Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis.

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“Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis…

Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis.

These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25849525

The role of the endocannabinoid system in pain.

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“Preparations of the Cannabis sativa plant have been used to analgesic effect for millenia, but only in recent decades has the endogenous system responsible for these effects been described.

The endocannabinoid (EC) system is now known to be one of the key endogenous systems regulating pain sensation, with modulatory actions at all stages of pain processing pathways.

The EC system is composed of two main cannabinoid receptors (CB1 and CB2) and two main classes of endogenous ligands or endocannabinoids (ECs).

The receptors have distinct expression profiles, with CB1 receptors found at presynaptic sites throughout the peripheral and central nervous systems (PNS and CNS, respectively), whilst CB2 receptor is found principally (but not exclusively) on immune cells.

The endocannabinoid ligands are lipid neurotransmitters belonging to either the N-acyl ethanolamine (NAEs) class, e.g. anandamide (AEA), or the monoacylglycerol class, e.g. 2-arachidonoyl glycerol (2-AG).

Both classes are short-acting transmitter substances, being synthesised on demand and with signalling rapidly terminated by specific enzymes. ECs acting at CB1 negatively regulate neurotransmission throughout the nervous system, whilst those acting at CB2 regulate the activity of CNS immune cells.

Signalling through both of these receptor subtypes has a role in normal nociceptive processing and also in the development resolution of acute pain states.

In this chapter, we describe the general features of the EC system as related to pain and nociception and discuss the wealth of preclinical and clinical data involving targeting the EC system with focus on two areas of particular promise: modulation of 2-AG signalling via specific enzyme inhibitors and the role of spinal CB2 in chronic pain states.”

http://www.ncbi.nlm.nih.gov/pubmed/25846617

http://www.thctotalhealthcare.com/category/pain-2/

Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid chromatography coupled with acidic potassium permanganate chemiluminescence detection.

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Journal of Separation Science

“Widely known for its recreational use, the cannabis plant also has the potential to act as an antibacterial agent in the medicinal field.

The analysis of cannabis plants/products in both pharmacological and forensic studies often requires the separation of compounds of interest and/or accurate identification of the whole cannabinoid profile.

In order to provide a complete separation and detection of cannabinoids, a new two-dimensional liquid chromatography method has been developed using acidic potassium permanganate chemiluminescence detection, which has been shown to be selective for cannabinoids.

This was carried out using a Luna 100 Å CN column and a Poroshell 120 EC-C18 column in the first and second dimension respectively. The method has utilised a large amount of the available separation space with a spreading angle of 48.4° and a correlation of 0.66 allowing the determination of more than 120 constituents and mass spectral identification of ten cannabinoids in a single analytical run.

The method has potential to improve research involved in the characterisation of sensitive, complex matrices. ”

http://www.ncbi.nlm.nih.gov/pubmed/25845561

http://onlinelibrary.wiley.com/doi/10.1002/jssc.201500088/abstract

Major urinary protein 1 interacts with cannabinoid receptor type 1 in fatty acid-induced hepatic insulin resistance in a mouse hepatocyte model.

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“Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids.

Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance.

The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA)…

Altogether, these findings suggest that the anti-HIR effect of AM251 via improvement of mitochondrial functions might occur in a MUP1-dependent manner.”

http://www.ncbi.nlm.nih.gov/pubmed/25843798

The interactive role of cannabinoid and vanilloid systems in hippocampal synaptic plasticity in rats.

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“Long-term potentiation (LTP) has been most thoroughly studied in the hippocampus, which has a key role in learning and memory. Endocannabinoids are one of the endogenous systems that modulate this kind of synaptic plasticity. The activation of the vanillioid system has also been shown to mediate synaptic plasticity in the hippocampus. In addition, immunohistochemical studies have shown that cannabinoid receptor type 1 (CB1) and vanilloid receptor 1 (TRPV1) are closely located in the hippocampus.

It seems that agonists of the vanilloid system modulate cannabinoid outputs that cause an increase in synaptic plastisity, while in contemporary consumption of two agonist, TRPV1 agonist can change production of endocannabinoid, which in turn result to enhancement of LTP induction. These findings suggest that the two systems may interact or share certain common signaling pathways in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/25843413

Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.

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“A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis.

In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis…

This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain.

This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25843054

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

Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

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“The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles.

Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin…

These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/25839900

What is Pinene and What Are the Benefits of this Cannabis Terpene?

