Category Archives: Pain

Cannabinoid system involves in the analgesic effect of protocatechuic acid.

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 “Protocatechuic acid is an antioxidant which is shown to have analgesic activity in limited studies. However, the mechanisms of action remain unclear.

OBJECTIVES:

It is aimed to investigate the possible contribution of cannabinoid system that supresses the nociceptive process by the activation of CB1 and CB2 receptors in central and peripheral levels of pain pathways, to the analgesic activity of protocatechuic acid.

RESULTS:

It was determined that protocatechuic acid has dose-dependent analgesic effect independently from locomotor activity and is comparable with effects of dipyrone and WIN 55,212-2. Pre-treatment with CB1 receptor antagonist AM251 significantly antagonized the protocatechuic acid-induced analgesia in the tail-immersion and writhing tests, whereas pre-treatment of CB2 receptor antagonist AM630 was found to be effective only in the tail-immersion test.

CONCLUSION:

It is concluded that cannabinoid modulation contributes to the analgesic effect of protocatechuic acid in spinal level rather than peripheral. CB1 receptor stimulation rather than CB2 receptor stimulation mediates the analgesic effect of protocatechuic acid in both levels, especially peripheral. Graphical abstract Protocatechuic acid inhibits pain response via cannabinoidergic system.”

https://www.ncbi.nlm.nih.gov/pubmed/31325037

https://link.springer.com/article/10.1007/s40199-019-00288-x

“Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea.”  https://en.wikipedia.org/wiki/Protocatechuic_acid

Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary

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Publication Cover

“Cannabis has been used for pain relief and to promote sleep for thousands of years. Over the past several decades in the United States (U.S.), a therapeutic role for cannabis in mainstream medicine has increasingly emerged. Medical cannabis patients consistently report using cannabis as a substitute for prescription medications. Both pain relief and sleep promotion are common reasons for cannabis use, and the majority of respondents who reported using cannabis for these reasons also reported decreasing or stopping their use of prescription or over-the-counter analgesics and sleep aids. While adult-use laws are frequently called “recreational,” implying that cannabis obtained through the adult use system is only for pleasure or experience-seeking, our findings suggest that many customers use cannabis for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/31264536

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1626953

“Cannabis Is An Effective Treatment Option For Pain Relief And Insomnia, Study Finds” https://www.inquisitr.com/5509672/cannabis-pain-medications-sleep/

“Marijuana Could Be The Alternative Pain Reliever Replacing Opioids”  https://www.medicaldaily.com/marijuana-alternative-pain-reliever-replacing-opioids-437974

Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors.

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“Central antinociceptive effects of cannabinoids have been well documented.

Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor.

This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin.

Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor.”

 https://www.ncbi.nlm.nih.gov/pubmed/9539680/
https://insights.ovid.com/pubmed?pmid=9539680

“The Endocannabinoid System and Pain. Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB1 and CB2 receptor subtypes. These studies suggest that manipulation of peripheral endocannabinoids may be promising strategy for the management of pain.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834283/

“The Analgesic Potential of Cannabinoids. Historically and anecdotally cannabinoids have been used as analgesic agents. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

Cannabinoid receptor 1 (CB1R) expression in rat dental pulp

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Oral Science International“Accumulating evidence supports the role of the cannabinoid system in providing an antinociceptive effect in various painful conditions.

This effect is mediated through the Cannabinoid receptor 1 (CB1R) expressed on nociceptive afferent nerve terminals.

To investigate whether this receptor plays a similar role in dental pain, we studied the presence and distribution of CB1R in rat dental pulp.

CB1R was present on nerve fibers in rat dental pulp and possibly plays a role in dental pain mechanisms.

Interestingly, CB1R has recently been demonstrated in human dental pulp.

This strongly suggests that CB1R could be a therapeutic target for dental pain management.”

https://www.sciencedirect.com/science/article/pii/S1348864312000031

Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp.

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Journal of Clinical Neuroscience Home“The cannabinoid receptor CB1 is involved in modulation of neuronal hypersensitivity and pain. The aim of this study was to evaluate CB1 receptor levels for the first time in dental pain. A total of 19 patients due for molar extraction were divided into two groups, those with existing dental pain (n=9), and those with no history of pain (n=10). Immunohistochemistry and computer image analysis was used to evaluate CB1-positive nerve fibres in tooth pulp, with neurofilament-immunostaining as a structural nerve marker. CB1-immunoreactive nerve fibres were scattered throughout the tooth pulp and often seen in nerve bundles, but the fibres did not penetrate the subodontoblastic layer. There was no statistically significant change in the CB1 nerve fibre percentage area in the painful group compared to the non-painful group (p=0.146); the neurofilament fibres were significantly reduced in the painful group compared to the controls (p=0.028), but there was no difference in the ratio of CB1 to neurofilaments between the two groups. Thus, CB1 expression is maintained by nerve fibres in painful human dental pulp, and peripherally-restricted CB1 agonists currently in development may advance the treatment of dental pain.”

https://www.ncbi.nlm.nih.gov/pubmed/20705472

https://www.jocn-journal.com/article/S0967-5868(10)00289-4/fulltext

Preparation of bivalent agonists for targeting the mu opioid and cannabinoid receptors.

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European Journal of Medicinal Chemistry

“In order to obtain novel pharmacological tools and to investigate a multitargeting analgesic strategy, the CB1 and CB2 cannabinoid receptor agonist JWH-018 was conjugated with the opiate analgesic oxycodone or with an enkephalin related tetrapeptide. The opioid and cannabinoid pharmacophores were coupled via spacers of different length and chemical structure. In vitro radioligand binding experiments confirmed that the resulting bivalent compounds bound both to the opioid and to the cannabinoid receptors with moderate to high affinity. The highest affinity bivalent derivatives 11 and 19 exhibited agonist properties in [35S]GTPγS binding assays. These compounds activated MOR and CB (11 mainly CB2, whereas 19 mainly CB1) receptor-mediated signaling, as it was revealed by experiments using receptor specific antagonists. In rats both 11 and 19 exhibited antiallodynic effect similar to the parent drugs in 20 μg dose at spinal level. These results support the strategy of multitargeting G-protein coupled receptors to develop lead compounds with antinociceptive properties.”

https://www.ncbi.nlm.nih.gov/pubmed/31220675

https://www.sciencedirect.com/science/article/pii/S0223523419304477?via%3Dihub

Opioid-Sparing Effects of Cannabinoids on Morphine Analgesia: Participation of CB1 and CB2 Receptors.

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British Journal of Pharmacology banner“Much of the opioid epidemic arose from abuse of prescription opioid drugs.

This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia.

CONCLUSIONS AND IMPLICATIONS:

The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31218677

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14769

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

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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

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.

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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.”

 https://www.ncbi.nlm.nih.gov/pubmed/31190969
https://www.dovepress.com/effectiveness-and-tolerability-of-thccbd-oromucosal-spray-as-add-on-me-peer-reviewed-article-JPR

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

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“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.”

 https://www.ncbi.nlm.nih.gov/pubmed/31191856
https://pubs.rsc.org/en/content/articlelanding/2019/MD/C8MD00595H#!divAbstract
Graphical abstract: Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain