Category Archives: Uncategorized

CB1 cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways.

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“Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation.

In a mouse model, we observed that activation of the cannabinoid receptor (CB)1during in vitro oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of the CB1 receptor, in vivo oocyte maturation was impaired and embryo development delayed. The CB2receptor was unable to rescue these effects. Finally, we confirmed abnormal oocyte maturation rather than impaired embryonic transport through the oviduct in CB1 knockouts.

Our data suggest that cannabinoid agonists may be useful in vitro maturation supplements. For in vitro fertilization patients intolerant to gonadotropins, this could be a promising and only option.”

https://www.ncbi.nlm.nih.gov/pubmed/28428264

Medical Marijuana Laws May Be Associated With A Decline In The Number Of Prescriptions For Medicaid Enrollees

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Health Affairs

“In the past twenty years, twenty-eight states and the District of Columbia have passed some form of medical marijuana law. Using quarterly data on all fee-for-service Medicaid prescriptions in the period 2007–14, we tested the association between those laws and the average number of prescriptions filled by Medicaid beneficiaries. We found that the use of prescription drugs in fee-for-service Medicaid was lower in states with medical marijuana laws than in states without such laws in five of the nine broad clinical areas we studied. If all states had had a medical marijuana law in 2014, we estimated that total savings for fee-for-service Medicaid could have been $1.01 billion. These results are similar to those in a previous study we conducted, regarding the effects of medical marijuana laws on the number of prescriptions within the Medicare population. Together, the studies suggest that in states with such laws, Medicaid and Medicare beneficiaries will fill fewer prescriptions.”      https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2016.1135?journalCode=hlthaff

“Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D” https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2015.1661

“US states that allow medical marijuana see drop in prescriptions for other drugs, study finds. American states that allow patients access to medical marijuana are seeing fewer prescriptions per doctor for pharmaceutical drugs in several disease categories where marijuana is a potential treatment, a study in Health Affairs has found.” http://www.bmj.com/content/354/bmj.i3942.full

Anandamide and 2-AG Are Endogenously Present within the Laterodorsal Tegmental Nucleus: Functional Implications for a role of eCBs in arousal.

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“Previously, we presented electrophysiological evidence for presence in mice brain slices of functional cannabinoid type I receptors (CB1Rs) within the laterodorsal tegmentum (LDT), a brain stem nucleus critical in control of arousal and rapid eye movement (REM) sleep. Further, using pharmacological agents, we provided data suggestive of the endogenous presence of cannabinoids (CBs) acting at LDT CB1Rs. However, in those studies, we were unable to identify the type(s) of CB ligands endogenously present in the LDT, and this information has not been provided elsewhere. Accordingly, we used the highly-sensitive liquid chromatography/mass spectrometry (LC-MS) method to determine whether N-arachidonoylethanolamide (Anandamide or AEA) and 2-arachidonyl glycerol (2-AG), which are both endogenous CB ligands acting at CB1Rs, are present in the LDT. Mice brain tissue samples of the LDT were assayed using ion trap LC-MS in selected ion monitoring mode. Chromatographic analysis and product-ion MS scans identified presence of the CBs, AEA and 2-AG, from LDT mouse tissue. Data using the LC-MS method show that AEA and 2-AG are endogenously present within the LDT and when coupled with our electrophysiological findings, lead to the suggestion that AEA and 2-AG act at electropharmacologically-demonstrated CB1Rs in this nucleus. Accordingly, AEA and 2-AG likely play a role in processes governed by the LDT, including control of states of cortical gamma band activity seen in alert, aroused states, as well as cortical and motor activity characteristic of REM sleep.”

https://www.ncbi.nlm.nih.gov/pubmed/28404451

Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: an fMRI pilot study.

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“Self-report studies indicate that cannabis could increase sexual desire in some users.

We hypothesized that intoxication increases activation of brain areas responsive to visual erotica, which could be useful in the treatment of hypoactive sexual desire disorder, a condition marked by a lack of sexual desire.

The aim of this study is to assess the aphrodisiacal properties of cannabis.

Cannabis intoxication increases activation of the right nucleus accumbens to erotic stimuli. This effect is limited to users whose prolactin is not elevated in response to intoxication.   This effect may be useful in the treatment of low sexual desire.”

https://www.ncbi.nlm.nih.gov/pubmed/28401285

Antibacterial Properties of Hemp and Other Natural Fibre Plants: A Review

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“Intervention against pathogenic bacteria using natural plant material has a long history. Plant materials also have been widely used as fillers and/or reinforcers in polymer composites. Some natural fibre plants, such as hemp, are regarded to possess antibacterial activity against a wide range of pathogenic bacteria. Innovative applications can be explored if they are incorporated in polymer composites. This review aims to compile the relevant investigations on antibacterial activity of hemp and other fibre plants such as jute, flax, kenaf, sisal, and bamboo. The antibacterial character might be contributed from cannabinoids, alkaloids, other bioactive compounds, or phenolic compounds of lignin. This review is intended to encourage utilization of hemp and other natural fibre plants in value-added diversified products. Some potential applications are also discussed.” https://www.researchgate.net/publication/270502952_Antibacterial_Properties_of_Hemp_and_Other_Natural_Fibre_Plants_A_Review
“Antibacterial Properties of Hemp and Other Natural Fibre Plants: A Review”  http://ojs.cnr.ncsu.edu/index.php/BioRes/article/view/BioRes_09_2_Khan_Antibacterial_Hemp_Fibre_Review

Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose-Fed Rats.

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“To investigate the effect of metabolic syndrome on the bladder cannabinoid receptors 1 and 2 (CB1/CB2) expression and function in the fructose-fed rats (FR).

