Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study

“Insomnia or difficulty falling and or staying asleep is experienced by up to 30% of the general population.

This randomised crossover double-blind placebo-controlled 6-week trial aimed to assess the tolerability and effectiveness of the Entoura-10:15 medicinal cannabis oil on sleep in adults with insomnia. A total of 29 participants with self-reported clinical insomnia completed the crossover trial. Participants were randomly allocated to receive placebo or active oil containing 10 mg/ml tetrahydrocannabinol (THC) and 15 mg/ml cannabidiol (CBD) over 2-weeks titrated 0.2-1.5 ml/day, followed by a 1-week wash-out period before crossover. Tolerability was assessed by daily diary. Effectiveness was measured by saliva midnight melatonin levels, validated questionnaires, i.e., the Insomnia Severity Index, and the Fitbit activity/sleep wrist tracker.

Entoura-10:15 medicinal cannabis oil was generally well tolerated, and was effective in improving sleep, whereby 60% of participants no longer classified as clinical insomniacs at the end of the 2-week intervention period. Midnight melatonin levels significantly improved in the active group by 30% compared to a 20% decline in the placebo group (p = 0.035). Medicinal cannabis oil improved both time and quality of sleep, in particular light sleep increased by 21 min/night compared to placebo (p = 0.041). The quality of sleep improved overall by up to 80% in the active group (pPhase2 = 0.003), including higher daily functioning (p = 0.032). Observed effects were more pronounced in Phase 2 due to the period effect and loss of blinding.

Entoura-10:15 medicinal cannabis oil was well tolerated and effective in improving sleep in adults with insomnia.”

https://pubmed.ncbi.nlm.nih.gov/36539991/

“In summary, our short-term trial suggests Entoura 10:15 medicinal cannabis oil, containing THC:CBD 10:15 and lesser amounts of other CBs and naturally occurring terpenes, to be well tolerated and effective in significantly improving sleep quality and duration, midnight melatonin levels, quality of life, and mood within 2-weeks in adults with insomnia.”

https://onlinelibrary.wiley.com/doi/10.1111/jsr.13793

Use of Cannabidiol in the Management of Insomnia: A Systematic Review

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“Background: Cannabidiol (CBD), one of the major cannabinoids derived from the cannabis plant, is available over the counter. CBD is often used by patients for the management of insomnia, yet research supporting CBDs effectiveness as a treatment for insomnia is inadequate. 

Objective: The objective of this review was to critically evaluate the literature regarding the therapeutic benefits of CBD in the management of insomnia. 

Methods: A comprehensive search of the following databases from inception to December 29, 2021, was conducted: Ovid MEDLINE® and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search included randomized controlled trials, nonrandomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports. Risk of bias was assessed with the Agency for Healthcare Research and Quality design-specific recommended criteria. 

Results: Thirty-four studies were eligible for inclusion. All studies reported improvement in the insomnia symptoms of at least a portion of their participants. Of the 34 studies, 19 studies used CBD predominant therapy and 21 studies used nearly equal ratios of CBD to Δ9-tetrahydrocannabinol (THC). Of the studies that performed hypothesis testing, 4 of 7 studies with a CBD predominant arm and 12 of 16 studies with a nearly equal ratio of CBD to THC arm reported significant improvement in insomnia outcomes. However, only 2 of the 34 studies focused on patients with insomnia, of which 1 study was a case report. Additionally, several studies used nonvalidated subjective measures, and most studies failed to include objective measures for symptom assessment. 

Conclusions: The results of our systematic review suggest that CBD alone or with equal quantities of THC may be beneficial in alleviating the symptoms of insomnia. Nevertheless, future research assessing CBDs effectiveness in population of patients specifically with insomnia utilizing validated subjective and objective measures is necessary before definitive inferences can be made.”

https://pubmed.ncbi.nlm.nih.gov/36149724/

https://www.liebertpub.com/doi/10.1089/can.2022.0122

Effects of Nabilone on Sleep Outcomes in Patients with Parkinson’s Disease: A Post-hoc Analysis of NMS-Nab Study

“Background: The synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson’s disease (PD) patients in comparison to placebo.

