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Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still…

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. 2020 Jan 23;10:1570.

doi: 10.3389/fphar.2019.01570. eCollection 2019.

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Tao Huang et al. Front Pharmacol. .

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Abstract

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. In vivo studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, χ2 test, and Student t-test were used to interpret the clinical and preclinical data. Changes in levels of circulating oleamide and its derivatives negatively correlate with improvement in complete spontaneous bowel movement (CSBM) in the MZRW group (Pearson r = -0.59, p = 0.00057). The same did not hold true for either Senna or placebo groups. Oleamide is a known regulator of intestinal motility. MZRW treatment resulted in reduced levels of circulating oleamide in FC patients. Experimental verification showed that MZRW attenuated oleamide-induced slow intestinal motility in mice. MZRW decreased oleamide levels in serum, ileum, and colon in normal mice, but increased expression of colonic fatty acid amide hydrolase (FAAH). In conclusion, MZRW improved bowel movement in FC by down-regulating oleamide, possibly by enhancing FAAH-mediated degradation. Our findings suggest a novel therapeutic strategy for FC.

Keywords: MaZiRenWan; fatty acid amide hydrolase; functional constipation; oleamide; pharmacometabolomics.

Figures

Figure 1

Figure 1

Serum pharmacometabolomics analysis of FC subjects from a three-armed, randomized, controlled clinical study. (A) Study design to investigate a metabolic biomarker associated with treatment efficacy in FC patients. Patients with paired serum samples were divided into three groups based on different treatment approaches: Placebo group (n = 24), Senna group (n = 31), and MZRW group (n = 30). For all patients, serum samples were acquired before and after treatment, at week 0 and week 10, respectively. Meanwhile, the number of complete spontaneous bowel movements per week (CSBM) for each patient were also recorded at the same time point, as well as at week 18. (B) The phamacometabolomic analysis flowchart for FC patients treated with different therapies. Metabolic features which are significantly and specifically associated with MZRW treatment were selected after calculations. (C) One metabolic feature (ID: 268) was found to be negatively correlated (Pearson r = -0.59, p = 0.00057) with change of CSBM (ΔCSBM) in the MZRW group, but not in the Senna or placebo group. (D) According to mass:charge ratio (m/z) and mass, feature 268 was identified as oleamide.

Figure 2

Figure 2

MZRW reduces circulating oleamide in FC patients. (A) Serum levels of oleamide pre-treatment (wk0) and post-treatment (wk10) in FC patients treated with Placebo, Senna, and MZRW. The differences at different time points were evaluated by paired, two-tailed Student t-test (ns, p > 0.05; **, p < 0.01). (B) Percentage of serum oleamide alterations in FC patients treated with Placebo, Senna, and MZRW. (C) Number of FC patients with up- or down-regulation of oleamide treated with Placebo, Senna, and MZRW.

Figure 3

Figure 3

MZRW attenuates oleamide-induced slow GI motility in mice. Mice were equally divided into four groups (n = 8/group). The control group were intraperitoneally (i.p.) injected with blank solution (5% EtOH), while the remaining groups were pre-treated with oleamide (10 mg/kg in 5% EtOH), at 30 min before MZRW treatment. During treatment, the control group and oleamide-only group were orally administered with saline water, while the remaining two groups were administered with MZRW low dose (10 g/kg) and MZRW high dose (20 g/kg), respectively. From the beginning of drug treatment, the fecal pellet number of mice were recorded every 30 min in 2h. The accumulated fecal pellet number was calculated and the statistical differences evaluated by one-way ANOVA and Student t-test in Prism 6 (*, p < 0.05; **, p < 0.01).

