Sleep Disorders

The AASM recommends against the use of medical cannabis in OSA, as efficacy, tolerability and safety are not sufficiently proven.

AASM position paper on medical cannabis treatment in obstructive sleep apnea (OSA); explicitly recommends AGAINST the use of medical cannabis/synthetic extracts in OSA due to insufficient evidence on effectiveness, tolerability and long-term safety. Somnolence documented as a common side effect; dronabinol (synthetic THC) not FDA-approved for OSA. OSA should be excluded from state medical cannabis programs.

Recreational cannabis use was associated in observational studies with poorer sleep quality, short and long sleep duration as well as more insomnia symptoms, while experimental studies showed no associations.

Comprehensive SR + meta-analysis across k=120 studies (102 observational, 19 experimental) on recreational cannabis use and sleep in the general population. In observational studies: current cannabis use associated with poorer sleep quality, short/long sleep duration, more insomnia symptoms and later chronotype vs. non-use; stronger in men and younger users. In experimental studies: no association between cannabis and sleep quality/sleep duration.

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis; moderate evidence for chronic pain and MS spasticity, low-quality evidence for improvement of sleep disorders (based on few studies with inconsistent outcomes).

Prazosin may show the best efficacy for insomnia, nightmares and sleep quality; SSRIs, mirtazapine, Z-drugs and benzodiazepines show low efficacy; risperidone and quetiapine have high risk of side effects without clear therapeutic benefit.

Network meta-analysis of k=99 RCTs (n=10.481) on pharmacotherapy for sleep disorders in the context of PTSD. Prazosin most effective for insomnia (SMD=-0.88, 95%CI [-1.22;-0.54]), nightmares (SMD=-0.44, 95%CI [-0.84;-0.04]) and sleep quality (SMD=-0.55, 95%CI [-1.01;-0.10]). Nabilone (a synthetic cannabinoid) mentioned as a promising option, but more research needed. SSRIs, mirtazapine, Z-drugs and benzodiazepines showed lack of efficacy. Confidence: very low to moderate due to underpowered individual comparisons.

Small improvement in sleep quality and sleep disturbance in chronic pain patients, but markedly increased risk of adverse effects such as dizziness (29%), drowsiness, dry mouth, fatigue and nausea (6–10%).

Systematic review + meta-analysis across k=39 RCTs (n=5.100), medical cannabis for sleep disturbances, median follow-up 35 days, 33/39 studies in chronic pain patients. Moderate to high evidence: in chronic pain, small improvement in sleep quality vs. placebo (modeled RD for achieving MID 8% [95% CI 3–12%]); reduction in sleep disturbance in non-cancer-related chronic pain RD 19% [95% CI 11–28%], in cancer pain very small improvement WMD -0.19 cm [95% CI -0.36 to -0.03]. Adverse effects: markedly increased risk of dizziness RD 29% [95% CI 16–50%], small increase in somnolence, dry mouth, fatigue, nausea (RD 6–10%).

Cannabinoids significantly improved sleep quality versus placebo (SMD 0,53; p=0,04), especially in patients with insomnia or poor sleep (SMD 0,60; p=0,02); non-CBD cannabinoids showed greater efficacy than CBD-only therapies.

Systematic review and meta-analysis across k=6 RCTs (n=1.077 patients) on cannabinoids vs. placebo for sleep quality. Cannabinoids significantly improved subjective sleep quality (SMD=0,53; 95% CI 0,03–1,02; p=0,04; I²=88%), especially in insomnia/poor sleep (SMD=0,60; 95% CI 0,09–1,11; p=0,02; I²=89%). Non-CBD cannabinoids showed higher efficacy (SMD=0,82; 95% CI 0,24–1,40; p=0,005), while pure CBD therapy had no significant effect (SMD=0,13; 95% CI −0,38 to 0,65; p=0,61).

Non-randomised studies showed favourable effects on Pittsburgh Sleep Quality Index up to 8 weeks; RCTs showed mixed results (nabilone better than amitriptyline on Insomnia Severity Index, THC reduced sleep latency), but all studies were of poor quality with high risk of bias.

