The Endocannabinoid System and its Modulation by Cannabidiol (CBD).

Image result for Altern Ther Health Med. “The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.”

https://www.ncbi.nlm.nih.gov/pubmed/31202198

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Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry.

Image result for J Pain Res.

“Objective: To evaluate effectiveness, tolerability and safety of an oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as add-on treatment in patients with severe chronic pain (SCP).

Conclusion: THC:CBD oromucosal spray proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain – especially of neuropathic origin.”

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Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain.

“Neuropathic pain is caused by a lesion or dysfunction in the nervous system, and it may arise from illness, be drug-induced or caused by toxin exposure. Since the discovery of two G-protein-coupled cannabinoid receptors (CB1 and CB2) nearly three decades ago, there has been a rapid expansion in our understanding of cannabinoid pharmacology. This is currently one of the most active fields of neuropharmacology, and interest has emerged in developing cannabinoids and other small molecule modulators of CB1 and CB2 as therapeutics for neuropathic pain. This short review article provides an overview of the chemotypes currently under investigation for the development of novel neuropathic pain treatments targeting CB1 receptors.”

Graphical abstract: Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain
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Safety and Efficacy of Medical Cannabis in Fibromyalgia

jcm-logo“Chronic pain may be treated by medical cannabis. Yet, there is scarce evidence to support the role of medical cannabis in the treatment of fibromyalgia. The aim of the study was to investigate the characteristics, safety, and effectiveness of medical cannabis therapy for fibromyalgia.

Results: Among the 367 fibromyalgia patients, the mean age was 52.9 ± 15.1, of whom 301 (82.0%) were women. Twenty eight patients (7.6%) stopped the treatment prior to the six months follow-up. The six months response rate was 70.8%. Pain intensity (scale 0–10) reduced from a median of 9.0 at baseline to 5.0 (p < 0.001), and 194 patients (81.1%) achieved treatment response. In a multivariate analysis, age above 60 years (odds ratio [OR] 0.34, 95% C.I 0.16–0.72), concerns about cannabis treatment (OR 0.36, 95% C.I 0.16–0.80), spasticity (OR 2.26, 95% C.I 1.08–4.72), and previous use of cannabis (OR 2.46 95% C.I 1.06–5.74) were associated with treatment outcome. The most common adverse effects were mild and included dizziness (7.9%), dry mouth (6.7%), and gastrointestinal symptoms (5.4%).

Conclusion: Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms. Standardization of treatment compounds and regimens are required.”

https://www.mdpi.com/2077-0383/8/6/807

“Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms.”  https://www.ncbi.nlm.nih.gov/pubmed/31195754

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Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain.

Archives of Oral Biology

“This study investigated whether local intramuscular injection of non-psychoactive cannabinoids, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC) and their combinations can decrease nerve growth factor (NGF)-induced masticatory muscle sensitization in female rats.

RESULTS:

In behavioral experiments, CBD (5 mg/ml) or CBN (1 mg/ml) decreased NGF-induced mechanical sensitization. Combinations of CBD/CBN induced a longer-lasting reduction of mechanical sensitization than either compound alone. No significant change in mechanical withdrawal threshold was observed in the contralateral masseter muscles and no impairment of motor function was found with the inverted screen test after any of the treatments. Consistent with behavioral results, CBD (5 mg/ml), CBN (1 mg/ml) and the combination of CBD/CBN (1:1 mg/ml) increased the mechanical threshold of masseter muscle mechanoreceptors. However, combining CBD/CBN (5:1 mg/ml) at a higher ratio reduced the duration of this effect. This may indicate an inhibitory effect of higher concentrations of CBD on CBN.

CONCLUSIONS:

These results suggest that peripheral application of these non-psychoactive cannabinoids may provide analgesic relief for chronic muscle pain disorders such as temporomandibular disorders and fibromyalgia without central side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31158702

https://www.sciencedirect.com/science/article/pii/S0003996919302249?via%3Dihub

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Medical Cannabis: Effects on Opioid and Benzodiazepine Requirements for Pain Control.

SAGE Journals

“The objective of this study was to determine if the use of medical cannabis affects the amount of opioids and benzodiazepines used by patients on a daily basis.

METHODS:

This single-center, retrospective cohort study evaluated opioid and benzodiazepine doses over a 6-month time period for patients certified to use medical cannabis for intractable pain. All available daily milligram morphine equivalents (MMEs) and daily diazepam equivalents (DEs) were calculated at baseline and at 3 and 6 months.

