Cannabinoids in Gynecological Diseases

Related image“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.”

https://www.karger.com/Article/FullText/499164

Modulation of the endocannabinoid system: vulnerability factor and new treatment target for stimulant addiction

Image result for frontiers in psychiatry“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

Endocannabinoid modulation of inflammatory hyperalgesia in the IFN-α mouse model of depression.

Brain, Behavior, and Immunity“Depression is a well-recognised effect of long-term treatment with interferon-alpha (IFN-α), a widely used treatment for chronic viral hepatitis and malignancy. In addition to the emotional disturbances, high incidences of painful symptoms such as headache and joint pain have also been reported following IFN-α treatment.

The endocannabinoid system plays an important role in emotional and nociceptive processing, however it is unknown whether repeated IFN-α administration induces alterations in this system.

The present study investigated nociceptive responding in the IFN-α-induced mouse model of depression and associated changes in the endocannabinoid system. Furthermore, the effects of modulating peripheral endocannabinoid tone on inflammatory pain-related behaviour in the IFN-α model was examined.

In summary, increasing peripheral endocannabinoid tone attenuates inflammatory hyperalgesia induced following repeated IFN-α administration. These data provide support for the endocannabinoid system in mediating and modulating heightened pain responding associated with IFNα-induced depression.”

https://www.ncbi.nlm.nih.gov/pubmed/31505257

“Inflammatory hyperalgesia is associated with altered endocannabinoid levels. Enhancing peripheral endocannabinoid tone attenuates IFN-α related hyperalgesia.”

https://www.sciencedirect.com/science/article/pii/S0889159119306063?via%3Dihub

The “entourage effect”: Terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders.

“Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders.

Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa, was suggested for their treatment.

The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids.

CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes.

Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids.

Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31481004

http://www.eurekaselect.com/174648/article

The cannabinoid receptor 1 is involved in renal fibrosis during chronic allograft dysfunction: Proof of concept.

Publication cover image“Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss.

The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD.

Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology.”

https://www.ncbi.nlm.nih.gov/pubmed/31469511

https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14570

Cannabinoids and Mental Health, Part 1: The Endocannabinoid System and Exogenous Cannabinoids.

Image result for j psychosoc nurs ment health serv“The increasing public acceptance of cannabis and the proliferation of cannabis products in the marketplace has coincided with more patients using the drug as a substitute for psychiatric medications or as an adjunctive treatment modality for psychiatric conditions, despite limited evidence of efficacy. With a goal of furthering harm-reduction efforts in psychiatric nursing, the current article reviews the fundamentals of the endocannabinoid system in humans and the exogenous phytocannabinoids that act on this regulatory neurotransmitter system. The basics of cannabis botany are also reviewed to help nurse clinicians understand the heterogeneous nature of cannabis products. This foundational knowledge will help improve clinical interactions with patients who use cannabis and provide the necessary understanding of cannabinoids needed to undertake further scientific query into their purported benefits in psychiatric disease states.”

https://www.ncbi.nlm.nih.gov/pubmed/31461513

Impaired brain endocannabinoid tone in the activity-based model of anorexia nervosa.

International Journal of Eating Disorders banner“Despite the growing knowledge on the functional relationship between an altered endocannabinoid (eCB) system and development of anorexia nervosa (AN), to date no studies have investigated the central eCB tone in the activity-based anorexia (ABA) model that reproduces key aspects of human AN.

These data demonstrate an altered brain eCB tone in ABA rats, further supporting the involvement of an impaired eCB system in AN pathophysiology that may contribute to the maintenance of some symptomatic aspects of the disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31456239

https://onlinelibrary.wiley.com/doi/abs/10.1002/eat.23157

Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review.

medicina-logo“Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances.

Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition.

The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients.

Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep.”

https://www.ncbi.nlm.nih.gov/pubmed/31450833

https://www.mdpi.com/1010-660X/55/9/525

Role of the endocannabinoidome in human and mouse atherosclerosis.

“The Endocannabinoid (eCB) system and its role in many physiological and pathological conditions is well described and accepted, and includes cardiovascular disorders. However, the eCB system has been expanded to an “-ome”; the endocannabinoidome (eCBome) that includes endocannabinoid-related mediators, their protein targets and metabolic enzymes, many of which significantly impact upon cardiometabolic health. These recent discoveries are here summarized with a special focus on their potential involvement in atherosclerosis. We described the role of classical components of the eCB system (eCBs, CB1 and CB2 receptors) and eCB-related lipids, their regulatory enzymes and molecular targets in atherosclerosis. Furthermore, since increasing evidence points to significant cross-talk between the eCBome and the gut microbiome and the gut microbiome and atherosclerosis, we explore the possibility that a gut microbiome – eCBome axis has potential implications in atherosclerosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31448709

http://www.eurekaselect.com/174465/article

“Oral cannabinoid therapy reduces progression of atherosclerosis”  https://www.medscape.com/viewarticle/787468

“The active ingredient in marijuana that produces changes in brain messages appears to fight atherosclerosis — a hardening of the arteries.” https://www.webmd.com/heart-disease/news/20050406/marijuana-chemical-fights-hardened-arteries

Cannabidivarin Treatment Ameliorates Autism-Like Behaviors and Restores Hippocampal Endocannabinoid System and Glia Alterations Induced by Prenatal Valproic Acid Exposure in Rats.

 Image result for frontiers in cellular neuroscience“Autism spectrum disorder (ASD) is a developmental condition whose primary features include social communication and interaction impairments with restricted or repetitive motor movements. No approved treatment for the core symptoms is available and considerable research efforts aim at identifying effective therapeutic strategies.

Emerging evidence suggests that altered endocannabinoid signaling and immune dysfunction might contribute to ASD pathogenesis. In this scenario, phytocannabinoids could hold great pharmacological potential due to their combined capacities to act either directly or indirectly on components of the endocannabinoid system and to modulate immune functions.

Among all plant-cannabinoids, the phytocannabinoid cannabidivarin (CBDV) was recently shown to reduce motor impairments and cognitive deficits in animal models of Rett syndrome, a condition showing some degree of overlap with autism, raising the possibility that CBDV might have therapeutic potential in ASD.

Here, we investigated the ability of CBDV treatment to reverse or prevent ASD-like behaviors in male rats prenatally exposed to valproic acid (VPA; 500 mg/kg i.p.; gestation day 12.5).

CBDV in symptomatic rats recovered social impairments, social novelty preference, short-term memory deficits, repetitive behaviors and hyperlocomotion whereas preventative treatment reduced sociability and social novelty deficits, short-term memory impairments and hyperlocomotion, without affecting stereotypies.

As dysregulations in the endocannabinoid system and neuroinflammatory markers contribute to the development of some ASD phenotypes in the VPA model, neurochemical studies were performed after symptomatic treatment to investigate possible CBDV’s effects on the endocannabinoid system, inflammatory markers and microglia activation in the hippocampus and prefrontal cortex.

Prenatal VPA exposure increased CB1 receptor, FAAH and MAGL levels, enhanced GFAP, CD11b, and TNFα levels and triggered microglia activation restricted to the hippocampus. All these alterations were restored after CBDV treatment.

These data provide preclinical evidence in support of the ability of CBDV to ameliorate behavioral abnormalities resembling core and associated symptoms of ASD. At the neurochemical level, symptomatic CBDV restores hippocampal endocannabinoid signaling and neuroinflammation induced by prenatal VPA exposure.”

https://www.ncbi.nlm.nih.gov/pubmed/31447649

https://www.frontiersin.org/articles/10.3389/fncel.2019.00367/full