Tag Archives: Cannabinoids

Endocannabinoid System Components: Overview and Tissue Distribution.

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 “Marijuana/cannabinoid research has been transformed into mainstream science during the last half-century. Evidence based research and remarkable biotechnological advances demonstrate that phytocannabinoids and endocannabinoid (eCBs) acting on cannabinoid receptors (CBRs) regulate various aspects of human physiological, behavioral, immunological and metabolic functions. The distribution and function of the components of the endocannabinoid system (ECS) in the central nervous system (CNS) and immune processes have garnished significant research focus with major milestones. With these advances in biotechnology, rapid extension of the ECS research in the periphery has gained momentum. In this chapter, we review the components and tissue distribution of this previously unknown but ubiquitous and complex ECS that is involved in almost all aspects of mammalian physiology and pathology.”

https://www.ncbi.nlm.nih.gov/pubmed/31332731

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_1

Endocannabinoids and endocannabinoid-like compounds modulate hypoxia-induced permeability in CaCo-2 cells via CB1, TRPV1, and PPARα.

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Biochemical Pharmacology“We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion.

CONCLUSIONS AND IMPLICATIONS:

A variety of endocannabinoids and endocannabinoid-like compounds modulate Caco-2 permeability in hypoxia/reoxygenation, which involves multiple targets, depending on whether the compounds are applied to the basolateral or apical membrane. CB1 antagonism and TRPV1 or PPARα agonism may represent novel therapeutic targets against several intestinal disorders associated with increased permeability.”

https://www.ncbi.nlm.nih.gov/pubmed/31325449

https://www.sciencedirect.com/science/article/abs/pii/S0006295219302722?via%3Dihub

Cannabinoid system involves in the analgesic effect of protocatechuic acid.

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 “Protocatechuic acid is an antioxidant which is shown to have analgesic activity in limited studies. However, the mechanisms of action remain unclear.

OBJECTIVES:

It is aimed to investigate the possible contribution of cannabinoid system that supresses the nociceptive process by the activation of CB1 and CB2 receptors in central and peripheral levels of pain pathways, to the analgesic activity of protocatechuic acid.

RESULTS:

It was determined that protocatechuic acid has dose-dependent analgesic effect independently from locomotor activity and is comparable with effects of dipyrone and WIN 55,212-2. Pre-treatment with CB1 receptor antagonist AM251 significantly antagonized the protocatechuic acid-induced analgesia in the tail-immersion and writhing tests, whereas pre-treatment of CB2 receptor antagonist AM630 was found to be effective only in the tail-immersion test.

CONCLUSION:

It is concluded that cannabinoid modulation contributes to the analgesic effect of protocatechuic acid in spinal level rather than peripheral. CB1 receptor stimulation rather than CB2 receptor stimulation mediates the analgesic effect of protocatechuic acid in both levels, especially peripheral. Graphical abstract Protocatechuic acid inhibits pain response via cannabinoidergic system.”

https://www.ncbi.nlm.nih.gov/pubmed/31325037

https://link.springer.com/article/10.1007/s40199-019-00288-x

“Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea.”  https://en.wikipedia.org/wiki/Protocatechuic_acid

Cannabidiol improves behavioural and neurochemical deficits in adult female offspring of the maternal immune activation (poly I:C) model of neurodevelopmental disorders.

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Brain, Behavior, and Immunity“Cognitive impairment is a major source of disability in schizophrenia and current antipsychotic drugs (APDs) have minimal efficacy for this symptom domain.

Cannabidiol (CBD), the major non-intoxicating component of Cannabis sativa L., exhibits antipsychotic and neuroprotective properties.

We recently reported the effects of CBD on cognition in male offspring of a maternal immune activation (polyinosinic-polycytidilic acid (poly I:C)) model relevant to the aetiology of schizophrenia; however, the effects of CBD treatment in females are unknown. Sex differences are observed in the onset of schizophrenia symptoms and response to APD treatment.

Furthermore, the endogenous cannabinoid system, a direct target of CBD, is sexually dimorphic in humans and rodents. Therefore, the present work aimed to assess the therapeutic impact of CBD treatment on behaviour and neurochemical signalling markers in female poly I:C offspring.

Overall, the findings of this study support the therapeutic benefits of CBD on recognition memory and sociability in female poly I:C offspring, and provide insight into the neurochemical changes that may underlie the therapeutic benefits of CBD in the poly I:C model.”

https://www.ncbi.nlm.nih.gov/pubmed/31326506

“These findings suggest that CBD is an efficacious treatment for behavioural and neurochemical changes in a female rodent model relevant to schizophrenia.”

https://www.sciencedirect.com/science/article/pii/S0889159119302806?via%3Dihub

Contrasting Roles of Cannabidiol as an Insecticide and Rescuing Agent for Ethanol-induced Death in the Tobacco Hornworm Manduca sexta.

