Category Archives: Uncategorized

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

Posted on by

“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

Posted on by

“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).

CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.

Cannabinoids can suppress inflammatory cytokines…

The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”

http://www.ncbi.nlm.nih.gov/pubmed/25704169

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway.

Posted on by

“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain.

In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function.

The CB1 receptor also confers neuroprotection in various experimental models of striatal damage…

Here, by using an array of pharmacological, genetic and pharmacogenetic approaches, we show that (1) CB1receptor engagement protects striatal cells from excitotoxic death via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin complex 1 pathway, which, in turn, (2) induces brain-derived neurotrophic factor (BDNF) expression through the selective activation of BDNF gene promoter IV, an effect that is mediated by multiple transcription factors.

Collectively, these findings unravel a molecular link between CB1 receptor activation and BDNF expression, and support the relevance of the CB1/BDNF axis in promoting striatal neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/25698444

4-hydroxy-3-methoxy-acetophenone-mediated long-lasting memory recovery, hippocampal neuroprotection, and reduction of glial cell activation after transient global cerebral ischemia in rats.

Posted on by

“4-Hydroxy-3-methoxy-acetophenone (apocynin) is a naturally occurring methoxy-substitute catechol that is isolated from the roots of Apocynin cannabinum (Canadian hemp) and Picrorhiza kurroa (Scrophulariaceae).

It has been previously shown to have antioxidant and neuroprotective properties in several models of neurodegenerative disease, including cerebral ischemia.

The present study investigates the effects of apocynin on transient global cerebral ischemia (TGCI)-induced retrograde memory deficits in rats.

The protective effects of apocynin on neurodegeneration and the glial response to TGCI are also evaluated.

The present results confirm that TGCI causes memory impairment in the AvRM and that apocynin prevents these memory deficits and attenuates hippocampal neuronal death in a sustained way.

These findings support the potential role of apocynin in preventing neurodegeneration and cognitive impairments following TGCI in rats.

The long-term protective effects of apocynin may involve inhibition of the glial response.”

http://www.ncbi.nlm.nih.gov/pubmed/25702923

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.

Posted on by

“First isolated from Cannabis in 1940 by Roger Adams, the structure of CBD was not completely elucidated until 1963.

Subsequent studies resulted in the pronouncement that THC was the ‘active’ principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD.

This was no doubt due to the belief that activity meant psychoactivity that was shown by THC and not by CBD.

In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years.

In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed.

Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD and combined THC plus CBD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25703248

Cannabinoids and capsaicin improve liver function following thioacetamide-induced acute injury in mice.

Posted on by

“We have shown the beneficial effects of cannabinoids in a murine model of hepatic encephalopathy following thioacetamide and now report their effects on the liver injury…

The similar pattern found between the effect of cannabinoids and their antagonists on brain and liver indicated that the therapeutic effect might be directed by the improvement in both organs through CB2 receptors and/or TRPV1 receptors.

Modulation of these systems may have therapeutic potential.”

http://www.ncbi.nlm.nih.gov/pubmed/19086956

http://www.thctotalhealthcare.com/category/liver-disease/

Cannabinoids suppress acute and anticipatory nausea in pre-clinical rat models of conditioned gaping.

Posted on by

“The sensation of nausea is one of the most debilitating human experiences. Current anti-emetic therapies are effective in reducing vomiting, but are less effective in reducing acute and delayed nausea and are completely ineffective in reducing anticipatory nausea.

Recent pre-clinical evidence using a selective rat model of nausea (conditioned gaping reactions) has revealed that cannabinoids have great promise as treatments for nausea and that their anti-nausea effects may be mediated by the interoceptive insular cortex.”

http://www.ncbi.nlm.nih.gov/pubmed/25691302

http://www.thctotalhealthcare.com/category/nauseavomiting/

Evaluation of Phytocannabinoids from High Potency Cannabis sativa using In Vitro Bioassays to Determine Structure-Activity Relationships for Cannabinoid Receptor 1 and Cannabinoid Receptor 2.

Posted on by

“Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber.

Over 500 compounds have been isolated from Cannabis sativa with approximately 105 being cannabinoids. Of those 105 compounds, Δ9-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis.

Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors.

Targeting the cannabinoid receptors has the potential to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and others.

Developing in vitro bioassays to determine binding and functional activity of compounds has the ability to lead researchers to develop a safe and effective drug that may target the cannabinoid receptors…”

http://www.ncbi.nlm.nih.gov/pubmed/25419092

Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium.

Posted on by

“Chronic neuroinflammatory disorders (such as HIV associated neurodegeneration) require treatment that decreases production of inflammatory factors by activated microglia and macrophages and protection of blood brain barrier (BBB) injury secondary to activation of brain endothelium.

Cannabioid type 2 receptor (CB2) is highly expressed on macrophages and brain microvasular enndothelial cells (BMVEC) and is upregulated in inflammation and HIV infection. It has been shown that CB2 activation dampened inflammatory responses in macrophages and BMVEC.

In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes.

These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled diminished secretion of proinflammatory factors.

These results indicate the potential utility of CB2agonists for the treatment of neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25666933

THE EFFECT OF PHYTOCANNABINOIDS ON AIRWAY HYPERRESPONSIVENESS, AIRWAY INFLAMMATION AND COUGH.

Posted on by

“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory and anti-tussive activity in the airways, but, information on the active cannabinoids, their receptors and the mechanisms for their effects is limited.

We compared the effects of Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid and tetrahydrocannabivarin…

The other cannabinoids did not influence cholinergic transmission and only Δ9-THC demonstrated effects on airway hyperresponsiveness, anti-inflammatory activity and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

http://jpet.aspetjournals.org/content/early/2015/02/05/jpet.114.221283.long