Cannabis, Cannabinoids, and Sleep: a Review of the Literature.

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“The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication.

Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia.

Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term.

Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas.

CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain.

Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.”

https://www.ncbi.nlm.nih.gov/pubmed/28349316

Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease.

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“Several cannabinoids afforded in experimental models of Huntington’s disease (HD).

We investigated whether a 1:1 combination of botanical extracts enriched in either ∆⁸-tetrahydrocannabinol (∆⁸-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex®, is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD.

A Sativex-like combination of phytocannabinoids administered to R6/2 mice at the onset of motor symptoms produced certain benefits on the progression of striatal deterioration in these mice, which supports the interest of this cannabinoid-based medicine for the treatment of disease progression in HD patients.”

https://www.ncbi.nlm.nih.gov/pubmed/28333097

Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity.

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“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (THC/CBD, Sativex®, nabiximols) is available in numerous countries worldwide for the treatment of multiple sclerosis (MS)-related moderate to severe spasticity in patients who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

Twelve weeks’ therapy with THC/CBD improved MS-related spasticity in patients with an inadequate response to other anti-spasticity agents who had undergone a successful initial trial of THC/CBD therapy, according to the results of a pivotal phase 3 trial.

Improvements in spasticity were maintained in the longer term with THC/CBD with no evidence of dose tolerance, and results of real-world studies confirm the effectiveness of THC/CBD in everyday clinical practice.

Improvements in health-related quality of life and activities of daily living were also seen with THC/CBD.

THC/CBD is generally well tolerated; adverse effects such as dizziness may occur whilst the THC/CBD dosage is being optimized.

THC/CBD has low abuse potential and a low risk of psychoactive effects.

In conclusion, THC/CBD oromucosal spray is a useful option for the treatment of MS-related spasticity not completely relieved with current anti-spasticity medication.”

https://www.ncbi.nlm.nih.gov/pubmed/28293911

Cannabis Reduces Opioid Dose in the Treatment of Chronic Non-Cancer Pain

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“Cannabinoids block pain responses in virtually every laboratory pain model tested.

In models of acute or physiological pain, cannabinoids are highly effective against thermal, mechanical, and chemical pain, and are comparable to opioids in potency and efficacy.1 In models of chronic pain, cannabinoids exhibit efficacy in the modulation of both inflammatory2 and neuropathic pain.3

Recent reviews describe an endogenous cannabinoid system involved in pain modulation that produces analgesia through the same brainstem circuitry involved in opioid analgesia.1., 4., 5., 6. Although co-administration of Δ-9-tetrahydrocannabinol (THC) with μ opioid agonists can potentiate the antinociceptive effects of each agent, an opioid is not required for cannabinoid analgesia.5., 6. Co-administration of a cannabinoid may lead to a lower opioid requirement. In an N-of-1 trial, oral THC reduced the pain of familial Mediterranean fever such that the use of breakthrough opioid for pain relief decreased significantly.7

Recently, in Canada, the Medical Marijuana Access Program allows patients to apply to Health Canada for access to dried cannabis for medicinal purposes. Although smoked cannabis is not an ideal delivery system, it is efficient and results in plasma concentration curves parallel to those seen after intravenous administration.8 We present three patients who used small doses of smoked marijuana in combination with an opioid.

These cases are consistent with preclinical work demonstrating that cannabinoids exhibit analgesic effects and may potentiate the antinociceptive effects of opioids. These patients were able to decrease the dose of opioid by 60–100% as compared to before the regular use of smoked marijuana. With the introduction of smoked marijuana, each patient reported better pain control.

Unfortunately, the source of smoked marijuana used by patients, and the percentage of THC in it, is unknown. All patients reported previous exposure to cannabis at some time in their lives before the onset of their pain, and the relevance of this experience also is unknown. Standardized measures of pain were not used, and the information presented was based on the patients’ verbal report when they presented for follow-up appointments at the Pain Management Unit. Nonetheless, these cases suggest that further research regarding the role of cannabinoids as analgesics and the combination of cannabinoids with opioids in the control of pain is needed.”

http://www.jpsmjournal.com/article/S0885-3924(03)00142-8/fulltext

A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

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“Cannabidiol (CBD) is the second most abundant phytocannabinoid, after Δ9-tetrahydrocannabinol (THC) and was first isolated from the cannabis extract in 1940.

Given the increasing clinical use of CBD, and the numerous effects of CBD in the cardiovascular system, the aim of the present study was to systematically review and analyse in vivo studies evaluating the effects of CBD on alterations in haemodynamics.

From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke.

This meta-analysis and systematic review has highlighted the haemodynamic effects of CBD administration in vivo.

The positive effects induced by CBD include maintaining the fall in BP after global hypoxia, reducing the increase in MBP and HR post-stress, and increasing BF in ischaemia-reperfusion models.

