Seriousness of medical condition(s)
The Sleep Health Foundation’s July 2019 report highlights:
- Prevalence of chronic insomnia was 14.8%, when classified by the International Classification of Sleep Disorders, version 3 criteria
- Over half (59.4%) of respondents overall report experiencing at least one sleep symptom three or more times a week (high frequency). These include trouble falling asleep, staying asleep or waking too early and not being able to get back to sleep (Reynolds et al, 2019)
- The type of symptom varied, with waking up overnight or early in the morning more common in older people and difficulty falling asleep more frequent in the young. Waking up a lot overnight was reported by 47% of those 65 years and over, compared with 22% of 18 to 24 year olds. Difficulty falling asleep was reported by 32% of 18 to 24 year olds and 25% of those 65 years and over
- Significantly more female respondents than male respondents reported “often or always” worrying about getting a good night’s sleep (31% vs 21%) and being overwhelmed by thoughts when trying to sleep (35% vs 25%)
- Of respondents, 48.8% reported that their daily routine does not provide adequate opportunity to sleep all or most of the time
More than half of adult Australians are suffering from at least one chronic sleep symptom that is affecting their ability to live a healthy, happy life, new research shows.
A report commissioned by Sleep Health Foundation reveals how common symptoms of insomnia is across the adult population. It found almost 60 per cent of people regularly experience at least one sleep symptom (like trouble falling or staying asleep), and 14.8 per cent have symptoms which could result in a diagnosis of clinical insomnia. (Amy C Reynolds, Sarah L Appleton, Tiffany K Gill & Robert J Adams, 2019)
Who could benefit from this treatment?
Clinical justification for using Medicinal Cannabis
- The medicinal cannabis’s suitability for the intended indication and
- the medicinal cannabis’s efficacy and expected benefits
Given how important quality sleep is for optimizing mental and physical wellbeing, it is alarming how pervasive sleep disturbances are throughout society (Ellis et al, 2012) The limited effectiveness and risk of undesirable and potentially dangerous side effects of conventional pharmaceutical sleep aids (Morin et al, 2012) result in nearly 50% dissatisfaction rates (Chung et al, 2016)
Evidence indicates that following cannabis use there may be a decrease in slow wave sleep (SWS) times and a corresponding increase in time spent in stage 2 sleep. Among those with a medical condition that impacts upon sleep, reductions in sleep disturbance (not necessarily causing early awakening) appear to improve quality of sleep (Gates et al, 2014)
In one study, 74% of the 1,000 interviewees said they used cannabis to help them sleep — 84% of whom said the cannabis had helped them, and over 83% said that they had since reduced or stopped taking over-the-counter or prescription sleep aids. The study suggests that cannabis could lower opioid use. However, the researchers caution that more needs to be done to understand the potential therapeutic benefits of cannabis. (Taylor & Francis Group, 2019)
CBD has demonstrated preliminary efficacy for a range of physical and mental health care problems. In the decade before 2012, there were only 9 published studies on the use of cannabinoids for medicinal treatment of pain; since then, 30 articles have been published on this topic, according to a PubMed search conducted in December 2017. Most notable was a study conducted at the University of California, San Diego’s Centre for Medicinal Cannabis Research that showed cannabis cigarettes reduced pain by 34% to 40% compared with placebo (17% to 20% decrease in pain) (Abrams et al, 2007). In particular, CBD appears to hold benefits for a wide range of neurologic disorders, including decreasing major seizures. A recent large, well-controlled study of paediatric epilepsy documented a beneficial effect of CBD in reducing seizure frequency by more than 50% (Devinsky et al, 2017). In addition to endorphin release, the “runner’s high” experience after exercise has been shown to be induced in part by anandamide acting on CB1 receptors, eliciting anxiolytic effects on the body. (Fuss et al, 2015)
A crossover study comparing CBD with nitrazepam found that high-dose CBD at 160 mg increased the duration of sleep. The higher doses of CBD that studies suggest are therapeutic for anxiety, insomnia, and epilepsy may also increase mental sedation (Shannon et al, 2012).