Systematic review + meta-analysis on cannabinoids in insomnia, k=5 studies (2 RCTs, 3 non-randomised studies), n=219 participants. Meta-analysis of 3 studies (Pittsburgh Sleep Quality Index): cannabinoids showed significant improvement at ≤4 weeks follow-up (MD -1.89, 95% CI -2.68 to -1.10, n=176) and at 8 weeks (MD -2.41, 95% CI -3.36 to -1.46, n=166).

Insufficient evidence for routine clinical use of cannabinoid therapies for sleep disorders due to lack of research and moderate to high risk of bias.

Systematic review on cannabinoid therapies for sleep disorders; k=26 studies (14 preclinical, 12 clinical). Insufficient evidence for routine clinical use in sleep disorders due to lack of research and moderate to high risk of bias in the majority of included studies. Promising preliminary evidence for future RCTs in sleep apnea, insomnia, PTSD-related nightmares, restless legs syndrome, REM sleep behavior disorder and narcolepsy.

Systematic review on cannabinoids and sleep; k not explicitly stated. Included RCTs and open-label studies on THC/CBD in MS, PTSD, chronic pain (sleep mostly secondary endpoint). Positive effects on sleep quality, sleep onset duration and nocturnal disturbances reported; limited by small sample sizes and methodological heterogeneity.

Moderate efficacy of cannabinoid-based medications in chronic pain and comorbidities such as sleep problems, anxiety and selected chronic conditions.

Clinical practice guideline on cannabis in chronic pain and comorbidities (including sleep disorders), based on SR of k=70 studies (19 SRs + 51 original studies). Moderate evidence for CBM efficacy in chronic pain; specific evidence for sleep problems as a common comorbidity. GRADE-based recommendations on dosage, titration and risk management.

Subjective sleep improvements in approximately 37% of RCTs and 58% of uncontrolled studies, but no improvements in sleep architecture; benefit mainly in pain-related disorders, not in neurological, psychiatric or sleep disorders.

Systematic review on cannabis dosing and administration in sleep disorders; k=31 studies (19 RCTs, 12 uncontrolled studies). Sleep improvements in 7/19 RCTs and 7/12 uncontrolled studies. Strongest evidence for pain-related sleep disorders; subjective sleep quality improved, but no objective changes in sleep architecture. Most common side effects: headache, sedation, dizziness (dose-dependent).

CBD showed anxiolytic effects in healthy and certain clinical populations without prominent effects on sleep, with an inverted U-shaped dose relationship and the CBD-to-THC ratio moderating the effects.

Systematic review on CBD (± THC) in anxiety disorders with co-occurring sleep disorders; k=58 studies in healthy and clinical populations. In healthy populations and certain non-cannabis-using clinical populations, CBD showed anxiolytic effects without pronounced sleep effects. Inverted U-shaped dose-response relationship and CBD:THC ratio moderated the effects. Mechanistically primary modulation of the endocannabinoid system and secondary regulation of neuroendocrine function.

All 34 studies reported improvements in insomnia symptoms in at least a portion of participants; however, only 4 of 7 CBD-predominant and 12 of 16 CBD+THC studies with hypothesis testing showed significant improvements, and only 2 studies focused on patients with insomnia.

Systematic review on CBD in insomnia; k=34 studies (only 2 focused on insomnia patients, of which 1 case report). Of 7 studies with a CBD-predominant arm, 4 showed significant improvement of insomnia outcomes; of 16 studies with nearly equal CBD:THC ratios, 12 showed significant improvement. Limitations: heterogeneous study designs, often non-validated subjective measurement instruments, lack of objective sleep measurements.

No high-quality evidence for cannabis in the treatment of psychological symptoms in cancer patients; only 6 of 15 RCTs suggested benefit, but no studies assessed cannabis efficacy as a primary outcome.

MASCC guideline on cannabis for psychological symptoms (anxiety, depression, insomnia) in cancer patients; systematic review of 2 SR and 15 RCTs (4 on sleep, 5 on mood, 6 on both); 6/15 RCTs showed benefit (5 for sleep, 1 for mood). Conclusion: no high-quality evidence for a recommendation until higher-quality research is available.

