Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis.

Posted on July 2, 2016 by David

“Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson’s disease (PD). The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use.

The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress.

We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1α (PGC-1α), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content.

… unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress.

We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27366949

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10314&path[]=32486

Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids

Posted on June 30, 2016 by David

“The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood.

We use a proteotoxicity model based upon the inducible expression of Aβ in a human central nervous system nerve cell line to characterize a distinct form of nerve cell death caused by intracellular Aβ.

It is shown that intracellular Aβ initiates a toxic inflammatory response leading to the cell’s demise. Aβ induces the expression of multiple proinflammatory genes and an increase in both arachidonic acid and eicosanoids, including prostaglandins that are neuroprotective and leukotrienes that potentiate death.

Cannabinoids such as tetrahydrocannabinol stimulate the removal of intraneuronal Aβ, block the inflammatory response, and are protective.

Altogether these data show that there is a complex and likely autocatalytic inflammatory response within nerve cells caused by the accumulation of intracellular Aβ, and that this early form of proteotoxicity can be blocked by the activation of cannabinoid receptors.”

http://www.nature.com/articles/npjamd201612

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons.” http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

Harnessing the Endocannabinoid 2-Arachidonoylglycerol to Lower Intraocular Pressure in a Murine Model.

Posted on June 23, 2016 by David

“Cannabinoids, such as Δ9-THC, act through an endogenous signaling system in the vertebrate eye that reduces IOP via CB1 receptors.

Endogenous cannabinoid (eCB) ligand, 2-arachidonoyl glycerol (2-AG), likewise activates CB1 and is metabolized by monoacylglycerol lipase (MAGL). We investigated ocular 2-AG and its regulation by MAGL and the therapeutic potential of harnessing eCBs to lower IOP.

Our data confirm a central role for MAGL in metabolism of ocular 2-AG and related lipid species, and that endogenous 2-AG can be harnessed to reduce IOP. The MAGL blocker KML29 has promise as a therapeutic agent, while JZL184 may have difficulty crossing the cornea.

These data, combined with the relative specificity of MAGL for ocular monoacylglycerols and the lack of desensitization in MAGL-/- mice, suggest that the development of an optimized MAGL blocker offers therapeutic potential for treatment of elevated IOP.”

http://www.ncbi.nlm.nih.gov/pubmed/27333182

The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

Posted on June 23, 2016 by David

“Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer.

The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.

Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/27324222

Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol.

Posted on June 22, 2016 by David

“Growth of the pathogenic amoeboflagellate Naegleria fowleri is inhibited by delta 9-tetrahydrocannabinol (delta 9-THC).

delta 9-THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment, but does not impair amoeboid movement. Calf serum at 10 and 20% (vol/vol) reduces the antiamoeba activity of delta 9-THC.

Only 1-methoxy delta 8-tetrahydrocannabinol, of 17 cannabinoids tested, failed to inhibit growth of N. fowleri.

Antinaeglerial activity was not markedly altered by opening the pyran ring, by converting the cyclohexyl ring to an aromatic ring, or by reversing the hydroxyl and pentyl groups on the benzene ring.

delta 9-THC prevented the cytopathic effect of N. fowleri on African green monkey (Vero) cells and human epithelioma (HEp-2) cells in culture. delta 9-THC afforded modest protection to mice infected with N. fowleri.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC352928/

https://aac.asm.org/content/16/5/674?maxtoshow=&hits=80&RESULTFORMAT=&fulltext=ma

“Naegleria fowleri, colloquially known as the “brain-eating amoeba“” https://en.wikipedia.org/wiki/Naegleria_fowleri

Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid

Posted on June 22, 2016 by David

“The flowering plants of the genus Cannabis, which mainly comprises the sativa and indica species, have been recognized for medical treatment for millennia.

Although Cannabis contains nearly 500 compounds from 18 chemical classes, its physiological effects derive mainly from a family of naturally occurring compounds known as plant cannabinoids or phytocannabinoids. Of the more than 100 phytocannabinoids that have been identified in Cannabis, among the most important and widely studied are its main psychoactive constituent, Δ⁹-tetrahydrocannabinol (Δ⁹-THC), and the most important nonpsychoactive component, cannabidiol (CBD). Other biologically active phytocannabinoids that have been isolated in Cannabis include Δ⁸-THC, cannabinol, Δ⁹-tetrahydrocannabivarin, and cannabidivarin.

In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ⁹-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF).

SGF converts CBD into the psychoactive components Δ⁹-THC and Δ⁸-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.

