Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice.

 Brain, Behavior, and Immunity

“Nicotine withdrawal is associated with cognitive deficits including attention, working memory, and episodic memory impairments.

Treatment with the non-psychoactive cannabinoid cannabidiol abolished memory impairment of nicotine withdrawal and microglia reactivity, reduced the expression of IL1β and IFNγ in the hippocampus and the prefrontal cortex, respectively, and normalized Ki67 levels. The nonsteroidal anti-inflammatory drug indomethacin also prevented cognitive deficits and microglial reactivity during withdrawal.

These data underline the usefulness of anti-inflammatory agents to improve cognitive performance during early nicotine abstinence.”

https://www.ncbi.nlm.nih.gov/pubmed/30391635

https://www.sciencedirect.com/science/article/pii/S0889159118302599?via%3Dihub

New insights on atherosclerosis: A cross-talk between endocannabinoid systems with gut microbiota.

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“The incidence of atherosclerosis is increasing rapidly all over the world. Inflammatory processes have outstanding role in coronary artery disease (CAD) etiology and other atherosclerosis manifestations. Recently attentions have been increased about gut microbiota in many fields of medicine especially in inflammatory diseases like atherosclerosis. Ineffectiveness in gut barrier functions and subsequent metabolic endotoxemia (caused by rise in plasma lipopolysaccharide levels) is associated with low-grade chronic inflammation i.e. a recognized feature of atherosclerosis. Furthermore, the role of trimethylamine-N-oxide (TMAO), a gut bacterial metabolite has been suggested in atherosclerosis development. On the other hand, the effectiveness of gut microbiota modulation that results in TMAO reduction has been investigated. Moreover, considerable evidence supports a role for the endocannabinoid system (ECS) in atherosclerosis pathology which affects gut microbiota, but their effects on atherosclerosis are controversial. Therefore, we presented some evidence about the relationship between gut microbiota and ECS in atherosclerosis. We also presented evidences that gut microbiota modulation by pre/probiotics can have significant influence on the ECS.

Even though there are many questions which have been unanswered, studies demonstrated that mucosal barrier function disruption and subsequent gut microbiota-derived endotoxemia could contribute to cardiometabolic diseases pathogenesis. As well, number of studies revealed that TMAO in systemic circulation can activate macrophages which lead to cholesterol accumulation and subsequent foam cells formation in atherosclerotic lesions. On the other hand, accumulating evidence proposes that ECS involved in many physiological processes that are related to maintenance of gut-barrier function and inflammation regulation. Hence, although present literature review provides beneficial evidence in support of crosstalk between ECS and gut microbiota, additional studies are needed to clarify whether gut microbiota modulation can alter ECS tone and inflammation levels or not.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203867/

The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information: Commissioned by the Crohn’s and Colitis Foundation.

Oxford University Press

“There is significant interest among patients and providers in using cannabis (marijuana) and its derivatives to treat a number of chronic illnesses, including inflammatory bowel disease. Despite the Schedule I classification of cannabis by the federal government, state governments have sought ways to make cannabis available for specific medical conditions, and some states have legalized cannabis outright. This white paper summarizes the preclinical data, clinical data, safety data, and the regulatory landscape as they apply to medical cannabis use in inflammatory bowel disease. Animal models of cannabinoid chemistry and physiology give evidence of anti-inflammatory, antidiarrheal, and nociceptive-limiting properties. Human studies have found benefit in controlling symptoms and improving quality of life, but no studies have established true disease modification given the absent improvement in biomarker profiles or endoscopic healing. Finally, this review describes the legal, regulatory, and practical hurdles to studying the risks and benefits of medical cannabis in the United States.”

https://www.ncbi.nlm.nih.gov/pubmed/30358848

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izy319/5144402?redirectedFrom=fulltext

Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion.

Image result for lipids in health and disease

“The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation.

The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).

CONCLUSIONS:

Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.”

“beta-caryophyllene (BCP), a sesquiterpene found as a common constituent of the essential oils of numerous food plants and primary component in Cannabis sativa L., is a dietary phytocannabinoid acting as selective agonist for CB2 receptor and peroxisome-proliferator activating receptor alpha (PPAR-alpha)”
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

Beta-caryophyllene protects diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-γ receptors.

Chemico-Biological Interactions

“Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects.

The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors.

BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30343038

https://www.sciencedirect.com/science/article/pii/S0009279718309347?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

Molecular Imaging of the Cannabinoid System in Idiopathic Parkinson’s Disease.

International Review of Neurobiology

“The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson’s disease.

Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson’s disease.

In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson’s disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/30314601

https://www.sciencedirect.com/science/article/pii/S0074774218300692?via%3Dihub

A systematic review on the neuroprotective perspectives of beta-caryophyllene.

Image result for phytother res

“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

Cannabinoid Delivery Systems for Pain and Inflammation Treatment.

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“There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions.

The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety.

The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes.

Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.”

https://www.ncbi.nlm.nih.gov/pubmed/30262735

https://www.mdpi.com/1420-3049/23/10/2478

Inflammation and CB2 signaling drive novel changes in the ocular lipidome and regulate immune cell activity in the eye.

Prostaglandins & Other Lipid Mediators

“Uveitis is inflammation of the uvea which consists of the iris, ciliary body and the choroid of the eye. Uveitis can lead to impaired vision and is responsible for 10% of all cases of blindness globally.

Using an endotoxin-induced uveitis (EIU) rodent model, our previous data implicated the endogenous cannabinoid system (ECS) in the amelioration of many of the components of the inflammatory response.

Here, we test the hypothesis that the reduction in inflammatory mediators in the EIU model by the CB2 agonist, HU308, is associated with changes in ECS endogenous ligands as well as related lipids, prostaglandins (PGs), 2-acyl glycerols, and lipoamines.

These data implicate ocular CB2 as a key component of lipid signaling in the eye and part of the regulatory processes of inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30232034

https://www.sciencedirect.com/science/article/pii/S109888231830025X?via%3Dihub

Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain.

“Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.

OBJECTIVES:

The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD’s potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.

RESULTS:

CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA’s effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.

CONCLUSION:

CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30225659

https://link.springer.com/article/10.1007%2Fs00213-018-5034-1