Cannabinoids show no clear effect on insomnia severity or sleep quality, possibly no effect on sleep onset and wake times, but are probably associated with frequent side effects.

Systematic review with meta-analysis on cannabinoids for insomnia; k=3 studies (2 RCTs). Unclear whether cannabinoids affect insomnia severity or sleep quality; possibly no effect on sleep onset latency, nocturnal awakening or daytime behaviour; frequent side effects likely.

Cannabinoids show mixed effects on various sleep parameters without a clear efficacy profile.

Systematic review (k=39 human studies) on cannabinoid effects on sleep: findings mixed — various effects on multiple sleep parameters reported, methodological deficiencies in the majority of studies prevent clear conclusions. The review documents the heterogeneous evidence base and the need for methodologically robust studies on cannabinoids in sleep disorders.

Eight of nine studies showed statistically significant positive effects on OSA markers (reduced apnea-hypopnea index, improved daytime sleepiness), but 70–80% of participants reported neuropsychiatric and gastrointestinal side effects.

SR of 9 studies (k=9: 7 experimental, 2 observational) on cannabinoids (mainly dronabinol) in obstructive sleep apnea; 8 of 9 studies showed statistically significant improvements (AHI reduction, daytime sleepiness); neuropsychiatric and gastrointestinal side effects in 70–80% of participants; median treatment duration 3 weeks.

20 mg CBN showed a non-significant effect on sleep quality, but significantly reduced nighttime awakenings and overall sleep disturbance with no effect on daytime sleepiness; addition of CBD did not enhance the effect.

n=293, double-blind RCT on cannabinol (CBN) for sleep disturbances over 7 nights. 20 mg CBN vs. placebo: non-significant trend for sleep quality (OR=2.26, 95% CI [0.93, 5.52], p=0.082), significant reduction in nighttime awakenings (95% CI [-0.96, -0.05], p=0.025) and overall sleep disturbance (95% CI [-2.59, -0.14], p=0.023). No improvement in sleep onset latency or WASO. Addition of CBD (10-100 mg) provided no additional benefit over CBN alone.

Dronabinol reduced the apnea-hypopnea index (AHI) dose-dependently and improved self-reported sleepiness (ESS) compared with placebo.

Phase II RCT, n=73 adults with moderate/severe obstructive sleep apnea (OSA); dronabinol 10 mg/day vs. placebo over 6 weeks. AHI reduction -12,9±4,3 events/h (p=0,003), Epworth Sleepiness Scale (ESS) -3,8±0,8 points from baseline (p<0,0001), -2,3±1,2 points vs. placebo (p=0,05). Highest treatment satisfaction at 10 mg (p=0,04). No change in sleep architecture or nocturnal oxygenation. Adverse events equivalent to placebo.

Sleep A (low THC + high botanicals) showed significant improvements in sleep disturbance, anxiety, stress and wellbeing compared to placebo; Sleep B showed no significant differences.

n=620 adults with sleep disturbances, 3-arm RCT over 4 weeks. Sleep A (0.35 mg THC + 75 mg hop/valerian) vs. Sleep B (0.85 mg THC + 20 mg hop/valerian) vs. placebo. Sleep A showed significant improvement in PROMIS Sleep Disturbance versus placebo (p<0.05, exact value not given); additionally reduction in anxiety, stress and improvement in wellbeing. Sleep B showed no significant differences versus placebo. Adverse events mild to moderate, no group differences.

Medical cannabis card led to improved self-reported insomnia symptoms, but to higher incidence and severity of cannabis use disorder and no significant improvement in pain, anxiety or depressive symptoms.

n=186 adults with medical cannabis card, prospective over 12 weeks; significant improvement in insomnia (ISI score: baseline 15.5 → 12 weeks 9.7, p0.001), pain and anxiety also reduced.

Marginal increase in the combined proportion of deep sleep and REM sleep by 1,3% compared to placebo (p=0,03), with no effect on total sleep time, resting heart rate, or heart rate variability.

n=125 persons with insomnia, double-blind crossover RCT over 4 weeks. CBD 300 mg + terpenes (1 mg each of linalool, myrcene, phytol, limonene, α-terpinene, α-terpineol, α-pinene, β-caryophyllene) vs. placebo. Primary endpoint (SWS+REM sleep percentage): marginally significant increase of 1.3% (SE 0.60%, 95% CI 0.1–2.5%, p=0.03). Stronger effects in participants with low baseline SWS+REM (up to 48 min/night increase). No effects on total sleep time, resting heart rate, or HRV. No adverse events.

