Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

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molecules-logo“In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite.

The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion.

The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers.

The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers.

In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.”

https://pubmed.ncbi.nlm.nih.gov/34205169/

https://www.mdpi.com/1420-3049/26/11/3389

Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

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ijms-logo“Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative.

Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs).

Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.”

https://pubmed.ncbi.nlm.nih.gov/34298921/

https://www.mdpi.com/1422-0067/22/14/7302

Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?

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BMJ Journals - Northern Devon Healthcare NHS Trust“Central pain after stroke due to brainstem infarction is very rare. Treatment is difficult and specific guidelines are lacking. This is the report of a 61-year-old female patient who, after a posterolateral left medulla oblongata insult with incomplete Wallenberg syndrome, subsequently developed a burning and tingling pain in the contralateral leg and a burning and shooting pain in the ipsilateral face in trigeminal branches 1 and 2. More than 3 years of therapy with amitriptyline, gabapentin, pregabalin and various grade II and III opioids was ineffective or showed intolerable side effects. The administration of tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio improved the pain situation and quality of life quickly and permanently. The encouraging results in the present case may suggest that treatment with medical cannabis should be considered in similar cases when standard therapies are insufficient.”

https://pubmed.ncbi.nlm.nih.gov/34230048/

https://casereports.bmj.com/content/14/7/e243072

Cannabinoids and their derivatives in struggle against melanoma

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SpringerLink“Melanoma is one of the most aggressive malignances in human. Recently developed therapies improved overall survival rate, however, the treatment of melanoma still remains a challenging issue.

This review attempts to summarize recent advances in studies on cannabinoids used in the setting of melanoma treatment.

Conclusions after analysis of available data suggest that cannabinoids limit number of metastasis, and reduce growth of melanoma. The findings indicate that cannabinoids induce apoptosis, necrosis, autophagy, cell cycle arrest and exert significant interactions with tumor microenvironment.

Cannabinoids should be rather considered as a part of multi-targeted anti-tumor therapy instead of being standalone agent. Moreover, cannabinoids are likely to improve quality of life in patients with cancer, due to different supportive effects, like analgesia and/or anti-emetic effects.

In this review, it was pointed out that cannabinoids may be potentially useful in the melanoma therapy. Nevertheless, due to limited amount of data, great variety of cannabinoids available and lack of clinical trials, further studies are required to determine an exact role of cannabinoids in the treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/34264513/

“The endocannabinoid system is dysregulated in numerous pathological conditions, including malignancies. Recently, cannabinoids have received increasing amount of interest in the setting of treatment of various cancers.  Cannabinoids seem to be promising agents in the setting of melanoma treatment. In the case of melanoma, most important actions of cannabinoids described so far are decrease of cells viability by increase of apoptosis, necrosis and cell cycle arrest. Moreover, cannabinoids slow down disease progress by reduction of metastasis and tumor vascularization. Due to large variety of cannabinoids, there are many potential derivatives, which may be found useful in the therapy of melanoma.”

https://link.springer.com/article/10.1007%2Fs43440-021-00308-1

Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

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molecules-logo“The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable.

Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma.

Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance.

Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/34202812/

https://www.mdpi.com/1420-3049/26/13/3866

Medical marijuana utilization in gynecologic cancer patients

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Gynecologic Oncology Reports“Medical marijuana (MM) use is common among cancer patients, but relatively little is known about the usage patterns and efficacy of MM used by gynecologic cancer patients.

Methods: Demographic and clinical data were collected for gynecologic cancer patients prescribed MM between May 2016 and February 2019. The electronic medical record was used to query formulation prescribed, usage patterns, length of use, symptom relief, and side effect profile. Descriptive statistics were calculated.

Results: Of 45 gynecologic cancer patients prescribed MM, 89% were receiving chemotherapy; 56% were undergoing primary treatment. MM was used for a median of 5.2 months (range 0.6-25.4). Over 70% of patients reported improvement in nausea/vomiting, compared to 36% of patients using MM for pain relief (p = 0.02). Of 41 patients with follow-up information, 71% found MM improved at least one symptom.

