Cannabinoid compounds in South African Cannabis sativa L.

Posted on May 23, 2015 by David

“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

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.

Posted on May 16, 2015 by David

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Delta9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

“Cannabinoid components of marijuana, such as (−)Δ9-tetrahydrocannabinol (THC), or the synthetic cannabinoid WIN55,212-2, have been shown to prevent glutamate- or NMDA-induced neurotoxicity in isolated neurons or in the brain via activation of the cannabinoid receptor subtype CB1.

…the nonpsychotropic component of marijuana, cannabidiol (CBD), and the synthetic nonpsychotropic cannabinoid, HU-211, as well as THC have been demonstrated as potent antioxidants and/or NMDA receptor antagonists that protect neuron cultures from glutamate-induced death or from oxidative stress.

… we demonstrated that THC and CBD are neuroprotective against NMDA-induced retinal injury and that their protective actions are in part because of an effect in reducing formation of lipid peroxides, nitrite/nitrate, and nitrotyrosine.

In addition to possessing neuroprotective or retinal neuroprotective activity as demonstrated here and elsewhere, cannabinoids such as THC, WIN55,212-2, endogenous cannabinoid 2-arachidonoylglycerol, as well as nonpsychotropic HU-211 have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models.

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

http://www.thctotalhealthcare.com/category/glaucoma-2/

Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain.

Posted on May 10, 2015 by David

“Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor.

Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states.

One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoidreceptors (CB) are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ)-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state.

The prevention of microglial accumulation and activation in the dorsal spinal cord was associated with limited development of a neuropathic pain state.

Cannabinoids demonstrated antinociceptive effects in this mouse model of DPN.

These results suggest that such interventions may also benefit humans with DPN, and their early introduction may also modify the development of the NeP state.” http://www.ncbi.nlm.nih.gov/pubmed/20236533

“Tetrahydrocannabinol (THC), a component in marijuana, acts at both CB1 and CB2 receptors, but other forms of cannabinoids such as cannabinol and cannabidiol act predominantly at CB2 receptors. Such CB2 agonists may be potential anti-inflammatory therapies, antagonizing the 2-AG-induced recruitment of microglia and impacting upon development of an inflammatory state. Such properties may permit the cannabinoids to act in the prevention of microglial activation, perhaps limiting the development of neuropathic pain.

The present data confirm the efficacy of cannabinoid agonists, both for the CB1 and CB2 receptor, in modulation of acute thermal and tactile hypersensitivity as features of neuropathic pain. Furthermore, CB1 agonism from the onset of the offending stimulus (diabetes) normally leading to neuropathic pain ameliorated the development of a neuropathic pain state.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/

http://www.thctotalhealthcare.com/category/neuropathic-pain/

The relationship between cannabidiol and psychosis: A review.

Posted on May 9, 2015 by David

“Cannabis sativa is the most widely used illicit drug in the world…

THC is considered responsible for the main psychotropic effects of the drug, while CBD seems to antagonize these effects, particularly those that induce psychosis.

The effects of Cannabis seem to depend on several variables related to the type of plant, its strength, usage patterns, and intersubjective variations.

CBD could be used to treat several conditions, including psychosis, when the current treatment is associated with significant side effects.

…further research involving the possible antipsychotic effect and other potential positive effects of Cannabis are needed.”

http://www.ncbi.nlm.nih.gov/pubmed/25954940

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

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

Posted on May 7, 2015 by David

“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.

Posted on May 7, 2015 by David

“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.

Posted on April 30, 2015 by David

“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/

Inhaled cannabis reduces pain in diabetic peripheral neuropathy patients, study suggests

Posted on April 29, 2015 by David

“A small study finds that inhaling cannabis could demonstrate a dose-dependent pain reduction in patients with diabetic peripheral neuropathy.

Researchers at the University of California, United States conducted a study in which 16 patients with painful diabetic peripheral neuropathy were given placebo, or single doses of cannabis.

These doses were either low (one per cent tetrahydrocannibinol, THC), medium (four per cent THC) or high (seven per cent THC).

Tests were first performed on baseline spontaneous pain, evoked pain and cognitive function. Subsequently, participants either inhaled the cannabis or placebo, with measurements of pain intensity and cognitive function assessed over a three-hour period.

The higher the content of THC participants inhaled, the less pain they felt. The high dose of THC had a significant effect when researchers evoked pain using foam brush and von Frey.

These are tools used to test neuropathic pain in patients – von Frey are a set of filaments that test the pain of a patients by pushing against the skin to assess when the sensation becomes painful.

Patients on the high dose of THC showed impaired performance on the neuropsychological tests, but researchers concluded the pain reduction of patients adds further evidence on the efficacy of cannabis in treating diabetic peripheral neuropathy.

The results of this study were published in the Journal of Pain and Palliative Care Pharmacology.

Earlier this month, the CBD compound in cannabis was reported by researchers as a potential treatment for diabetes.”

http://www.diabetes.co.uk/news/2015/apr/inhaled-cannabis-reduces-pain-in-diabetic-peripheral-neuropathy-patients,-study-suggests-95680845.html

“Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.” http://www.ncbi.nlm.nih.gov/pubmed/25843054

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

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

Posted on April 29, 2015 by David

“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes.

Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.

During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.

In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.

For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.

This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.

We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25916739

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

Alkylindole-sensitive receptors modulate microglial cell migration and proliferation.

Posted on April 29, 2015 by David

“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