300 mg CBD reduced sleep disturbances significantly more than 50 mg CBD, but not significantly more than placebo.

n=63 persons with elevated trait-worry (mean age 29,3 years), randomised double-blind to 300 mg CBD, 50 mg CBD or placebo daily over 2 weeks. 300 mg CBD showed significantly stronger reduction of sleep disturbances and sleep quality vs. 50 mg CBD (B=-0,39, t=-2,59, p<0,05, d=0,08), but NOT vs. placebo (B=-0,32, t=-2,09, p=0,10, d=0,07). No effects on sedation or cognitive impairment.

CBTi-CB-TM showed significantly stronger improvement in insomnia severity scores and higher remission rates than the control group; it also reduced cannabis use shortly before bedtime.

n=57 pilot RCT (43 women, age 37,6±12,8 years) with chronic insomnia and cannabis use for sleep ≥3×/week; telemedicine CBT-i for cannabis users (CBTi-CB-TM, n=30) vs. sleep hygiene education (SHE-TM, n=27). ISI scores improved significantly more in CBTi-CB-TM (β=-2,83; SE=0,84; p=0.004; d=0.81); at 8-week follow-up: 60% CBTi-CB-TM vs. 14,8% SHE-TM in insomnia remission (χ²=12,8; p=0.0003). Both groups showed a small reduction in cannabis use (β=-0,10; SE=0,05; p=0.026); CBTi-CB-TM showed a greater reduction in cannabis use within 2 h before bedtime (-29,1±7,9% vs. +2,6±8,0%; p=0.008).

CBT-I effectively reduced insomnia symptoms in young adults with alcohol use and insomnia, independent of cannabis use during treatment.

Secondary analysis of an RCT on CBT-I in young adults with insomnia (n=56); 46% used cannabis during treatment (Ø 23% of treatment days). Cannabis use did NOT moderate CBT-I efficacy on insomnia severity (b=-0.002, p=0.99). CBT-I was effective independent of cannabis use.

CBD 150 mg was similar to placebo on most sleep measures, but showed greater wellbeing and better objective sleep efficiency after 2 weeks.

n=30 pilot RCT, CBD 150 mg sublingual (n=15) vs. placebo (n=15) in primary insomnia over 2 weeks. No significant difference in insomnia severity, SOL, SE or WASO (all p>0.05). CBD group showed higher wellbeing over the entire period (difference=2,60; SE=1,20; p<0.05) and better objective sleep efficiency after 2 weeks (difference=6,85%; SE=2,95; p<0.05). Conclusion: 150 mg CBD similar to placebo on most sleep outcomes, with superior psychological wellbeing.

Cognitive performance was unaffected by nightly CBD supplementation (all p > 0,05); subjective mood improvements (calmness, clarity, coordination), but more frequent side effects (dry mouth).

RCT (parallel) with n=30 patients (primary insomnia), 150 mg CBD daily sublingual 60 min before bedtime over 2 weeks vs. placebo (after 1-week placebo run-in phase). Cognitive performance (attention, executive function, reasoning, information processing, working/episodic memory) unimpaired by nightly CBD supplementation (all p>0,05). CBD group reported significantly more calmness, clear-headedness, coordination and dry mouth than placebo (all p<0,05). Favorable safety profile for daytime cognitive functioning.

Nabilone was superior to amitriptyline with regard to sleep quality (Insomnia Severity Index difference 3,2) and marginally better for restfulness, with acceptable tolerability.

n=29 fibromyalgia patients with chronic insomnia, nabilone (0,5–1,0 mg before bedtime) vs. amitriptyline (10–20 mg) in crossover design over 2 weeks each. Nabilone significantly better on the Insomnia Severity Index (difference=3,2; 95% CI 1,2–5,3) and marginally better for restfulness (LSEQ difference=0,5; 95% CI 0,0–1,0). No effects on pain, mood or quality of life. Adverse events more frequent under nabilone (dizziness, nausea, dry mouth).

