Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

http://www.thctotalhealthcare.com/category/liver-disease/

Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders.

“Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs.

There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult…

In this study, we investigated the involvement of cannabinoid system…

Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care.”

http://www.ncbi.nlm.nih.gov/pubmed/23585028

http://www.thctotalhealthcare.com/category/autism/

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313

Cannabinoid receptor type 2 activation in atherosclerosis and acute cardiovascular diseases.

“In the last decades, the cannabinoid system (comprising synthetic and endogenous cannabinoid agonists and antagonists, their receptors and degrading enzymes) has been shown to induce potent immunomodulatory activities in atherogenesis and acute ischemic complications.

Differently from the other cannabinoid receptors in which controversial results are reported, the selective activation of the cannabinoid receptor type 2 (CB2) has been shown to play anti-inflammatory and protective actions within atherosclerotic vessels and downstream ischemic peripheral organs.

CB2 is a transmembrane receptor that triggers protective intracellular pathways in cardiac, immune and vascular cells in both in human and animal models of atherosclerosis…

medications activating CB2 function in the circulation or peripheral target organs might be a promising approach against atherogenesis.

This review updates evidence from preclinical studies on different CB2-triggered pathways in atherosclerosis and acute ischemic events.”

http://www.ncbi.nlm.nih.gov/pubmed/25245379

Neuropathic orofacial pain: cannabinoids as a therapeutic avenue.

“Neuropathic orofacial pain (NOP) exists in several forms including pathologies such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN) and postherpetic neuralgia (PHN).

The pathophysiology of some of these conditions is still unclear and hence treatment options tend to vary and include a wide variety of treatments including cognitive behavior therapy, anti-depressants, anti-convulsants and opioids; however such treatments often have limited efficacy with a great amount of inter-patient variability and poorly tolerated side effects.

Analgesia is one the principal therapeutic targets of the cannabinoid system and many studies have demonstrated the efficacy of cannabinoid compounds in the treatment of neuropathic pain.

This review will investigate the potential use of cannabinoids in the treatment of symptoms associated with NOP.”

http://www.ncbi.nlm.nih.gov/pubmed/25150831

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Cannabis-Based Medicine Reduces Multiple Pathological Processes in AβPP/PS1 Mice.

“Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer’s disease (AD).

The present study supports this hypothesis demonstrating that delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage.

Moreover, THC + CBD reduced learning impairment in AβPP/PS1 mice.

…suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Aβ peptide.

Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role…

In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.”

Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

Figure 1.

“To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology…

Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1…

…our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.

CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).”

http://www.fasebj.org/content/22/10/3685.long

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

CBD prevents excessive lipogenesis induced by “pro-acne agents&#x...

“Acne vulgaris is the most common human skin disease, affecting quality of life of millions worldwide…

Investigation of the cutaneous cannabinoid system seems to be a promising choice when searching for novel therapeutic possibilities…

“Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris…

These data, together with our current findings, point to a promising, cost-effective, and, likely, well-tolerated new strategy for treating acne vulgaris, the most common human skin disease…

…given the extensively documented accumulation of phytocannabinoids from smoked marijuana in the pilosebaceous unit (where they become incorporated into the hair shaft), it is very likely that CBD can reach the sebaceous glands as well, can accumulate, and may well reach “therapeutically sufficient” concentrations there.

Moreover, it is very important to note that, besides the systemic application, one should keep in mind the possibility of the topical administration.”

 http://www.jci.org/articles/view/64628

“Schematic overview of the cellular “anti-acne trinity” of CBD and its proposed mechanism of action.”

Schematic overview of the cellular “anti-acne trinity” of ...

 

[The cannabinoid system and its importance in the perinatal period].

“The cannabinoid system has been recently described, including the endogenous ligands, mainly arachidonic acid derivatives, and their specific receptors. Endocannabinoids are involved in the modulation of synaptic transmission, through which they exert their psychoactive, motor and antinociceptive effects, among others; they also exert extraneural effects, mainly immunomodulation and vasodilation.

Recent data suggest that the cannabinoid system might play an important role in human ontogeny and could participate in the implantation and early development of the embryo, in fetal brain development, and in the beginning of breast feeding after birth.

In addition, the vasodilatory effect of cannabinoids, together with inhibition of the release of excitotoxic amino acids and cytokines, as well as modulation of oxidative stress and the toxic production of nitric oxide, justify the growing evidence pointing to a possible neuroprotective effect of cannabinoids in perinatal asphyxia.”

http://www.ncbi.nlm.nih.gov/pubmed/16266619