Treatment of spasticity in multiple sclerosis: new perspectives regarding the use of cannabinoids.

“Spasticity remains a prevalent symptom in multiple sclerosis, with a significant associated disability and quality of life impairment… Cannabinoids provide a new way for therapy.

A delta-9-tetrahydrocannabinol plus cannabidiol (1:1) association, administered through an oromucosal route, has been approved in several countries including Spain; it causes a specific effect on CB(1) and CB(2) receptors, with traditional psychotropic cannabis actions being minimized.

Randomized, placebo-controlled trials, as well as longer-term open-label extensions, have shown a clear-cut efficacy to reduce spasticity and their associated symptoms in those patients refractory to other therapies, with a good tolerability/safety profile.

No tolerance, abuse or addictive issues have been found…”

http://www.ncbi.nlm.nih.gov/pubmed/23011861

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

“Cannabinoids, the biologically active constituents of marijuana (Cannabis sativa)…

Plant-derived cannabinoids, including Δ9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells…

cannabinoids were shown to inhibit the proliferation of several human cancer cell lines, including leukemia…

Together, these data suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocation played a critical role in THC-induced apoptosis in Jurkat cells…

THC and other cannabinoids can induce apoptosis in a variety of tumor cell lines, thereby raising the possibility of the use of cannabinoids as novel anticancer agents…”

Full text: http://mcr.aacrjournals.org/content/4/8/549.long

Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach.

“Delta(9)-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro. In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects.

 Results showed clear synergistic interactions between THC and the cytotoxic agents in leukemic cells…

 Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.”

http://www.ncbi.nlm.nih.gov/pubmed/18608861

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

“Plant-derived cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main psychoactive and nonpsychoactive components of cannabis, respectively, possess myriad pharmacological properties…

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects…

Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.”

Full text: http://www.jleukbio.org/content/81/6/1512.long

Marijuana’s Active Ingredient Targets Deadly Brain Cancer – WebMD

“If results of a recent rat study hold true in human trials, marijuana could be the treatment of choice for patients with malignant glioma — an especially aggressive and often fatal form of brain cancer.

 No, rats haven’t started smoking pot. But when researchers injected tumorous animals with cannabinoids — the drug’s active ingredient — about a third of them went into remission, and another third lived significantly longer than untreated rats.

The findings appear in the March issue of the journal Nature Medicine

According to lead researcher Manuel Guzmán, PhD, his team’s previous studies showed that cannabinoids could stop growth and kill cancer cells but did not harm normal cells. The current work examined the action behind this effect and whether it would also work in living animals…

The researchers first caused tumors in the brains of 18 rats. They then injected the animals over the course of seven days with either a natural or artificial cannabinoid, or a placebo for comparison. Additional groups of healthy, tumor-free rats also received the various treatments…

All of the untreated animals with tumors died between days 12 and 18, but those treated with the cannabinoids lived much longer, and had significantly smaller tumors…

There were no negative side effects at all in the healthy animals receiving treatment.”

More:http://www.webmd.com/cancer/news/20000228/marijuanas-active-ingredient-targets-deadly-brain-cancer

“Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation” http://www.nature.com/nm/journal/v6/n3/abs/nm0300_313.html

Pot Slows Cancer in Test Tube – WebMD

“THC and another marijuana-derived compound slow the spread of cervical and lung cancers, test-tube studies suggest.

The new findings add to the fast-growing number of animal and cell-culture studies showing different anticancer effects for cannabinoids, chemical compounds derived from marijuana.

Cannabinoids, and sometimes marijuana itself, are currently used to lessen the nausea and pain experienced by many cancer patients. The new findings — suggest that cannabinoids may have a direct anticancer effect.

“Cannabinoids’ … potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials,” conclude Robert Ramer, PhD, and Burkhard Hinz, PhD, of the University of Rostock, Germany…

Doses of THC that reduce pain in cancer patients yield blood concentrations much higher than the concentrations needed to inhibit cancer invasion.

“Thus the effects of THC on cell invasion occurred at therapeutically relevant concentrations,” Ramer and Hinz note…

Ramer and Hinz report the findings in the Jan. 2, 2008 issue of the Journal of the National Cancer Institute.”

More: http://www.webmd.com/cancer/news/20071226/pot-slows-cancer-in-test-tube

“Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1”: http://jnci.oxfordjournals.org/content/100/1/59.long

Marijuana Inhibits Tumors

Towards a better Cannabis drug.

“Opium smoking has been mostly replaced by i.v. injection of morphine and heroin and we see cocaine sniffing rather than chewing of coca leaves. Cannabis use – be it of marijuana, hashish or bhang – differs.

Any cannabis cognoscente will insist that the crude material is ‘much better’ than pure Δ9 – tetrahydrocannabinol (THC), the only major psychoactive constituent of cannabis (Mechoulam et al., 1970).

Indeed, although pure THC is available as a drug (named Dronabinol) it is apparently not used illicitly.

The pharmacological/biochemical basis for this difference is not clear and is presumably due to several factors. A major reason seems to be the pharmacokinetic difference between cannabis smoking and the oral administration of THC.

 On smoking, the cannabis effects are noted almost immediately, while a 1.5 – 2 hour delay is observed on oral administration.

A further factor may be conditioning to the smell, although there are no published data along these lines. A further factor may be the presence of the terpenoid CB2 agonist beta-caryophyllene in cannabis (Gertsch et al., 2008).

CB2 agonists are well known to cause numerous effects (mostly of a protective nature) which may counteract some of the effects of THC (Pacher & Mechoulam, 2011).”

http://www.ncbi.nlm.nih.gov/pubmed/24024867

Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model.

“The aim of this study was to investigate the effect of an organic cannabis extract on β-cell secretory function in an in vivo diet-induced obese rat model and determine the associated molecular changes within pancreatic tissue…

These results suggest that the cannabis extract protects pancreatic islets against the negative effects of obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/22421529

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabis-Derived Drug for Type 2 Enters Phase 2

“Cannabis-based drug for type 2s on the way?”

 
“A British drug company is looking to medical marijuana- or at least a derivative of it-to help treat a variety of different diseases, including type 2 diabetes.

The company, GW Pharma, is in the process of creating a collection of cannabinoid-based drugs, including one that takes aim at diabetes. The first of this type of drug the company has produced is Sativex, a nasal spray used to treat spasms associated with multiple sclerosis. Sativex has been okayed in eight countries, and is currently awaiting FDA approval in the United States.

The diabetes drug, GWP4204, is currently in its second phase of testing after a small but successful double-blind study. That study featured 62 type 2 patients who received various levels of the oral-administered drug or a placebo.”

More: http://diabeteshealth.com/read/2013/07/20/7933/cannabis-derived-drug-for-type-2-enters-phase-2–