- any unknown or expected adverse effects, risks and safety issues & d. related toxicology:
A systematic review by Whiting et al. (2015) stated in their conclusions that “Cannabinoids were associated with an increased risk of short-term adverse effects”.
According to the Guidance for the Use of Medicinal Cannabis in Australia: Overview, Therapeutics Good Administration (2017):
Cannabis is not appropriate for patients who:
- Are under the age of 25 (with the exception of intractable epilepsy or severe pain syndrome)
- Have a personal history or strong family history of psychosis
- Have a current or past cannabis use disorder, or active substance use disorder
- Have unstable respiratory or cardiovascular disease (including angina, peripheral vascular disease, cerebrovascular disease, arrhythmias)
- Are pregnant, planning to become pregnant, or breastfeeding
Cannabis should be authorized with caution in patients who:
- Smoke tobacco
- Have risk factors for cardiovascular disease
- Are heavy users of alcohol
- Are taking sedating medications or any other medication metabolized by the CYP450 pathway
- At risk or have liver disease
Drug Interactions – CYP P450 Enzyme System
THC and CBD are metabolized by Cytochrome P450 enzyme system, including CYP1A2, CYP2C9, CYP2D6, CYP2C19 and CYP3A4. Based on in vitro and animal studies with cannabis, there is a potential for interactions with the medications metabolized by the P450 enzymes (2C9, 2C19, 3A4). It’s notable, however, that the inhibitory effects in vitro and in animal models were only seen at exposures significantly higher than the maximum observed in clinical trials. For instance, in clinical trials were Sativex® has been taken concomitantly with other drugs metabolized by the Cytochrome P450 enzyme system, no clinically apparent drug-drug interactions have been seen in these trials at clinical doses. In an in vitro study with 1:1% (v/v) THC botanical drug substance (BDS) and CBD BDS, no relevant induction of the Cytochrome P450 enzymes was seen for human CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in human hepatocytes at doses of up to 1µM (314ng/mL) (Stout and Cimino, 2014).
Potential drug interactions
Increasing THC concentration:
Examples of inhibitors:
– Antidepressants (e.g. Fluoxetine, Fluvoxamine)
– Proton Pump Inhibitors (e.g. Omeprazole)
– Macrolides (Clarithromycin, Erythromycin)
– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)
– Calcium Antagonists (e.g. Diltiazem, Verapamil)
– HIV protease inhibitors (e.g. Ritonavir)
– Grapefruit juice
Increasing CBD concentration:
– Metabolized by CYP 2C19 and CYP 3A4
– Bioavailability could be increased by many of the same substances as for THC
Decreasing THC and CBD concentration:
- CYP 2C9 and 3A4 Inducers accelerate THC and CBD metabolism
- Examples of inducers:
– Saint John’s Wort
Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen in the study by Gaston et al (2017) on interactions between cannabidiol (Epidiolex®) and commonly used antiepileptic drugs. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with supraphysiological doses of CBD (e.g. 1000mg/kg).
- Caution with blood thinners like Warfarin, Heparin, Clopidogrel (Plavix)
- Additionally, pharmacodynamic interactions should be expected between cannabis and drugs with sympathomimetic activity (tachycardia, hypertension), central nervous system depressants (drowsiness, ataxia), and drugs with anticholinergic effects (tachycardia, drowsiness).
Many of these drug interactions can be mitigated in complex patients with polypharmacy by slowly titrating cannabis.
Approved treatments for this medical condition
Sleep disorders require a multidisciplinary approach that includes lifestyle and behaviour modifications. There are several pharmaceutical products available for the treatment of pain.
The recommended sequence of medication trials for patients experiencing insomnia is
- Short- or intermediate-acting benzodiazepine receptor agonists (BzRAs) or the melatonin agonist ramelteon.
- Alternative short- or intermediate-acting BzRAs or ramelteon if the initial agent was ineffective.
- Sedating antidepressants (e.g., trazodone, amitriptyline, doxepin, or mirtazapine).
- The combination of a BzRA or ramelteon with a sedating antidepressant.
