Cannabis and Sleep Disturbances: What You Need to Know
Sleep disturbances are the most common health problem in America. Those with sleep issues are poorly served by prescription and over-the-counter sleeping pills and other pharmaceuticals, which have serious risks.
CBD and other plant cannabinoids show promise for treating insomnia, sleep apnea, narcolepsy, and other sleep-related disorders.
Although sleep is essential for our health, its biological purpose is not fully understood. Oddly, the seemingly inactive state of sleep is actually a dynamic and critical process that helps us store memories, build immunity, repair tissue, regulate metabolism and blood pressure, control appetite and blood sugar, and process learning, along with a myriad of other physiological processes – all of which are regulated by the endocannabinoid system (ECS).
According to the National Institute of Neurological Disorders and Stroke at the National Institute of Health (NIH), new findings suggest “sleep plays a housekeeping role that removes toxins in your brain that build up while you are awake.”
Poor sleep is the number one reported medical complaint in the Unites States and a serious public health concern. The average adult needs between seven and eight hours of sleep per day. Yet, 10-30 million Americans regularly don’t get enough sleep.
Over 60 percent of American adults report having problems sleeping several nights per week.
Over 40 million Americans suffer from more than 70 different sleep disorders. The most common sleep-related ailments include:
- Insomnia - when one cannot fall asleep or stay asleep.
- Sleep apnea - which involves impaired breathing while sleeping.
- Restless leg syndrome - characterized by tingling, discomfort and even pain in the legs that increases at night and is relieved by movement.
- Circadian rhythm disorders - when one’s internal clock is off and one’s sleep patterns are disturbed.
- Parasomnias - which entails abnormal movements and activities while sleeping, including sleep walking and nightmares.
- Excessive daytime sleepiness - when an individual experiences persistent drowsiness during daylight hours from narcolepsy or another medical condition.
Poor sleep is a risk factor for serious illness. Compared to people who get enough sleep, adults who are short-sleepers (less than 7 hours per 24-hour period) are more likely to experience one or more of 10 chronic health conditions, including obesity, heart disease, diabetes, arthritis, stroke and depression.
Those with chronic illnesses are at greater risk for insomnia, which exacerbates their discomfort. Comorbid medical disorders – including conditions that cause hypoxemia (abnormally low blood oxygen levels) and dyspnea (difficult or labored breathing), gastroesophageal reflux disease, pain, and neurodegenerative diseases – have a 75-95 percent increased risk of insomnia.
Pills that killIn 2016, according to the industry research firm MarketsandMarkets, Americans spent $3.38 billion on prescription sedatives and hypnotics, over-the-counter (OTC) sleep drugs, and herbal sleep aids. It’s projected that the market for such products will experience about a 4.5 percent growth rate between now and 2021.
The quest for good night’s sleep can be hazardous to one’s health. Daniel F. Kripke, MD, sleep expert and co-founder of Research at Scripps Clinic Vitebri Family Sleep Center, discusses the dangers of sleep aids in his paper “Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit.”
Dr. Kripke reviewed 40 studies conducted on prescription sleeping pills, which include hypnotic drugs such as zolpidem (Ambien, Edlmar, Intermezzo and Zolpimist), temazepam (Restoril), eszopiclone (Lunesta), zaleplon (Sonata), triazolam (Halcion), flurazepam (Dalmane and Dalmadorm), quazepam, and other barbiturates used for sleep. Of these 40 studies, thirty-nine found that consumption of hypnotics is “associated with excess mortality” to the tune of a 4.6 times greater risk of death for hypnotic users.
Grim statistics: 10,000 deaths per year are directly caused by and attributed to hypnotic drugs, based on medical examiner data. However, large epidemiological studies suggest the number of fatalities may actually be closer to 300,000-500,000 per year. The difference can be attributed to underreported use of hypnotics at the time of death and the fact that prescription hypnotics are rarely listed as the cause of death.
