Determination of cannabinoids in hemp nuts products in Taiwan by HPLC-MS/MS coupled with chemometric analysis: Quality evaluation and a pilot human study.

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“Hemp nuts are mature cannabis seeds obtained after hulling and stir-frying that are commonly used in traditional Chinese medicine for treating functional constipation. In this work, we screened hemp nut products, classified them, and verified the legality of consuming them.

A total of 18 products were purchased from Taiwan, China and Canada. Validated high-performance liquid chromatography with tandem mass spectrometry methods were developed for analyzing the cannabinoid (i.e., Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol) content of the products and the concentration of urinary 11-nor-9-carboxy-THC.

Chemometric techniques, namely hierarchical clustering analysis (HCA) and principal component analysis (PCA), were applied for rapidly classifying 11 concentrated powder products in Taiwan. A pilot human study comprising single and multiple administrations of a product with 1.5 µg/g of THC was conducted to examine the urinary 11-nor-9-carboxy-THC concentration. Through optimization of 32 full factorial design, using 60% isopropanol as the extraction solvent exhibited the highest yield ofcannabinoids and was applied as the optimal condition in further analysis.

The results of HCA and PCA on quality evaluation were in well agreement; however, the tested products possessed distinct CBD-to-THC ratios which ranged widely from 0.1:1 to 46.8:1. Particularly, the products with CBD-to-THC ratios higher than 1:1 were the majority in Taiwan.

Our data suggested that all the tested hemp nut products met the Taiwan restriction criteria of 10 µg/g of THC. We propose a usual consumption amount of hemp nut products in Taiwan would unlikely to violate the cut-off point of 15 ng/mL of urinary 11-nor-9-carboxy-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/27590030

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses

Psychopharmacology

“Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.”  http://link.springer.com/article/10.1007/s00213-016-4383-x

“Cannabis reduces short-term motivation to work for money”  https://www.sciencedaily.com/releases/2016/09/160901211303.htm

Selective modulator of cannabinoid receptor type 2 reduces memory impairment and infarct size during cerebral hypoperfusion and vascular dementia.

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“Vascular dementia is the highly devastating neurodegenerative disorder after Alzheimer’s disease (AD) and mainly found in aged people but the effectual therapeutic target is still not there.

Chronic cerebral hypoperfusion (CCH) has been broadly found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive deteriorate on.

This study has been framed to examine the role of a selective agonist of cannabinoid receptor type 2(CB2); 1-phenylisatin in CCH induced VaD.

These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin.

Hence, it may be suggested that modulation of cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD.

Therefore, selective agonists of CB2 receptors may be a potential research target for the alleviation of VaD.”

http://www.ncbi.nlm.nih.gov/pubmed/27586843

Peltatoside Isolated from Annona crassiflora Induces Peripheral Antinociception by Activation of the Cannabinoid System.

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“Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine.

This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction.

Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action.

Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.”

http://www.ncbi.nlm.nih.gov/pubmed/27574895

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Endocannabinoid mechanism for orofacial antinociception induced by electroacupuncture in acupoint St36 in rats.

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“This study was conducted with the aim of evaluating whether electroacupuncture (EA) at acupoint St36 could produce antinociception through the activation of an endocannabinoid mechanism.

CONCLUSION:

This study demonstrated for the first time that the CB1 cannabinoid receptor participates in the antinociceptive effect induced by EA.”

http://www.ncbi.nlm.nih.gov/pubmed/27573715

Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18.

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“G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology.”

http://www.ncbi.nlm.nih.gov/pubmed/27572937

“Cannabinoid receptor activates spermatozoa”               http://medicalxpress.com/news/2016-08-cannabinoid-receptor-spermatozoa.html

Cannabinoid 2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy.

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“Proliferative vitreoretinopathy (PVR) can develop after ocular trauma or inflammation and is a common complication of surgery to correct retinal detachment.

Currently, there are no pharmacological treatments for PVR.

Cannabinoids acting at cannabinoid 2 receptor (CB2R) can decrease inflammation and fibrosis.

The objective of this study was to examine the anti-inflammatory actions of CB2R as a candidate novel therapeutic target in experimental PVR.

In conclusion, our results indicate that intervention at early stage PVR with CB2R agonists reduces ocular inflammation and disease severity.

CB2R may represent a therapeutic target to prevent PVR progression and vision loss.”

http://www.ncbi.nlm.nih.gov/pubmed/27569993

Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures.

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“The endocannabinoid system has been implicated in the modulation of adult neurogenesis.

Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures.

There is an emerging consensus that endocannabinoid signaling plays a major role in adult neurogenesis.

Cannabinoids act on at least two types of receptors, the type 1 and type 2 cannabinoid receptors (CB1R and CB2R), which are, respectively, predominantly distributed in the central nervous system (CNS) and immune system, although some studies have described the presence of low levels of CB2R in the brain.

Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

 Collectively, CB1R agonists render neurons less excitable and thus promote neuroprotection.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660454/

Targeting the endocannabinoid system: future therapeutic strategies.

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“The endocannabinoid system (ECS) is involved in many physiological regulation pathways in the human body, which makes this system the target of many drugs and therapies. In this review, we highlight the latest studies regarding the role of the ECS and the drugs that target it, with a particular focus on the basis for the discovery of new cannabinoid-based drugs. In addition, we propose some key steps, such as the creation of a cannabinoid-receptor interaction matrix (CRIM) and the use of metabolomics, towards the development of improved and more specific drugs for each relevant disease.”

http://www.ncbi.nlm.nih.gov/pubmed/27554802

Orchestrated activation of mGluR5 and CB1 promotes neuroprotection.

“The metabotropic glutamate receptor 5 (mGluR5) and the cannabinoid receptor 1 (CB1) exhibit a functional interaction, as CB1 regulates pre-synaptic glutamate release and mGluR5 activation increases endocannabinoid synthesis at the post-synaptic site. Since both mGluR5 and CB1promote neuroprotection, we delineated experiments to investigate a possible link between CB1 and mGluR5 activation in the induction of neuroprotection using primary cultured corticostriatal neurons. We find that either the pharmacological blockade or the genetic ablation of either mGluR5 or CB1 can abrogate both CB1– and mGluR5-mediated neuroprotection against glutamate insult. Interestingly, decreased glutamate release and diminished intracellular Ca2+ do not appear to play a role in CB1 and mGluR5-mediated neuroprotection. Rather, these two receptors work cooperatively to trigger the activation of cell signaling pathways to promote neuronal survival, which involves MEK/ERK1/2 and PI3K/AKT activation. Interestingly, although mGluR5 activation protects postsynaptic terminals and CB1 the presynaptic site, intact signaling of both receptors is required to effectively promote neuronal survival. In conclusion, mGluR5 and CB1 act in concert to activate neuroprotective cell signaling pathways and promote neuronal survival.”