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“Pinene (or α-pinene) is an aromatic compound commonly found in cannabis that smells a lot like – you guessed it – a forest of pine trees.” http://www.leafly.com/news/cannabis-101/what-is-pinene-and-what-are-the-benefits-of-this-cannabis-terpene

“Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity. Previous studies have suggested that α-pinene, a common volatile plant metabolite, may have anti-inflammatory effects in human chondrocytes, thus exhibiting potential antiosteoarthritic activity… The data obtained show isomer- and enantiomer-selective anti-inflammatory and anticatabolic effects of α-pinene in human chondrocytes, (+)-α-pinene being the most promising for further studies to determine its potential value as an antiosteoarthritic drug.” http://www.ncbi.nlm.nih.gov/pubmed/24455984

“The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis. In the present study, the therapeutic effect and underlying mechanism of α-pinene (α-PN) in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model were investigated… Taken together, we suggest that α-PN is a promising anti-allergic agent and may be useful in the clinical management of AR.” http://www.ncbi.nlm.nih.gov/pubmed/25242385

“Structural and Thermodynamic Basis of (+)-α-Pinene Binding to Human Cytochrome P450 2B6… (+)-α-Pinene is a monoterpene hydrocarbon that is widely distributed in the environment and a potent P450 2B inhibitor. “ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754432/

“Inhibitory effects of α-pinene on hepatoma carcinoma cell proliferation… Taken together, these findings indicate that α-pinene may be useful as a potential anti-tumor drug.” http://www.ncbi.nlm.nih.gov/pubmed/24815485

“Synergistic Antitumor Effect of α-pinene and β-pinene with Paclitaxel against Non-small-cell Lung Carcinoma (NSCLC).” http://www.ncbi.nlm.nih.gov/pubmed/25188609

“Biological activities of α-pinene and β-pinene enantiomers. The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells.” http://www.ncbi.nlm.nih.gov/pubmed/23442885

“Microbial Synthesis of Pinene” http://pubs.acs.org/doi/abs/10.1021/sb4001382

“Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells.” http://www.ncbi.nlm.nih.gov/pubmed/15066217

“Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis. Acute pancreatitis (AP) is a complicated inflammatory disease that has an unknown underlying pathogenesis. Because alpha-pinene can modulate inflammation, we examined whether alpha-pinene plays a role in AP… These findings suggest that alpha-pinene has an anti-inflammatory effect during cerulein-induced AP.” http://www.ncbi.nlm.nih.gov/pubmed/22982349

Antiepileptic potential of cannabidiol analogs.

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“In audiogenic seizure (AGS) susceptible rats, the acute (intraperitoneal and intravenous) dose-response effects of (–)-cannabidiol (CBD) for preventing AGS and for causing rototod neurotoxicity (ROT) were determined.

Also, the anti-AGS and ROT effects of 10 CBD analogs, given in intravenous doses equivalent to the AGS-ED50 (15 mg/kg) and ROT-ID50 (31 mg/kg) of CBD, were ascertained.

Compared to CBD, (–)-CBD diacetate and (–)-4-(2′-olivetyl)-alpha-pinene were equally effective whereas (–)-CBD monomethyl ether, (–)-CBD dimethyl ether, (–)-3′-acetyl-CBD monoacetate, (+)-4-(2′-olivetyl)-alpha-pinene, (–)-and (+)-4-(6′-olivetyl)-alpha-pinene, (+/-)-AF-11, and olivetol were less effective anticonvulsants. Except for (–)- and (+)-4-(2′-olivetyl)-alpha-pinene and olivetol, all analogs showed less ROT than CBD.

Also, CBD and all analogs were not active in tetrahydrocannabinol seizure-susceptible rabbits, the latter a putative model of cannabinoid psychoactivity in humans.

These data suggest anticonvulsant requirements of 2 free phenolic hydroxyl groups, exact positioning of the terpinoid moiety in the resorcinol system and correct stereochemistry.

Moreover, findings of separation of anticonvulsant from neurotoxic and psychoactive activities, notably with CBD diacetate, suggest that additional structural modifications of CBD may yield novel antiepileptic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/7298873

http://www.thctotalhealthcare.com/category/epilepsy-2/

Clearing the Smokescreen: The Current Evidence on Cannabis Use

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“The therapeutic potential of cannabis is one of the factors driving the push for legalization of cannabis use…

Decisions regarding the legal status of cannabis have long been framed (for the public at least) with reference to the perceived health risks and harms associated with use. Yet, drug policy and legislation relating to the use of cannabis are rarely based on the scientific evidence of the known risks and harms.

There are many reasons for this discrepancy, with the politicization of cannabis use, where ideology and moralizing are given precedence over the science, being one.

Thus, we begin this research topic with Aggarwal discussion of how such politicization has contributed to the current smokescreen that is obscuring our understanding of cannabis, including the impact it has on the ability of researchers to collect and disseminate accurate information about the effects of cannabis use.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358058/