Dr. Kripke concludes that even limited use of sleeping pills causes “next day functional impairment,” increases risk of “on-the-road driver-at-fault crashes,” increases falls and accidental injuries especially among seniors, is associated with “2.1 times” as many new depression incidents compared to randomized placebo recipients, and increases the risk of suicide. Furthermore, the use of opioids combined with hypnotics – two known dose-dependent respiratory suppressants – can be extremely dangerous, especially when mixed with alcohol and other drugs.1
Alarming dataAnother concern: Data from controlled hypnotics trials resulted in 12 cancers in hypnotic participants compared to zero cancers in the placebo group. (When the FDA conducted the same audit, they found 13 cancers.) But it is unclear if the hypnotics were a causative factor in these cancers or if they were promoting progression of cancer that had previously gone undetected. Animal and in vitro (test tube/petri dish) studies also attest to the pro-cancer potential of hypnotics. To learn more visit Dr. Kripke’s website.
In addition to these risks, meta-data (combined data) from placebo-controlled randomized clinical trials showed participants in the hypnotic groups had a 44 percent higher infection rate than the placebo participants.
Are over-the-counter sleep aids any better? These also have adverse side effects. Most OTC sleeping pills (Benadryl and others) have the antihistamine diphenhydramine as the primary ingredient. It can knock you out, but it’s unlikely to provide truly restful sleep.
In an email exchange with Project CBD, Dr. Kripke writes: “Usage of diphenhydramine is associated with developing Alzheimer’s disease, though which is cause and which is effect is certainly unclear. One well-known aspect of diphenhydramine is that it is anticholinergic [blocks the neurotransmitter acetylcholine], that produces some heart symptoms sometimes as well as digestive symptoms such as constipation. In some patients, also, diphenhydramine at night causes rather a lot of daytime sleepiness.”
A large number of OTC sleep aids also include acetaminophen, a pain reliever that has a narrow therapeutic window – meaning at one dose it’s therapeutic, but the slightest increase can be toxic to the liver. All too often consumers don’t read the warning labels about these drugs and consume them with alcohol and other meds. This can cause liver toxicity and/or fatal respiratory suppression.
OTC sleep aids are intended only for occasional or short-term use – never more than two weeks at one time. Although it is not typically reported in the published literature, those who use OTC and prescription sleep aids find that once they start it’s hard to stop.
The endocannabinoid system and sleepGiven the problems with conventional soporifics, medical scientists have been exploring other ways to improve sleep by targeting the endocannabinoid system (ECS). As the primary homeostatic regulator of human physiology, the ECS plays a major role in the sleep-wake cycle and other circadian processes.
Italian scientist Vicenzo DiMarzo summarized the broad regulatory function of the endocannabinoid system in the phrase “Eat, sleep, relax, protect and forget.”
How we fall asleep, stay asleep, wake up, and remain awake is part of an internal biological process regulated by our circadian rhythms and our endocannabinoid system. Circadian rhythms govern a diverse array of actions in the body, including hormone production, heart rate, metabolism, and when to go to sleep and wake up.
It’s as if we have an internal biochemical timer or clock that keeps track of our need for sleep, guides the body to sleep and then influences the intensity of sleep. This biological mechanism is affected by external forces such as travel, medication, food, drink, environment, stress and more.
Key question: Does the endocannabinoid system regulate our experience of circadian rhythms or vice versa?
Evidence of a strong relationship between the two is observed in the sleep-wake cycle fluctuations of anandamide and 2-AG (the brain’s own marijuana-like molecules), along with the metabolic enzymes that create and break down these endogenous cannabinoid compounds.
Anandamide is present in the brain at higher levels at night and it works with the endogenous neurotransmitters oleamide and adenosine to generate sleep. Conversely, 2AG is higher during the day, suggesting that it is involved in promoting wakefulness.
The highly complex sleep-wake cycle is driven by a variety of neurochemicals and molecular pathways.2 Both anandamide and 2AG activate CB1cannabinoid receptors that are concentrated in the central nervous system, including parts of the brain associated with regulating sleep.