Figure 4

Figure 4

MZRW down-regulates oleamide through enhancing expression of FAAH in normal mice. (A) Mice were treated with MZRW and saline (control group). The fecal pellet number was recorded at 15, 30, 60, and 120 min. At each time point, the fecal pellet number in the MZRW and the control treatment group was compared with Student t-test (*, p < 0.05). (B) Oleamide levels in serum, ileum, and colon tissues in normal mice treated with saline (control) and MZRW. Two groups were compared using Student t-test (*, p < 0.05) (C) The relative mRNA expression of FAAH in ileum and colon tissues in normal mice treated by saline (control) and MZRW. The effect of MZRW treatment on mRNA expression was evaluated by Student t-test (ns, p > 0.05; *, p < 0.05). (D) The western blot results of FAAH in colonic tissues of mice treated with saline (control) and MZRW. (E) The relative protein expression level of FAAH in colonic tissues. Two groups were compared using Student t-test (*, p < 0.05).

References

    1. Álvarez-Sánchez B., Priego-Capote F., Castro M. D. L. D. (2010. a). Metabolomics analysis II. Preparation of biological samples prior to detection. TrAC Trends In Anal. Chem. 29, 120–127. 10.1016/j.trac.2009.12.004 – DOI
    1. Álvarez-Sánchez B., Priego-Capote F., Luque De Castro M. D. (2010. b). Metabolomics analysis I. Selection of biological samples and practical aspects preceding sample preparation. TrAC Trends In Anal. Chem. 29, 111–119. 10.1016/j.trac.2009.12.003 – DOI
    1. Bashashati M., Storr M. A., Nikas S. P., Wood J. T., Godlewski G., Liu J., et al. (2012). Inhibiting fatty acid amide hydrolase normalizes endotoxin-induced enhanced gastrointestinal motility in mice. Br. J. Pharmacol. 165, 1556–1571. 10.1111/j.1476-5381.2011.01644.x – DOI PMC PubMed
    1. Bashashati M., Nasser Y., Keenan C. M., Ho W., Piscitelli F., Nalli M., et al. (2015). Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation. Br. J. Pharmacol. 172, 3099–3111. 10.1111/bph.13114 – DOI PMC PubMed
    1. Capasso R., Matias I., Lutz B., Borrelli F., Capasso F., Marsicano G., et al. (2005). Fatty acid amide hydrolase controls mouse intestinal motility in vivo. Gastroenterology 129, 941–951. 10.1053/j.gastro.2005.06.018 – DOI PubMed

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Florida high school official fired for using legal medical marijuana

Gulf War veteran Mike Hickman used legal medical cannabis instead of dangerous opioids. When district officials found out, they fired him.

The post Florida high school official fired for using legal medical marijuana appeared first on Leafly.

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When a fight broke out among students at Belleview High School in central Florida, school official Mike Hickman entered the fray and put his body on the line to intervene. Nothing in the school’s administrative code tasked him with risking himself to secure his students’ safety, but he did so anyway.

A school official’s good deed didn’t go unpunished: He was fired after stepping in to stop a schoolyard fight.

A Marine combat veteran who suffered serious injuries while serving in the 1990-1991 Gulf War, Hickman has spent the past thirty years living with chronic pain from those wounds—and from a string of surgeries he underwent to heal them. For a time he relied on prescribed opioids for relief, but then found cannabis worked far better. He could gain relief without the serious side effects—and risk of addiction and overdose—that came with opioid use.

Hickman performed his job at Belleview—where he worked as the school’s student services manager—admirably, for years, while privately managing his medical condition.

Then came the schoolyard fight.

Punished for his good deed

It happened a year ago, in Nov. 2019.

While breaking up the brawl, Hickman suffered a new injury—one serious enough to require a visit to a worker’s compensation doctor. Acting on behalf of his employer, that doctor required him to submit a urine sample. The sample wasn’t part of Hickman’s treatment. Its only purpose was to test for drug use.

When the urine test came back positive for THC, Hickman’s 10 years of service to Marion County Public Schools ended. The Marion County School Board fired Mike Hickman, pointing to district policy prohibiting employees from using cannabis for any reason, even if that use takes place off school grounds and at the recommendation of a physician.

