THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

Posted on June 26, 2018 by David Worrell

“Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB₁ (CB₁R) and CB₂ (CB₂R) receptors and the effects of the compound on agonist activation of those receptors and of CB₁–CB₂ heteroreceptor complexes. The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling. In conclusion, the results presented in this study reveal that the non-psychotropic phytocannabinoid, CBG, may exert beneficial actions with therapeutic potential via cannabinoid receptors.” https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full

“International Multi-Centre Collaboration Reveals that Cannabigerol Acts Directly on Cannabinoid Receptors CB1 and CB2” https://www.prnewswire.com/news-releases/international-multi-centre-collaboration-reveals-that-cannabigerol-acts-directly-on-cannabinoid-receptors-cb1-and-cb2-300671024.html

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Inhibition of endocannabinoid degradation rectifies motivational and dopaminergic deficits in the Q175 mouse model of Huntington's disease.

Posted on June 22, 2018 by David Worrell

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“Prominent motor deficits (e.g., chorea) that typify Huntington’s disease (HD) arise following a prolonged prodromal stage characterized by psychiatric disturbances. Apathy, a disorder of motivation characterized by diminished goal-directed behavior, is one of the earliest and most common psychiatric symptoms in HD, but the underlying neurobiology is unclear and treatment options are limited. Alterations in the endocannabinoid (eCB) and dopamine systems represent prominent pathophysiological markers in HD that-similar to motivational deficits-present early and decline across disease progression. Whether changes in dopamine and eCB systems are associated with specific behavioral impairments in HD and whether these deficits are amenable to viable treatments is unknown. Here, we show that dopaminergic encoding of effortful drive progressively declines with age in an HD mouse model, and is restored by elevating tissue levels of the eCB 2-arachidonoylglycerol (2-AG) through targeted inhibition of its enzymatic degradation. This work supports aberrant dopaminergic encoding of reward as a neurobiological correlate of apathy in HD, and indicates that cannabinoid receptor-based therapies may benefit neuropsychiatric care for HD.” https://www.ncbi.nlm.nih.gov/pubmed/29925886 https://www.nature.com/articles/s41386-018-0107-8

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Medicinal Cannabinoids in Palliative Care.

Posted on June 21, 2018 by David Worrell

British Journal of Clinical Pharmacology banner

“The treatment of symptoms in people with palliative diagnoses begins with meticulous clinical assessment with treatment choice (s) selected based on an understanding of the symptom aetiology and the evidence which underpins its treatment. Increasingly the merits of palliative care have been established earlier in the disease trajectory where treatment outcomes may include increased survival and maintenance of function. There is strong public support for the availability of medicinal cannabis, particularly for people with palliative diagnoses. There are several areas where there is potential for symptom benefits through modulation of the endocannabinoid system, though clinical data to date has been inconclusive in key symptoms such as pain and nausea, and data from other settings such as chemotherapy-induced nausea and vomiting not readily extrapolated. Ideally exploration of medicinal cannabinoids should occur within a clinical trial to accelerate the evidence base to inform practice. In people with refractory symptoms the consideration of unregistered products or off label prescribing should be guided by the potential influences of pharmacokinetic, pharmacodynamic and drug-drug interactions, supported by an informed discussion with the patient, and regular review of net clinical benefit.” https://www.ncbi.nlm.nih.gov/pubmed/29923616 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13671

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Cannabidiol did not induce teratogenicity or neurotoxicity in exposed zebrafish embryos.

Posted on June 15, 2018 by David Worrell

“Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa that has been used for the treatment of severe epilepsy as well as other diseases of nervous system. However, toxicity studies of CBD have great relevance to guarantee the patients safety. In this context, morphological analyses of zebrafish can contribute to evaluate the teratogenic potential, as well as evaluation of acetylcholinesterase activity and motor activity of zebrafish are valuable tools to verify the neurotoxicity potential. In the present work, we use this methodology to test the toxicity of CBD to zebrafish embryos. No malformation was observed in morphological analysis of embryos exposed to all tested concentrations of CBD. Embryos exposed to CBD did not show differences in acetylcholinesterase activity, but embryos exposed to CBD 20-300 μg/L were 1.4 up to 1.7-fold more active when compared to the control. Despite that, at 48 hpf, motor activity returned to control values. Our results suggest that the effects observed after CBD exposure are intimately related to CB1 receptor that is present in zebrafish since early stages of development. The present work showed early light effects induced by CBD exposure in concentrations that did not alter biochemical activity.”

https://www.ncbi.nlm.nih.gov/pubmed/29902416

https://www.sciencedirect.com/science/article/pii/S0009279718302163

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The Role of Cannabinoids in the Setting of Cirrhosis.

Posted on June 13, 2018 by David Worrell

“Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.” https://www.ncbi.nlm.nih.gov/pubmed/29890719 http://www.mdpi.com/2305-6320/5/2/52]]>

Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?

