Aerobic exercise is a widely adopted practice, not solely for enhancing fitness and reducing the risk of various diseases but also for its ability to uplift mood and aid in addressing depression and anxiety disorders. Within the scope of this narrative review, we seek to consolidate current insights into the endocannabinoid-mediated regulation of stress and the brain\'s reward mechanism resulting from engaging in aerobic exercise. A comprehensive search was conducted across Medline, SPORTDiscus, Pubmed, and Scopus, encompassing data available until November 30, 2023. This review indicates that a bout of aerobic exercise, particularly of moderate intensity, markedly augments circulating levels of endocannabinoids - N-arachidonoyl-ethanolamine (AEA) and 2-acylglycerol (2-AG), that significantly contributes to mood elevation and reducing stress in healthy individuals.  The current understanding of how aerobic exercise impacts mental health and mood improvement is still unclear. Moderate and high-intensity aerobic exercise modulates stress through a negative feedback mechanism targeting both the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system, thereby facilitating stress regulation crucial role in endocannabinoid synthesis, ultimately culminating in the orchestration of negative feedback across multiple tiers of the HPA axis, coupled with its influence over cortical and subcortical brain structures. The endocannabinoid has been observed to govern the release of neurotransmitters from diverse neuronal populations, implying a universal mechanism that fine-tunes neuronal activity and consequently modulates both emotional and stress-related responses. Endocannabinoids further assume a pivotal function within brain reward mechanisms, primarily mediated by CB1 receptors distributed across diverse cerebral centers. Notably, these endocannabinoids partake in natural reward processes, as exemplified in aerobic exercise, by synergizing with the dopaminergic reward system. The genesis of this reward pathway can be traced to the ventral tegmental area, with dopamine neurons predominantly projecting to the nucleus accumbens, thereby inciting dopamine release in response to rewarding stimuli.

Cannabis use has increased sharply in the last 20 y among adults, including reproductive-aged women. Its recent widespread legalization is associated with a decrease in risk perception of cannabis use during breastfeeding. However, the effect of cannabis use (if any) on milk production and milk composition is not known. This narrative review summarizes current knowledge related to maternal cannabis use during breastfeeding and provides an overview of possible pathways whereby cannabis might affect milk composition and production. Several studies have demonstrated that cannabinoids and their metabolites are detectable in human milk produced by mothers who use cannabis. Due to their physicochemical properties, cannabinoids are stored in adipose tissue, can easily reach the mammary gland, and can be secreted in milk. Moreover, cannabinoid receptors are present in adipocytes and mammary epithelial cells. The activation of these receptors directly modulates fatty acid metabolism, potentially causing changes in milk fatty acid profiles. Additionally, the endocannabinoid system is intimately connected to the endocrine system. As such, it is probable that interactions of exogenous cannabinoids with the endocannabinoid system might modify release of critical hormones (e.g., prolactin and dopamine) that regulate milk production and secretion. Nonetheless, few studies have investigated effects of cannabis use (including on milk production and composition) in lactating women. Additional research utilizing robust methodologies are needed to elucidate whether and how cannabis use affects human milk production and composition.

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.

Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers\' attention and emerged as a potential therapeutical target for the treatment of various diseases. In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings. Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.

BACKGROUND: Relapse rates in Anorexia Nervosa (AN) remain high, warranting exploration of further treatments. Cannabinoid agonists are of interest as they have shown successful outcomes in the treatment of associated conditions, such as post-traumatic stress disorder. This scoping review explores the endocannabinoid system (ECS), benefits/harms/null effects of cannabinoid treatment, and harms of cannabis use in AN.
METHODS: PubMed, PsycINFO, Cochrane, and Web of Science were searched for studies published between 2010 and August 2023, with human participants that explored the ECS, cannabinoid treatment, or cannabis use, and included 1 or more keywords for both cannabis and AN in the title and or abstract. Reports describing secondary anorexia, reports not available in English, grey literature, reports combining data from AN with other conditions, and reports only reporting the prevalence of cannabis abuse/dependence were excluded. Data were extracted from 17 reports (n = 15 studies). For the ECS, outcomes included genetics such as allele expression related to the ECS, cannabinoid receptor availability, and circulating levels of endocannabinoids. For benefits/harms/null effects of cannabinoid treatment, outcomes included changes in weight, eating disorder (ED) symptoms, physical activity (PA), and hormones. For harms of cannabis use, outcomes included genetics related to cannabis use disorder and associations between cannabis use and ED symptoms.
RESULTS: Eight studies (n = 8 reports) found abnormalities in the ECS in AN including expression of related alleles, genotypes, and haplotypes, availability of cannabinoid receptors, and levels of endocannabinoids. Three studies (n = 5 reports) found benefits/harms/null effects of cannabinoid treatment. Benefits included weight gain, improved ED symptoms and reduced PA, while null effects included no changes in weight or ED symptoms, and harms included increased PA and lowered adipose hormones. Four studies (n = 4 reports) expanded upon harms of cannabis use, including genetic predispositions to cannabis use disorder, and compensatory behaviors related to cannabis use.
CONCLUSIONS: Limited evidence suggests that abnormalities in the ECS in AN may render cannabis a potential treatment for weight restoration and associated symptoms. Future research may wish to investigate individualized dosing approaches to maximize beneficial effects while minimizing harms. Level II Evidence: Scoping Review.
Anorexia Nervosa (AN) affects people from various backgrounds causing notable physical and mental impairments. A recovery process that is successful for everyone who has the condition does not exist. Due to high relapse rates in AN, exploring further treatments is imperative. Cannabis has shown promise in treatments of other psychiatric disorders, some of which also occur in those with AN; thus, an overview of the available research is warranted. This scoping review presents results from studies about the relationship between cannabis and AN. Results suggest that individuals with AN have abnormalities in a biological system that interacts with cannabis, proposing the potential usefulness of cannabis for recovery. Although some studies reported benefits of cannabis for AN, including weight gain, improved eating disorder (ED) symptoms, and reduced physical activity (PA), other studies suggested no changes in weight or ED symptoms, increased PA, and worsened appetite hormone levels. Lastly, some studies suggested that individuals at higher risk of developing AN may be at greater risk for developing cannabis use disorder, and that cannabis use may be associated with ED symptoms. Future studies should examine individualized dosing of cannabis in AN to maximize benefits and minimize harms.

