The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.

“…there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival.

Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells…

The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17583570

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

Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.

“The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM)…

KEY FINDINGS:

THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoidreceptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.

SIGNIFICANCE:

The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins.

The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB.”

http://www.ncbi.nlm.nih.gov/pubmed/24742657

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

Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery.

“Chemotherapeutic treatment results in chronic pain in an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics an urgent one. We compared the effects of prophylactic cannabinoids as a preventative strategy for suppressing development of paclitaxel-induced nociception…

Our results support the therapeutic potential of cannabinoids for suppressing chemotherapy-induced neuropathy in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/24742127

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

[Therapeutic use of cannabis derivatives].

“The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action…

Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis…”

http://www.ncbi.nlm.nih.gov/pubmed/24701869

The detection of THC, CBD and CBN in the oral fluid of Sativex® patients using two on-site screening tests and LC-MS/MS.

“Sativex® is an oromucosal spray used to treat spasticity in multiple sclerosis sufferers in some European countries, the United Kingdom, Canada and New Zealand. The drug has also recently been registered by the Therapeutic Goods Administration (TGA) in Australia for treatment of multiple sclerosis.

Sativex® contains high concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with the former being the subject of random roadside drug tests across Australia to detect cannabis use.

This pilot study aims to determine whether or not patients taking Sativex® will test positive to THC using these roadside screening tests. Detectable levels of THC, CBD and cannabinol (CBN) in their oral fluid were also confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study was a double-blind, placebo controlled design.

In conclusion, Sativex® users may test positive for THC by roadside drug testing within 2-3h of use. Confirmatory analysis can identify Sativex® treatment through use of THC/CBD ratios, however, these ratios would unlikely be sufficient to differentiate non-medicinal cannabis use from Sativex® use if both are taken concurrently.”

http://www.ncbi.nlm.nih.gov/pubmed/24699310

Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction

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“Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions..

Cannabinoids are compounds derived from the Cannabis sativa plant and exert many effects on the immune system. Cannabinoids have potential as therapeutic agents in several different disease conditions, including experimental autoimmune hepatitis, Multiple Sclerosis, and Graft vs. Host Disease…

This report suggested a role of the endogenous cannabinoid system in regulation of allergic inflammation.

These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body employs to down-regulate immune response to foreign antigens as well as combat autoimmunity.

Targeting of this system could yield valuable therapeutics in the future.”

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093954

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.

Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.

In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.

Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.

The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/19832688

Cannabinoids for pain and nausea

“This is an exciting time for cannabinoid research. The discovery of cannabinoid CB1receptors (expressed by central and peripheral neurones) and CB2 receptors (expressed mainly by immune cells) and endogenous agonists for these receptors has renewed the scientific community’s interest. Independently of these developments society at large has continued an aggressive debate about the therapeutic use of cannabinoids, including demands for their more liberal availability. Cannabinoids have been suggested to have therapeutic value as analgesics and in various conditions, including migraine headaches, nausea and vomiting, wasting syndrome and appetite stimulation in HIV-infected patients, muscle spasticity due to multiple sclerosis or spinal cord injury, movement disorders such as Parkinson’s disease, epilepsy, and glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120661/

Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth.

“Because THC-like compounds are used to inhibit nausea and induce appetite in cancer patients, and anandamide appears to be an endogenous orexigenic mediator, the finding of possible antitumor effect for these substances might have a tremendous potential for therapeutic intervention in preventing the progression of cancer and, at the same time, in alleviating its symptoms.

Because multiple pathways are important for the proliferation of tumor cells and because combination therapies are often more effective than single-drug administration, cannabimimetic substances may complement other anticancer agents…”

http://www.fasebj.org/content/early/2001/12/02/fj.01-0320fje.long

“[Targeting the RAS signalling pathway in cancer].”  http://www.ncbi.nlm.nih.gov/pubmed/21715253

“Targeting the RAS oncogene.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804031/

Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

“Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs.

The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment.

Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation.”

http://www.ncbi.nlm.nih.gov/pubmed/20399844