Posted on June 12, 2018 by David Worrell

“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.”

https://www.ncbi.nlm.nih.gov/pubmed/29317072

https://www.medical-hypotheses.com/article/S0306-9877(17)30861-7/fulltext

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Ischemia/Reperfusion Model Impairs Endocannabinoid Signaling and Na+/K+ ATPase Expression and Activity in Kidney Proximal Tubule Cells.

Posted on June 12, 2018 by David Worrell

“LLC-PK1 cells, an immortalized epithelial cell line derived from pig renal proximal tubules, express all the major players of the endocannabinoid system (ECS) such as CB1, CB2 and TRPV1 receptor, as well as the main enzymes involved in the biosynthesis and degradation of the major endocannabinoids named 2-arachidonoylglycerol, 2-AG and anandamide, AEA. Here we investigated whether the damages caused by ischemic insult either in vitro using LLC-PK1 cells exposed to antimycin A (an inductor of ATP-depletion) or in vivo using Wistar rats in a classic renal ischemia and reperfusion (IR) protocol, lead to changes in AEA and 2-AG levels, as well as altered expression of genes from the main enzymes involved in the regulation of the ECS. Our data show that the mRNA levels of CB1 receptor gene were downregulated, while the transcript levels of monoacylglycerol lipase (MAGL), the main 2-AG degradative enzyme, are upregulated in LLC-PK1 cells after IR model. Accordingly, IR was accompanied by a significant reduction in the levels of 2-AG and AEA, as well as of the two endocannabinoid related molecules, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in LLC-PK1 cells. In kidney cortex homogenates, the AEA levels were selectively significantly decreased. In addition, we found that both the in vitro and in vivo model of IR caused a reduction in the expression and activity of the Na⁺/K⁺ATPase. These changes were reversed by the CB1/CB2 agonist WIN55,212, in a CB1-receptor dependent manner on LLC-PK1 IR model. In conclusion, the ECS and Na⁺/K⁺ ATPase are down-regulated following IR model in LLC-PK1 cells and rat kidney. We suggest that CB1 agonists might represent a potential strategy to reverse the consequences of IR injury in kidney tissues.” https://www.ncbi.nlm.nih.gov/pubmed/29890144 https://www.sciencedirect.com/science/article/pii/S0006295218302132]]>

The Lateral Habenula Directs Coping Styles Under Conditions of Stress Via Recruitment of the Endocannabinoid System.

Posted on June 12, 2018 by David Worrell

“The ability to effectively cope with stress is a critical determinant of disease susceptibility. The lateral habenula (LHb) and the endocannabinoid (ECB) system have independently been shown to be involved in the selection of stress coping strategies, yet the role of ECB signaling in the LHb remains unknown.

CONCLUSIONS:

Alterations in LHb ECB signaling may be relevant for development of stress-related pathologies in which LHb dysfunction and stress-coping impairments are hallmark symptoms.” https://www.ncbi.nlm.nih.gov/pubmed/29887035 https://www.biologicalpsychiatryjournal.com/article/S0006-3223(18)31473-2/fulltext

“Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood.” https://www.ncbi.nlm.nih.gov/pubmed/27317195

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Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis

Posted on June 12, 2018 by David Worrell

“The cannabinoid system exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, yet not all effects of cannabinoid-like compounds seen can be attributed to the cannabinoid 1 receptor (CB₁ R) or cannabinoid 2 receptor (CB₂ R). The recently de-orphaned GPR55 has been shown to be activated by numerous cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor. Here we examined the role of GPR55 activation in NSC proliferation and early adult neurogenesis.

CONCLUSIONS AND IMPLICATIONS:

Together, these findings suggest GPR55 activation as a novel target and strategy to regulate NSC proliferation and adult neurogenesis.” https://www.ncbi.nlm.nih.gov/pubmed/29888782 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14387

“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

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Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity.

Posted on June 12, 2018 by David Worrell

“Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are two substances from cannabis sativa that have been implicated in the treatment of mental and neurological disorders. We concentrated on a previously validated neuroimaging phenotype, fronto-striatal connectivity across different striatal seeds, because of this loop’s relevance to executive functioning, decision making, salience generation and motivation and its link to various neuropsychiatric conditions. Therefore, we studied the effect of THC and CBD on fronto-striatal circuitry by a seed-voxel connectivity approach using seeds from the caudate and the putamen. We conducted a cross-over pharmaco-fMRI study in 16 healthy male volunteers with placebo, 10 mg oral THC and 600 mg oral CBD. Resting state was measured in a 3 T scanner. CBD lead to an increase of fronto-striatal connectivity in comparison to placebo. In contrast to our expectation that THC and CBD show opposing effects, THC versus placebo did not show any significant effects, probably due to insufficient concentration of THC during scanning.

The effect of CBD on enhancing fronto-striatal connectivity is of interest because it might be a neural correlate of its anti-psychotic effect in patients.”

https://www.ncbi.nlm.nih.gov/pubmed/29887287

https://www.europeanneuropsychopharmacology.com/article/S0924-977X(18)30113-5/fulltext

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