RESULTS:

A total of 77 patients were included in the final analysis. There was a statistically significant decrease in median MME from baseline to 3 months (-32.5 mg; P = 0.013) and 6 months (-39.1 mg; P = 0.001). Additionally, there was a non-statistically significant decrease in median DE at 3 months (-3.75 mg; P = 0.285) and no change in median DE from baseline to 6 months (-0 mg; P = 0.833). Conclusion and Relevance: Over the course of this 6-month retrospective study, patients using medical cannabis for intractable pain experienced a significant reduction in the number of MMEs available to use for pain control. No significant difference was noted in DE from baseline. Further prospective studies are warranted to confirm or deny the opioid-sparing effects of medical cannabis when used to treat intractable pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31129977

https://journals.sagepub.com/doi/abs/10.1177/1060028019854221?journalCode=aopd

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Age-related differences in Δ⁹-tetrahydrocannabinol-induced antinociception in female and male rats.

Cover image for Experimental and Clinical Psychopharmacology

“Given the use of cannabis as an analgesic by a broadening age range of patients, the aim of this study was to determine whether the antinociceptive effects of Δ9-tetrahydrocannabinol (THC) differ by age.

On the tail withdrawal test, THC was significantly more effective in middle-aged adult than in young adult rats and significantly less effective in adolescent than in young adult rats.

Sex differences in THC’s antinociceptive effects were consistent across the 3 ages examined, with greater THC effects observed in females than males of each age. Age-related differences in THC’s locomotor-suppressing effect were also observed, with the greatest effect in young adult female rats. Serum THC levels were slightly higher in adolescent than in young adult rats, and levels of the active metabolites 11-OH-THC and cannabinol, as well as the inactive metabolite 11-nor-9-carboxy-THC, did not differ between adolescent and young adult rats.

These results suggest that the pain-relieving effects of THC may be more limited in adolescents than in adults and that these age-related differences in THC effect are not attributable to differential absorption or metabolism of THC.”

https://www.ncbi.nlm.nih.gov/pubmed/31120286

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000257

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Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.

APA's header logo

“Chronic pain states have resulted in an overreliance on opioid pain relievers, which can carry significant risks when used long term. As such, alternative pain treatments are increasingly desired.

Although emerging research suggests that cannabinoids have therapeutic potential regarding pain, results from studies across pain populations have been inconsistent. To provide meta-analytic clarification regarding cannabis’s impact on subjective pain, we identified studies that assessed drug-induced pain modulations under cannabinoid and corresponding placebo conditions.

Results revealed that cannabinoid administration produced a medium-to-large effect across included studies, Cohen’s d = -0.58, 95% confidence interval (CI) [-0.74, -0.43], while placebo administration produced a small-to-medium effect, Cohen’s d = -0.39, 95% CI [-0.52, -0.26]. Meta-regression revealed that cannabinoids, β = -0.43, 95% CI [-0.62, -0.24], p < .05, synthetic cannabinoids, β = -0.39, 95% CI [-0.65, -0.14], p < .05, and sample size, β = 0.01, 95% CI [0.00, 0.01], p < .05, were associated with marked pain reduction.

These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/31120281

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000281

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Supplementation of Cannabis sativa L. leaf powder accelerates functional recovery and ameliorates haemoglobin level following an induced injury to sciatic nerve in mouse model.

Image result for Pak J Pharm Sci.

“Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss.

Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury.

A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress.

The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group.

This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.”

https://www.ncbi.nlm.nih.gov/pubmed/31103973

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CB2 receptor deletion on myeloid cells enhanced mechanical allodynia in a mouse model of neuropathic pain.

 Scientific Reports“Neuropathic pain can develop after nerve injury, leading to a chronic condition with spontaneous pain and hyperalgesia.

Pain is typically restricted to the side of the injured nerve, but may occasionally spread to the contralateral side, a condition that is often referred to as mirror-image pain.

Mechanisms leading to mirror-image pain are not completely understood, but cannabinoid CB2 receptors have been implicated.

In this study, we use genetic mouse models to address the question if CB2 receptors on neurons or on microglia/macrophages are involved.

We conclude that CB2 receptors on microglia and macrophages, but not on neurons, modulate neuropathic pain responses.”

https://www.ncbi.nlm.nih.gov/pubmed/31097758

https://www.nature.com/articles/s41598-019-43858-4

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