CB1 receptors modulate neurotransmitter release in a manner that dials back excessive neuronal activity, thereby reducing anxiety, pain, and inflammation. CB1 receptor expression is thus a key factor in modulating sleep homeostasis.
This is not the case, however, with respect to the CB2, the cannabinoid receptor located primarily in immune cells, the peripheral nervous system, and metabolic tissue. Whereas CB1 receptor expression reflects cyclical circadian rhythms, no such fluctuations have been described for the CB2 receptor.
The challenge of studying and treating sleep disturbances is complicated by the fact that sleep disorders are symptomatic of many chronic illnesses. In many cases, poor sleep results in chronic illness, and chronic illness always involves an underlying imbalance or dysregulation of the endocannabinoid system. Although we still have much to learn about the relationship between the ECS and circadian rhythms, it’s clear that adequate quality sleep is a critical component of restoring and maintaining one’s health.
Cannabis for slumberCannabinoids have been used for centuries to promote sleepiness and to help people stay asleep. In the acclaimed medical reference Materia Medica, published in the 18th century, cannabis was listed as a ‘narcotica’ and ‘anodyna’ (pain reliever). Its reintroduction to Western medicine by Sir William B. O’Shaughnessy in 1843 led to studies that underscored the remedial properties of “Indian hemp” for sleep disorders.
“Of all anaesthetics ever proposed, Indian hemp is the one which produced a narcotism most closely resembling the natural sleep without causing any extraordinary excitement of the vessels, or any particular suspension of secretions, or without fear of a dangerous reaction, and consecutive paralysis,” German researcher Bernard Fronmueller observed in 1860.
Nine years later Fronmueller reported that in 1000 patients with sleep disturbance, Indian hemp produced cures in 53 percent, partial cure in 21.5 percent, and little or no effects in 25.5 percent.
Sleep-related problems continue to drive a large percentage of people to seek relief with cannabis.
Poor sleep and lack of sleep cause physiological changes in the body after just one night, resulting in slower reaction times, deceased cognitive performance, less energy, aggravated pain and inflammation, and in many cases overeating or cravings for high-fat, high-carbohydrate “comfort” foods.
A 2014 study by Babson et al notes that approximately 50 percent of long-term cannabis consumers (over 10 years) report using cannabis as a sleep aid. Among medical marijuana patients, 48 percent report using cannabis to help with insomnia.
Another study revealed that 40 percent of insomniacs also suffer from anxiety and depression or another a psychiatric disorder. (Roth, 2007) Would it surprise you to learn that people with mood disorders who use cannabis have the highest rates of sleep benefit at 93 percent? (Babson & Bonn-Miller, 2014)
What about specific plant cannabinoids for sleep?
Cannabidiol (CBD) is alerting or mildly stimulating in moderate doses, while its psychoactive counterpart delta 9-tetrahydrocannabinol (THC) tends to be sedating. However, the science is somewhat paradoxical.
Research data and anecdotal accounts indicate that CBD and THC have differential effects on sleep – both can be alerting or sedating depending on dosage.
The biphasic dose response triggered by CBD and THC is one of the factors that may contribute to conflicting research results with respect to cannabinoids and sleep.3
The association between low-dose cannabidiol and increased wakefulness underscores CBD’s potential as a treatment for narcolepsy and other variants of excessive daytime sleepiness.
Curiously, CBD can help people fall asleep as well as stay awake. An insomnia study indicated that the administration of 160 mgs of CBD decreased nighttime sleep interruptions and increased total sleep time, suggesting that high-dose CBD therapy can improve the quality and duration of sleep.
In addition to showing promise as a safe and effective alternative to conventional psychiatric treatments for insomnia, cannabidiol can reduce symptoms of REM behavior disorder (RBD), which is characterized by the acting out of vivid, intense, and sometimes violent dreams. A preliminary study examined the efficacy of CBD in patients with both Parkinson’s disease and RBD and the results were encouraging.