Objectives: To characterize the effects of nabilone on different sleep outcomes in PD patients.

Methods: We performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).

Results: After open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).

Conclusions: This post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.”

https://pubmed.ncbi.nlm.nih.gov/35937495/

“Despite the limitations, we found positive effect of nabilone on clinically-relevant sleep problems in PD.”

https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mdc3.13471

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

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“Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells.

The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain.

THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.”

https://pubmed.ncbi.nlm.nih.gov/35796920/

“Tetrahydrocannabinol (THC) and cannabidiol (CBD) combination medicines and CBD-only medicines are prospective new treatments for chronic pain, stress, anxiety, depression, and insomnia, which are all medical conditions in need of better therapeutics. Both THC/CBD combination and CBD-only medicines could provide effective new treatment options for pain and mental health, respectively, and both have good safety and tolerability profiles relative to the current treatments.

THC and CBD combination medicines have a good safety and tolerability profile that is appropriate for opioid stage (stage 2–3) treatment of chronic pain. Low-dose CBD could be used as an initial treatment for chronic pain and for stress, anxiety, depression, and insomnia. High quality efficacy evidence is best for THC/CBD combination medicines for chronic pain and CBD-only medicines for stress and anxiety. “

https://link.springer.com/article/10.1007/s10787-022-01020-z

Healing of a Chronic Pressure Injury in a Patient Treated With Medical Cannabis for Pain and Sleep Improvement: A Case Report

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“Background: A small body of evidence suggests medical cannabis may facilitate wound healing, but the exact mechanism of this effect is unclear.

Purpose: This case report describes a patient with a pressure injury (PI) who received cannabis oil treatment for pain management and sleep improvement.

Methods: A 37-year-old woman with multiminicore disease, scoliosis, short-chain acyl-CoA dehydrogenase deficiency, and epilepsy presented to the Neurology Centre of Toronto with chronic pain and sleep disturbance, including difficulty initiating and maintaining sleep. She also had a 5-year history of a PI between her right iliac crest and right rib cage that had progressively worsened. The patient received a medical cannabis oil protocol that used a combination of cannabidiol and tetrahydrocannabinol.

Results: Cannabis oil was effective in treating pain and sleep difficulties. Unexpectedly, during the first 2 weeks of treatment, the PI started to heal and was almost completely closed at the 2-month follow-up.

Conclusion: Although it is unknown if the observed healing of this refractory PI was indirectly or directly related to the cannabidiol and tetrahydrocannabinol treatment, the potential relationships among pain, sleep disturbance, cannabis treatment, and healing should be explored.”

https://pubmed.ncbi.nlm.nih.gov/35030093/

“This case report provides an account of a patient who began using orally administered medical cannabis oil for sleep disturbances and pain management and subsequently experienced rapid healing of a chronic PI.”

https://www.hmpgloballearningnetwork.com/site/wmp/case-report/healing-chronic-pressure-injury-patient-treated-medical-cannabis-pain-and

An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample

“Background: Little is known about cannabis use for insomnia in individuals with depression, anxiety, and comorbid depression and anxiety. To develop a better understanding of distinct profiles of cannabis use for insomnia management, a retrospective cohort study was conducted on a large naturalistic sample.

Methods: Data were collected using the medicinal cannabis tracking app, Strainprint®, which allows users to monitor and track cannabis use for therapeutic purposes. The current study examined users managing insomnia symptoms in depression (n = 100), anxiety (n = 463), and comorbid depression and anxiety (n = 114), for a total of 8476 recorded sessions. Inferential analyses used linear mixed effects modeling to examine self-perceived improvement across demographic variables and cannabis product variables.

Results: Overall, cannabis was perceived to be efficacious across all groups, regardless of age and gender. Dried flower and oral oil were reported as the most used and most efficacious product forms. In the depression group, all strains were perceived to be efficacious and comparisons between strains revealed indica-dominant (Mdiff = 1.81, 95% CI 1.26-2.36, Padj < .001), indica hybrid (Mdiff = 1.34, 95% CI 0.46-2.22, Padj = .045), and sativa-dominant (Mdiff = 1.83, 95% CI 0.68-2.99, Padj = .028) strains were significantly more efficacious than CBD-dominant strains. In anxiety and comorbid conditions, all strain categories were perceived to be efficacious with no significant differences between strains.

