Cannabinoids for Cancer-related Pain Management: An Update on Therapeutic Applications and Future Perspectives

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“Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management.

Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids.

Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials.

In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief.”

https://pubmed.ncbi.nlm.nih.gov/38423660/

https://ar.iiarjournals.org/content/44/3/895

The effect of cannabinoids on wound healing: A review

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“Background and aims: Cannabis and its various derivatives are commonly used for both recreational and medicinal purposes. Cannabinoids have been shown to have anti-inflammatory properties. Inflammation is an important component of wound healing and the effect of cannabinoids on wound healing has become a recent topic of investigation. The objective of this article is to perform a comprehensive review of the literature to summarize the effects of cannabinoids on wound healing of the skin and to guide future avenues of research.

Methods: A comprehensive literature review was performed to evaluate the effects of cannabinoids on cutaneous wound healing.

Results: Cannabinoids appear to improve skin wound healing through a variety of mechanisms. This is supported through a variety of in vitro and animal studies. Animal studies suggest application of cannabinoids may improve the healing of postsurgical and chronic wounds. There are few human studies which evaluate the effects of cannabinoids on wound healing and many of these are case series and observational studies. They do suggest cannabinoids may have some benefit. However, definitive conclusions cannot be drawn from them.

Conclusion: While further human studies are needed, topical application of cannabinoids may be a potential therapeutic option for postsurgical and chronic wounds.”

https://pubmed.ncbi.nlm.nih.gov/38410495/

https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1908

The effects of cannabidiol against Methotrexate-induced lung damage

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“Methotrexate (MTX) is a widely used medication for various cancers, yet its use is associated with adverse effects on organs, notably the lungs.

Cannabidiol (CBD), known for its antioxidant and anti-inflammatory properties, was investigated for its potential protective effects against MTX-induced lung injury.

Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (single 20 mg/kg intraperitoneal dose), MTX + CBD (single 20 mg/kg MTX with 0.1 ml of 5 mg/kg CBD for 7 days intraperitoneally) and CBD only (for 7 days). Lung tissues were analysed using histopathological, immunohistochemical and PCR methods after the study. Histopathological assessment of the MTX group revealed lung lesions like hyperemia, edema, inflammatory cell infiltration and epithelial cell loss. Immunohistochemical examination showed significant increases in Cas-3, tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) expressions. PCR analysis indicated elevated expressions of apoptotic peptidase activating factor 1 (Apaf 1), glucose-regulated protein 78 (GRP 78), CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome C (Cyt C), along with reduced B-cell lymphoma-2 (BCL 2) expressions in the MTX group, though not statistically significant.

Remarkably, CBD treatment reversed these findings.

This study highlights CBD’s potential in mitigating MTX-induced lung damage, suggesting its therapeutic promise.”

https://pubmed.ncbi.nlm.nih.gov/38388876/

“The findings from this study underscore the remarkable effectiveness of CBD in preventing histopathological damage within the lungs induced by MTX. The marked reduction observed in hyperemia, edema and infiltration, coupled with its notable reparative effects on epithelial loss, highlights the multifaceted benefits of CBD in mitigating pulmonary issues of MTX. Importantly, the statistical analysis revealed a significant improvement across all histopathological scoring parameters (p < 0.001). This reinforces the potential of CBD as a promising therapeutic agent for MTX-induced lung lesions and warrants further exploration in clinical settings. This study has demonstrated for the first time the reparative effects of CBD on the pathological findings induced by MTX in the lungs. There is now a need for novel and comprehensive research on the therapeutic utilization of CBD for this purpose.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13992

Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto

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“Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed.

The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination.

As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo.”

https://pubmed.ncbi.nlm.nih.gov/38393124/

https://www.mdpi.com/2414-6366/9/2/35

The Role of Cannabidiol in Liver Disease: A Systemic Review

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“Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in Cannabis sativa, has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD’s potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice.

This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.”

https://pubmed.ncbi.nlm.nih.gov/38397045/

https://www.mdpi.com/1422-0067/25/4/2370

Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress

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“Cancer and chemotherapy can both cause cachexia, a complex multi-organ syndrome characterized by body weight loss, due to adipose tissue and skeletal muscle wasting. Changes in body weight and muscle mass are predictive of response to chemotherapy, incidence of treatment-related complications and, ultimately, patient survival, but there are currently still no clear therapeutic strategies to counteract cachexia.

