Category Archives: Pain

Non-Intoxicating Cannabinoids in Visceral Pain

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“Cannabis and cannabis products are becoming increasingly popular options for symptom management of inflammatory bowel diseases, particularly abdominal pain. While anecdotal and patient reports suggest efficacy of these compounds for these conditions, clinical research has shown mixed results. To date, clinical research has focused primarily on delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is a ligand of classical cannabinoid receptors (CBRs). CBD is one of a large group of nonintoxicating cannabinoids (niCBs) that mediate their effects on both CBRs and through non-CBR mechanisms of action. Because they are not psychotropic, there is increasing interest and availability of niCBs. The numerous niCBs show potential to rectify abnormal intestinal motility as well as have anti-inflammatory and analgesic effects. The effects of niCBs are frequently not mediated by CBRs, but rather through actions on other targets, including transient receptor potential channels and voltage-gated ion channels. Additionally, evidence suggests that niCBs can be combined to increase their potency through what is termed the entourage effect. This review examines the pre-clinical data available surrounding these niCBs in treatment of abdominal pain with a focus on non-CBR mechanisms”

https://pubmed.ncbi.nlm.nih.gov/37883662/

https://www.liebertpub.com/doi/10.1089/can.2023.0113.

Cannabis Use Is Associated With Fewer Filled Opioid Prescriptions After Treatment of Proximal Humerus Fractures

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“The purpose of this study was to use a large claims database to determine if there is a difference in opioid use after operative intervention for proximal humerus fractures in patients with known cannabis use compared with those who do not report cannabis use. The PearlDiver database was queried to find all patients who underwent proximal humerus open reduction and internal fixation. A group of patients with reported cannabis use or dependence was matched to a cohort without known cannabis use. Between the two groups, differences in the number of opioid prescriptions filled in the postoperative period (within 3 days), the morphine milligram equivalents (MMEs) prescribed in total and per day, and the number of opioid prescription refills were explored. There were 66,445 potential control patients compared with 1260 potential study patients. After conducting the propensity score match, a total of 1245 patients were included in each group. The patients in the cannabis group filled fewer opioid prescriptions (P=.045) and were prescribed fewer total MMEs (P=.044) in the first 3 days postoperatively. Results of this study indicate that patients who use cannabis products may use fewer opioids after proximal humerus open reduction and internal fixation.”

https://pubmed.ncbi.nlm.nih.gov/37921529/

https://journals.healio.com/doi/10.3928/01477447-20231027-07

Cannabidiol as an Alternative Analgesic for Acute Dental Pain

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“Odontogenic pain can be debilitating, and nonopioid analgesic options are limited. This randomized placebo-controlled clinical trial aimed to assess the effectiveness and safety of cannabidiol (CBD) as an analgesic for patients with emergency acute dental pain. Sixty-one patients with moderate to severe toothache were randomized into 3 groups: CBD10 (CBD 10 mg/kg), CBD20 (CBD 20 mg/kg), and placebo. We administered a single dose of respective oral solution and monitored the subjects for 3 h. The primary outcome measure was the numerical pain differences using a visual analog scale (VAS) from baseline within and among the groups. Secondary outcome measures included ordinal pain intensity differences, the onset of significant pain relief, maximum pain relief, changes in bite force within and among the groups, psychoactive effects, mood changes, and other adverse events. Both CBD groups resulted in significant VAS pain reduction compared to their baseline and the placebo group, with a maximum median VAS pain reduction of 73% from baseline pain at the 180-min time point (P < 0.05). CBD20 experienced a faster onset of significant pain relief than CBD10 (15 versus 30 min after drug administration), and both groups reached maximum pain relief at 180-min. Number needed to treat was 3.1 for CBD10 and 2.4 for CBD20. Intragroup comparisons showed a significant increase in bite forces in both CBD groups (P < 0.05) but not in the placebo group (P > 0.05). CBD20 resulted in a significant difference in mean percent bite force change in the 90- and 180-min time points compared to the placebo group (P < 0.05). Compared to placebo, sedation, diarrhea, and abdominal pain were significantly associated with the CBD groups (P < 0.05). There were no other significant psychoactive or mood change effects. This randomized trial provides the first clinical evidence that oral CBD can be an effective and safe analgesic for dental pain.”

https://pubmed.ncbi.nlm.nih.gov/37910667/

“This study showed for the first time that pure CBD could provide more than 70% analgesia to patients with emergency dental pain and increase their bite force during the analgesic effect while maintaining a safe drug profile with minimal side effects. This novel study can catalyze the use of CBD as an alternative analgesic to opioids for acute inflammatory pain conditions, which could ultimately help to address the opioid epidemic.”

https://journals.sagepub.com/doi/10.1177/00220345231200814

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice

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“Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. 

Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. 

Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. 

Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.”

https://pubmed.ncbi.nlm.nih.gov/37903029/

https://www.liebertpub.com/doi/10.1089/can.2023.0093

Chronic Cannabigerol as an Effective Therapeutic for Cisplatin-Induced Neuropathic Pain

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“Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60-70% of baseline levels (p < 0.001 for all), 24 h after the last injection. Additionally, we found that daily treatment with CBG did not evoke tolerance and did not incur significant weight change or adverse events. The efficacy of CBG was independent of the estrous cycle phase. Therefore, chronic CBG administration can provide at least 24 h of antinociceptive effect in mice. These findings support the study of CBG as a long-lasting neuropathic pain therapy, which acts without tolerance in both males and females.”

https://pubmed.ncbi.nlm.nih.gov/37895913/

https://www.mdpi.com/1424-8247/16/10/1442

Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases

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“Introduction: Medical cannabis may provide a treatment option for chronic neuropathic pain. However, empirical disease-specific data are scarce.

Methods: This is a retrospective observational study including 99 patients with chronic neuropathic pain. These patients received medical cannabis by means of inhaling dried flowers with tetrahydrocannabinol content of <12-22% at a maximal daily dose of 0.15-1 g. Up to six follow-ups were carried out at intervals of 4-6 weeks. Pain severity, sleep disturbance, general improvement, side effects, and therapy tolerance at the follow-up consultations were assessed in interviews and compared with the baseline data using non-parametric Wilcoxon signed-rank test.

Results: Within 6 weeks on the therapy, median of the pain scores decreased significantly from 7.5 to 4.0 (p < 0.001). The proportion of patients with severe pain (score >6) decreased from 96% to 16% (p < 0.001). Sleep disturbance was significantly improved with the median of the scores decreased from 8.0 to 2.0 (p < 0.001). These improvements were sustained over a period of up to 6 months. There were no severe adverse events reported. Mild side effects reported were dryness in mucous tissue (5.4%), fatigue (4.8%), and increased appetite (2.7%). Therapy tolerance was reported in 91% of the interviews.

Conclusion: Medical cannabis is safe and highly effective for treating neuropathic pain and concomitant sleep disturbance.”

https://pubmed.ncbi.nlm.nih.gov/37900896/

https://karger.com/mca/article/6/1/89/860557/Medical-Cannabis-Alleviates-Chronic-Neuropathic

Chronic wound-related pain, wound healing and the therapeutic potential of cannabinoids and endocannabinoid system modulation

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“Chronic wounds represent a significant burden on the individual, and the healthcare system. Individuals with chronic wounds report pain to be the most challenging aspect of living with a chronic wound, with current therapeutic options deemed insufficient. The cutaneous endocannabinoid system is an important regulator of skin homeostasis, with evidence of system dysregulation in several cutaneous disorders. Herein, we describe the cutaneous endocannabinoid system, chronic wound-related pain, and comorbidities, and review preclinical and clinical evidence investigating endocannabinoid system modulation for wound-related pain and wound healing. Based on the current literature, there is some evidence to suggest efficacy of endocannabinoid system modulation for promotion of wound healing, attenuation of cutaneous disorder-related inflammation, and for the management of chronic wound-related pain. However, there is 1) a paucity of preclinical studies using validated models, specific for the study of chronic wound-related pain and 2) a lack of randomised control trials and strong clinical evidence relating to endocannabinoid system modulation for wound-related pain. In conclusion, while there is some limited evidence of benefit of endocannabinoid system modulation in wound healing and wound-related pain management, further research is required to better realise the potential of targeting the endocannabinoid system for these therapeutic applications.”