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Go on opioids, or lose your job

District officials offered to limit his punishment to a suspension if Hickman ended his use of medical cannabis. Forced to choose between his career as an educator and the medicine that secures his quality of life, Hickman chose his medicine.

Mike Hickman’s medication is legal according to state law. But it’s against school district policy.

Medical cannabis has been legal in Florida since 2016, when 71% of voters approved a state constitutional amendment allowing doctors to recommend it to their patients. And according to a 2019 article from MJ Biz Daily, business is now “booming, with an average of nearly two dispensaries opening each week across the state.”

There’s no disputing the legality of Mike Hickman’s cannabis use under state law. Nor does anyone allege that he came to work impaired, or that he failed in any way to perform his official duties with the utmost skill and professionalism.

But after months of hearings and legal wrangling, none of that mattered. On Nov. 4, the Marion Public School Board voted 5-0 to terminate his employment.

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What about the children?

Hickman has declined to discuss the case publicly. Shortly after the school board’s Nov. 4 decision, Hickman’s attorney, Mark Herdman, told a local reporter the action “was just another unfortunate decision handed down by the Marion County School Board to fire yet another good employee.”

But to lose your employment, including your place in the lives of countless young people who look up to you as an educator, a mentor, and a pillar of the community, goes far beyond a simple job loss. Seeing someone who served his country with honor, and was wounded in the field of battle, be sacked for choosing a safe, effective medicine exposes a terrible hypocrisy at the heart of the War on Drugs.

For decades, America’s weed warriors have justified their destructive prohibition against a beneficial plant by appealing to the fate of “the children.” What message, they ask, would it send to allow a combat veteran to smoke a joint or use a cannabis salve in the privacy of his own home instead of popping dangerous, addictive pills?

The real question is what lesson will Mike Hickman’s students learn from a society that publicly shames and summarily dismisses an upstanding citizen for something that should be nobody’s business but his own.

A cannabis Catch-22

Contacted by Leafly, several school board members directed questions to Kevin Christian, the district’s head of public relations.

District officials scrambled to find a way to justify Hickman’s firing. At issue is a long-outdated zero-tolerance policy for a medication that’s now legal.

At first Christian tried to frame the issue as Hickman’s failure to disclose his use of medical cannabis to school authorities prior to failing his drug test—“that’s really a big portion of what the school board expressed concern over”—though he eventually conceded that nothing in the school board’s policy would have prevented Hickman from being fired on the spot for simply making such a disclosure.

In fact, that policy specifically lists marijuana among prohibited substances, with no consideration of whether it’s legal under state law. This zero-tolerance approach to maintaining a “drug free workplace” has remained unaltered for decades. The school board failed to update the district’s policies in any way following the legalization of medical cannabis in Florida four years ago.

School board hiding behind federal law

Even now, the school board says the fact that cannabis remains federally illegal prevents them for making any further allowances, since public schools receive federally funding that could theoretically be cut off if they permit even a single exception.

Back in 2019, a committee in the US House of Representatives directed the Office of Personnel Management to review policies surrounding the hiring and firing of federal employees in states with legal cannabis, writing:

The Committee encourages OPM to review its policies and guidelines regarding hiring and firing of individuals who use marijuana in states where that individual’s private use of marijuana is not prohibited under the law of the State. These policies should reflect updated changes to the law on marijuana usage and clearly state the impact of marijuana usage on Federal employment.

But so far, no such action has been taken at the federal level.

Meanwhile in Florida, a bill “prohibiting an employer from taking adverse personnel action against an employee or job applicant who is a qualified patient using medical marijuana” was introduced in early 2020, but died in committee.

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Stuck in one of Florida’s medical marijuana deserts? Help may be on the way

The next employee may ignore the fight

The Marion County School Board voted unanimously to terminate him despite overwhelming support for Hickman from students, faculty, parents, and the Marion Education Association, a local teachers union.

“Imagine if this employee just sat back and let the two students continue to fight without regard for their safety,” Chris Altobello, Marion Education Association executive director, told the Ocala Star-Banner newspaper after Hickman’s firing. “We wouldn’t be here right now.”