Obstructive sleep apnea (OSA) is a prevalent form of sleep disorder breathing that affects nine percent of American adults. Research involving animal models of this condition has shown that THC and the endogenous cannabinoid oleamide are effective in reducing sleep apnea events. (Babson 2017) Human studies indicate that dronabinol, a FDA-approved synthetic version of THC, reduces sleep apnea and is safe and well tolerated.
Additionally, cannabinol (CBN), most commonly associated with aged cannabis, is said to potentiate the sedative properties of THC when these two cannabinoids are used together, although this notion may be more modern-day marijuana folklore than scientific fact.
Pain and sleep
Besides the desire for good sleep, treating pain is another common reason for using cannabis. Chronic pain is a major public health issue that directly affects around 20 percent of U.S. adults, many of whom also suffer from diminished sleep. Sometimes it’s hard to know if the pain is causing sleeplessness or if sleeplessness is triggering the pain.
Patients seeking both pain relief and better sleep may achieve positive results with cannabinoids and other cannabis components.4 In their paper “Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis-Based Medicine,” Russo et al summarized 13 studies that examined varying cannabis preparations for pain and sleep.
Of particular interest is a Phase II study, involving 24 patients with intractable multiple sclerosis, which compared three different preparations: Tetranabinex (a high THC product); Nabindolex (high CBD); and Sativex® (an almost a 1:1 THC:CBD sublingual remedy).
Different cannabinoid ratios helped in various ways: “Compared to placebo, the CBD-predominant extract significantly improved pain, the THC-predominant extract yielded significant improvement in pain, muscle spasm, spasticity and appetite, and combined THC:CBD extracts (Sativex®) significantly improved muscle spasm and sleep.”
The authors concluded that a combination of CBD and THC (15 mg of each) “improved sleep synergistically.” Of the thirteen studies profiled in this paper, seven showed improvements in sleep. Six of the seven were conducted with Sativex®, the 1:1 CBD:THC sublingual spray, indicating that balanced a cannabinoid profile facilitates sleep improvements among patients with chronic pain.5
The gift of forgetting
The use of cannabis is prevalent among those who suffer from post-traumatic stress disorder (PTSD). A small open trial conducted in Israel showed that 5 mg of smoked THC twice a day resulted in improved sleep and reduced frequency of nightmares in patients with PTSD. (Mechoulam, 2015) This directly correlates with similar test results involving nabilone, a synthetic THC-like drug.
Memory processing occurs when we are asleep, so it stands to reason that someone suffering from PTSD– especially those who experience nightmares – would benefit by using cannabis or cannabinoids to sleep better.
At first glance, it may appear that cannabis is merely a coping mechanism for PTSD patients; it is sometimes negatively characterized this way in the medical literature. Thus far, the majority of studies involving cannabinoids and PTSD have been conducted from an addiction perspective – will cannabis harm PTSD patients and turn them into addicts? – but that may be changing.
Increasingly researchers are recognizing the limitations of the addiction framework, which overlooks the crucial role that the endocannabinoid system plays in helping us forget painful memories, a normal process that is somehow dysregulated when one experiences PTSD.
In some cases, THC and other plant cannabinoids can provide enough relief so that PTSD sufferers are able to embark upon the task of making sense of their traumatic memories and begin the healing process. None of that can happen without quality sleep.
“If you can’t sleep your world goes to hell in a hand basket real fast,” said Al Byrne, a U.S. Navy veteran and medical marijuana advocate.
Many military veterans and victims of sexual abuse are using cannabis to treat their PTSD-related symptoms. A 2016 case study provided clinical data that validated the use of CBD-rich oil as a safe and effective treatment for reducing anxiety and improving sleep in a young girl with PTSD.
Pharmaceuticals provided minimal relief for a 10-year-old girl who had been sexually abused as a young child. And her meds caused major adverse side effects. But a CBD-rich oil regimen resulted in “a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.”