It is possible that beneficial effects of CBD on haemodynamics occurs when the cardiovascular system is abnormally altered, suggesting that CBD may be used as a treatment for various cardiovascular disorders, such as hypertension, myocardial infarction and stroke.”

http://journal.frontiersin.org/article/10.3389/fphar.2017.00081/full

Cannabis in Chinese Medicine: Are Some Traditional Indications Referenced in Ancient Literature Related to Cannabinoids?

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“Cannabis sativa L. has been cultivated in China for millennia for use as a fiber, food, and medicine. Cannabis sativa L. (Cannabaceae) has a long history of utilization as a fiber and seed crop in China, and its achenes (“seeds”) as well as other plant parts have been recorded in Chinese medical texts for nearly 2000 years.

While the primary applications of cannabis in Chinese medicine center around the use of the achenes, ancient indications for the female inflorescence, and other plant parts include conditions such as pain and mental illness that are the subject of current research into cannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC).

In this article, prominent historical applications of cannabis in Chinese medicine are chronologically reviewed, and indications found in ancient Chinese literature that may relate to cannabinoids such as CBD and Δ9-THC are investigated.

In recent years, cannabinoids such as CBD and Δ9-THC have attracted increased attention in the context of modern pharmacology and popular Western culture, yet little research has been done to explore the historical applications of cannabis in Chinese medicine. Given China’s long history of hemp cultivation and its rich body of un-translated medical literature, it is surprising that little academic attention has focused on exploring the ways in which cannabis was used in Chinese medicine. The importance of cannabis as a fiber and food crop in ancient China, combined with the extensive use of the achenes in medicine, makes the Chinese historical record particularly valuable.

Bencao literature opens a window into the history and culture of ancient Chinese medicine. As all parts of the cannabis plant were recorded in bencao texts, the Chinese medical literature can help to clarify many details about the historical applications of cannabis in Chinese medicine, as well as providing clues into the historical prevalence of different biotypes as ancient Chinese farmers gradually selected superior varieties for fiber and seed crops.

The significant differences in how cannabis has been employed in Chinese vs. Western medicine likely relate to differences between drug and fiber biotypes as well as cultural factors, but thus far minimal research has focused on exploring this issue. Similarly, minimal attention has been given to the topic of CBD in Chinese medical history, as even fiber-rich biotypes of cannabis that were not associated with drug use may have had potential therapeutic applications related to CBD. While this modest review can only scratch the surface of the Chinese medical literature of cannabis and the questions it raises, it is hoped that further research will help to further elucidate these questions using a multidisciplinary approach.”

http://journal.frontiersin.org/article/10.3389/fphar.2017.00108/full

Cannabis for Pain and Headaches: Primer.

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“Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research.

Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders.

Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects.  Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects.

This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.”

https://www.ncbi.nlm.nih.gov/pubmed/28281107

Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

 

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“The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases.

Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies.

This article reviews the most important current data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy.

Expert commentary: From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity.

Clinical trials have confirmed its efficacy and tolerability.

Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.”

https://www.ncbi.nlm.nih.gov/pubmed/28276775

Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go?

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“Fifty years after the discovery of Δ9-tetrahydrocannabinol (THC) as the psychoactive component of Cannabis, we are assessing the possibility of translating this herb into clinical treatment of inflammatory bowel diseases (IBDs).

Here, a discussion on the problems associated with a potential treatment is given.

From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite.

Single ingredients from Cannabis, such as THC and cannabidiol, commonly described as cannabinoids, are responsible for these effects. Synthetic cannabinoid receptor agonists are also termed cannabinoids, some of which, like dronabinol and nabilone, are already available with a narcotic prescription.

Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided.

Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.”

Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

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“Tetrahydrocannabinol (THC) is the main psychoactive substance in cannabis. Cannabidiol (CBD) is a cannabinoid that appears in cannabis resin but rarely in herbal cannabis. In recent years, many positive attributes have been ascribed to CBD. Is cannabis that contains CBD less harmful than cannabis without CBD? Are people who smoke cannabis resin, therefore, less susceptible to psychosis or less likely to become addicted than are people who smoke herbal marijuana?

Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD).

Most recreational users will never be faced with persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction.

Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC.

Few or no adverse effects of CBD have been proffered, and where CBD has been found to have an effect, it is usually in a “positive” (i.e., salubrious) direction. The evidence favoring a beneficial effect of CBD therefore merits further investigation in studies in which the amounts and ratios of CBD and THC correspond to the daily practices of recreational cannabis use.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797438/

“Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC.” https://www.ncbi.nlm.nih.gov/pubmed/24137134

“CBD may also potentiate some of Δ9-THC’s beneficial effects as it reduces Δ9-THC’s psychoactivity to enhance its tolerability and widen its therapeutic window.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707667/