Conclusions: In terms of perceptions, individuals with depression, anxiety, and both conditions who use cannabis for insomnia report significant improvements in symptom severity after cannabis use. The current study highlights the need for placebo-controlled trials investigating symptom improvement and the safety of cannabinoids for sleep in individuals with mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/35484520/

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Treatment of social anxiety disorder and attenuated psychotic symptoms with cannabidiol

See the source image “Anxiety disorders in young people are frequently comorbid with other mental disorders and respond unsatisfactorily to first-line treatment in many cases.

Here, we report the case of a 20-year-old man with severe social anxiety disorder, major depressive disorder, insomnia and attenuated psychotic symptoms despite ongoing treatment with cognitive behavioural therapy and mirtazapine who was treated with adjunctive cannabidiol (CBD) in doses between 200 and 800 mg/day for 6 months.

During treatment with CBD, he experienced subjective benefits to his anxiety, depression and positive symptoms during treatment that were confirmed by clinicians and by standardised research instruments.

Findings from this case study add to existing evidence in support of the safety of CBD and suggest that it may be useful for young people with treatment refractory anxiety and for attenuated psychotic symptoms.”

https://pubmed.ncbi.nlm.nih.gov/33028567/

https://casereports.bmj.com/content/13/10/e235307

Cannabis: An Emerging Treatment for Common Symptoms in Older Adults

Journal of the American Geriatrics Society “Background/objectives: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.

Design: Anonymous survey.

Setting: Geriatrics clinic.

Participants: A total of 568 adults 65 years and older.

Intervention: Not applicable.

Measurements: Survey assessing characteristics of cannabis use.

Results: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%).

The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis “somewhat” or “extremely” helpful in managing one of these conditions, with few adverse effects.

Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking).

Conclusion: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.”

https://pubmed.ncbi.nlm.nih.gov/33026117/

https://onlinelibrary.wiley.com/doi/10.1111/jgs.16833

“Study Finds Older Adults Using Cannabis to Treat Common Health Conditions”  https://health.ucsd.edu/news/releases/Pages/2020-10-07-study-finds-older-adults-using-cannabis-to-treat-common-health-conditions.aspx

Cannabis use is associated with greater total sleep time in middle-aged and older adults with and without HIV: A preliminary report utilizing digital health technologies

“Current literature on the effect of cannabis use on sleep quality is mixed, and few studies have used objectively-measured sleep measures or real-time sampling of cannabis use to examine this relationship.

The prevalence of cannabis use among older adults and persons living with HIV has increased in recent years, and poor sleep quality is elevated in these populations as well. However, research examining cannabis-sleep relationships in these populations is lacking. Thus, we aimed to examine the relationship between daily cannabis use and subsequent objectively-measured sleep quality in middle-aged and older adults with and without HIV.

In this pilot study, seventeen (11 HIV+, 6 HIV-) adults aged 50-70 who consumed cannabis completed four daily smartphone-based surveys for 14 days, in which they reported their cannabis use (yes/no) since the last survey. Participants also wore actigraphy watches during the 14-day period to objectively assess sleep quality (i.e., efficiency, total sleep time, and sleep fragmentation).

In linear mixed-effects models, cannabis use was significantly associated with greater subsequent total sleep time (β=0.56; p=0.046). Cannabis use was not related to a change in sleep efficiency (β=1.50; p=0.46) nor sleep fragmentation (β=0.846, p=0.756) on days with cannabis use versus days without cannabis use.

These preliminary results indicate cannabis use may have a positive effect on sleep duration in middle-aged and older adults. However, future studies with larger sample sizes that assess cannabis use in more detail (e.g., route of administration, dose, reason for use) are needed to further understand this relationship.”

https://pubmed.ncbi.nlm.nih.gov/32905460/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/59