Despite persistent challenges with dosing and administration, CBD-based therapies have a good safety profile and a potential for efficacy in the treatment of a variety of medical conditions. The rapidly evolving sciences of drug delivery and cannabinoid pharmacology may soon lead to breakthroughs that will improve access to the benefits of this pharmacological class of agents. In addition, current technologies, such as transdermal-based therapy, may be able to eliminate the potential for psychotropic effects due to this acid-catalyzed cyclization by delivering CBD through the skin and into the neutral, nonreactive environment of the systemic circulation.”

http://online.liebertpub.com/doi/10.1089/can.2015.0004

Hypothermia induced by delta9-tetrahydrocannabinol in rats with electrolytic lesions of preoptic region.

Posted on June 21, 2016 by David

“The preoptic region (POR) is a primary central site for thermoregulation. Bilateral lesions of POR disrupt thermoregulation, and in rats, produce a characteristic syndrome including hyperthermia.

delta9-Tetrahydrocannabinol (delta9-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that delta9-THC induces hypothermia at a site other than POR.

These data demonstrate that delta9-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although delta9-THC does not appear to act primarily at POR to induce hypothermia, it is evident than an intact POR plays a role in modifying the duration and magnitude of delta9-THC induced hypothermia.”

http://www.ncbi.nlm.nih.gov/pubmed/996043

Cannabinoids in the Brain: New Vistas on an Old Dilemma

Posted on June 18, 2016 by David

“The use of cannabis as a therapeutic and recreational substance goes back to thousands of years throughout Asia, Middle East, Southern Africa, and South America.

The discovery of Δ-9-tetrahydrocannabinol (Δ9-THC) by Mechoulam and Gaoni in the midsixties as the major psychoactive constituent of cannabis sativa led to another important discovery, namely, its specific binding site that was isolated and cloned in 1990. This first cannabinoid receptor was coined CB1R and triggered a number of investigations on its expression, localization, and function within the body tissue including the brain, in various species. This was followed by the discovery in 1992 of the first endocannabinoid (eCB), anandamide, followed by another cannabinoid receptor CB2R and a second endocannabinoid called 2-arachidonoylglycerol (2-AG). Later on, some of the enzymes responsible for their synthesis (N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD); diacylglycerol lipase (DAGL)) and degradation (fatty acid amide hydrolase (FAAH); monoacylglycerol lipase (MAGL)) were identified.

Studies on the expression and localization of the cannabinoid receptors in the brain have burgeoned in the last decade and have furnished valuable data on their putative involvement in various sensory-motor and cognitive functions in diverse animal species, including Man. These studies have recently received substantial attention from pharmaceutical companies as a potential source for novel treatments. Additionally, the dilemma of legalizing the use of cannabis in some countries makes the investigation on cannabinoid systems more momentous. This special issue is therefore timely and brings historical and groundbreaking novel research on the role of these cannabinoid receptors in the mammalian central nervous system (CNS).

We hope that the collected papers in this special issue will contribute to the understanding of the various mechanisms involved in the functions of the endocannabinoid system and the development of new pharmaceutical tools to treat visual disorders.”

http://www.hindawi.com/journals/np/2016/9146713/

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease.

Posted on June 12, 2016 by David

“Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment.

After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect.

Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis.

When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent.

Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord.

PERSPECTIVE:

A cross-over, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months in order to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/27286745

CANNABIS CHEMICALS STOP PROSTATE CANCER GROWTH

Posted on June 11, 2016 by David

Image result for bjc british journal of cancer

“ACTIVE chemicals in cannabis have been shown to halt prostate cancer cell growth according to research published in the British Journal of Cancer*.

Researchers from the University of Alcala, in Madrid tested the effects of the active chemicals in cannabis called cannabinoids** on three human prostate cancer cell lines – called PC-3, DU-a45 and LNCaP.

The prostate cancer cells carry molecular ‘garages’- called receptors- in which cannabinoids can ‘park’.

The scientists showed for the first time that if cannabinoids ‘park’ on a receptor called CB2, the cancer cells stop multipyling.

“This research suggest that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of the cannabinoids in treatment.”

To confirm the findings the scientists switched off the CB2 receptors – or ‘closed the garage doors’- on the prostate cells. When cannabinoids were then added to cells without the CB2 receptor, the prostate cancer cells carried on dividing and growing. This suggests that cannabinoids connect with the CB2 receptors on prostate cancer cells to stop cell division and spread.

Professor Ines Diaz-Laviada, study author at the University of Alcala said: “Our research shows that there are areas on prostate cancer cells which can recognise and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.””

http://www.nature.com/bjc/press_releases/p_r_aug09_6605248.html

https://www.news-medical.net/news/20090821/Cannabis-chemicals-stop-prostate-cancer-growth.aspx

www.thctotalhealthcare.com

Category Archives: THC (Delta-9-Tetrahydrocannabinol)