https://pubmed.ncbi.nlm.nih.gov/37865988/

“Modulation of the endocannabinoid system may be beneficial for wound-related pain. Cannabinoid-based therapeutics may promote wound healing and reduce inflammation.”

https://www.sciencedirect.com/science/article/pii/S0753332223015123?via%3Dihub

The Place of Cannabinoids in the Treatment of Gynecological Pain

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“Cannabis sativa (L), a plant with an extensive history of medicinal usage across numerous cultures, has received increased attention over recent years for its therapeutic potential for gynecological disorders such as endometriosis, chronic pelvic pain, and primary dysmenorrhea, due at least in part to shortcomings with current management options. Despite this growing interest, cannabis inhabits an unusual position in the modern medical pharmacopoeia, being a legal medicine, legal recreational drug, and an illicit drug, depending on jurisdiction. To date, the majority of studies investigating cannabis use have found that most people are using illicit cannabis, with numerous obstacles to medical cannabis adoption having been identified, including outdated drug-driving laws, workplace drug testing policies, the cost of quality-assured medical cannabis products, a lack of cannabis education for healthcare professionals, and significant and persistent stigma. Although currently lacking robust clinical trial data, a growing evidence base of retrospective data, cohort studies, and surveys does support potential use in gynecological pain conditions, with most evidence focusing on endometriosis. Cannabis consumers report substantial reductions in pelvic pain, as well as common comorbid symptoms such as gastrointestinal disturbances, mood disorders such as anxiety and depression, and poor sleep. Substitution effects were reported, with >50% reduction or cessation in opioid and/or non-opioid analgesics being the most common. However, a substantial minority report not disclosing cannabis consumption to their health professional. Therefore, while such deprescribing trends are potentially beneficial, the importance of medical supervision during this process is paramount given the possibility for withdrawal symptoms.”

https://pubmed.ncbi.nlm.nih.gov/37831340/

“Cannabis, whether purchased illicitly, or obtained through legal means, is commonly used by those with chronic pelvic pain, especially people with endometriosis. People report several benefits from using cannabis, including being able to reduce their normal medications including opioid based painkillers, but often don’t tell their health professional about this. This could lead to issues with withdrawal symptoms, so clinicians should be aware of the high prevalence of use of cannabis in this population.”

https://link.springer.com/article/10.1007/s40265-023-01951-z

Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies

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“Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases.

Some of these include central nervous system (CNS) diseases and dysfunctions such as forms of epilepsy, multiple sclerosis, Parkinson’s disease, pain and neuropsychiatric disorders. In addition, the endogenously produced cannabinoid lipids, endocannabinoids, are critical for normal CNS function, and if controlled or modified, may represent an additional therapeutic avenue for CNS diseases. This review discusses in vitro cellular, ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies. In addition, the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases.

Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/37843213/

https://journals.lww.com/nrronline/fulltext/2024/04000/cannabinoids_and_endocannabinoids_as_therapeutics.22.aspx

Applications of Cannabinoids in Neuropathic Pain: An Updated Review

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“Neuropathic pain is experienced due to injury to the nerves, underlying disease conditions or toxicity induced by chemotherapeutics. Multiple factors can contribute to neuropathic pain such as central nervous system (CNS)-related autoimmune and metabolic disorders, nerve injury, multiple sclerosis and diabetes. Hence, development of pharmacological interventions to reduce the drawbacks of existing chemotherapeutics and counter neuropathic pain is an urgent unmet clinical need.

Cannabinoid treatment has been reported to be beneficial for several disease conditions including neuropathic pain.

Cannabinoids act by inhibiting the release of neurotransmitters from presynaptic nerve endings, modulating the excitation of postsynaptic neurons, activating descending inhibitory pain pathways, reducing neural inflammation and oxidative stress and also correcting autophagy defects. This review provides insights on the various preclinical and clinical therapeutic applications of cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) in various diseases and the ongoing clinical trials for the treatment of chronic and acute pain with cannabinoids.

Pharmacological and genetic experimental strategies have well demonstrated the potential neuroprotective effects of cannabinoids and also elaborated their mechanism of action for the therapy of neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/37824417/

https://www.dl.begellhouse.com/journals/3667c4ae6e8fd136,7ec6441519bff684,786cb61f3f1ec955.html