Medicinal cannabis significantly improved sleep: 60% of participants were no longer clinical insomniacs after 2 weeks, melatonin increased by 30% (vs. a 20% decrease under placebo), light sleep increased by 21 min/night (p=0.041), sleep quality improved by up to 80% (p=0.003).

n=29 adults with clinical insomnia, randomized double-blind placebo-controlled crossover over 6 weeks (2 weeks active/placebo, 1 week wash-out). Entoura-10:15 oil (10 mg/ml THC + 15 mg/ml CBD, titrated 0,2–1,5 ml/day): 60% no longer met clinical insomnia criteria after 2 weeks; midnight melatonin +30% vs. −20% placebo (p=0,035); light sleep +21 min/night vs. placebo (p=0,041); sleep quality improvement up to 80% in phase 2 (p=0,003).

Acute CBD administration (300 mg) showed no significant effects on the sleep-wake cycle of healthy subjects.

n=27 healthy subjects (1 drop-out), cross-over RCT, CBD 300 mg vs. placebo, 8h polysomnography. CBD showed no significant effects on the sleep-wake cycle (p>0.05). In contrast to benzodiazepines or SSRIs, a single anxiolytic dose of CBD does not affect normal sleep architecture in healthy individuals.

ZTL-101 significantly improved insomnia severity (ISI -5,07), increased total sleep time (+64,6 min) and sleep quality compared with placebo, with good tolerability.

RCT (cross-over) with n=23 patients (chronic insomnia ≥3 months), 2 weeks nightly sublingual cannabinoid extract (ZTL-101) vs. placebo. ZTL-101 reduced ISI by -5,07 units (95% CI [-7,28 to -2,86], p=0,0001), self-reported sleep onset latency by -8,45 min (p=0,04), increased total sleep time by +64,6 min (p<0,0001) and sleep quality by +0,74 units (p<0,0001). Actigraphy: WASO -10,2 min (p=0,002), TST +33,4 min (p<0,001), SE +2,9% (p=0,005). No serious adverse events; 40 mild non-serious events (36 under ZTL-101).

No notable next-day impairment in cognitive and psychomotor function or driving simulation; a small deterioration in the Stroop test and a slight increase in perceived sedation without clinical relevance.

n=20 adults with insomnia (16 female, mean age 46,1 years), randomised double-blind crossover to 10 mg THC + 200 mg CBD vs. placebo. No 'next day' impairment in 27/28 cognitive and psychomotor tests (≥9h post-treatment). Small reduction (-1,4%, p=0,016, d=-0,6) in Stroop colour task accuracy; small increase (+8,6, p=0,042, d=0,3) in sedation rating after 10h. No differences in simulated driving performance vs. placebo.

THC/CBD reduced total sleep time and suppressed REM sleep, without objective impairment of daytime wakefulness, but with increased self-reported sleepiness.

n=20 patients with DSM-5-diagnosed insomnia, single dose THC 10 mg + CBD 200 mg vs. placebo. THC/CBD reduced total sleep time by −24,5 min (p=0,05, d=−0,5) and REM sleep by −33,9 min (p<0,001, d=−1,5), prolonged REM latency by +65,6 min (p=0,008, d=0,7). No change in Wake After Sleep Onset (+10,7 min, p>0,05). High-density EEG showed regional gamma decrease in N2, delta decrease in N3, and beta/alpha increase in REM. No objective alertness effect the following day, but slight subjective sleepiness (+0,42 points, p=0,02, d=0,22).

n=20 adults with insomnia diagnosis (DSM-5/ICSD-3, ISI≥15), randomised placebo-controlled cross-over study on cannabinol (CBN) 30 mg vs. 300 mg vs. placebo. Primary endpoint WASO (Wake After Sleep Onset) without significant reduction (300 mg: -6,3 min [95% CI: -18,2 to +5,5], p=0,29, dz=-0,22; 30 mg: -4,0 min [-15,9 to +7,9], p=0,50, dz=0,11). Secondary outcomes with 300 mg CBN: increase in NREM-2 sleep (p=0,03, dz=0,54), improved subjective sleep quality (p=0,005, dz=0,56), reduction in sleep onset latency (p=0,004, dz=-0,74) and EEG arousal indices (p=0,02, dz=-0,65). Overall 247 mild to moderate adverse events across all arms.

