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

In Vitro Antiproliferative Effect of Cannabis Extract PHEC-66 on Melanoma Cell Lines

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“Melanoma, an aggressive form of skin cancer, can be fatal if not diagnosed and treated early. Melanoma is widely recognized to resist advanced cancer treatments, including immune checkpoint inhibitors, kinase inhibitors, and chemotherapy. Numerous studies have shown that various Cannabis sativa extracts exhibit potential anticancer effects against different types of tumours both in vitro and in vivo. This study is the first to report that PHEC-66, a Cannabis sativa extract, displays antiproliferative effects against MM418-C1, MM329 and MM96L melanoma cells. Although these findings suggest that PHEC-66 has promising potential as a pharmacotherapeutic agent for melanoma treatment, further research is necessary to evaluate its safety, efficacy, and clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/37887294/

“In conclusion, the results of this study demonstrate that PHEC-66 extract derived from Cannabis sativa exerts a significant cytotoxic effect on MM418-C1, MM329, and MM96L melanoma cell lines while having a lesser effect on human keratinocytes (HaCaT), human epidermal melanocytes (HEM), and normal human dermal fibroblasts (NHDF). Although the mechanism of PHEC-66’s anti-melanoma activity remains unknown, this study suggests it may induce apoptotic and necrotic cell death pathways. Further research is necessary to fully comprehend the underlying mechanisms of PHEC-66’s actions and assess its potential as a natural source of anticancer compounds.”

https://www.mdpi.com/2073-4409/12/20/2450

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

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

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“Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH.

Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders.

Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol’s ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol’s role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms.

Overall, the review underscores cannabidiol’s promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.”

https://pubmed.ncbi.nlm.nih.gov/37841923/

“These results suggest that CBD may be an effective treatment against ICH-induced OS.”

https://www.frontiersin.org/articles/10.3389/fphar.2023.1247550/full

EXPLORING THE RELATIONSHIP BETWEEN MARIJUANA SMOKING AND COVID-19 OUTCOMES

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“PURPOSE: Marijuana use is becoming increasingly prevalent worldwide, yet the full spectrum of its effects largely remains unknown. Although cannabinoids have immunomodulatory properties, there remains a significant gap in our understanding of the potential impact of marijuana use on COVID-19 outcomes. The purpose of the study is to compare the outcomes of COVID-19 infection on individuals who use marijuana and those who do not.

METHODS: National Inpatient Sample Database was used to sample individuals admitted with the diagnosis of COVID-19. Patients were divided into two groups based on marijuana use. Baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data or age under 18 were excluded. Greedy propensity matching using R was performed to match marijuana users to non-users 1:1 on age, race, gender, and 17 other comorbidities including chronic lung disease. Univariate analysis pre- and post-match were performed. Binary logistic regression was performed post-match. A p-value of <0.05 was considered statistically significant.

RESULTS: Out of 322,214 patients included in the study, 2,603 were marijuana users. Marijuana users were younger and had higher prevalence of tobacco use. However, other comorbidities including obstructive sleep apnea, obesity, hypertension, and diabetes mellitus were more prevalent in marijuana non-users. On univariate analysis, marijuana users had significantly lower rates of intubation (6.8% vs 12%), acute respiratory distress syndrome (ARDS) (2.1% vs 6%), acute respiratory failure (25% vs 52.9%) and severe sepsis with multiorgan failure (5.8% vs 12%). They also had lower in-hospital cardiac arrest (1.2% vs 2.7%) and mortality (2.9% vs 13.5%). After 1:1 matching, marijuana users had lower rates of intubation (OR: 0.64 [0.51-0.81]; p<0.01), ARDS (OR: 0.39 [0.26-0.58]; p<0.01), acute respiratory failure (OR: 0.53 [0.47-0.61]; p<0.01), severe sepsis with multiorgan failure (OR: 0.68 [0.52-0.89]; p<0.01) and lower mortality (OR: 0.48 [0.33-0.69]; p<0.01)

CONCLUSIONS: Marijuana smokers had better outcomes and mortality compared to non-users. The beneficial effect of marijuana use may be attributed to its potential to inhibit viral entry into cells and prevent the release of proinflammatory cytokines, thus mitigating cytokine release syndrome.