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components-tetrahydrocannabinol (THC) and cannabidiol (CBD)-or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement.

Cannabinoids play critical roles in human pathophysiology through the cannabinoid (CB) receptors and non-CB receptors on variety of cells, tissues, and organs. Microvasculature with the inside bloodstream containing the plasmatic and cellular components exerts multiple functions in maintaining tissue and organ physiology through microcirculation. This review focusses on the impact of cannabinoids on the microvasculature, including mechanisms mediated by both CB receptor-related pathways and CB receptor-independent pathways.

Background: Cannabidiol (CBD), a nonintoxicating constituent of the cannabis plant, recently gained a lot of interest among athletes, since it is no longer considered as a prohibited substance by the World Anti-Doping Agency. The increasing prevalence of CBD use among athletes is driven by a perceived improvement in muscle recovery and a reduction in pain. However, compelling evidence from intervention studies is lacking and the precise mechanisms through which CBD may improve muscle recovery remain unknown. This highlights the need for more scientific studies and an evidence-based background. In the current review, the state-of-the-art knowledge on the effects of CBD on skeletal muscle tissue is summarized with special emphasis on the underlying mechanisms and molecular targets. More specifically, the large variety of receptor families that are believed to be involved in CBD\'s physiological effects are discussed. Furthermore, in vivo and in vitro studies that investigated the actual effects of CBD on skeletal muscle metabolism, inflammation, tissue regeneration, and anabolism are summarized, together with the functional effects of CBD supplementation on muscle recovery in human intervention trials. Overall, CBD was effective to increase the expression of metabolic regulators in muscle of obese mice (e.g., Akt, glycogen synthase kinase-3). CBD treatment in rodents reduced muscle inflammation following eccentric exercise (i.e., nuclear factor kappa B [NF-κB]), in a model of muscle dystrophy (e.g., interleukin-6, tumor necrosis factor alpha) and of obesity (e.g., COX-2, NF-κB). In addition, CBD did not affect in vitro or in vivo muscle anabolism, but improved satellite cell differentiation in dystrophic muscle. In humans, there are some indications that CBD supplementation improved muscle recovery (e.g., creatine kinase) and performance (e.g., squat performance). However, CBD doses were highly variable (between 16.7 and 150 mg) and there are some methodological concerns that should be considered. Conclusion: CBD has the prospective to become an adequate supplement that may improve muscle recovery. However, this research domain is still in its infancy and future studies addressing the molecular and functional effects of CBD in response to exercise are required to further elucidate the ergogenic potential of CBD.

OBJECTIVE: Endocannabinoid pathways have been proposed to affect the underlying pathophysiology of tinnitus. The aim of this study is to evaluate the scope and findings of existing literature on the relationship between cannabis and cannabinoid pathways and tinnitus.
METHODS: We conducted a review of animal, clinical and survey studies investigating the relationship between the use of cannabis-derived agents and tinnitus. Using pertinent keywords and MeSH terms on PubMed, relevant studies were identified, yielding four animal studies, two large cross-sectional survey studies, one clinical cross-over study, and one case report.
RESULTS: Animal studies revealed that cannabinoid receptor expression in the cochlear nucleus varied with tinnitus symptomatology and the use of cannabinoid agents either increased or had no effect on tinnitus-related behavior. Survey studies yielded conflicting results between cannabis use and tinnitus in the general population. Clinical data is largely lacking, although a small cohort study showed a dose-dependent relationship between tetrahydrocannabinol consumption and frequency of tinnitus episodes in patients receiving treatment for cancer.
CONCLUSIONS: While animal studies have revealed that cannabinoid receptors likely have a role in modulating auditory signaling, there is no compelling data either from animal or human studies for the use of cannabinoids to alleviate tinnitus. Further research is necessary to elucidate their precise role to guide development of therapeutic interventions.
METHODS: NA.

The endocannabinoid system (ECS) is natural physiological system in the humans. The presence of the ECS system involves different roles in body. The endocannabinoid system involves regulation of most of the centers, which regulates the hunger and leads to changes in the weight. In the present article, we reviewed the role of natural cannabinoid compounds in metabolic disorders and related complications. We studied variety of a plant-derived cannabinoids in treating the metabolic syndrome including stoutness, fatty acid liver diseases, insulin obstruction, dementia, hypertension, lipid abnormalities, non-alcoholic steatohepatitis, endothelial damage, and polycystic ovarian syndrome and so on. The activation of cannabinoid receptors demonstrates a significant number of beneficial approaches concerning metabolic syndrome and reduces the pro-inflammatory cytokines on account of aggravation, decreased oxidative stress and uneasiness, diminishes liver fibrosis, with reduces adiponectin. Pre-clinical investigations of plant-derived cannabinoids resulted in promising outcomes. The different distinctive plant-derived cannabinoids were discovered like cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), and cannabidiol (CBG). It has been observed that endogenous cannabinoids and plant-derived cannabinoids have an advantageous impact on limiting the metabolic disorder arising due to lifestyle changes.