Category Archives: Pain

Cannabinoid Receptors and Their Relationship With Chronic Pain: A Narrative Review

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CB1-versus-CB2-receptors “The burden of chronic pain has affected many individuals leading to distress and discomfort, alongside numerous side effects with conventional therapeutic approaches.

Cannabinoid receptors are naturally found in the human body and have long been an interest in antinociception. These include CB1 and CB2 receptors, which are promising candidates for the treatment of chronic inflammatory pain.

The mechanism of action of the receptors and how they approach pain control in inflammatory conditions show that it can be an adjunctive approach towards controlling these symptoms. Numerous studies have shown how the targeted approach towards these receptors has activated them promoting a release in cytokines, all leading to anti-inflammatory effects and immune system regulation.

Cannabinoid activation of glycine and gamma-aminobutyric acid (GABA) models also showed efficacy in pain management. Chronic conditions such as osteoarthritis were shown to also benefit from this considerable treatment. However, it is unclear how the cannabinoid system works in relation with the pain pathway. Therefore, in this review we aim to analyse the role of the cannabinoid system in chronic inflammatory pain.”

https://pubmed.ncbi.nlm.nih.gov/33072446/

https://www.cureus.com/articles/39887-cannabinoid-receptors-and-their-relationship-with-chronic-pain-a-narrative-review

The CB2 Agonist β-Caryophyllene in Male and Female Rats Exposed to a Model of Persistent Inflammatory Pain

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frontiers – Page 2 – Retraction Watch “Cannabinoids help in pain treatment through their action on CB1 and CB2 receptors.

β-caryophyllene (BCP), an ancient remedy to treat pain, is a sesquiterpene found in large amounts in the essential oils of various spice and food plants such as oregano, cinnamon, and black pepper. It binds to the CB2 receptor, acting as a full agonist.

Sex differences in the BCP-induced analgesic effect were studied by exposing male and female rats to a persistent/repeated painful stimulation.

In conclusion, long-term intake of BCP appears to be able to decrease pain behaviors in a model of repeated inflammatory pain in both sexes, but to a greater degree in males.”

https://pubmed.ncbi.nlm.nih.gov/33013287/

https://www.frontiersin.org/articles/10.3389/fnins.2020.00850/full

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Cannabis: An Emerging Treatment for Common Symptoms in Older Adults

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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

Chronic treatment with cannabidiolic acid (CBDA) reduces thermal pain sensitivity in male mice and rescues the hyperalgesia in a mouse model of Rett syndrome

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Neuroscience “Rett syndrome (RTT) is a rare neurologic disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available.

Recent evidence suggests that non-euphoric phytocannabinoids (pCBs) extracted from Cannabis sativa may represent innovative therapeutic molecules for RTT, with the cannabinoid cannabidivarin having beneficial effects on behavioural and brain molecular alterations in RTT mouse models.

The present study evaluated the potential therapeutic efficacy for RTT of cannabidiolic acid (CBDA; 0.2, 2, 20 mg/kg through intraperitoneal injections for 14 days), a pCB that has proved to be effective for the treatment of nausea and anxiety in rodents.

This study demonstrates that systemic treatment with the low dose of CBDA has anti-nociceptive effects and reduces the thermal hyperalgesia in 8-month old MeCP2-308 male mice, a validated RTT mouse model. CBDA did not affect other behavioural or molecular parameters.

These results provide support to the antinociceptive effects of CBDA and stress the need for further studies aimed at clarifying the mechanisms underlying the abnormal pain perception in RTT.”

https://pubmed.ncbi.nlm.nih.gov/33010341/

“Chronic treatment with CBDA reduces pain sensitivity in wild type mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0306452220306254?via%3Dihub

Use of cannabidiol (CBD) for the treatment of chronic pain

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Best Practice & Research Clinical Anaesthesiology “Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach.

Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment.

The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising.

This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.”

https://pubmed.ncbi.nlm.nih.gov/33004159/

https://www.sciencedirect.com/science/article/pii/S1521689620300458?via%3Dihub

CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons

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 “Cannabidiol (CBD) is reported to produce pain relief, but the clinically relevant cellular and molecular mechanisms remain uncertain.

The TRPV1 receptor integrates noxious stimuli and plays a key role in pain signaling. Hence, we conducted in vitro studies, to elucidate the efficacy and mechanisms of CBD for inhibiting neuronal hypersensitivity in cultured rat sensory neurons, following activation of TRPV1.

Results: DRG neurons treated with 10 and 50 µMol/L CBD showed calcium influx, but not at lower doses. Neurons treated with capsaicin demonstrated robust calcium influx, which was dose-dependently reduced in the presence of low dose CBD (IC50 = 100 nMol/L). The inhibition or desensitization by CBD was reversed in the presence of forskolin and cyclosporin. Forskolin-stimulated cAMP levels were significantly reduced in CBD treated neurons.

Conclusion: CBD at low doses corresponding to plasma concentrations observed physiologically inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization. CBD also facilitated calcineurin-mediated TRPV1 inhibition. These mechanisms may underlie nociceptor desensitization and the therapeutic effect of CBD in animal models and patients with acute and chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/32982390/

https://www.dovepress.com/cbd-effects-on-trpv1-signaling-pathways-in-cultured-drg-neurons-peer-reviewed-article-JPR

Medical cannabis and cognitive performance in middle to old adults treated for chronic pain

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“Cannabis exposure is becoming more common in older age but little is known about how it is associated with brain health in this population.

This study assesses the relationship between long-term medical cannabis (MC) use and cognitive function in a sample of middle-aged and old chronic pain patients.