- Other sedating agents, such as antiepilepsy medications or atypical antipsychotics.
(Lie et al, 2015)
Why is medicinal cannabis appropriate for use?
Standard treatments, as listed above, are not always effective for symptomatic control of insomnia and importantly are associated with a range of side effects. Whilst some people are able to tolerate these, in many cases, they are not and/or the long-term potential side effects of their use may be unacceptable. Side effects for those individual drugs can be found at MIMS.
The immediate dangers of sleeping pills range from minor fatigue to coma. Some of these side effects can even lead to deadly overdoses. Some patients experience undesired side-effects from sleep medications, including, but not limited to:
- Dry mouth
- Difficulty with coordination
- Daytime drowsiness
- Memory loss
- Unusual dreams
- Itching and swelling
- Depressed breathing rate
Dependency and withdrawal can also be problematic in patients with insomnia who are taking these medications long-term.
Effects of THC and CBD on sleep quality and the sleep–wake cycle have been experienced in some patients. The effects on REM have been found to vary by dosage such that high-dose CBD increased REM sleep latency on the day of administration and midrange dose CBD decreased REM sleep latency the day after administration. Meanwhile, Hsiao and colleagues found that CBD blocked anxiety-induced REM sleep suppression but had no effect on NREM sleep. This work is further supported by a recent case report in which administration of CBD oil reduced insomnia symptoms and PTSD-related sleep disturbances. Together, these findings suggest that CBD may impact sleep quality through its anxiolytic effects (Shannon et al, 2019)
- Abrams D.I. et al. Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology 2007.68(7):515-521
- Bachhuber, M., Arnsten, J., & Wurm, G. (2019). Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary. Journal Of Psychoactive Drugs, 51(5), 400-404. doi: 10.1080/02791072.2019.1626953
- Chung, S., Youn, S., Yi, K., Park, B., & Lee, S. (2016). Sleeping Pill Administration Time and Patient Subjective Satisfaction. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 12(1), 57–62. https://doi.org/10.5664/jcsm.5394
- Devinsky, O., Cross, J., Laux, L., Marsh, E., Miller, I., & Nabbout, R. et al. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal Of Medicine, 376(21), 2011-2020. doi: 10.1056/nejmoa1611618
- Ellis, J. G., Perlis, M. L., Neale, L. F., Espie, C. A., & Bastien, C. H. (2012). The natural history of insomnia: focus on prevalence and incidence of acute insomnia. Journal of psychiatric research, 46(10), 1278–1285. https://doi.org/10.1016/j.jpsychires.2012.07.001
- Fuss, J., Steinle, J., Bindila, L., Auer, M., Kirchherr, H., Lutz, B., & Gass, P. (2015). A runner’s high depends on cannabinoid receptors in mice. Proceedings Of The National Academy Of Sciences, 112(42), 13105-13108. doi: 10.1073/pnas.1514996112
- Gates, P., Albertella, L., & Copeland, J. (2014). The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Medicine Reviews, 18(6), 477-487. doi: 10.1016/j.smrv.2014.02.005
- Lie, J. D., Tu, K. N., Shen, D. D., & Wong, B. M. (2015). Pharmacological Treatment of Insomnia. P & T : a peer-reviewed journal for formulary management, 40(11), 759–771.
- Morin, C. M., & Benca, R. (2012). Chronic insomnia. Lancet (London, England), 379(9821), 1129–1141. https://doi.org/10.1016/S0140-6736(11)60750-2
- Shannon, S. (2019). Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente Journal. doi: 10.7812/tpp/18-041
- Vigil, J. M., Stith, S. S., Diviant, J. P., Brockelman, F., Keeling, K., & Hall, B. (2018). Effectiveness of Raw, Natural Medical CannabisFlower for Treating Insomnia under Naturalistic Conditions. Medicines (Basel, Switzerland), 5(3), 75. https://doi.org/10.3390/medicines5030075
- Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313(24):2456-73. Errata in: JAMA 2016;315(14):1522, JAMA 2015;314(21):2308, JAMA 2015;314(5):520, JAMA 2015;314(8):837.