“Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions.
Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported.
However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.”
“Neuropathic pain is one of the most invalidating symptoms in patients with Fabry disease (FD), affecting their quality of life, it is linked to small fiber neuropathy and it may not respond to available disease specific treatments. We report the case of a 32 years old man with classic FD and severe neuropathic pain who, after the failure of several standard pharmaceutical approaches, was treated with medical cannabis with relief of nocturnal pain and sleep improvement.”
“In conclusion: although more evidence is needed, this case report suggests that the use of medical cannabis could be considered as a pain treatment option for patient with FD, in particular for nocturnal pain relief, when other pharmacological approaches have failed.”
“Terpenes in Cannabis sativa exert analgesic effects, but the mechanisms are uncertain. We examined the effects of 10 terpenes on capsaicin responses in an established model of neuronal hypersensitivity. Adult rat DRG neurons cultured with neurotrophic factors NGF and GDNF were loaded with Fura2AM for calcium imaging, and treated with individual terpenes or vehicle for 5 min, followed by 1 µMol capsaicin. In vehicle treated control experiments, capsaicin elicited immediate and sustained calcium influx. Most neurons treated with terpenes responded to capsaicin after 6-8 min. Few neurons showed immediate capsaicin responses that were transient or normal. The delayed responses were found to be due to calcium released from the endoplasmic reticulum, as they were maintained in calcium/magnesium free media, but not after thapsigargin pre-treatment. Terpene inhibition of calcium influx was reversed after washout of medium, in the absence of terpenes, and in the presence of the Na+/K+ ATPase inhibitor ouabain, but not CB1 or CB2 receptor antagonists. Thus, terpenes inhibit capsaicin evoked calcium influx by Na+/K+ ATPase activation. Immunofluorescence showed TRPV1 co-expression with α1β1 Na+/K+ ATPase in most neurons while others were either TRPV1 or α1β1 Na+/K+ ATPase positive.”
“The neuromodulatory effects of cannabinoids have been recognized for millenia in traditional medicine, including for pain relief. Following the opioid crisis, attention has been focussed on developing alternatives including cannabinoid-based pain therapies, as chronic pain remains an unmet need. The best known of the phytocannabinoids is Δ9tetrahydrocannabinol (THC), the only known psychoactive component, along with many other cannabinoids with potential therapeutic benefits, such as cannabidiol (CBD), and cannabigerol (CBG) [2]. Amongst the several hundred components in Cannabis sativa are terpenes, which are produced in small and varying amounts in different cultivars of C. sativa, leading to potential variation in their effects [3]. Some of these, including limonene, phytol, borneol, terpineol, and caryophyllene, provide pain relief via calcium channel inhibition [4]. Similarly, antinociceptive and anti-tumour effects of α-phellandrene were reported, although the mechanisms were unknown. Terpenes as a class of compounds are generally described as safe by the FDA, with low toxicity that extends their efficacy to a variety of indications including chronic pain and anxiety.”
“Background: Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only targeting pain intensity. However, this hypothesis has not been previously systematically tested.
Method: A retrospective internet survey was used in a sample of Finnish chronic pain patients (40 MC users and 161 opioid users). The patients evaluated statements describing positive and negative phenomenological effects of the medicine. The two groups were propensity score matched to control for possible confounding factors.
Results: Exploratory factor analysis revealed three experience factors: Negative Side Effects, Positive Holistic Effects, and Positive Emotional Effects. The MC group (matched n = 39) received higher scores than the opioid group (matched n = 39) in Positive Emotional Effects with large effect size (Rank-Biserial Correlation RBC = .71, p < .001), and in Holistic Positive Effects with medium effect size (RBC = .47, p < .001), with no difference in Negative Side Effects (p = .13). MC and opioids were perceived as equally efficacious in reducing pain intensity. Ratings of individual statements were exploratively examined in a post hoc analysis.
Conclusion: MC and opioids were perceived to be equally efficacious in reducing pain intensity, but MC additionally positively affected broader pain-related factors such as emotion, functionality, and overall sense of wellbeing. This supports the hypothesis that MC alleviates pain through holistically altering the pain experience.”
“The results of the present study support the hypothesis that the effects of MC on pain experience are more holistic than those of opioids. MC may alleviate pain through affecting a broad range of pain-related experience experiental factors such as relaxation, improved sleep and mood, being able not to react to the pain, as well as a sense of control. These holistic effects of MC could explain the inconsistencies in clinical trials, where focus has mainly been on pain intensity instead of broader pain phenomenology. The results highlight the importance of taking these holistic effects into account in treating patients with MC, considering them as part of the therapeutic process.”
“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.”
“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.”
“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.”
“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.”
“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.”
“Overall, these findings suggest that CBD will be a promising component in biomaterial-based therapeutic approaches for the treatment of inflammatory pathomechanisms.”
“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.”
