Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype.

Posted on February 19, 2017 by David

Image result for Biol Psychiatry.

“Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF₁) receptors in limbic brain regions.

Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress.

In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling.

Here, we used genetically selected Marchigian Sardinian P (msP) rats carrying an innate overexpression of CRF₁receptors to study the role of constitutive upregulation in CRF systems on amygdalar eCB function and persistent anxiety-like effects.

Treatment with an FAAH inhibitor relieves sensitized glutamatergic responses in msPs and attenuates the anxiety-like phenotype.

Pathological anxiety and stress hypersensitivity are driven by constitutive increases in CRF₁ signaling that dysregulate N-arachidonoylethanolamine signaling mechanisms and reduce neuronal inhibitory control of CeA glutamatergic synapses.”

https://www.ncbi.nlm.nih.gov/pubmed/28209423

Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.

Posted on February 19, 2017 by David

Image result for Pharmacol Ther.

“Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body. Importantly, recent observations demonstrate that 2-AG represents a quantitatively important source for arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. Accordingly, MGL-mediated 2-AG degradation affects lipid signaling by cannabinoid receptor-dependent and independent mechanisms. Recent genetic and pharmacological studies gave important insights into MGL’s role in (patho-)physiological processes, and the enzyme is now considered as a promising drug target for a number of disorders including cancer, neurodegenerative and inflammatory diseases. This review summarizes the basics of MG (2-AG) metabolism and provides an overview on the therapeutic potential of MGL.”

https://www.ncbi.nlm.nih.gov/pubmed/28213089

Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.

Posted on February 19, 2017 by David

Image result for Clin Chem Lab Med.

“Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting.

The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone.

Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids.

Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions.

As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.”

https://www.ncbi.nlm.nih.gov/pubmed/28207408

Cannabis cultivation: Methodological issues for obtaining medical-grade product.

Posted on February 19, 2017 by David

Image result for epilepsy & behavior

“As studies continue to reveal favorable findings for the use of cannabidiol in the management of childhood epilepsy syndromes and other disorders, best practices for the large-scale production of Cannabis are needed for timely product development and research purposes. The processes of two institutions with extensive experience in producing large-scale cannabidiol chemotype Cannabis crops-GW Pharmaceuticals and the University of Mississippi-are described, including breeding, indoor and outdoor growing, harvesting, and extraction methods. Such practices have yielded desirable outcomes in Cannabis breeding and production: GW Pharmaceuticals has a collection of chemotypes dominant in any one of eight cannabinoids, two of which-cannabidiol and cannabidivarin-are supporting epilepsy clinical trial research, whereas in addition to a germplasm bank of high-THC, high-CBD, and intermediate type cannabis varieties, the team at University of Mississippi has established an in vitro propagation protocol for cannabis with no detectable variations in morphologic, physiologic, biochemical, and genetic profiles as compared to the mother plants. Improvements in phytocannabinoid yields and growing efficiency are expected as research continues at these institutions.”

https://www.ncbi.nlm.nih.gov/pubmed/28202406

GPR55: a new promising target for metabolism?

Posted on February 16, 2017 by David

Image result for Journal of Molecular Endocrinology

“GPR55 is a G-protein coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.” https://www.ncbi.nlm.nih.gov/pubmed/28196832

“GPR55 – a putative “type 3” cannabinoid receptor in inflammation.” https://www.ncbi.nlm.nih.gov/pubmed/26669245

http://www.thctotalhealthcare.com/tag/gpr55/

Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.

Posted on February 14, 2017 by David

Image result for Iran Red Crescent Med J.

“A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans.

This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.).

When compared to the controls, NF significantly improved wound contraction after day 10. Histopathological and immunohistochemical findings confirmed the efficacy of the NF.

CONCLUSIONS:

A new therapeutic remedy was introduced for the treatment of burn wounds.

Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.”

https://www.ncbi.nlm.nih.gov/pubmed/28191338

Endocannabinoid-dependent protection against kainic acid-induced long-term alteration of brain oscillations in guinea pigs.

