Drive (Safety outcome)

    Time frame: Morning after drug administration

    Average speed and standard deviation of speed is measured across the 'standard' and 'divided attention' sub-sections of a ~30 minute simulated driving task. Assessed within 2 h after wake (comparison between each CBN dose versus placebo).

  8. Distance Headway During Next-day Post-Wake Simulated Drive (Safety outcome)

    Time frame: Morning after drug administration

    Average distance headway (i.e., distance between the driver's vehicle and vehicle immediately in front) and standard deviation of distance headway is measured across the 'car following' sub-section of a ~30-minute simulated driving task. Assessed within 2 h after wake at both treatment sessions (comparison between each CBN dose versus placebo).

  9. Subjective Mood Evaluation (Safety outcome)

    Time frame: Immediately after and morning after drug administration

    The Abbreviated Profile of Mood States (POMS) consists of 40 items measuring domains of 'tension', 'depressed', 'anger', 'vigour', 'fatigue', and 'concentration'. Participants respond to each item using 5-point Likert scales ranging from 0 (Not at all) to 4 (Extremely). A total mood disturbance score is calculated by summing negative domains and subtracting positive domains. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).

  10. Subjective Drug Effects (Safety outcome)

    Time frame: Immediately after and morning after drug administration

    The Drug Effects Questionnaire (DEQ) assesses the extent to which participants feel a drug effects, feel high, like the effects, dislike the effects, want more of the substance, and feel sedated, on self-rating 100mm visual analogue scales. A total mood disturbance score is calculated by summing negative domains and subtracting positive domains. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).

  11. Postural sway (Safety outcome)

    Time frame: Immediately after and morning after drug administration

    Centre-of-pressure (COP) during computerised static posturography. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).

  12. Behavioural Alertness and Reaction Time (Safety outcome)

    Time frame: Morning after drug administration

    Psychomotor Vigilance Test (PVT) is administered twice the next-day (comparison between each CBN dose versus placebo).

  13. Overnight Declarative Memory Consolidation (Safety outcome)

    Time frame: Morning after drug administration

    Word pair recall scores measured using the computerised Word Pairs Task (WPT). Administered pre-drug administration and next-day (comparison between each CBN dose versus placebo).

  14. Overnight Procedural Memory Consolidation (Safety outcome)

    Time frame: Morning after drug administration

    Motor sequence learning measured using the computerised Finger Tapping Task (FTT). Administered pre-drug administration and next-day (comparison between each CBN dose versus placebo).

  15. Resting Wake Electroencephalography (EEG) Power After Sleep (Post-Wake Effects) (Safety Outcome)

    Time frame: Morning after drug administration

    Resting wake EEG power during the Karolinska Drowsiness Test (KDT) upon wake: 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. Power spectral analysis is applied to EEG signals from polysomnography, after artefacts are detected and removed. Comparison between each CBN dose versus placebo.

  16. Subjective sleepiness after sleep

    Time frame: Morning after drug administration

    The Karolinska Sleepiness Scale (KSS) is a 10-item measure of subjective drowsiness. Participants respond to each item using a 9-point Likert scale ranging from 1 (Extremely alert) to 9 (Extremely sleepy). Higher scores are indicative of increased drowsiness. The KSS will be collected in accordance with the KDT protocol but will not be analysed due to insufficient statistical power.

  17. Resting Wake Electroencephalography (EEG) Power Before Sleep (Acute Effects)(Exploratory outcome)

    Time frame: Immediately after drug administration

    Resting wake EEG power during the KDT prior to sleep: 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. Power spectral analysis is applied to EEG signals from polysomnography, after artefacts are detected and removed. Comparison between each CBN dose versus placebo.

  18. Subjective sleepiness after sleep (acute effects) (Exploratory outcome)

    Time frame: Immediately after drug administration

    The KSS is a 10-item measure of subjective drowsiness. Participants respond to each item using 9-point Likert scales ranging from 1 (Extremely alert) to 9 (Extremely sleepy). Higher scores are indicative of higher drowsiness. The KSS will be collected in accordance with the KDT protocol but will not be analysed due to insufficient statistical power.

  19. Plasma cannabinoid concentrations (Exploratory outcome)

    Time frame: Immediately after and morning after drug administration

    Presence of cannabinoids (CBN, delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) (e.g., 11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC, 7-OH-CBD, 7-COOH-CBD), and endocannabinoids and related molecules (e.g., 2-Arachidonoylglyceroland anandamide) and their metabolites in plasma samples.

  20. Urinary cannabinoid concentrations (Exploratory outcome)

    Time frame: Immediately after and morning after drug administration

    Presence of cannabinoids (CBN, THC, and CBD) and their metabolites (11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC, 7-OH-CBD, 7-COOH-CBD) in urine samples.

  21. Salivary cannabinoid concentrations (Exploratory outcome)

    Time frame: Immediately after and morning after drug administration

    Presence of cannabinoids (THC, CBN) and their metabolites (11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC) in saliva samples.

Sponsors and collaborators

Lead sponsor

Woolcock Institute of Medical Research

Other

Collaborators

  • University of Sydney

Registry information

Official study 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

Acronym: CUPID

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Apr 25, 2022
Registry last updated
Feb 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.