This is not an isolated example. CBD-rich oil, an increasingly popular treatment for anxiety and sleep problems, has emerged in recent years as a viable alternative to Big Pharma drugs.
Dosing for slumber
Cannabis therapeutics is personalized medicine – and this is certainly true with respect to using the herb and its components to treat sleep disorders. The effectiveness of cannabis as a sleep aid is highly variable, depending on the individual user, how the remedy is administered, its cannabinoid ratio and aromatic terpene profile, the timing and dosage – all these factors come into play and influence different outcomes.
Success may rest upon how well one manages the psychoactive qualities of cannabis. As with any medicine, there are some risks involved when consuming cannabis to sleep better. Short-term use of cannabis may decrease sleep onset latency (how long it takes to fall asleep). But this improvement may weaken over time. Tolerance develops with chronic consumption, which can impair long term sleep quality.
Too much of a good thing can be problematic for frequent recreational cannabis users, who may begin to experience a reduction in slow-wave deep sleep, leaving the individual feeling like they are not well rested. Could this be because recreational users tend to prefer large amounts of THC-dominant cannabis varieties?
Sleep disturbance, ironically, is perhaps the most notable withdrawal symptom when a heavy user stops smoking marijuana. Compared to kicking addictive pharmaceuticals, cannabis withdrawal is a minor discomfort with symptoms typically lasting for a few days (sometimes a few weeks) after cessation. And cannabis, unlike prescription and over-the-counter sleep aids, has never killed anyone.
Medical cannabis users often experience better outcomes with lower doses, especially when they are treating something in addition to sleep disturbances, such as pain, spasticity, or post traumatic stress disorder. Based on the available literature reviewed by Project CBD, it appears that a 1:1 CBD:THCpreparation will most likely confer restorative sleep. Cannabis-naïve patients may find relief with as little as 2.5 mg of THC and 2.5mg CBD. A somewhat higher dose – 5 to 15 mg each of THC and CBD – may work wonders for experienced cannabis users.
The combination of odiferous terpenes present in a given cannabis strain or product can also significantly impact sleep. Individual terpenes have sedating or stimulating effects, thus affecting the sleep-wake cycle. Terpenes can be therapeutic in their own right. As important modulators of cannabinoids, terpenes contribute significantly to how a given cannabis strain or cultivar makes one feel.
Sedating terpenes include terpinolene, nerolidol, phytol, linalool, and myrcene. In addition to causing the infamous “couch-lock” effect at high levels (+0.5%), myrcene can be mildly stimulating at lower levels. Those trying to address pain and sleep issues should consider cannabis remedies that include beta-caryophyllene, as this terpene is also a strong anti-inflammatory and pain-reliever.
Practical Tips for Improving Sleep
In a study published in the Journal of the American Medical Association, 27 percent of respondents indicated that they used complementary, non-pharmaceutical therapies for fatigue and 26.4 percent for sleep deprivation.
Here are a few simple lifestyle modifications and holistic healing options that may improve your sleep quality.
- Create an inviting sleep environment. Having a comfortable bed in a relaxing environment is key to quality sleep. Reduce outside or harsh overhead lighting and maintain a comfortable temperature for sleeping. And, reduce noise. If you are a light sleeper consider using a white noise machine to drown out unwanted sound. Salt lamps may help clean the air by reducing negative ions (and provide enough light to get to the bathroom without intruding on sleep).
- Have a sleep routine. Going to bed and waking at the same time seven days a week is optimal. Additionally, it is helpful for some people to have a relaxing bedtime routine that lets the mind know it is time to get sleepy. This may include a small warm cup of milk or green tea 45 minutes to an hour before bed, or a few simple yoga stretches to relax, or an Epsom salt bath.
- Avoid overstimulation. It is best not to have a television in the bedroom and not to watch violence shows before bedtime, especially for those with adrenal fatigue. Avoid reading or using your phone, laptop or tablet in bed.
