Category Archives: Endocannabinoid System

The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats.

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International Immunopharmacology“Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response.

In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats.

The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1β, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1β, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels.

In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart.

Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.”

https://www.ncbi.nlm.nih.gov/pubmed/31767546

“CB2 receptors are expressed in many tissues including immune cells. Activation of CB2 receptors has been shown to have anti-inflammatory effect.”

https://www.sciencedirect.com/science/article/pii/S1567576919318351?via%3Dihub

Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice.

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molecules-logo“Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology.

The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation.

This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R).

BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion.

The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC.

Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.”

https://www.ncbi.nlm.nih.gov/pubmed/31766439

https://www.mdpi.com/1420-3049/24/23/4239

“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 is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Reduced cannabinoid 2 receptor activity increases susceptibility to induced seizures in mice.

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Publication cover image“The endocannabinoid system (ECS) is comprised of cannabinoid receptors 1 and 2 (CB1R and CB2R), endogenous ligands, and regulatory enzymes, and serves to regulate several important physiological functions throughout the brain and body.

Recent evidence suggests that the ECS may be a promising target for the treatment of epilepsy, including epilepsy subtypes that arise from mutations in the voltage-gated sodium channel SCN1A.

The objective of this study was to explore the effects of modulating CB2R activity on seizure susceptibility.

Our results demonstrate that reduced CB2R activity is associated with increased seizure susceptibility. CB2Rs might therefore provide a therapeutic target for the treatment of some forms of epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31758544

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16388

Association between cannabis and the eyelids: A comprehensive review.

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Publication cover image“Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients.

There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug.

These include: ptosis induction, an “eyelid tremor” appearance and blepharospasm attenuation.

Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors.

The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear.

Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/31747112

https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13687

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

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Image result for ovid journal“This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders.

It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use.

RECENT FINDINGS:

There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking.

New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD.

SUMMARY:

The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31714262

https://insights.ovid.com/crossref?an=00001504-900000000-99165

Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy.

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Publication cover image“Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2).

The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo.

CONCLUSIONS:

Activation of CB2 decreased severity of CYP-induced cystitis and ameliorated bladder inflammation. CB2 activation is protective in cystitis through the activation of autophagy and AMPK-mTOR pathway may be involved in the initiation of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/31729056

https://onlinelibrary.wiley.com/doi/abs/10.1002/nau.24205

Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.

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European Journal of Pharmacology

“Δ9-THC suppresses cisplatin-induced vomiting through activation of cannabinoid CB1 receptors.

Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT3-and neurokinin NK1-receptors to induce vomiting. Δ9-THC can inhibit vomiting caused either by the serotonin precursor 5-HTP, or the 5-HT3 receptor selective agonist, 2-methyserotonin.

In the current study, we explored whether Δ9-THC and related CB1/CB2 receptor agonists (WIN55,212-2 and CP55,940) inhibit vomiting evoked by SP (50 mg/kg, i.p.) or the NK1 receptor selective agonist GR73632 (5 mg/kg, i.p.). Behavioral methods were employed to determine the antiemetic efficacy of cannabinoids in least shrews.

Our results showed that administration of varying doses of Δ9-THC (i.p. or s.c.), WIN55,212-2 (i.p.), or CP55,940 (i.p.) caused significant suppression of SP-evoked vomiting in a dose-dependent manner. When tested against GR73632, Δ9-THC also dose-dependently reduced the evoked emesis.

The antiemetic effect of Δ9-THC against SP-induced vomiting was prevented by low non-emetic doses of the CB1 receptor inverse-agonist/antagonist SR141716A (<10 mg/kg). We also found that the NK1 receptor antagonist netupitant can significantly suppress vomiting caused by a large emetic dose of SR141716A (20 mg/kg).

In sum, Δ9-THC and related cannabinoids suppress vomiting evoked by the nonselective (SP) and selective (GR73632) neurokinin NK1 receptor agonists via stimulation of cannabinoid CB1 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/31738934

https://www.sciencedirect.com/science/article/pii/S0014299919307587?via%3Dihub

Cannabidiol as a potential treatment for psychosis

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Image result for therapeutic advances in psychopharmacology“Accumulating evidence implicates the endocannabinoid system in the pathophysiology of psychosis.

If the endocannabinoid system plays a role in psychosis pathophysiology, it raises the interesting possibility that pharmacological compounds that modulate this system may have therapeutic value.

Cannabidiol (CBD), a phytocannabinoid constituent of Cannabis sativa, has been heralded as one such potential treatment.

Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action.

In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders.

In sum, CBD currently represents a promising potential novel treatment for patients with psychosis.”

https://journals.sagepub.com/doi/10.1177/2045125319881916

https://www.ncbi.nlm.nih.gov/pubmed/31741731

Relieving tension: effects of cannabinoids on vagal afferent sensitivity.

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Publication cover image“Endocannabinoids are produced within the gastrointestinal (GI) tract and modulate energy homeostasis and food intake, at least in part, via vagally-dependent actions. The recent paper by Christie et al., [Christie, et al. J Physiol, 2019] demonstrate, for the first time, that cannabinoids exert biphasic effects on the mechanosensitivity of tension-sensitive gastric vagal afferents. At higher concentrations, anandamide increased vagal afferent sensitivity in a CB1 and TRPV1 receptor dependent manner. At lower concentrations, however, anandamide decreased afferent mechanosensitivity; while this was also dependent upon CB1 and TRPV1 receptors, it also appeared dependent upon signaling via the potent orexigenic neurohormone, ghrelin. These results provide further evidence to support the remarkable degree of neuroplasticity within vagal afferent signaling, and suggest that untangling the complex interactions of cannabinoid effects on food intake and energy homeostasis will require careful physiological and pharmacological investigations.”

https://www.ncbi.nlm.nih.gov/pubmed/31707736

https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP279173

“A clear understanding of the mechanisms which mediate these events may provide novel therapeutic targets for the treatment of gastrointestinal disorders due to vago-vagal pathway malfunctions.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318799/

Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease.

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Neuropharmacology

“Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson’s disease (PD). Pain is a prevalent PD’s non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available.

Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception.

Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1).

We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD.

Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.”

https://www.ncbi.nlm.nih.gov/pubmed/31706993

“The CBD treatment decreases hyperalgesia and allodynia in experimental parkinsonism.”

https://www.sciencedirect.com/science/article/pii/S0028390819303703?via%3Dihub

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