THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

Progress in Brain Cannabinoid CB2 Receptor Research: From Genes to Behavior.

Posted on January 8, 2019 by David Worrell

Neuroscience & Biobehavioral Reviews

“The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB_2A is the major transcript isoform, while CB_2A and CB_2B transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30611802

https://www.sciencedirect.com/science/article/pii/S0149763418308297?via%3Dihub

Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

Posted on January 4, 2019 by David Worrell

“Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.

OBJECTIVE AND METHODS:

The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.

RESULTS:

Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen’s d ≥ 1.0). The brain areas responsible for the above mentioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.

CONCLUSION:

Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.”

https://www.ncbi.nlm.nih.gov/pubmed/30604182

https://link.springer.com/article/10.1007%2Fs00213-018-5127-x

n-3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids

Posted on December 30, 2018 by David Worrell

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

“Anandamide, the first identified endogenous cannabinoid and TRPV1 agonist, is one of a series of endogenous N-acylethanolamines, NAEs. We have generated novel assays to quantify the levels of multiple NAEs in biological tissues and their rates of hydrolysis through fatty acid amide hydrolase. This range of NAEs was also tested in rapid response assays of CB₁, CB₂ cannabinoid and TRPV1 receptors. The data indicate that PEA, SEA and OEA are not endocannabinoids or endovanilloids, and that the higher endogenous levels of these metabolites compared to polyunsaturated analogues are a correlate of their slow rates of hydrolysis. The n-6 NAEs (AEA, docosatetraenoyl and docosapentaenoyl derivatives) activated both CB₁ and CB₂ receptors, as well as TRPV1 channels, suggesting them to be ‘genuine’ endocannabinoids and ‘endovanilloids’. The n-3 NAEs (eicosapentaenoyl, docosapentaenoyl and docosahexaenoyl derivatives) activated CB₂ receptors and some n-3 NAEs (docosapentaenoyl and docosahexaenoyl derivatives) also activated TRPV1 channels, but failed to activate the CB₁ receptor. We hypothesise that the preferential activation of CB₂ receptors by n-3 PUFA NAEs contributes, at least in some part, to their broad anti-inflammatory profile.” https://www.ncbi.nlm.nih.gov/pubmed/30591150 https://www.sciencedirect.com/science/article/pii/S1388198118302026?via%3Dihub

]]>

Selective Activation of Cannabinoid Receptor 2 Attenuates Myocardial Infarction via Suppressing NLRP3 Inflammasome.

Posted on December 18, 2018 by David Worrell

“The administration of cannabinoid receptor 2 (CB2R) agonist has been reported to produce a cardioprotective effect against the pathogenesis and progression of myocardial infarction (MI). Here in this study, we investigated the specific mechanism related to inflammatory suppression. JWH-133 was used for the activation of CB2R. Taken together, we demonstrated for the first time the cardioprotective effect of CB2R agonist and its NLRP3 inflammasome-related mechanism in MI.”

https://www.ncbi.nlm.nih.gov/pubmed/30554372

https://link.springer.com/article/10.1007%2Fs10753-018-0945-x

]]>

Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.

Posted on December 15, 2018 by David Worrell

“It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness. THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly. Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies.

RESULTS:

We now report that a single topical application of THC lowered IOP substantially (∼28%) for 8 hours in male mice. This effect is due to combined activation of CB1 and GPR18 receptors each of which has been shown to lower ocular pressure when activated. We also found that the effect was sex-dependent, being stronger in male mice, and that mRNA levels of CB1 and GPR18 were higher in males. Far from inactive, CBD was found to have two opposing effects on ocular pressure, one of which involved antagonism of tonic signaling. CBD prevents THC from lowering ocular pressure.

CONCLUSIONS:

We conclude that THC lowers IOP by activating two receptors-CB1 and GPR18-but in a sex-dependent manner. CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC.” https://www.ncbi.nlm.nih.gov/pubmed/30550613 https://iovs.arvojournals.org/article.aspx?articleid=2718702

]]>

Chemical characterization of leaves, male and female flowers from spontaneous cannabis (Cannabis sativa var. spontanea) growing in Hungary.

Posted on December 15, 2018 by David Worrell

“Cannabis sativa var. spontanea is a spontaneous form of hemp with a low content of psychoactive cannabinoids and can be considered as a valuable source of other phytoconstituents to be used in nutraceuticals or for their health promoting properties. Chemical data on this hemp variety are rather scarce. In this paper we report a comprehensive phytochemical characterization of leaves, male and female inflorescences of C. sativa var. spontanea growing wild in Hungary. The results indicated that female inflorescence essential oil contains high amounts of the CB2 agonists (E)-caryophyllene (28.3%) and cannabidiol (CBD) (24.9%), whereas leaves and male inflorescence essential oils contained lower amounts of both compounds. HPLC-MS allowed to quantify CBD and CBD-A in the ethyl acetate extracts from leaves, male and female inflorescences; they were 0.3, 0.8 and 0.9%, and 0.2, 0.3 and 0.4%, respectively. Flavonoids were formed by C-glycosides and glucuronic acids of kaempferol and apigenin, with a total content of 3.8, 6.1 and 7.8 mg/g in methanolic extracts from leaves, male and female inflorescences, respectively. Based on these results, C. sativa var. spontanea may represent an important source of CB2 agonists and bioflavonoids to be used in nutraceuticals, cosmetics and pharmaceuticals.” https://www.ncbi.nlm.nih.gov/pubmed/30548994 https://onlinelibrary.wiley.com/doi/abs/10.1002/cbdv.201800562

]]>

Cannabinoid 2 receptor attenuates inflammation during skin wound healing by inhibiting M1 macrophages rather than activating M2 macrophages.

Posted on December 12, 2018 by David Worrell

“The anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation. Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation. However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.

In summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation.

These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.” https://www.ncbi.nlm.nih.gov/pubmed/30534003 https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-018-0201-z]]>

Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons.

Posted on December 8, 2018 by David Worrell

“Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation.” https://www.ncbi.nlm.nih.gov/pubmed/30508607 https://www.sciencedirect.com/science/article/pii/S0166432818311987?via%3Dihub]]>

Cannabinoid receptor 2 agonist prevents local and systemic inflammatory bone destruction in rheumatoid arthritis.

Posted on December 8, 2018 by David Worrell

“Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the non-inflamed synovium and bone tissues. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis.” https://www.ncbi.nlm.nih.gov/pubmed/30508319 https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3637]]>

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans.

Posted on December 8, 2018 by David Worrell

“Endocannabinoid peptides, or “pepcans,” are endogenous ligands of the CB1 cannabinoid receptor. Depending on their length, they display diverse activity: For instance, the nona-peptide Pepcan-9, also known as hemopressin, is a powerful inhibitor of CB1, whereas the longer variant Pepcan-12, which extends by only three amino acid residues at the N-terminus, acts on both CB1 and CB2 as an allosteric modulator. These findings open the way to structure-driven design of selective peptide modulators of CB1.” https://www.ncbi.nlm.nih.gov/pubmed/30505835 https://www.frontiersin.org/articles/10.3389/fmolb.2018.00100/full]]>