Hickman, Altobello added, was no more impaired “than someone who took an aspirin for a headache. They implied that this is tantamount to smoking pot in the boys bathroom!”

Lazy policy results in a good man’s firing

Eventually a review process landed the case before Judge Suzanne Van Wyk of the state Division of Administrative Hearings in Tallahassee. Wyk upheld Hickman’s firing, though not without reservations.

In an eight-page decision, Van Wyk noted Hickman’s argument that it’s unfair to punish someone for using legal medical cannabis when the school board would not object to him “teaching under the influence of opioid pain medications, which he took for years prior to the availability of medical marijuana.”

Still, the best deal offered to Hickman was to stop using cannabis and return to work after a 20-day suspension. Or, put another way: Keep suffering in pain; or take dangerous, addictive pills; or lose your job.

Mike Hickman chose his health and lost his job.

That’s a choice nobody should ever face.

David Bienenstock's Bio Image

David Bienenstock

Veteran cannabis journalist David Bienenstock is the author of “How to Smoke Pot (Properly): A Highbrow Guide to Getting High” (2016 – Penguin/Random House), and the co-host and co-creator of the podcast “Great Moments in Weed History with Abdullah and Bean.” Follow him on Twitter @pot_handbook.

View David Bienenstock’s articles

Source: https://www.leafly.com/news/politics/florida-high-school-official-fired-for-using-legal-medical-marijuana

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CBD/CBG mixture

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Visit our community site for vetted suppliers at http://theCBD.place. It’s time that this subject was given more internet exposure. We are here to discuss topics related to medical marijuana and our experiences using CBD. Please do not assume that anyone here is a medical professional.

Source: https://www.reddit.com/r/CBD/comments/k0867y/cbdcbg_mixture/

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Abrasive Sensitivity of Engineering Polymers and a Bio-Composite under Different Abrasive Conditions

Two different test systems were designed to evaluate the tribological behavior of five engineering plastics (Polyamide-PA grades and Ultra High Molecular Weight Polyethylene-UHMW-PE) and a fully degradable bio-composite (Polylactic Acid-PLA/hemp fibers) targeted to agricultural machinery abrasive conditions. Pin-on-plate tests were performed with different loads, sliding velocity and abrasive particles. The material response was further investigated in a slurry containing abrasive test system…

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Two different test systems were designed to evaluate the tribological behavior of five engineering plastics (Polyamide-PA grades and Ultra High Molecular Weight Polyethylene-UHMW-PE) and a fully degradable bio-composite (Polylactic Acid-PLA/hemp fibers) targeted to agricultural machinery abrasive conditions. Pin-on-plate tests were performed with different loads, sliding velocity and abrasive particles. The material response was further investigated in a slurry containing abrasive test system with different sliding velocities and distances, abrasive media compositions and impact angles. The abrasive wear, the change of the 3D surface roughness parameters, the friction force and contact temperature evolution were also analyzed as a function of the materials’ mechanical properties (H,E,σy,σc,εB,σF,σM) and the dimensionless numbers derived from them. Using the IBM SPSS 25 software, multiple linear regression models were used to statistically evaluate the measured data and to examine the sensitivity of the material properties and test system characteristics on the tribological behavior. For both test setups, the system and material characteristics influencing the dependent variables (wear, friction, heat generation) and the dimensionless numbers formed from the material properties were ranked using standardized regression coefficients derived from the regression models. The abrasion sensitivity of the tested materials were evaluated taking into account a wide range of influencing parameters.

Keywords: abrasive wear; bio-polymer; engineering plastics; mechanical properties; pin-on-plate; regression model; slurry.

Source: https://pubmed.ncbi.nlm.nih.gov/33228186/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=18gXB4q-CV5o0kQDSCt3HqwNcsXbn1PxqekJlWJaIbT8zAG16G&fc=20200804213200&ff=20201124115248&v=2.13.0

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