Results: Mean age was 63 ± 6 and 60 ± 5 years in the non-exposed and MC patients, respectively. Groups did not significantly differ in terms of cognitive performance measures. Furthermore, none of the MC use patterns were associated with cognitive performance.

Discussion and conclusions: These results suggest that use of whole plant MC does not have a widespread impact on cognition in older chronic pain patients. Considering the increasing use of MC in older populations, this study could be a first step towards a better risk-benefit assessment of MC treatment in this population. Future studies are urgently needed to further clarify the implications of late-life cannabis use for brain health.”

https://pubmed.ncbi.nlm.nih.gov/32964502/

https://onlinelibrary.wiley.com/doi/10.1111/dar.13171

“No Ill Effects for Older Adults Using Medical Marijuana for Pain, Study Says. A study looking at older adults with chronic pain found no no significant difference in cognitive performance when comparing them with matched patients who did not use medical marijuana.” https://www.ajmc.com/view/no-ill-effects-for-older-adults-using-medical-marijuana-for-pain-study-says

The Impact of Medical Cannabis on Intermittent and Chronic Opioid Users with Back Pain: How Cannabis Diminished Prescription Opioid Usage

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View details for Cannabis and Cannabinoid Research cover image“To determine if cannabis may be used as an alternative or adjunct treatment for intermittent and chronic prescription opioid users.

Results: There were no between-group differences based on demographic, experiential, or attitudinal variables. We found that 50.8% were able to stop all opioid usage, which took a median of 6.4 years (IQR=1.75-11 years) after excluding two patients who transitioned off opioids by utilizing opioid agonists. For those 29 patients (47.5%) who did not stop opioids, 9 (31%) were able to reduce opioid use, 3 (10%) held the same baseline, and 17 (59%) increased their usage. Forty-eight percent of patients subjectively felt like cannabis helped them mitigate their opioid intake but this sentiment did not predict who actually stopped opioid usage. There were no variables that predicted who stopped opioids, except that those who used higher doses of cannabis were more likely to stop, which suggests that some patients might be able to stop opioids by using cannabis, particularly those who are dosed at higher levels.

Conclusions: In this long-term observational study, cannabis use worked as an alternative to prescription opioids in just over half of patients with low back pain and as an adjunct to diminish use in some chronic opioid users.”

https://pubmed.ncbi.nlm.nih.gov/32923663/

“Cannabis has been used for centuries as an analgesic and has been shown to reduce chronic pain. In this long-term observational study of a single-center cannabis medical practice site, the addition of cannabis use worked as an alternative to prescription opioids in 50% of patients with chronic back pain. It worked as an adjunct to diminish use in some chronic opioid users. There was only one variable that predicted those who were able to stop opioids suggesting that some patients might be able to stop opioids by using cannabis and that those who do not stop opioids may not be titrated at doses of cannabis high enough to achieve the desired effect necessary to diminish or stop their opioid usage.”

https://www.liebertpub.com/doi/10.1089/can.2019.0039

No Evidence of Altered Reactivity to Experimentally Induced Pain Among Regular Cannabis Users

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Clinical Journal of Pain,Philadelphia - Gainbuzz“Recent years have seen an increase in the adoption of cannabinoid medicines, which have demonstrated effectiveness for the treatment of chronic pain.

However, the extent to which frequent cannabis use (CU) influences sensitivity to acute pain has not been systematically examined. Such a determination is clinically relevant in light of hypersensitivity to pain associated with prolonged use of other analgesics such as opioids, and reports of increased pain sensitivity to experimentally induced pain during acute cannabis intoxication.

This study explored differences in measures of pain intensity and tolerance. The authors hypothesized that individuals who report frequent CU would demonstrate greater experimental pain sensitivity.

Results: Frequent CU was not associated with hyperalgesia as cannabis users and nonusers did not exhibit differences on measures of pain tolerance (t (78)=-0.05; P=0.96), sensitivity (t (78)=-0.83; P=0.41), or intensity (t (78)=0.36; P=0.72).

Discussion: Frequent cannabis users did not demonstrate hyperalgesia. This finding should help to inform evaluations of the relative harms and benefits of cannabis analgesic therapies.”

https://pubmed.ncbi.nlm.nih.gov/32433075/

https://journals.lww.com/clinicalpain/Abstract/2020/08000/No_Evidence_of_Altered_Reactivity_to.4.aspx

“Pain tolerance among cannabis users. Unlike opioids, long-term cannabis use does not increase sensitivity to pain. “This study should come as good news to patients who are already using cannabis to treat pain,” says co-author Zach Walsh, who leads the UBC Therapeutic Recreational and Problematic Substance Use Lab which hosted the study. “Increases in pain sensitivity with opioids can really complicate an already tough situation; given increasing uptake of cannabis-based pain medications it’s a relief that we didn’t identify a similar pattern with cannabinoids.”

https://www.sciencedaily.com/releases/2020/09/200910120105.htm

Insights on cannabidiol’s antiallodynic and anxiolytic mechanisms of action in a model of neuropathic pain

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PAIN Impact Factor Increase to 6.029 - IASP“Recent studies have shown that cannabidiol (CBD) could have a great therapeutic potential for treating disorders such as chronic pain and anxiety. In the target article, the authors propose that CBD modulates serotonergic transmission and reverses allodynia and anxiety-like behaviour in a rat model of neuropathic pain. Furthermore, this study shows an antinociceptive effect mediated by TRPV1 and partially by 5-HT1A receptors, as well as an anxiolytic effect mediated by 5-HT1A receptors.”

https://pubmed.ncbi.nlm.nih.gov/32766463/

https://journals.lww.com/painrpts/Fulltext/2019/10000/Insights_on_cannabidiol_s_antiallodynic_and.10.aspx

“Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain”  https://pubmed.ncbi.nlm.nih.gov/30157131/