CLINICAL IMPLICATIONS: The significant decrease in mortality and complications warrants further investigation of the association between marijuana use and COVID-19. Our study highlights a topic of future research for larger trials especially considering the widespread use of marijuana.”

https://journal.chestnet.org/article/S0012-3692(23)02201-8/fulltext

“Study Finds Cannabis Users Had Better Covid-19 Outcomes”

https://www.forbes.com/sites/ajherrington/2023/10/13/study-finds-cannabis-users-had-better-covid-19-outcomes/?sh=67f274281eb1

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

Pharmacohistory of Cannabis Use-A New Possibility in Future Drug Development for Gastrointestinal Diseases

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“Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.”

https://pubmed.ncbi.nlm.nih.gov/37834122/

“Taken together, the future of cannabis and cannabinoids research for gastrointestinal disorders involves a comprehensive understanding of their mechanisms of action, multi-centred rigorous clinical trials, personalized medicine approaches, and continued exploration of formulation development and safety considerations. These efforts have the potential to yield novel therapeutic options and improve the quality of life for patients with gastrointestinal disorders.”

https://www.mdpi.com/1422-0067/24/19/14677

Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study

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“Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells (EGC) and macrophages. Different studies indicate that phytocannabinoids could play a possible role in the treatment of inflammatory bowel disease (IBD) by relieving the symptoms involved in the disease.

Phytocannabinoids act through the endocannabinoid system, which is distributed throughout the mammalian body in the cells of the immune system and in the intestinal cells. Our in vitro study analyzed the putative anti-inflammatory effect of nine selected pure cannabinoids in J774A1 macrophage cells and EGCs triggered to undergo inflammation with lipopolysaccharide (LPS). The anti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNFα transcription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and transcription in EGCs.

Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti-inflammatory effect in both J774A1 macrophages and EGCs compared to the other phytocannabinoids tested herein.

We then performed RNA-seq analysis of EGCs exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGCs revealed 23 differentially expressed genes (DEG) compared to the treatment with only LPS. Pretreatment with THC resulted in 26 DEG, and pretreatment with THC-COOH resulted in 25 DEG. To evaluate which biological pathways were affected by the different phytocannabinoid treatments, we used the Ingenuity platform. We show that THC treatment affects the mTOR and RAR signaling pathway, while THC-COOH mainly affects the IL6 signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/37834076/

https://www.mdpi.com/1422-0067/24/19/14628

Non-Psychoactive Phytocannabinoids Inhibit Inflammation-Related Changes of Human Coronary Artery Smooth Muscle and Endothelial Cells

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“Atherosclerosis is associated with vascular smooth muscle cell proliferation, chronic vascular inflammation, and leukocyte adhesion.

In view of the cardioprotective effects of cannabinoids described in recent years, the present study investigated the impact of the non-psychoactive phytocannabinoids cannabidiol (CBD) and tetrahydrocannabivarin (THCV) on proliferation and migration of human coronary artery smooth muscle cells (HCASMC) and on inflammatory markers in human coronary artery endothelial cells (HCAEC).

In HCASMC, CBD and THCV at nontoxic concentrations exhibited inhibitory effects on platelet-derived growth factor-triggered proliferation (CBD) and migration (CBD, THCV). When interleukin (IL)-1β- and lipopolysaccharide (LPS)-stimulated HCAEC were examined, both cannabinoids showed a concentration-dependent decrease in the expression of vascular cell adhesion molecule-1 (VCAM-1), which was mediated independently of classical cannabinoid receptors and was not accompanied by a comparable inhibition of intercellular adhesion molecule-1. Further inhibitor experiments demonstrated that reactive oxygen species, p38 mitogen-activated protein kinase activation, histone deacetylase, and nuclear factor κB (NF-κB) underlie IL-1β- and LPS-induced expression of VCAM-1. In this context, CBD and THCV were shown to inhibit phosphorylation of NF-κB regulators in LPS- but not IL-1β-stimulated HCAEC. Stimulation of HCAEC with IL-1β and LPS was associated with increased adhesion of monocytes, which, however, could not be significantly abolished by CBD and THCV.

In summary, the results highlight the potential of the non-psychoactive cannabinoids CBD and THCV to regulate inflammation-related changes in HCASMC and HCAEC. Considering their effect on both cell types studied, further preclinical studies could address the use of CBD and THCV in drug-eluting stents for coronary interventions.”

https://pubmed.ncbi.nlm.nih.gov/37830604/

https://www.mdpi.com/2073-4409/12/19/2389