“An increased risk of cardiovascular events on a population level was not observed on “4/20.””
https://www.ncbi.nlm.nih.gov/pubmed/31542258
https://www.onlinecjc.ca/article/S0828-282X(19)30356-3/fulltext
Druggable Targets of the Endocannabinoid System: Implications for the Treatment of HIV-Associated Neurocognitive Disorder.
“HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms.
The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation.
Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND.
Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.”
https://www.ncbi.nlm.nih.gov/pubmed/31539547
https://www.sciencedirect.com/science/article/abs/pii/S0006899319305219?via%3Dihub
Medical cannabis for chronic pain: can it make a difference in pain management?
“Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.
Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns.
Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management.
The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol.
More countries have decided to legalise the medicinal use of cannabis and marijuana.
Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications.”
https://www.ncbi.nlm.nih.gov/pubmed/31535218
https://link.springer.com/article/10.1007%2Fs00540-019-02680-y
The Impact of Cannabinoid Receptor 2 Deficiency on Neutrophil Recruitment and Inflammation.
“Neutrophil trafficking into damaged or infected tissues is essential for the initiation of inflammation, clearance of pathogens and damaged cells, and ultimately tissue repair. Neutrophil recruitment is highly dependent on the stepwise induction of adhesion molecules and promigratory chemokines and cytokines.
A number of studies in animal models have shown the efficacy of cannabinoid receptor 2 (CB2) agonists in limiting inflammation in a range of preclinical models of inflammation, including colitis, atherosclerosis, multiple sclerosis, and ischemia-reperfusion injury.
Recent work in preclinical models of inflammation raises two questions: by what mechanisms do CB2 agonists provide anti-inflammatory effects during acute inflammation and what challenges exist in the translation of CB2 modulating therapeutics into the clinic.”
The Endocannabinoid System of Animals.
“The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species as primitive as the Hydra. Insects, apparently, are devoid of this, otherwise, ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems.
The endocannabinoid system (ECS) has been defined to consist of three parts, which include (1) endogenous ligands, (2) G-protein coupled receptors (GPCRs), and (3) enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date.
The endocannabinoids are anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors (GPCR) have been described as part of this system, with other putative GPC being considered.
Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed phytocannabinoids.
The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.”
Insights into the role of cannabis in the management of inflammatory bowel disease.
“Cannabis, a drug made up of the flowers and buds of the Cannabis sativa plant, has been used therapeutically for centuries. Ancient Chinese cultures have reported use in their medical practices, dating back as early as 2700 BC. Although widely used recreationally during the 19th and 20th centuries, the use of medical cannabis has exploded over the last decade, as a result of mainstream cultural acceptance and legalization in several countries around the world.
Over the last decade, interest in the therapeutic potential of cannabis and its constituents (e.g. cannabidiol) in the management of inflammatory bowel diseases (IBD) has escalated. Cannabis has been increasingly approved for a variety of medical conditions in several jurisdictions around the world.
In animal models, cannabinoids have been shown to improve intestinal inflammation in experimental models of IBD through their interaction with the endocannabinoid system. However, the few randomized controlled trials of cannabis or cannabidiol in patients with IBD have not demonstrated efficacy in modulating inflammatory disease activity.
Cannabis may be effective in the symptomatic management of IBD. Given the increasing utilization and cultural acceptance of cannabis, physicians need to be aware of its safety and efficacy in order to better counsel patients. The aim of this review is to provide an overview of the role of cannabis in the management of patients with IBD.
There is emerging evidence that cannabis may play a role in the management of patients with IBD. Many patients are already using cannabis to help manage symptoms associated with the disease, and physicians cannot ignore this when taking histories and managing their patients.”
Cannabinoids in Gynecological Diseases
“The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in many physiological and pathological conditions. The ligands of the ECS are the endocannabinoids, whose actions are mimicked by exogenous cannabinoids, such as phytocannabinoids and synthetic cannabinoids. Responses to the ligands of the ECS are mediated by numerous receptors like the classical cannabinoid receptors (CB1 and CB2) as well as ECS-related receptors, e.g., G protein-coupled receptors 18 and 55 (GPR18 and GPR55), transient receptor potential ion channels, and nuclear peroxisome proliferator-activated receptors. The ECS regulates almost all levels of female reproduction, starting with oocyte production through to parturition. Dysregulation of the ECS is associated with the development of gynecological disorders from fertility disorders to cancer. Cannabinoids that act at the ECS as specific agonists or antagonists may potentially influence dysregulation and, therefore, represent new therapeutic options for the therapy of gynecological disorders.”
