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| Name | Class |
|---|---|
| University of Sydney | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 30 mg Cannabinol (CBN) | Experimental | Single fixed dose administered 2 hours prior to habitual sleep onset. |
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| 300 mg Cannabinol (CBN) | Experimental | Single fixed dose administered 2 hours prior to habitual sleep onset. |
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| Placebo | Placebo Comparator | Single fixed dose administered 2 hours prior to habitual sleep onset. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Sleep Spindles During Non-Rapid Eye Movement (NREM) Sleep (Tertiary outcome) | 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. | Night 1 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Camilla Hoyos, MPH, PhD | Woolcock Institute of Medical Research | Principal Investigator |
| Brendon Yee, MBChB, FRACP, FCCP, PhD | Woolcock Institute of Medical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Woolcock Institute of Medical Research | Glebe | New South Wales | 2095 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41698831 | Derived | Lavender IG, Marshall NS, McCartney D, Cho G, Irwin C, Suraev A, Gordon R, Arnold JC, D'Rozario AL, Gordon CJ, Saini B, Sivam S, Zheng Y, Grunstein RR, Yee BJ, McGregor IS, Hoyos CM. Cannabinol for Acute Treatment of Insomnia Disorder in a Randomized Placebo-Controlled Crossover Trial. J Sleep Res. 2026 Feb 16:e70284. doi: 10.1111/jsr.70284. Online ahead of print. | |
| 37612115 |
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Non-identifiable IPD will be shared upon reasonable request to the Chief Investigators.
Non-identifiable IPD will become available one year after the Actual Study Completion Date and will be available for 10 years.
Individual participant level meta-analyses of congruent studies
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D002187 | Cannabinol |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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Single site allocation: Randomised Intervention model: Crossover Masking: Double-blind (participant, investigator) Primary purpose: Pilot
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Double-blind: Eligible participants will be assigned to one of six possible treatment orders using a pre-populated randomisation schedule. Study staff (including the study investigators, the clinical trials coordinator and the study medical officer) and the participants will be blinded. Allocation concealment will be managed by the trial epidemiologist and drug distributor who will not have any contact with participants or involvement in day-to-day trial activities. Traditional polysomnographic (PSG) measures will be scored by a PSG technician who will not be aware of participant treatment, nor will they meet the participant. The study drug and matched placebo are expected to be identical in their visual appearance, taste, or smell. A mint-flavoured lozenge will be administered immediately prior to the study drug to mask any possible differences in taste.
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| 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. |
|
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| 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. |
|
| 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 |
| Electroencephalogram (EEG) Arousal Index (Tertiary outcome) | 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. | Night 1 |
| Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep (Tertiary outcome) | 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 |
| Next day post-wake subjective sleep evaluation (LSEQ) (Tertiary outcome) | 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). | Morning after drug administration |
| Next day post-wake subjective sleep evaluation (RCSQ) (Tertiary outcome) | 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). | Morning after drug administration |
| Standard Deviation of Lateral Position (SDLP) During Next-day Post-Wake Simulated Drive (Safety outcome) | 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). | Morning after drug administration |
| Speed During Next-day Post-Wake Simulated Drive (Safety outcome) | 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). | Morning after drug administration |
| Distance Headway During Next-day Post-Wake Simulated Drive (Safety outcome) | 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). | Morning after drug administration |
| Subjective Mood Evaluation (Safety outcome) | 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). | Immediately after and morning after drug administration |
| Subjective Drug Effects (Safety outcome) | 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). | Immediately after and morning after drug administration |
| Postural sway (Safety outcome) | 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). | Immediately after and morning after drug administration |
| Behavioural Alertness and Reaction Time (Safety outcome) | Psychomotor Vigilance Test (PVT) is administered twice the next-day (comparison between each CBN dose versus placebo). | Morning after drug administration |
| Overnight Declarative Memory Consolidation (Safety outcome) | 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). | Morning after drug administration |
| Overnight Procedural Memory Consolidation (Safety outcome) | 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). | Morning after drug administration |
| Resting Wake Electroencephalography (EEG) Power After Sleep (Post-Wake Effects) (Safety Outcome) | 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. | Morning after drug administration |
| Subjective sleepiness after sleep | 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. | Morning after drug administration |
| Resting Wake Electroencephalography (EEG) Power Before Sleep (Acute Effects)(Exploratory outcome) | 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. | Immediately after drug administration |
| Subjective sleepiness after sleep (acute effects) (Exploratory outcome) | 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. | Immediately after drug administration |
| Plasma cannabinoid concentrations (Exploratory outcome) | 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. | Immediately after and morning after drug administration |
| Urinary cannabinoid concentrations (Exploratory outcome) | 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. | Immediately after and morning after drug administration |
| Salivary cannabinoid concentrations (Exploratory outcome) | Presence of cannabinoids (THC, CBN) and their metabolites (11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC) in saliva samples. | Immediately after and morning after drug administration |
| Lavender I, McCartney D, Marshall N, Suraev A, Irwin C, D'Rozario AL, Gordon CJ, Saini B, Grunstein RR, Yee B, McGregor I, Hoyos CM. Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder ('CUPID' study): protocol for a randomised, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial. BMJ Open. 2023 Aug 23;13(8):e071148. doi: 10.1136/bmjopen-2022-071148. |
| D001523 |
| Mental Disorders |