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

Posted on November 1, 2023 by David

“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

Posted on October 30, 2023 by David

“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

Posted on October 30, 2023 by David

“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

Applications of Cannabinoids in Neuropathic Pain: An Updated Review

Posted on October 17, 2023 by David

“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

Cannabidiol attenuates inflammatory impairment of intestinal cells expanding biomaterial-based therapeutic approaches

Posted on October 2, 2023 by David

“Cannabis-based biomaterials have the potential to deliver anti-inflammatory therapeutics specifically to desired cells, tissues, and organs, enhancing drug delivery and the effectiveness of anti-inflammatory treatment while minimizing toxicity. As a major component of Cannabis, Cannabidiol (CBD) has gained major attention in recent years because of its potential therapeutic properties, e.g., for restoring a disturbed barrier resulting from inflammatory conditions. The aim of this study was to test the hypothesis that CBD has beneficial effects under normal and inflammatory conditions in the established non-transformed intestinal epithelial cell model IPEC-J2. CBD induced a significant increase in transepithelial electrical resistance (TER) values and a decrease in the paracellular permeability of [³H]-D-Mannitol, indicating a strengthening effect on the barrier. Under inflammatory conditions induced by tumor necrosis factor alpha (TNFα), CBD stabilized the TER and mitigated the increase in paracellular permeability. Additionally, CBD prevented the barrier-disrupting effects of TNFα on the distribution and localization of sealing TJ proteins. CBD also affected the expression of TNF receptors. These findings demonstrate the potential of CBD as a component of Cannabis-based biomaterials used in the development of novel therapeutic approaches against inflammatory pathogenesis.”

https://pubmed.ncbi.nlm.nih.gov/37779918/

“Overall, these findings suggest that CBD will be a promising component in biomaterial-based therapeutic approaches for the treatment of inflammatory pathomechanisms.”

https://www.sciencedirect.com/science/article/pii/S2590006423002685?via%3Dihub

Cannabidiol acts as molecular switch in innate immune cells to promote the biosynthesis of inflammation-resolving lipid mediators

Posted on August 31, 2023 by David

“Cannabinoids are phytochemicals from cannabis with anti-inflammatory actions in immune cells. Lipid mediators (LM), produced from polyunsaturated fatty acids (PUFA), are potent regulators of the immune response and impact all stages of inflammation. How cannabinoids influence LM biosynthetic networks is unknown. Here, we reveal cannabidiol (CBD) as a potent LM class-switching agent that stimulates the production of specialized pro-resolving mediators (SPMs) but suppresses pro-inflammatory eicosanoid biosynthesis. Detailed metabololipidomics analysis in human monocyte-derived macrophages showed that CBD (i) upregulates exotoxin-stimulated generation of SPMs, (ii) suppresses 5-lipoxygenase (LOX)-mediated leukotriene production, and (iii) strongly induces SPM and 12/15-LOX product formation in resting cells by stimulation of phospholipase A₂-dependent PUFA release and through Ca²⁺-independent, allosteric 15-LOX-1 activation. Finally, in zymosan-induced murine peritonitis, CBD increased SPM and 12/15-LOX products and suppressed pro-inflammatory eicosanoid levels in vivo. Switching eicosanoid to SPM production is a plausible mode of action of CBD and a promising inflammation-resolving strategy.”

https://pubmed.ncbi.nlm.nih.gov/37647900/

https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(23)00249-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945623002490%3Fshowall%3Dtrue

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study

Posted on August 31, 2023 by David

“The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta-9-tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within-subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5-h test sessions. Measures of experimental and self-reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed-effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low-dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk-benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.”

https://pubmed.ncbi.nlm.nih.gov/37644897/

https://onlinelibrary.wiley.com/doi/10.1111/adb.13317

Cannabis Versus Opioids for Pain

Posted on August 20, 2023 by David

“In the human body, pain is an inherent alarm system that activates when there is actual or potential damage, directing an individual’s attention toward the issue. Pain is a frequently cited reason for seeking healthcare or medical assistance. Pain encompasses various elements, including nociception, the perception of pain, suffering, and pain behaviors. Although pain is a fundamental mechanism, it can become burdensome when it persists for an extended period, leading to suffering and pain-related behaviors. Chronic and unrelenting pain can cause psychological, physical, and emotional distress, adding further strain to individuals.

The search for an ideal pain relief medication has been an ongoing endeavor since ancient times, as certain types of pain still lack definitive treatment options. Several strategies have been developed to address intractable pain that does not respond to nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids being the mainstay in many pain management protocols. In recent years, there has been growing and promising evidence suggesting the potential effectiveness of cannabinoids in the management of chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/34424653/

Can cannabidiol have an analgesic effect?

Posted on August 20, 2023 by David

“Background: Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system.

Objectives and methods: We have prepared a literature review based on the latest available literature regarding the analgesic effects of CBD. CBD has a wide range of effects on the human body. In this study, we will present the potential mechanisms responsible for the analgesic effect of CBD. To the best of our knowledge, this is the first review to explore the analgesic mechanisms of CBD.

Results and conclusion: The analgesic effect of CBD is complex and still being researched. CBD models the perception of pain by acting on G protein-coupled receptors. Another group of receptors that CBD acts on are serotonergic receptors. The effect of CBD on an enzyme of potential importance in the production of inflammatory factors such as cyclooxygenases and lipoxygenases has also been confirmed. The presented potential mechanisms of CBD’s analgesic effect are currently being extensively studied.”

https://pubmed.ncbi.nlm.nih.gov/37584368/

https://onlinelibrary.wiley.com/doi/10.1111/fcp.12947

Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis

Posted on July 25, 2023 by David

“Background: Accumulating evidence has indicated that cannabis substitution is often used as a harm reduction strategy among people who use unregulated opioids (PWUO) and people living with chronic pain. We sought to investigate the association between cannabis use to manage opioid cravings and self-reported changes in opioid use among structurally marginalized PWUO.

Methods: The data were collected from a cross-sectional questionnaire administered to PWUO in Vancouver, Canada. Binary logistic regression was used to analyze the association between cannabis use to manage opioid cravings and self-reported changes in unregulated opioid use.

Results: A total of 205 people who use cannabis and opioids were enrolled in the present study from December 2019 to November 2021. Cannabis use to manage opioid cravings was reported by 118 (57.6%) participants. In the multivariable analysis, cannabis use to manage opioid cravings (adjusted Odds Ratio [aOR] = 2.13, 95% confidence interval [CI]: 1.07, 4.27) was significantly associated with self-reported reductions in opioid use. In the sub-analyses of pain, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among people living with moderate to severe pain (aOR = 4.44, 95% CI: 1.52, 12.97). In the sub-analyses of males and females, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among females (aOR = 8.19, 95% CI: 1.20, 55.81).

Conclusions: These findings indicate that cannabis use to manage opioid cravings is a prevalent motivation for cannabis use among PWUO and is associated with self-assessed reductions in opioid use during periods of cannabis use. Increasing the accessibility of cannabis products for therapeutic use may be a useful supplementary strategy to mitigate exposure to unregulated opioids and associated harm during the ongoing drug toxicity crisis.”

https://pubmed.ncbi.nlm.nih.gov/37481875/

https://www.sciencedirect.com/science/article/abs/pii/S0955395923001603?via%3Dihub

www.thctotalhealthcare.com

Category Archives: Chronic Inflammatory and Neuropathic Pain