Evaluation of the effects of cannabinoids CBD and CBG on human ovarian cancer cells in vitro
“Ovarian cancer, with over a 90% reoccurrence within 18 months of treatment, and approximately a 30% mortality rate after 5 years, is the leading cause of death in cases of gynaecological malignancies. Acquired resistance, and toxic side effects by clinically used agents are major challenges associated with current treatments, indicating the need for new approaches in ovarian cancer treatment.
Increased tumour cell proliferation associated with upregulation of cannabinoid (CB) receptors has been observed in ovarian cancer. As cannabinoids reported to bind to CB receptors, and can potentially modulate their downstream signalling, this raises the possibility of cannabinoids as potential anticancer drugs for ovarian cancer treatment.
Amongst the cannabinoids, non-psychoactive CBD and CBG have been shown to have anticancer activities towards prostate and colon cancer cells through multiple mechanisms of action. However, CBD and CBG have yet to be investigated in relation to ovarian cancer therapy either in vitro or in vivo.
Aim:
The aims of this study were to evaluate the potential cytotoxic effects of CBD and CBG in human ovarian cancer cells, their ability to potentiate existing clinically used agents for ovarian cancer, and to perform initial mode of action studies in vitro.
Conclusions:
Both CBD and CBG showed preferential cytotoxicity against the ovarian cancer cells analysed compared to the non-cancer cells; however, this was less than for carboplatin. Importantly, in contrast to carboplatin, CBD and CBG showed similar activity towards cisplatin sensitive and cisplatin resistant cells indicating distinctive mechanisms of action to platinum drugs.
Preferential cytotoxicity towards cancer cells in vitro and ability to potentiate carboplatin and overcome cisplatin resistance identify CBD and CBG as promising candidates that warrant further investigation, both in terms of detailed mechanism of action studies and also in vivo studies to assess whether this promising activity translates into an in vivo setting and their potential for further progression towards the clinic.”
Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1.
“Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that attracted a great attention for its therapeutic potential against different pathologies including skin diseases.
However, although the efficacy in preclinical models and the clinical benefits of CBD in humans have been extensively demonstrated, the molecular mechanism(s) and targets responsible for these effects are as yet unknown.
Herein we characterized at the molecular level the effects of CBD on primary human keratinocytes using a combination of RNA sequencing (RNA-Seq) and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS).
Functional analysis revealed that CBD regulated pathways involved in keratinocyte differentiation, skin development and epidermal cell differentiation among other processes. In addition, CBD induced the expression of several NRF2 target genes, with heme oxygenase 1 (HMOX1) being the gene and the protein most upregulated by CBD. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrated that the induction of HMOX1 mediated by CBD, involved nuclear export and proteasomal degradation of the transcriptional repressor BACH1.
Notably, we showed that the effect of BACH1 on HMOX1 expression in keratinocytes is independent of NRF2. In vivo studies showed that topical CBD increased the levels of HMOX1 and of the proliferation and wound-repair associated keratins 16 and 17 in the skin of mice.
Altogether, our study identifies BACH1 as a molecular target for CBD in keratinocytes and sets the basis for the use of topical CBD for the treatment of different skin diseases including atopic dermatitis and keratin disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/31518892
https://www.sciencedirect.com/science/article/pii/S2213231719306470?via%3Dihub
Modulation of the endocannabinoid system: vulnerability factor and new treatment target for stimulant addiction
“Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction.
This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction.
A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.
Interestingly, emerging human data supports a role for ECBS modulation in vulnerability to psychostimulant addiction, and more significantly in addictive behaviors among dependent individuals. Accumulating evidence thus points to the ECBS as a critical target for the development of pharmacotherapies for the treatment of addiction to psychostimulants.
Given the various neuropharmacological actions of exogenous cannabinoids, and their ability to modulate the acute reinforcing effects of drugs, data on Δ9-THC and CBD is particularly promising as to the potential use of cannabinoids in relapse prevention strategies for psychostimulant-dependent individuals.”
https://www.frontiersin.org/articles/10.3389/fpsyt.2013.00109/full