CBD improved sleep duration and reduced dream recall in insomniacs and showed antiepileptic effect in treatment-refractory patients.

Placebo-controlled RCT (n=15 insomniacs): CBD 160 mg led to significantly longer sleep than placebo; all three CBD doses (40, 80, 160 mg) resulted in significantly less dream recall than placebo. Comparator reference: 5 mg nitrazepam as active control.

IHL-42X showed significant reduction of AHI compared to placebo at all three doses (low: -19,7, medium: -17,5, high: -16,4 vs. placebo: -2,8 events/hour), without serious adverse effects.

n=11, randomised double-blind placebo-controlled crossover study (dose titration); dronabinol + acetazolamide (IHL-42X) vs. placebo in obstructive sleep apnea (AHI ≥15/h). AHI reduction versus placebo: low dose −19,7±27,1, medium −17,5±23,3, high −16,4±23,8 events/h (all p<.05 vs. placebo −2,8±21,0). ODI3% reduction medium dose −15,4±19,0 vs. placebo (p<.05). ESS and mood unchanged; no serious adverse effects.

Dronabinol significantly reduced the apnea-hypopnea index after 21 days without worsening of sleep architecture.

Single-arm dose escalation study (n=17 adults with apnea-hypopnea index ≥15/h); dronabinol (Δ9-THC) 2,5–10 mg daily over 21 nights; mean AHI reduction ΔAHI=-14,1 ±17,5 (p=0,007) versus baseline; no worsening of sleep architecture; no serious adverse reactions.

Higher THC:CBD ratio significantly improves neuropathic pain, insomnia and depression, but not anorexia and PTSD flashbacks; anxiety benefits most from a 1:1 ratio.

Retrospective real-world study (n=2.431, 26.150 observations): Higher THC:CBD ratio significantly associated with improvement of insomnia OR=2,93 (95% CI 1,75–4,91; p<0,001). Cannabis with high THC content shows the strongest effect on sleep quality compared to higher CBD content.

Patients reported significant improvements in all 8 domains of quality of life (SF-36) following cannabis treatment, which mostly persist over time, with improvements ranging from 6,60 to 18,31 points depending on domain (all p < 0,001).

n=3.148 medical cannabis users (Australia), prospective over 3 months; improvement in sleep quality: PROMIS Sleep Disturbance T-score reduction –2.5 (95% CI –2.9 to –2.1, p0.001), anxiety/depression also improved.

CBD reduced RBD event frequency promptly and substantially in all 4 Parkinson's patients.

Case series (n=4) in Parkinson's patients with REM sleep behaviour disorder (RBD): CBD administration produced a prompt and substantial reduction in the frequency of RBD episodes without side effects in all 4 treated patients.

Cannabis products show minimal to no effects on sleep disorders and can have harmful effects in some individuals.

Comprehensive narrative review on cannabis products in sleep disorders (insomnia, hypersomnia, sleep apnea, parasomnias, RLS): Most studies are observational; few published RCTs show minimal to no efficacy on sleep disorders; possible negative effects in some patients. Cannabis withdrawal can trigger sleep disorders and promote relapse. Further research on differential cannabinoid effects is needed.

CBD shows therapeutic potential for insomnia, THC might shorten sleep latency but impair sleep quality in the long term; synthetic cannabinoids might help short-term in sleep apnea; overall result: mixed findings with need for further controlled research.

Narrative overview on cannabis and sleep (literature up to 2014, detailed from 2014). Preliminary evidence: CBD shows therapeutic potential in insomnia; THC might shorten sleep latency but impair sleep quality in the long term. Synthetic cannabinoids (nabilone, dronabinol) show short-term benefit in obstructive sleep apnea. CBD promising in REM sleep behaviour disorder and excessive daytime sleepiness; nabilone reduces PTSD-associated nightmares and improves sleep in chronic pain patients. Research overall at an early stage with mixed results.