Category Archives: Pain

Analyzing the role of cannabinoids as modulators of Wnt/β-catenin signaling pathway for their use in the management of neuropathic pain.

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Bioorganic & Medicinal Chemistry Letters

“Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/β-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/30871771

https://www.sciencedirect.com/science/article/pii/S0960894X19301428?via%3Dihub

CBD as the New Medicine in the Pain Provider’s Armamentarium.

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“As providers who currently treat some chronic pain patients with CBD oil as part of a multimodal analgesic treatment regimen, we have found great benefit of this new weapon recently being utilized in our armamentarium. As mentioned in the article, the current political climate surrounding CBD is both vague and ever-changing, which can and does impact treatment and subsequent patient outcomes as pain medicine providers. If we want to make cannabis and CBD into a legitimate medicinal treatment, there must be more regulations on CBD oil production and accurate labeling. Patients will continue to seek CBD oil as an additional option to treat their chronic pain as it gains popularity, so it is our duty as providers to protect them and ensure they have safe options of this new medication to choose from.”
https://www.ncbi.nlm.nih.gov/pubmed/30868477

Role of endocannabinoid system in dopamine signalling within the reward circuits affected by chronic pain.

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Pharmacological Research

“The association between chronic pain, depression and anxiety has gained particular attention due to high rates of comorbidity. Recent data demonstrated that the mesolimbic reward circuitry is involved in the pathology of chronic pain. Interestingly, the mesolimbic reward circuit participates both in pain perception and in pain relief.

The endocannabinoid system (ECS) has emerged as a highly relevant player involved in both pain perception and reward processing. Targeting ECS could become a novel treatment strategy for chronic pain patients.

However, little is known about the underlying mechanisms of action of cannabinoids at the intersection of neurochemical changes in reward circuits and chronic pain. Because understanding the benefits and risks of cannabinoids is paramount, the aim of this review is to evaluate the state-of-art knowledge about the involvement of the ECS in dopamine signalling within the reward circuits affected by chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/30831242

https://www.sciencedirect.com/science/article/abs/pii/S1043661819300088?via%3Dihub

Cannabinoids: a new approach for pain control?

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“To analyze available data related to the use of cannabinoids in medicine, with a special focus on pain management in cancer. The use of cannabis for medical purposes is growing but there are still numerous questions to be solved: effectiveness, safety, and specific indications.

RECENT FINDINGS:

There is considerable variation between countries in the approaches taken, reflecting a variety of historical and cultural factors and despite few randomized controlled studies using natural cannabinoids, there is a trend to state that the use of cannabis should be taken seriously as a potential treatment of cancer-related pain. Cannabidiol, a nontoxic phytocannabinoid with few side-effects is promising in various indications in medicine.

SUMMARY:

The endocannabinoid system is a potential therapeutic target. Cannabinoids may be considered as potential adjuvant in cancer-related pain management. Cannabidiol appears to be the drug of choice. Analgesic trial designs should evolve to get closer to real-life practice and to avoid biases.”

https://www.ncbi.nlm.nih.gov/pubmed/30789867

https://insights.ovid.com/crossref?an=00001622-900000000-00002

New Insights in Cannabinoid Receptor Structure and Signaling.

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“Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic targets for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.

CONCLUSION:

In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.”

https://www.ncbi.nlm.nih.gov/pubmed/30767756

http://www.eurekaselect.com/170011/article

Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (Bedrocan).

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International Journal of Pharmacy Practice banner

“Our main aim was to investigate the short-term therapeutic effects, safety/tolerability and potential side effects of the cannabis galenical preparation (Bedrocan) in patients with a range of chronic conditions unresponsive to other treatments.

METHODS:

In this retrospective, ‘compassionate use’, observational, open-label study, 20 patients (age 18-80 years) who had appealed to our ‘Second Opinion Medical Consulting Network’ (Modena, Italy), were instructed to take sublingually the galenical oil twice a day for 3 months of treatment. The usual starting dose was low (0.5 ml/day) and gradually titrated upward to the highest recommended dose (1 ml/day). Tolerability and adverse effects were assessed at baseline and monthly thereafter during the treatment period through direct contact (email or telephone) or visit if required. Patients’ quality of life was evaluated at baseline and 3 months using the medical outcome short-form health survey questionnaire (SF-36).

KEY FINDINGS:

From baseline to 6 months post-treatment, SF-36 scores showed: reductions in total pain (P < 0.03); improvements in the physical component (P < 0.02); vitality (P < 0.03); social role functioning (P < 0.02); and general health state (P < 0.02). No changes in role limitations (P = 0.02) due to emotional state (e.g. panic, depression, mood alteration) were reported. Monthly reports of psychoactive adverse effects showed significant insomnia reduction (P < 0.03) and improvement in mood (P < 0.03) and concentration (P < 0.01).

CONCLUSIONS:

These data suggest that a cannabis galenical preparation may be therapeutically effective and safe for the symptomatic treatment of some chronic diseases. Further studies on the efficacy of cannabis as well as cannabinoid system involvement in the pathophysiology are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/30768819

https://onlinelibrary.wiley.com/doi/full/10.1111/ijpp.12514

Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases

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British Journal of Dermatology banner

“Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care‐based interventions.

Opioid‐based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients.

Cannabinoid‐based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB.

We present three patients with EB who were prescribed pharmaceutical‐grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol.

All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.”

https://www.ncbi.nlm.nih.gov/pubmed/30347109

https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.17341

“Cannabinoids Could Help Manage EB-related Pain, Study Suggests”  https://epidermolysisbullosanews.com/2019/02/08/cannabinoids-could-help-manage-eb-related-pain-study-suggests/

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

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“Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy.

Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism.

Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions.

The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well.

Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia.

The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30721403

https://link.springer.com/article/10.1007%2Fs40122-019-0114-4

Qualifying Conditions Of Medical Cannabis License Holders In The United States.

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Health Affairs

“The evidence for cannabis‘s treatment efficacy across different conditions varies widely, and comprehensive data on the conditions for which people use cannabis are lacking. We analyzed state registry data to provide nationwide estimates characterizing the qualifying conditions for which patients are licensed to use cannabis medically. We also compared the prevalence of medical cannabis qualifying conditions to recent evidence from the National Academies of Sciences, Engineering, and Medicine report on cannabis‘s efficacy in treating each condition. Twenty states and the District of Columbia had available registry data on patient numbers, and fifteen states had data on patient-reported qualifying conditions. Chronic pain is currently and historically the most common qualifying condition reported by medical cannabis patients (64.9 percent in 2016). Of all patient-reported qualifying conditions, 85.5 percent had either substantial or conclusive evidence of therapeutic efficacy. As medical cannabis use continues to increase, creating a nationwide patient registry would facilitate better understanding of trends in use and of its potential effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30715980

https://www.healthaffairs.org/doi/10.1377/hlthaff.2018.05266

Ketamine induces central antinociception mediated by endogenous cannabinoids and activation of CB1 receptors.

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Neuroscience Letters

“The participation of endocannabinoids in central and peripheral antinociception induced by several compounds has been shown by our group.

In this study, we investigated the effect of endocannabinoids on the central antinociception induced by ketamine.

It was concluded that central antinociception induced by ketamine involves the activation of CB1 cannabinoidreceptors.

Mobilization of cannabinoids might be required for the activation of those receptors, since inhibitors of the endogenous cannabinoids potentiate the effect of Ketamine.”

https://www.ncbi.nlm.nih.gov/pubmed/30716423

https://www.sciencedirect.com/science/article/abs/pii/S0304394019300771?via%3Dihub