Category Archives: Pain

Protective role of neuronal and lymphoid cannabinoid CB 2 receptors in neuropathic pain

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 eLife logo“Cannabinoid CB2 receptor (CB2) agonists are potential analgesics void of psychotropic effects.

Peripheral immune cells, neurons and glia express CB2, however the involvement of CB2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2 agonist JWH133 in wild-type and knockout mice lacking CB2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2 knockouts and was increased in mice defective in neuronal CB2 knockouts suggestive of increased spontaneous pain. Interestingly, CB2-positive lymphocytes infiltrated the injured nerve and possible CB2transfer from immune cells to neurons was found. Lymphocyte CB2depletion also exacerbated JWH133 self-administration and inhibited antinociception.

This work identifies a simultaneous activity of neuronal and lymphoid CB2that protects against spontaneous and evoked neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/32687056/

https://elifesciences.org/articles/55582

Patient Perception Regarding Potential Effectiveness of Cannabis for Pain Management

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Home Page: The Journal of Arthroplasty“Self-reported cannabis use has increased since its recent legalization in many states.

The primary objective of this study is to describe patients’ beliefs regarding the potential effectiveness of cannabis and gauge patient acceptance of these compounds if prescribed by a physician.

Patients strongly agree or agree that cannabis can help with sleep or anxiety.

Patients believe that cannabis may be helpful for pain management after total joint arthroplasty (TJA) and are willing to use if prescribed by their orthopedic provider.”

https://pubmed.ncbi.nlm.nih.gov/32684396/

https://www.arthroplastyjournal.org/article/S0883-5403(20)30716-6/pdf

The pharmacokinetics, efficacy, and safety of a novel selective‐dose cannabis inhaler in patients with chronic pain: A randomized, double‐blinded, placebo‐controlled trial

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European Journal of Pain“Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis.

Objective

To test the pharmacokinetics, analgesic effect, cognitive performance and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ9‐Tetrahydrocannabinol (THC) in patients with chronic pain.

Methods

In a randomized, three‐arms, double‐blinded, placebo‐controlled, cross‐over trial, 27 patients received a single inhalation of Δ9‐THC: 0.5mg, 1mg, or a placebo.

Δ9‐THC plasma levels were measured at baseline and up to 150‐min post‐inhalation. Pain intensity and safety parameters were recorded on a 10‐cm visual analogue scale (VAS) at pre‐defined time points. The cognitive performance was evaluated using the selective sub‐tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results

Following inhalation of 0.5 mg or 1mg, Δ9‐THC plasma C max ± SD were 14.3 ± 7.7 and 33.8 ± 25.7 ng/ml. T max ± SD were 3.7 ± 1.4 and 4.4 ± 2.1 min, and AUC0 → infinity±SD were 300 ± 144 and 769 ± 331 ng*min/ml, respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150‐min. The 1‐mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.

Conclusion

This feasibility trial demonstrated that a metered‐dose cannabis inhaler delivered precise and low THC doses, produced a dose‐dependent and safe analgesic effect in patients with neuropathic pain/ complex‐regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.

Significance

Evidence suggests that cannabis‐based medicines are an effective treatment for chronic pain in adults. The pharmacokinetics of THC varies as a function of its route of administration. Pulmonary assimilation of inhaled THC causes rapid onset of analgesia. However, currently used routes of cannabinoids delivery provide unknown doses, making it impossible to implement a pharmaceutical standard treatment plan. A novel selective‐dose cannabis inhaler delivers significantly low and precise doses of THC, thus allowing the administration of inhaled cannabis‐based medicines according to high pharmaceutical standards. These low doses of THC can produce safe and effective analgesia in patients with chronic pain.

To the best of our knowledge, it is the first time that the delivery of selective, significantly low, and precise therapeutic single doses of inhaled THC demonstrates an analgesic effect. It allows patients to reach the optimum balance between symptom relief and controlled side effects, enabling patients to regain their quality of life. In addition, this metered‐dose cannabis inhaler enables the individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically using accepted pharmaceutical models.”

https://onlinelibrary.wiley.com/doi/10.1002/ejp.1605

“Study Finds Microdosing THC Reduces Pain Levels”  https://www.painnewsnetwork.org/stories/2020/7/1/study-finds-microdosing-thc-reduces-pain-levels

Medical Cannabis for the Management of Pain and Quality of Life in Chronic Pain Patients: A Prospective Observational Study

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Pain Medicine (Journal) by Oxford University Press

“Objective: To evaluate the short-term and long-term effects of plant-based medical cannabis in a chronic pain population over the course of one year.