- Exercise daily. Regardless if your preference is jogging, weightlifting, gardening, walking or tai chi, do some form of exercise every day. But avoid exercising within two hours of bedtime.
- Avoid stimulants after 1PM. Caffeine, alcohol, tobacco, certain herbal supplements and drugs may leave you feeling “hyper” and overstimulated, which can impede the brain’s ability to transition into sleep.
- Aromatherapy. Many of the sedating essential oil components present in cannabis can also be found in other plants at your local grocery or natural products store, along with misters that spay the oil into the air. Aromatherapy can be relaxing and very helpful to induce sleep. Lavender essential oil, for example, can be help to manage certain sleep disorders.
- Use sleep supporting herbs. It is best to work with a healer or someone knowledgeable about herbs and supplements instead of buying whatever sleep cure is touted on the internet. Herbs that have sleep-promoting properties include Valerian, Kava, German Chamomile, Roman Chamomile, Passion Flower, California Poppy, Hops, Lemon Balm, Linden, Skullcap, and Oats. Visit the American Herbalist Guild to find a qualified practitioner.
- Nutritional supplements. Consult your physician about products made with Kava, calming minerals, and taking the right kind of magnesium at night.
- Other therapies. In addition to cannabis, safe holistic healing alternatives include cognitive-behavioral therapy for insomnia, and bright light therapy for circadian rhythm disorders.
Footnotes
1 In 2014, there were 47,055 accidental opiate overdose deaths. Dr. Daniel Kripke estimates one third of them also involved various hypnotics as a cause of death. It should be noted that cannabis has been shown to improve safety and effectiveness of opiates making it possible for the patient to take a lower dose, thereby reducing the risk of side-effects including death. In some cases, cannabis can replace both the opiate as an effective painkiller and the hypnotic.
2 Highly complex, the sleep-wake cycle is driven by various neurochemicals and brain pathways. Neuroscientist and sleep researcher Dr. Eric Murillo-Rodriguez, says that “Sleep is generated by sleep-promoting neurons placed in the anterior hypothalamus that utilize GABA to inhibit wake-promoting regions in the hypothalamus and brainstem. Then, the brainstem regions inhibited during wake and slow wave sleep become active during rapid eye movement sleep (REM).”
3 In “The effects of cannabinoid administration on sleep: a systematic review of human studies,” Gates et al scrutinized cannabis-related sleep studies prior to 2012. But they found “little consistency in the results [of] six studies with objective sleep measures. Slow wave sleep was described as increasing for a week in one study, whereas three studies reported a decrease in slow wave sleep, and one study showed no change. Rapid eye movement sleep was reported to increase in one study, decrease in a second study, while four studies showed no effect. Stage two sleep [see sidebar] was reported to increase in two studies, while four studies showed no effect. Sleep latency was reported to increase in one study, decrease on a high THC dose in a second study, while two studies showed no effect and two studies did not measure sleep latency.”
4A 2014 article by Babson & Bonn-Miller indicated that over 83 percent of surveyed patients taking cannabis for pain said they experienced improved sleep.
5Nicholson et al had similar results in a double-blind placebo-controlled with a 4-way crossover design study evaluating the effect of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness in eight subjects ages 21-34 years old. A cross-over design is one where each group of participants take two or more interventions; in this case four different preparations were tested, including THC (15 mg) alone; THC and CBD together (5 mg each and 15 mg each); and a placebo. They scientists found that “although impaired memory was observed the next day when 15 mg THC was given alone overnight, there were no effects on memory when 15 mg THC was ingested with 15 mg CBD.” They also found that the effects of THC and CBD appeared to be dose dependent as evidenced by the fact that 7.5 mg of THC did not impair memory, but 15 mg did.
Copyright, Project CBD. May not be reprinted without permission.