Conclusions: Among a small sample of gynecologic cancer patients prescribed MM for symptom management, self-reported follow-up indicated symptom relief for the majority of patients and minimal therapy-related side effects. This data can prove useful for counseling gynecologic cancer patients on the efficacy and side effects of MM.”

https://pubmed.ncbi.nlm.nih.gov/34258360/

“Among a small cohort of gynecologic cancer patients prescribed MM for symptom management, the majority reported improvement in at least one disease or treatment-related symptom and reported minimal side effects. Further larger prospective studies are needed to investigate specific formulations and indications in this patient population, but our data indicate that it is a safe and useful adjunct for symptom management among a diverse cohort of women with gynecologic cancer.”

https://www.sciencedirect.com/science/article/pii/S2352578921001247?via%3Dihub

An Observational, Longitudinal Study of Cognition in Medical Cannabis Patients over the Course of 12 Months of Treatment: Preliminary Results

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Journal of the International Neuropsychological Society“Cannabis use has increased dramatically across the country; however, few studies have assessed the long-term impact of medical cannabis (MC) use on cognition. Studies examining recreational cannabis users generally report cognitive decrements, particularly in those with adolescent onset. As MC patients differ from recreational consumers in motives for use, product selection, and age of onset, we assessed cognitive and clinical measures in well-characterized MC patients over 1 year. Based on previous findings, we hypothesized MC patients would not show decrements and might instead demonstrate improvements in executive function over time.

Method: As part of an ongoing study, MC patients completed a baseline visit prior to initiating MC and evaluations following 3, 6, and 12 months of treatment. At each visit, patients completed a neurocognitive battery assessing executive function, verbal learning/memory, and clinical scales assessing mood, anxiety, and sleep. Exposure to delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) was also quantified.

Results: Relative to baseline, MC patients demonstrated significant improvements on measures of executive function and clinical state over the course of 12 months; verbal learning/memory performance generally remained stable. Improved cognitive performance was not correlated with MC use; however, clinical improvement was associated with higher CBD use. Analyses suggest cognitive improvements were associated with clinical improvement.

Conclusions: Study results extend previous pilot findings, indicating that MC patients may exhibit enhanced rather than impaired executive function over time. Future studies should examine distinctions between recreational and MC use to identify potential mechanisms related to cognitive changes and the role of clinical improvement.”

https://pubmed.ncbi.nlm.nih.gov/34261553/

https://www.cambridge.org/core/journals/journal-of-the-international-neuropsychological-society/article/abs/an-observational-longitudinal-study-of-cognition-in-medical-cannabis-patients-over-the-course-of-12-months-of-treatment-preliminary-results/369296C94054A5055552AAA8A20CA9FA

Spiritual Benefit from Cannabis

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Publication Cover“Like many mind-altering plants, cannabis has been part of spiritual practices for thousands of years. It has deep roots in Hinduism, Islam, Rastafarianism, and indigenous traditions in Asia, Africa, and elsewhere. Yet almost no attention has been given to how contemporary adults employ it spiritually. A sample of 1087 participants (mean age = 38.9) completed an online survey assessing their use of cannabis and other substances, as well as spiritual and psychological characteristics. Spiritual benefit from cannabis was reported by 66.1% of the sample, and 5.5% reported it had sometimes been a spiritual hindrance. A MANOVA showed that those who reported spiritual benefit differed significantly from those who did not on several outcome variables, and a post hoc descriptive discriminant analysis revealed that expansiveness motivation, non-theistic daily spiritual experience, meditation frequency, and two mindfulness facets contributed most to differentiating the two groups. The majority of the sample (63%) was free of cannabis use disorder. Compared to disordered groups, the non-disordered group was significantly older and scored lower on experiential avoidance, psychological distress, and several motives for use. Results suggest that spiritual motives for cannabis use may be widespread. Implications for future research on spiritual use of cannabis are discussed.”

https://pubmed.ncbi.nlm.nih.gov/34225558/

https://www.tandfonline.com/doi/abs/10.1080/02791072.2021.1941443?journalCode=ujpd20

Marijuana Use and the Risk of Early Ischemic Stroke: The Stroke Prevention in Young Adults Study

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Stroke logo“Few studies have examined the dose-response and temporal relationships between marijuana use and ischemic stroke while controlling for important confounders, including the amount of tobacco smoking. The purpose of our study was to address these knowledge gaps.

Results: After adjusting for other risk factors, including the amount of current tobacco smoking, marijuana use was not associated with ischemic stroke, regardless of the timing of use in relationship to the stroke, including ever use, use within 30 days, and use within 24 hours.

Conclusions: These analyses do not demonstrate an association between marijuana use and an increased risk of early-onset ischemic stroke, although statistical power was limited for assessing the association among very heavy users.”

https://pubmed.ncbi.nlm.nih.gov/34266309/

https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.032811

Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review

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IBRO Neuroscience Reports“Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP).

Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain.

Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP.

The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option.

Clinical evidence shows that smoked cannabis alleviates HIV-NP.” 

https://pubmed.ncbi.nlm.nih.gov/34179865/

“Smoked cannabis has been shown to be effective for managing HIV-NP in two RCTs.”

https://www.sciencedirect.com/science/article/pii/S2667242121000051?via%3Dihub