Posted on February 14, 2017 by David

Image result for Brain Research journal

“Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes.

Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage.

We employed wide frequency range (0.1-300 Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction.

To clarify whether the activation of endocannabinoid (eCB) system can influence toxic KA action, AM404, an eCB reuptake inhibitor, and URB597, an inhibitor of fatty acid amide hydrolase, were applied.

Our results demonstrate the protective potential of the eCB system during excitotoxic influences.”

https://www.ncbi.nlm.nih.gov/pubmed/28192082

Cannabinoids activate monoaminergic signaling to modulate key C. elegans behaviors.

Posted on February 12, 2017 by David

Image result for J Neurosci

“Cannabis or marijuana, a popular recreational drug, alters sensory perception and exerts a range of potential medicinal benefits.

The present study demonstrates that the endogenous cannabinoid receptor agonists, 2-arachidonoylglycerol (2-AG) and anandamide (AEA) activate a canonical cannabinoid receptor in C. elegans and also modulate monoaminergic signaling at multiple levels.

2-AG or AEA inhibit nociception and feeding through a pathway requiring the cannabinoid-like receptor, NPR-19. 2-AG or AEA activate NPR-19 directly and cannabinoid-dependent inhibition can be rescued in npr-19 null animals by the expression of a human cannabinoid receptor, CB₁, highlighting the orthology of the receptors.

Cannabinoids also modulate nociception and locomotion through an NPR-19-independent pathway requiring an α_2A-adrenergic-like octopamine receptor, OCTR-1, and a 5-HT_1A-like receptor, SER-4, that involves a complex interaction among cannabinoid, octopaminergic and serotonergic signaling. 2-AG activates OCTR-1 directly. In contrast, 2-AG does not activate SER-4 directly, but appears to enhance SER-4-dependent serotonergic signaling by increasing endogenous 5-HT.

This study defines a conserved cannabinoid signaling system in C. elegans, demonstrates the cannabinoid-dependent activation of monoaminergic signaling and highlights the advantages of studying cannabinoid signaling in a genetically-tractable whole animal model.

SIGNIFICANCE STATEMENTCannabis sativa causes euphoria and exerts a wide range of medicinal benefits. For years, cannabinoids have been studied at the cellular level using tissue explants with conflicting results. To better understand cannabinoid signaling, we have used the C. elegans model to examine the effects of cannabinoids on behavior. The present study demonstrates that mammalian cannabinoid receptor ligands activate a conserved cannabinoid signaling system in C. elegans and also modulate monoaminergic signaling, potentially impacting an array of disorders, including anxiety and depression. This study highlights the potential role of cannabinoids in modulating monoaminergic signaling, and the advantages of studying cannabinoid signaling in a genetically-tractable, whole-animal model.”

https://www.ncbi.nlm.nih.gov/pubmed/28188220

Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic.

Posted on February 7, 2017 by David

Image result for trends in neurosciences

“Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.”

https://www.ncbi.nlm.nih.gov/pubmed/28162799

The effects of synthetic cannabinoids on executive function.

Posted on February 6, 2017 by David

Image result for Psychopharmacology (Berl)

“There is a growing use of novel psychoactive substances (NPSs) including synthetic cannabinoids. Synthetic cannabinoid products have effects similar to those of natural cannabis but the new synthetic cannabinoids are more potent and dangerous and their use has resulted in various adverse effects. The purpose of the study was to assess whether persistent use of synthetic cannabinoids is associating with impairments of executive function in chronic users.

Synthetic cannabinoid users performed significantly worse than both recreational and non-cannabis users on the n-back task (less accuracy), the Stroop task (overall slow responses and less accuracy), and the long-term memory task (less word recall). Additionally, they have also shown higher ratings of depression and anxiety compared with both recreational and non-users groups.

This study showed impairment of executive function in synthetic cannabinoid users compared with recreational users of cannabis and non-users. This may have major implications for our understanding of the long-term consequences of synthetic cannabinoid based drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/28160034