Sources
- Americal Sleep Association. (2017, July 7). Sleep Statistics. Retrieved from American Sleep Associaton:https://www.sleepassociation.org/sleep/sleep-statistics/
- Babson, Kim A., Bonn-Miller, Marcel O. (2014). Sleep Disturbances: Implications for Cannabis Use, Cananbis Use Cessation, and Cananbis Use Treatment. Current Addiction Reports, 109-114.
- Babson, Kimberly A. and James Sottile, Danielle Morabito. 2017. “Cannabis, Cannabinoids, and Sleep: Review of the Literature.” Current Psychiatry Report.
- Centers for Disease Control and Prevention. (2017, May 2). Sleep & Sleep Disorders. Retrieved from Centers for Disease Control and Prevention: https://www.cdc.gov/sleep/data_statistics.html
- Ferguson, G. and Ware, M.A. (2015). Review Article: Sleep, Pain and Cananbis. Journal of Sleep Disorders & Therapy,https://www.omicsgroup.org/journals/review-article-sleep-pain-and-cannab….
- Gates, Peter J and Lucy Albertella, Jan Copeland (2014). The effects of cannabinoid administration on sleep: a systemc review of human studies. Sleep Medicine Reviews,https://www.researchgate.net/profile/Peter_Gates/publication/260604558_T….
- Gyllenhaal, Charlotte, et al. Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Medicine, Vol. 4, No. 3, pp 229-251, 2000.
- Kripke, D. (2016). Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit [version 1;.F1000 Research, https://mechanism.ucsd.edu/teaching/f16/cogs200/Kripke%202016%20F1000Res….
- Lee, Martin A. Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific. New York: Scribner, 2013.
- Mechoulam, R. (2015). Cannabis - The Israeli perspective. Basic Clinical Physiology Pharmacology,https://www.researchgate.net/profile/Raphael_Mechoulam2/publication/2823….
- Mechoulam, Raphael and L.A. Parker (2013). The Endocannaboind System and the Brain. The Annual Review of Psychology, 21-47.
- Murillo-Rodriquez, Eric and Jose Carlos Pastrana-Trejo, Mireille Salas-Crisostomo, and Miriel de-la-Cruz (2016). The Endocannabinoids System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. CNS &Neurological Disorders - Drug Targets, 370-379.
- Murillo-Rodriguez, E. (2008). The role of the CB1 receptor in the regulation of sleep. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 1420-1427.
- National Institute of Health. (2017). Brain Basics: Understanding Sleep. Retrieved from National Institute of Health: National Institute of Neurological Disorders and Stroke: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understa…
- National Institute of Neurological Disorders & Stroke. (2017, July 23). Brain Basics; Understanding Sleep. Retrieved from National Institute of Neurological Disorders and Stroke: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understa…
- Nicholson, A. N., Turner, C., Stone, B. M., & Robson, P. J. (2004). Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Journal of Clinical Pharmacology, 305-313.
- Pava, Matthew J., Alexandros Makriyannis, David M. Lovinger (2016). Endocannabinoids Signaling Regulates Sleep Stability. PLoSOne, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152473.
- Pava, Matthew J. et al (2014). Endocannabinoid Modulation of Cortical Up-States and NREM Sleep. PLoSONE,http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088672.
- Prospero-Garcia, Oscar et al (2016). Endocannabinoids and sleep. Neuroscience and Beobehavioral Reviews, 671-679.
- Russo, Ethan B. (2007). Cannabis, Pain and Sleep: Lessons from Therapeutic Clinical Trials of Sativex, a Cannabis-Based Medicine. Chemistry & Biodiversity, 1729-1743.
- Russo, E. B. (2001). Handbook of Psychotropic Herbs. Bringhamptom: The Hawthorne Press, Inc.
- Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effect. British Journal of Pharmacology, 1344-1364.
- Roth, T. (2007). Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical Sleep Medicine, S7-S10.
- Shannon, Scott and Janet Opila-Lehman. (2016) Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Permanente Journal. Fall 2016.
- Scheet, F. A. (2016). Hungry for Sleep: A Role for Endocannabinoids. Sleep, 495-496.