Endocannabinoid signaling in female reproductive events: a potential therapeutic target?

“Nearly 30 years after the discovery in 1964 of the psychoactive ingredient of cannabis (Cannabis sativa), Δ9-tetrahydrocannabinol, its endogenous counterparts were discovered and collectively termed endocannabinoids (eCBs): N-arachidonoylethanolamine (anandamide) in 1992 and 2-arachidonoylglycerol in 1995.

Since then, intense research has identified additional eCBs and an ensemble of proteins that bind, synthesize and degrade them, the so-called eCB system.

Altogether, these new compounds have been recognized as key mediators of several aspects of human pathophysiology, and in particular of female fertility.

Here, the main features of the eCB system are presented, in order to put in a better perspective the relevance of eCB signaling in virtually all steps of human reproduction and to highlight emerging hopes that elements of this system might indeed become novel targets to combat fertility problems.”

http://www.ncbi.nlm.nih.gov/pubmed/26126134

Chronic administration of Δ9-tetrahydrocannabinol induces intestinal anti-inflammatory microRNA expression during acute simian immunodeficiency virus infection of rhesus macaques.

“Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression…

These results support a role for differential miRNA induction in THC-mediated suppression of intestinal inflammation. Whether similar miRNA modulation occurs in other tissues requires further investigation.

IMPORTANCE:

Gastrointestinal (GI) tract disease/inflammation is a hallmark of HIV/SIV infection.

Previously, we showed that chronic treatment of SIV-infected macaques with Δ9-tetrahydrocannabinol (Δ9-THC) increased survival and decreased viral replication and infection-induced gastrointestinal inflammation.

Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory microRNA expression profile in the intestine…

Overall, our results show that selective upregulation of anti-inflammatory miRNA expression contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/25378491

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

Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production.

“Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions…

The present study was designed to investigate the central (CB1) and the peripheral (CB2)cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia.

The antagonist for the CB2, but not CB1 receptor antagonist abolished the protective effect of THC.

In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors.

Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors.

L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC.

Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production.

An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/16444588

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells.

“Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression.

Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts…

Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection.”

http://www.ncbi.nlm.nih.gov/pubmed/26034207

Cannabinoid compounds in South African Cannabis sativa L.

“Dagga (Cannabis sativa L.) samples were collected from various geographical regions of South Africa. These were classified into age, sex and plant part and the cannabinoids were analysed quantitatively by gas-liquid chromatography and mass spectrometry. Analytical results show that there appears to be at least three chemovariants of Cannabis sativa growing in South Africa with respect to relative cannabinoid content. One of these variants appears to be unique to Southern Africa. It also appears that South African C. sativa ranks among the world’s more potent C. sativa variants in terms of its delta 9-tetrahydrocannabinol content.”

http://www.ncbi.nlm.nih.gov/pubmed/6102121

Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1.

“The anti-tumor properties of cannabinoids have recently been evidenced, mainly with delta9-tetrahydrocannabinol (THC).

Here we investigated whether the most potent endogenous cannabinoid, arachidonylethanolamide (AEA), could be a candidate.

We observed that AEA induced apoptosis in long-term and recently established glioma cell lines via aberrantly expressed vanilloid receptor-1 (VR1).

In contrast with their role in THC-mediated death, both CB1 and CB2 partially protected glioma against AEA-induced apoptosis.

These data show that the selective targeting of VR1 by AEA or more stable analogues is an attractive research area for the treatment of glioma.”

http://www.ncbi.nlm.nih.gov/pubmed/15453094

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

Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.

“Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines.

The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect…

Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/15047233

http://www.thctotalhealthcare.com/category/cervical-cancer/

Differential role of cannabinoids in the pathogenesis of skin cancer.

“Cannabinoids (CB) like ∆9-tetrahydrocannabinol (THC) can induce cancer cell apoptosis and inhibit angiogenesis.

Here we investigated the role of exogenous and endogenous cannabinoids in mouse skin cancer.

THC significantly inhibited tumor growth of transplanted HCmel12 melanomas in a CB receptor-dependent manner in vivo through antagonistic effects on its characteristic pro-inflammatory microenvironment.

Our results confirm the value of exogenous cannabinoids for the treatment of melanoma…”

http://www.ncbi.nlm.nih.gov/pubmed/25921771

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

Alkylindole-sensitive receptors modulate microglial cell migration and proliferation.

“Ligands targeting G protein-coupled receptors (GPCR) expressed by microglia have been shown to regulate distinct components of their activation process, including cell proliferation, migration and differentiation into M1 or M2 phenotypes.

Cannabinoids, including the active component of the Cannabis plant, tetrahydrocannabinol (THC), and the synthetic alkylindole (AI) compound, WIN55212-2 (WIN-2), activate two molecularly identified GPCRs: CB1 and CB2 .

Our results suggest that microglia express functional AI-sensitive receptors that control select components of their activation process.

Agonists of these novel targets might represent a novel class of therapeutics to influence the microglial cell activation process. ”

http://www.ncbi.nlm.nih.gov/pubmed/25914169

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting.

“Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment.

We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin.

The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity.

These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.”

http://www.ncbi.nlm.nih.gov/pubmed/16197970

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