Results: Medical cannabis treatment was associated with improvements in pain severity and interference (P < 0.001) observed at one month and maintained over the 12-month observation period. Significant improvements were also observed in the SF-12 physical and mental health domains (P < 0.002) starting at three months. Significant decreases in headaches, fatigue, anxiety, and nausea were observed after initiation of treatment (P ≤ 0.002). In patients who reported opioid medication use at baseline, there were significant reductions in oral morphine equivalent doses (P < 0.0001), while correlates of pain were significantly improved by the end of the study observation period.

Conclusions: Taken together, the findings of this study add to the cumulative evidence in support of plant-based medical cannabis as a safe and effective treatment option and potential opioid medication substitute or augmentation therapy for the management of symptoms and quality of life in chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/32556203/

https://academic.oup.com/painmedicine/article-abstract/doi/10.1093/pm/pnaa163/5859722?redirectedFrom=fulltext

Non-opioid Analgesics and the Endocannabinoid System

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 Balkan Medical Journal“Non-steroidal anti-inflammatory drugs (NSAIDs) are known to produce antinociceptive effects mainly through peripheral COX-inhibition. Paracetamol and dipyrone are different from classical NSAIDs, because they exert weak anti-inflammatory activity; mechanisms other than peripheral COX inhibition appear to play role in their antinociceptive actions. In this review, we specified classical NSAIDs, paracetamol and dipyrone as “non-opioid analgesics” and discussed the mechanisms mediating participation of the endocannabinoid system in the antinociceptive effects of these analgesics. Non-opioid analgesics and their metabolites may activate cannabinoid receptors. In addition, several mechanisms are implicated in the elevation of endocannabinoid levels following administration of non-opioid analgesics. Of these, reduction of endocannabinoid degradation via FAAH and/or COX-2 inhibition, accumulation of arachidonic acid to endocannabinoid biosynthesis following COX inhibition, inhibition of cellular uptake of endocannabinoids directly or following inhibition of nitric oxide synthase production, and induction of endocannabinoid release are among the proposed mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/32551466/

http://balkanmedicaljournal.org/uploads/pdf/pdf_BMJ_2226.pdf

Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Equine Dorsal Root Ganglia

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Publication cover image“Growing evidence recognises cannabinoid receptors as potential therapeutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain.

As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated.

Conclusions: This study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia. These findings could be of particular relevance for future functional studies assessing the effects of cannabinoids in horses to manage pain.”

https://pubmed.ncbi.nlm.nih.gov/32524649/

https://beva.onlinelibrary.wiley.com/doi/abs/10.1111/evj.13305

A Balanced Approach for Cannabidiol Use in Chronic Pain

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Frontiers in Pharmacology (@FrontPharmacol) | Twitter “Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life.

CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations.

In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.”

https://pubmed.ncbi.nlm.nih.gov/32425793/

https://www.frontiersin.org/articles/10.3389/fphar.2020.00561/full

www.frontiersin.org

The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model

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life-logo“Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice.

Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas.

Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain.

The present study shows for the first time that common, commercially available, and easily reproducible full-spectrum hemp oil induces significant anti-allodynic effects with a bell-shaped pain sensitivity effect peeking between 2 and 4 h and lasting over 6 h. The study provides evidence that phytochemical extracts of the Cannabis plant, even with relatively low levels of THC, can significantly improve mechanical pressure pain in animals with established chronic neuropathic hypersensitivity.”

https://www.mdpi.com/2075-1729/10/5/69/htm

“Legal Cannabis hemp oil effectively treats chronic neuropathic pain: study”   https://medicalxpress.com/news/2020-05-legal-cannabis-hemp-oil-effectively.html

Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.

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European Journal of Pharmaceutics and Biopharmaceutics“The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.”

https://www.ncbi.nlm.nih.gov/pubmed/32422168

https://www.sciencedirect.com/science/article/abs/pii/S0939641120301375?via%3Dihub

Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review.

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 Journal of opioid management (in SafetyLit)“Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.

DISCUSSION:

CBD appears to have antisnociceptive and anti-inflammatory effects on opioid-naive patients with neuro-pathic and radicular pain. Of note, the patients in this case series used the same CBD cream: Baskin Essentials Body Wellness Cream (400 mg CBD per two oz.) Conclusion: Hemp-derived CBD in a transdermal cream provided significant symptom and pain relief for the patients described in this case series. Based on these results, we believe further investigation is warranted to see if CBD-containing products should have a more prominent role in the treatment of acute and chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32421842