“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
Tag Archives: cannabis
Cannflavin A and B, prenylated flavones from Cannabis sativa L.
“Two novel prenylated flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract of Cannabis sativa L. Both compounds inhibited prostaglandin E2 production by human rheumatoid synovial cells in culture.”
Isolation from Cannabis sativa L. of cannflavin–a novel inhibitor of prostaglandin production.
“The isolation from Cannabis sativa L. of an inhibitor of prostaglandin (PG) E2 production by cultured rheumatoid synovial cells is described. This agent, for which the name Cannflavin has been coined, is distinct from cannabinoids on the basis of isolation procedure, preliminary structural analysis and biological properties. The activity of Cannflavin has been compared with several established anti-inflammatory drugs and the major cannabinoids.”
Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase
“Hemp seeds are of great nutritional value, containing all essential amino acids and fatty acids in sufficient amount and ratio to meet the dietary human demand.
Hemp seeds do not contain cannabinoids, and because of their high contents of ω-3 fatty acids, are enjoying a growing popularity as a super-food to beneficially affect chronic inflammation.
Seeds also lack the typical phenolics of hemp leaves and inflorescences, but we found that sprouting, while not triggering the production of cannabinoids, could nevertheless induce the production of the anti-inflammatory prenylflavonoids cannflavins A and B.
This effect was especially marked in Ermo, a cannabinoid-free variety of Cannabis sativa L. Microsomal prostaglandin E2 synthase (mPGES-1) and 5-lipoxygenase (5-LO) were identified as the molecular targets of cannflavins A and B, solving an almost three-decade old uncertainty on the mechanism of their the anti-inflammatory activity.
No change on the fatty acid profile was observed during sprouting, and the presence of lipophilic flavonoids combines with the high concentration of ω-3 essential acids to qualify sprouts from Ermo as a novel anti-inflammatory hemp food product worth considering for mass production and commercial development.”
http://www.sciencedirect.com/science/article/pii/S2213434414000176
Cannabinoid signalling in glioma cells
“Cannabinoids, originally derived from Cannabis sativa, as well as their endogenous and synthetic counterparts, were shown to induce apoptosis of glioma cells in vitro and tumour regression in vivo via their specific receptors, cannabinoid receptors CB1 and/or CB2.
CB2 are abnormally expressed in human gliomas and glioma cell lines. Most of the analysed gliomas expressed significant levels of CB2 receptor and the extent of CB2 expression in the tumour specimens was related to tumour malignancy.
A synthetic cannabinoid, WIN 55,212-2, down-regulated the Akt and Erk signalling pathways in C6 glioma cells that resulted in reduction of phosphorylated Bad levels, mitochondrial depolarization and activation of caspase cascade leading to apoptosis.
We examined whether synthetic cannabinoids with different receptor specificity: WIN55,212-2 (a non-selective CB1/CB2 agonist) and JWH133 (a CB2-selective agonist) affect survival of four human glioma cell lines and three primary human glioma cell lines.
WIN-55,212-2 decreased cell viability in all examined cell lines and induced cell death. Susceptibility of the cells to JWH133 treatment correlated with the CB2 expression. Cannabinoids triggered a decrease of mitochondrial membrane potential, cleavage of caspase-9 and effector caspases.
Induction of cell death by cannabinoid treatment led to the generation of a pro-apoptotic sphingolipid ceramide and disruption of signalling pathways crucial for regulation of proliferation and survival. Increased ceramide levels induced ER-stress and autophagy in drug-treated glioblastoma cells.
We conclude that cannabinoids are efficient inhibitors of human glioma cells growth, once the cells express specific type of cannabinoid receptor.”
http://springerplus.springeropen.com/articles/10.1186/2193-1801-4-S1-L11
Does cannabidiol have a role in the treatment of schizophrenia?
“Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant.
In this regard, cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia.
However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia.”
The endocannabinoid system – a target for the treatment of LUTS?
“Lower urinary tract symptoms (LUTS) are common in all age groups and both sexes, resulting in tremendous personal suffering and a substantial burden to society.
Antimuscarinic drugs are the mainstay of symptom management in patients with LUTS, although their clinical utility is limited by the high prevalence of adverse effects, which often limit patients’ long-term adherence to these agents.
Data from controversial studies in the 1990s revealed the positive effects of marijuana-based compounds on LUTS, and sparked an interest in the possibility of treating bladder disorders with cannabis.
Increased understanding of cannabinoid receptor pharmacology and the discovery of endogenous ligands of these receptors has prompted debate and further research into the clinical utility of exogenous cannabinoid receptor agonists relative to the unwanted psychotropic effects of these agents.
Currently, the endocannabinoid system is considered as a potential drug target for pharmacological management of LUTS, with a more favourable adverse event profile than antimuscarinic agents.”
Researcher explores effects of cannabinoids on blood pressure
“Hypertension — or high blood pressure — is a long-term, high-risk condition for millions of people worldwide.
At the moment, synthetic beta-blockers are one of the most common drugs prescribed to treat hypertension.
But what if a natural drug, marijuana, which has been known for 5,000 years, could be used in the treatment of high blood pressure?
Andrei Derbenev, associate professor of physiology in the Tulane University School of Medicine, recently received a four-year, $1.5 million research grant from the National Institutes of Health to study how cannabinoids — the compounds of cannabis (another name for marijuana) — affect a brain stem area involved in blood pressure control.
His research may have important clinical applications for the treatment of hypertension.
He is identifying the cells in the sympathetic nervous system linked to the kidneys, a key organ in hypertension. (The sympathetic nervous system is the part of the autonomic nervous system that stimulates the body’s “fight or flight” response. Overactivity of the sympathetic nervous system is a cause of high blood pressure.)
He and his research team are studying the effect of exogenous cannabinoids — from the marijuana plant — and endogenous cannabinoids —those naturally produced within the body.
Cannabis “has lots of different chemicals inside. Some of them are painkillers. Some of them, we don’t know what they are doing.”
People ask Derbenev all the time: Is marijuana good? Is it bad? But the debate, he says, should be, instead, “Which works? Which does not work?”
About a decade ago, Derbenev led a study about the effect of cannabinoids on the parasympathetic nervous system, the part of the autonomic nervous system that stimulates the body to “rest and digest.” In that investigation, his team showed the mechanism by which cannabis can reduce digestive spasms and thus decrease vomiting. It’s a finding of great interest to cancer patients experiencing nausea while undergoing chemotherapy.”
https://news.tulane.edu/news/researcher-explores-effects-cannabinoids-blood-pressure
Medical Marijuana for Epilepsy?
“Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring.”
Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis.
“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.”