Cannabidiol (CBD) is a bioactive phytocannabinoid produced from a plant named Cannabis sativa. In recent years, CBD has demonstrated beneficial effects on maintaining skeletal muscle mass, function and metabolism in models of muscular dystrophy or diet-induced obesity.

Here, we used a model of myotubes in culture to evaluate the potential beneficial effects of CBD on cisplatin-induced skeletal muscle wasting. 24-h cisplatin treatment resulted in a ≈30% reduction in myotube diameter, driven by a drastic reduction in protein synthesis rate and a twofold increase in proteolysis. 24-h cisplatin treatment also significantly increased myotube TBARS content, catalase activity and antioxidant system mRNA levels (GPX1, SOD1, SOD2 and CAT) indicating increased oxidative stress. 24-h cisplatin treatment also increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4 and VDAC1, which are involved in mitochondrial respiration and control of apoptosis.

Importantly, CBD was found to antagonize chemotherapy-induced C2C12 myotube atrophy by promoting protein homeostasis and reducing oxidative stress. Our results show that CBD could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.”

https://pubmed.ncbi.nlm.nih.gov/38406827/

https://journals.physiology.org/doi/abs/10.1152/ajpcell.00622.2023

Targeting the endocannabinoid system for the management of low back pain

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“Low back pain (LBP) is a major unmet clinical need. The endocannabinoid system (ECS) has emerged as a promising therapeutic target for pain, including LBP. This review examines the evidence for the ECS as a therapeutic target for LBP. While preclinical studies demonstrate the potential of the ECS as a viable therapeutic target, clinical trials have presented conflicting findings. This review underscores the need for innovative LBP treatments and biomarkers and proposes the ECS as a promising avenue for their exploration. A deeper mechanistic understanding of the ECS in LBP could inform the development of new pain management strategies.”

https://pubmed.ncbi.nlm.nih.gov/38401317/

https://www.sciencedirect.com/science/article/pii/S1471489224000080?via%3Dihub

Tetrahydrocannabinol and Cannabidiol for Pain Treatment-An Update on the Evidence

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“In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available.

Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression.

On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain.

Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly.

The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.”

https://pubmed.ncbi.nlm.nih.gov/38397910/

https://www.mdpi.com/2227-9059/12/2/307

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial

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“Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was 1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization.

Results Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events.

Conclusions Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.”

https://pubmed.ncbi.nlm.nih.gov/38405890/

https://www.medrxiv.org/content/10.1101/2024.02.16.24302843v1

Therapeutic Potential of Cannabinoid Profiles Identified in Cannabis L. Crops in Peru

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“Cannabis is a plant that is cultivated worldwide, and its use is internationally regulated, but some countries have been regulating its medicinal, social, and industrial uses. This plant must have arrived in Peru during the Spanish conquest and remains widely cultivated illicitly or informally to this day. However, new regulations are currently being proposed to allow its legal commercialization for medicinal purposes.

Cannabis contains specific metabolites known as cannabinoids, some of which have clinically demonstrated therapeutic effects. It is now possible to quantitatively measure the presence of these cannabinoids in dried inflorescences, thus allowing for description of the chemical profile or “chemotype” of cannabinoids in each sample.

This study analyzed the chemotypes of eight samples of dried inflorescences from cannabis cultivars in four different regions of Peru, and based on the significant variation in the cannabinoid profiles, we suggest their therapeutic potential.

The most important medical areas in which they could be used include the following: they can help manage chronic pain, they have antiemetic, anti-inflammatory, and antipruritic properties, are beneficial in treating duodenal ulcers, can be used in bronchodilators, in muscle relaxants, and in treating refractory epilepsy, have anxiolytic properties, reduce sebum, are effective on Methicillin-resistant Staphylococcus aureus, are proapoptotic in breast cancer, can be used to treat addiction and psychosis, and are effective on MRSA, in controlling psoriasis, and in treating glioblastoma, according to the properties of their concentrations of cannabidiol, cannabigerol, and Δ9-tetrahydrocannabinol, as reviewed in the literature. On the other hand, having obtained concentrations of THC, we were able to suggest the psychotropic capacity of said samples, one of which even fits within the legal category of “non-psychoactive cannabis” according to Peruvian regulations.”

https://pubmed.ncbi.nlm.nih.gov/38397908/

https://www.mdpi.com/2227-9059/12/2/306