Category Archives: Uncategorized

The importance of 15-lipoxygenase inhibitors in cancer treatment.

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Cancer and Metastasis Reviews

“Cancer-targeted therapy is an expanding and successful approach in treatment of many types of cancers. One of the main categories of targeted therapy is use of small molecule inhibitors. 15-Lipoxygenase (15-LOX) is an enzyme which reacts with polyunsaturated fatty acids and produces metabolites that are implicated in many important human diseases, such as cancer.

Considering the role of 15-LOX (mainly 15-LOX-1) in the progression of some cancers, the discovery of 15-LOX inhibitors could potentially lead to development of novel cancer therapeutics and it can be claimed that 15-LOX inhibitors might be suitable as chemotherapy agents in the near future.

This article reviews relevant publications on 15-LOX inhibitors with focus on their anticancer activities in vitro and in vivo. Many 15-LOX inhibitors have been reported for which separate studies have shown their anticancer activities. This review paves the way to further explore the mechanism of their antiproliferative effects via 15-LOX inhibition.”

 https://www.ncbi.nlm.nih.gov/pubmed/29882120
https://link.springer.com/article/10.1007%2Fs10555-018-9738-9

“Cannabidiol-2′,6′-Dimethyl Ether, a Cannabidiol Derivative, Is a Highly Potent and Selective 15-Lipoxygenase Inhibitor”  http://dmd.aspetjournals.org/content/37/8/1733.long

“Δ9-tetrahydrocannabinol and its major metabolite Δ9-tetrahydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.”  https://www.ncbi.nlm.nih.gov/pubmed/20891010

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

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Neurochemical Research

“Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion.

Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh).

Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD.

Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.”

https://www.ncbi.nlm.nih.gov/pubmed/29876791

https://link.springer.com/article/10.1007%2Fs11064-018-2565-0

Medicinal cannabis: presenting possible treatment modalities for the future

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“Cannabis is the most popular recreational drug used in the world. It is estimated that 178 million people aged 15–64 years used cannabis at least once in 2012.

Cannabis or cannabinoids used to manage medical conditions is referred to as medicinal cannabis. There are various formulations of cannabis available on the market.

Cannabis can be administered orally, sublingually, or topically; it can be smoked, inhaled, mixed with food, or made into tea. It can be taken in herbal form, extracted naturally from the plant, gained by isomerization of cannabidiol (CBD), or manufactured synthetically.

The commercially available prescribed cannabinoids include dronabinol capsules, nabilone capsules, and the oromucosal spray nabiximols.

Canada and the Netherlands have government-run programs in which dedicated companies supply quality-controlled herbal cannabis. In the United States, 23 states and Washington, DC (May 2015) have introduced laws permitting the medical use of cannabis; other countries have similar laws.”

https://www.ncbi.nlm.nih.gov/pubmed/29870436

https://insights.ovid.com/crossref?an=01787381-201806000-00001

Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

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“Movement disorders such as Parkinson’s disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/29867488

https://www.frontiersin.org/articles/10.3389/fphar.2018.00482/full

Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.

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BPS (Pharm)

“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.

The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC.”

https://www.ncbi.nlm.nih.gov/pubmed/26377899

“A number of studies now support the view that cannabidiol (CBD) may reduce the negative psychotropic effects of THC while enhancing its positive therapeutic actions. Our results are consistent with the notion that cannabis plant strains that contain THC and CBD at 1:1 ratios may be preferable to street cannabis for medicinal applications because they maximize therapeutic efficacy while minimizing the adverse effects of THC.”  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13333

Effects of cannabidiol plus naltrexone on motivation and ethanol consumption.

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“The aim of this study was to explore if the administration of naltrexone (NTX) together with cannabidiol (CBD) may improve the efficacy in reducing alcohol consumption and motivation rather than any of the drugs given separately.

The administration of CBD + NTX significantly reduced motivation and ethanol intake in the oral self-administration procedure in a greater proportion than the drugs given alone. Only the combination of both drugs significantly reduced Oprm1, TH and 5-HT1A gene expressions in the NAc, VTA and DR, respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD + NTX but had no effects by itself.

CONCLUSION AND IMPLICATIONS:

The combination of low doses of CBD plus NTX resulted more effective to reduce ethanol consumption and motivation to drink. These effects, appears to be mediated, at least in part, by 5-HT1A receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/29859012

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14380

“Naltrexone belongs to a class of drugs known as opiate antagonists. It works in the brain to prevent opiate effects (e.g., feelings of well-being, pain relief). It also decreases the desire to take opiates. This medication is also used to treat alcohol abuse. It can help people drink less alcohol or stop drinking altogether. It also decreases the desire to drink alcohol when used with a treatment program that includes counseling, support, and lifestyle changes.” https://www.webmd.com/drugs/2/drug-7399/naltrexone-oral/details

“Cannabidiol reduces ethanol consumption, motivation and relapse in mice. Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.”   https://www.ncbi.nlm.nih.gov/pubmed/28194850

Marijuana use and fecundability in a North American preconception cohort study.