CONCLUSION:

CB1/CB2 receptors mediate rat bladder relaxation through the PKA and KATP pathway. The CB1 receptor may play a more prominent role. The response is decreased in the FR bladder due to reduced expressions of the cannabinoid receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/28386998

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep.

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“A prior epidemiological study identified a reduction in opioid overdose deaths in US states that legalized medical cannabis (MC). One theory to explain this phenomenon is a potential substitution effect of MC for opioids. This study evaluated whether this substitution effect of MC for opioids also applies to other psychoactive medications.

New England dispensary members ( n = 1,513) completed an online survey about their medical history and MC experiences. Among respondents that regularly used opioids, over three-quarters (76.7%) indicated that they reduced their use since they started MC. This was significantly ( p < 0.0001) greater than the patients that reduced their use of antidepressants (37.6%) or alcohol (42.0%). Approximately two-thirds of patients decreased their use of anti-anxiety (71.8%), migraine (66.7%), and sleep (65.2%) medications following MC which significantly ( p < 0.0001) exceeded the reduction in antidepressants or alcohol use. The patient’s spouse, family, and other friends were more likely to know about their MC use than was their primary care provider.

In conclusion, a majority of patients reported using less opioids as well as fewer medications to treat anxiety, migraines, and sleep after initiating MC. A smaller portion used less antidepressants or alcohol. Additional research is needed to corroborate these self-reported, retrospective, cross-sectional findings using other data sources.”

https://www.ncbi.nlm.nih.gov/pubmed/28372506

Binding Site Characterization of AM1336, a Novel Covalent Inverse Agonist at Human Cannabinoid 2 Receptor, Using Mass Spectrometric Analysis.

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“Cannabinoid 2 receptor (CB2R), a Class A G-protein coupled receptor (GPCR), is a promising drug target in a wide array of pathological conditions. Rational drug design has been hindered due to our poor understanding of the structural features involved in ligand binding. Binding of a high-affinity biarylpyrazole inverse agonist AM1336 to a library of the human CB2 receptor (hCB2R) cysteine-substituted mutants provided indirect evidence that two cysteines in transmembrane helix-7 (H7) were critical for the covalent attachment. Here, we used proteomics analysis of the hCB2R with bound AM1336 to directly identify peptides with covalently attached ligand and applied in-silico modeling for visualization of the ligand-receptor interactions. The hCB2R, with affinity tags (FlaghCB2His6), was produced in a baculovirus-insect cell expression system and purified as a functional receptor using immunoaffinity chromatography. Using mass spectrometry-based bottom-up proteomic analysis of the hCB2R-AM1336 we identified a peptide with AM1336 attached to the cysteine C284(7.38) in H7. The hCB2R homology model in lipid bilayer accommodated covalent attachment of AM1336 to C284(7.38), supporting both biochemical and mass spectrometric data. This work consolidates proteomics data and in-silico modeling, and integrates with our ligand-assisted protein structure (LAPS) experimental paradigm to assist in structure-based design of cannabinoid antagonist/inverse agonists.”

https://www.ncbi.nlm.nih.gov/pubmed/28374590

Comparative antinociceptive effect of arachidonylcyclopropylamide, a cannabinoid 1 receptor agonist & lignocaine, a local anaesthetic agent, following direct intrawound administration in rats.

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“Treatment of inflammatory pain with opioids is accompanied by unpleasant and, at times, life-threatening side effects.

Cannabis produces antinociception as well as psychotropic effects. It was hypothesized that peripheral cannabinoid receptors outside the central nervous system could be selectively activated for relief of pain.

This study was undertaken to measure the antinociceptive effect of type 1 cannabinoid receptor (CB1r) agonist arachidonylcyclopropylamide (ACPA) in a rat model of inflammatory pain after intrawound administration and the effects were compared with lignocaine.

Lignocaine attenuated evoked pain behaviour whereas ACPA decreased guarding score. This difference was likely due to blockade of sodium ion channels and the activation of peripheral CB1r, respectively. Central side effects were absent after ACPA treatment. Further studies need to be done to assess the effect of ACPA treatment in clinical conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/28361827

Regulation of Cell Surface CB2 Receptor during Human B Cell Activation and Differentiation.

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“Cannabinoid receptor type 2 (CB2) is the primary receptor pathway mediating the immunologic consequences of cannabinoids.

We recently reported that human peripheral blood B cells express CB2 on both the extracellular membrane and at intracellular sites, where-as monocytes and T cells only express intracellular CB2. To better understand the pattern of CB2 expression by human B cells, we examined CD20+ B cells from three tissue sources.

Both surface and intracellular expression were present and uniform in cord blood B cells, where all cells exhibited a naïve mature phenotype (IgD+/CD38Dim). While naïve mature and quiescent memory B cells (IgD–/CD38–) from tonsils and peripheral blood exhibited a similar pattern, tonsillar activated B cells (IgD–/CD38+) expressed little to no surface CB2.

We hypothesized that regulation of the surface CB2 receptor may occur during B cell activation. Consistent with this, a B cell lymphoma cell line known to exhibit an activated phenotype (SUDHL-4) was found to lack cell surface CB2 but express intracellular CB2.

Furthermore, in vitro activation of human cord blood resulted in a down-regulation of surface CB2 on those B cells acquiring the activated phenotype but not on those retaining IgD expression. Using a CB2 expressing cell line (293 T/CB2-GFP), confocal microscopy confirmed the presence of both cell surface expression and multifocal intracellular expression, the latter of which co-localized with endoplasmic reticulum but not with mitochondria, lysosomes, or nucleus.

Our findings suggest a dynamic multi-compartment expression pattern for CB2 in B cells that is specifically modulated during the course of B cell activation.”

 https://www.ncbi.nlm.nih.gov/pubmed/28364261