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Scientific Reports “Cannabis sativa, also known as marijuana or hemp, produces a non-psychoactive compound cannabidiol (CBD). To investigate the defensive role of CBD, a feeding preference assay was performed with tobacco hornworm Manduca sexta. The larvae clearly show feeding preference towards the Cannabis tissue containing low CBD over high CBD. While the larva avoided the high CBD diet, we investigated detrimental effects of CBD in the insects’ diet. Contrasted to the performance on low CBD-infused artificial diet (AD), larvae reared on the high CBD diet suffer significantly reduced growth and increased mortality. Through testing different carriers, we found that the increase of EtOH in the diet is negatively correlated with insect development and behaviors. Notably, CBD treatment significantly improved ethanol-intoxicated larval survival rate by 40% and also improved diet searching activity, resulting in increased diet consumption. Electrophysiology results revealed that the CBD-treated ganglia had delayed but much larger response with electric stimuli in comparison to the larvae reared on AD only and EtOH-added diet. Our results show CBDs’ defensive role against pest insects, which suggests its possible use as an insecticide. We also provide evidence that CBD alleviates alcohol-induced stress; consequently, improving the performance and viability of M. sexta larvae.”

https://www.ncbi.nlm.nih.gov/pubmed/31324859

https://www.nature.com/articles/s41598-019-47017-7

Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts.

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“Herein, we report the antioxidant activity of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in pure and mixed solutions at different ratios, as well as of six different Cannabis sativa extracts containing various proportions of CBD and THC by using spectrophotometric (reducing power assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), hypochlorous acid (HOCl) scavenging assays) and electrochemical methods (cyclic voltammetry and differential pulse voltammetry).

The isolated cannabinoids, the different stoichiometric ratios of CBD and THC, and the natural extracts proved to have remarkable antioxidant properties in all the methods employed in this work.

The antioxidant activity of CBD and THC was compared against that of the well-defined antioxidants such as ascorbic acid (AA), resveratrol (Resv) and (-)-epigallocatechin-3-gallate (EGCG). Clear evidence of the synergistic and antagonistic effects between CBD and THC regarding to their antioxidant activities was observed.

Moreover, a good correlation was obtained between the optical and electrochemical methods, which proved that the reported experimental procedures can easily be adapted to determine the antioxidant activity of extracts from various Cannabis sativa species and related compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31318364

https://pubs.rsc.org/en/content/articlelanding/2019/AN/C9AN00890J#!divAbstract

Graphical abstract: Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts

Allostatic load and the cannabinoid system: implications for the treatment of physiological abnormalities in post-traumatic stress disorder (PTSD).

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Image result for cns spectrums“It is becoming clear that post-traumatic stress disorder (PTSD) is not simply a psychiatric disorder, but one that involves pervasive physiological impairments as well. These physiological disturbances deserve attention in any attempt at integrative treatment of PTSD that requires a focus beyond the PTSD symptoms themselves. The physiological disturbances in PTSD range over many systems, but a common thread thought to underlie them is that the chronic effects of PTSD involve problems with allostatic control mechanisms that result in an excess in what has been termed “allostatic load” (AL).

A pharmacological approach to reducing AL would be valuable, but, because of the large range of physiological issues involved – including metabolic, inflammatory, and cardiovascular systems – it is unclear whether there exists a simple comprehensive way to address the AL landscape. In this paper, we propose that the cannabinoid system may offer just such an approach, and we outline evidence for the potential utility of cannabinoids in reducing many of the chronic physiological abnormalities seen in PTSD which are thought to be related to excess AL.” https://www.ncbi.nlm.nih.gov/pubmed/31303187
https://www.cambridge.org/core/journals/cns-spectrums/article/allostatic-load-and-the-cannabinoid-system-implications-for-the-treatment-of-physiological-abnormalities-in-posttraumatic-stress-disorder-ptsd/F85D2588638C20BE9DD86DEC2F768242

Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary.

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Image result for Nutrition and Metabolic Insights“Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level.

The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard.

Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States.

This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.” https://www.ncbi.nlm.nih.gov/pubmed/31308686

https://journals.sagepub.com/doi/10.1177/1178638819847480

S-Adenosyl-L-Methionine (SAMe), Cannabidiol (CBD), and Kratom in Psychiatric Disorders: Clinical and Mechanistic Considerations.

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Brain, Behavior, and Immunity“Given the limitations of prescription antidepressants, many individuals have turned to natural remedies for the management of their mood disorders.

We review three selected natural remedies that may be of potential use as treatments for depressive disorders and other psychiatric or neurological conditions.

The best studied and best supported of these three remedies is S-adenosyl-L-methionine (SAMe), a methyl donor with a wide range of physiological functions in the human organism.

With the increasing legalization of cannabis-related products, cannabidiol (CBD) has gained popularity for various potential indications and has even obtained approval in the United States and Canada for certain neurological conditions.

Kratom, while potentially useful for certain individuals with psychiatric disorders, is perhaps the most controversial of the three remedies, in view of its greater potential for abuse and dependence.

For each remedy, we will review indications, doses and delivery systems, potential anti-inflammatory and immunomodulatory action, adverse effects, and will provide recommendations for clinicians who may be considering prescribing these remedies in their practice.” https://www.ncbi.nlm.nih.gov/pubmed/31301401

https://www.sciencedirect.com/science/article/pii/S0889159119302788?via%3Dihub

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

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Image result for jama network

“This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment.”   https://www.ncbi.nlm.nih.gov/pubmed/31305874
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737918
“nabiximols: An herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains a standardized extract of tetrahydrocannabinol (THC), the non-psychoactive cannabinoid cannabidiol (CBD), other minor cannabinoids, flavonoids, and terpenes from two cannabis plant varieties.” https://www.cancer.gov/publications/dictionaries/cancer-drug/def/nabiximols
“Cannabis treatment counters addiction: First study of its kind. Trial shows cannabis replacement therapy can be effective” https://www.sciencedaily.com/releases/2019/07/190715114247.htm