Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

Posted on July 12, 2016 by David

cpb

“Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol.

Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC).

The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG.

The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene.

The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.

There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/20118579

Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.

Posted on July 10, 2016 by David

“Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.” http://www.ncbi.nlm.nih.gov/pubmed/2897447

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

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

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

RNA-seq analysis of delta -9-tetrahydrocannabinol-treated T cells reveals altered gene expression profiles that regulate immune response and cell proliferation.

Posted on June 10, 2016 by David

“Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. Δ9-tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells.

In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4+ T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4+ T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down regulated by THC. On the other hand miR-146a which has been shown to induce apoptosis was up regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC.

In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation.”

http://www.ncbi.nlm.nih.gov/pubmed/27268054

Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

Posted on June 4, 2016 by David

“Most human Δ⁹-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano^®, e-cigarettes) further stimulates a need for rodent models of this route of administration.

This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a polyethylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers.

The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels.

This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt “vaping” for the administration of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/27256501

Need for Methods to Investigate Endocannabinoid Signaling.

Posted on June 2, 2016 by David

“Endocannabinoids (eCBs) are endogenous lipids able to activate cannabinoid receptors, the primary molecular targets of the cannabis (Cannabis sativa) active principle Δ(9)-tetrahydrocannabinol. During the last 20 years, several N-acylethanolamines and acylesters have been shown to act as eCBs, and a complex array of receptors, metabolic enzymes, and transporters (that altogether form the so-called eCB system) has been shown to finely tune their manifold biological activities. It appears now urgent to develop methods and protocols that allow to assay in a specific and quantitative manner the distinct components of the eCB system, and that can properly localize them within the cell. A brief overview of eCBs and of the proteins that bind, transport, and metabolize these lipids is presented here, in order to put in a better perspective the relevance of methodologies that help to disclose molecular details of eCB signaling in health and disease. Proper methodological approaches form also the basis for a more rationale and effective drug design and therapeutic strategy to combat human disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27245886

www.thctotalhealthcare.com

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