“Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models.
The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat…
The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.”
“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.
When these tumors are in advanced stages, few therapeutic options are available.
Therefore, it is essential to search for new treatment modalities to fight this disease.
Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.
The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.
Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”
http://www.sciencedirect.com/science/article/pii/S209050681400027X
“While the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain less than 10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wildtype tumours.
Targeting autophagy is a novel means to promote cancer cell death in chemotherapy-resistant tumours and the aim of the present study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma.
Treatment with Δ9-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability and activation of apoptosis, while co-treatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro.
Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wildtype melanoma xenografts substantially inhibited melanoma viability, proliferation and tumour growth paralleled by an increase in autophagy and apoptosis compared to standard single agent temozolomide.
Collectively our findings suggest THC activates non-canonical autophagy-mediated apoptosis of melanoma cells, suggesting cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.”
“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…”
“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.”
“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex.
Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.
Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH).
By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and we demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs.
Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption.
Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD.
Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.
These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy towards epilepsy and other neurological disorders.”
“The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice…
Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses.”
“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
“… a systematic review to assess the effectiveness of cannabis extracts and cannabinoids in the management of chronic nonmalignant neuropathic pain…
Randomized placebo-controlled trials (RCTs) involving cannabis and cannabinoids for the treatment of chronic nonmalignant pain were selected…
Evaluation of these studies suggested that cannabinoids may provide effective analgesia in chronic neuropathic pain conditions that are refractory to other treatments.
Conclusion: Cannabis based medicinal extracts used in different populations of chronic nonmalignant neuropathic pain patients may provide effective analgesia in conditions that are refractory to other treatments. ”
http://www.ncbi.nlm.nih.gov/pubmed/25635955
http://www.thctotalhealthcare.com/category/neuropathic-pain/
“Pro-inflammatory cytokines, growth and angiogenic factors released by leukocytes are involved in carcinogenesis and cancer progression, but they are also crucial for fighting tumour growth and spreading.
We have previously demonstrated that endocannabinoids modulate cell-to-cell crosstalk during inflammation. Here, we investigated the inflammatory and tumourigenic properties of endocannabinoids in a human urinary bladdercarcinoma cell line…
Collectively, these findings suggest that CB receptors may play distinct roles in cancer biology, depending on the specific ligand employed.
The in vivo assessment of the role of CB receptors in inflammation and cancer might be instrumental in broadening the understanding about bladder cancer biology.”