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“The influence of marijuana use on human fertility has not been well studied. We evaluated the association between female and male use of marijuana and fecundability in Pregnancy Study Online, a prospective cohort of North American couples.

RESULTS:

Men (14.2%) were more likely than women (11.6%) to be marijuana users. FRs for female marijuana use <1 and ≥1 time/week relative to non-use were 0.99 (95% CI 0.85 to 1.16) and 0.98 (95% CI 0.80 to 1.20), respectively. FRs for male marijuana use <1 and ≥1 time/week relative to non-use were 0.87 (95% CI 0.66 to 1.15) and 1.24 (95% CI 0.90 to 1.70), respectively. Associations for frequent marijuana use (≥1 time/week) were attenuated among non-smoking men (FR=1.21, 95% CI 0.84 to 1.74), but stronger among men reporting intercourse ≥4 times/week (FR=1.35, 95% CI 0.72 to 2.53).

CONCLUSIONS:

In this preconception cohort study, there was little overall association between female or male marijuana use and fecundability.”

https://www.ncbi.nlm.nih.gov/pubmed/29273628

http://jech.bmj.com/content/72/3/208

“BU: Marijuana use does not lower chances of getting pregnant”  https://www.eurekalert.org/pub_releases/2018-01/buso-bmu012218.php 

“New Study Says Marijuana Use Does Not Affect Fertility”  https://www.civilized.life/articles/marijuana-not-affect-fertility/

“New Study Says Marijuana Does Not Reduce Fertility In Men Or Women”  https://www.civilized.life/articles/new-study-says-marijuana-does-not-reduce-fertility-in-men-or-women/

Including cannabinoids in the treatment of painful schwannomatosis.

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“A 47‐year‐old man, affected by Schwannomatosis, presented a very severe pain (10/10, NRS) with paroxysmal shooting episodes, allodynia, paresthesia, and dysesthesia; in parallel, the patient had lost weight (from 70 to 49 kg) and experienced fatigue and deep depression. The previous pain prescription, including opioids and antineutopathic drugs, was fully ineffective. We progressively substituted this therapy with 15 drops, 3 times/daily, of THC/CBD in a concentration ratio 5:1, equal to 15 mg of active substance each time, reaching improvement in pain intensity (6/10) and in several other aspects as mood and quality of life”

https://www.ncbi.nlm.nih.gov/pubmed/29845778  

https://onlinelibrary.wiley.com/doi/abs/10.1002/brb3.1011

“Schwannomatosis is a rare genetic disorder that results in tumors (called schwannomas) that grow on the peripheral nerves throughout the body. It is recognized most often in people over the age of 30. Schwannomatosis can cause severe, debilitating pain and neurological dysfunction.”  https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neurofibromatosis/schwannomatosis/index.html

The effect of hemp seed and linseed addition on the quality of liver pâtés.

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“Liver p&acirc;t&eacute;s are popular all over the world, but they usually contain high amounts of animal fats. It may be beneficial to improve their dietetic value by decreasing the saturated fatty acid content, while maintaining their sensory quality. One way to do this is to add ingredients which are rich in polyunsaturated fatty acids, such as hemp seed or linseed. Hemp seeds are valuable because of their fat and protein content and linseed is known for its high &alpha;-linolenic fatty acid (ALA) content. Both are good sources of fiber.

RESULTS:

The addition of hemp and linseed increased the fat content. The fatty acid profile improved signifi- cantly. There were more polyunsaturated fatty acids and the n-6 to n-3 ratio was reduced in both products containing oil seeds compared to the control sample, which is important from the health point of view. The color parameters were not changed. The hardness, chewiness and adhesiveness increased in products contain- ing oil seeds. Those products received higher scores in sensory analysis.

CONCLUSIONS:

The quality of the p&acirc;t&eacute;s with added oil seed is comparable to or better than the traditional ones. The products with both hemp and linseed can be treated as a good source of n-3 fatty acids. The amount of ALA is high enough to label the product as a source of n-3 fatty acids.”

 https://www.ncbi.nlm.nih.gov/pubmed/29803219

The Pharmacological Inhibition of Fatty Acid Amide Hydrolase Prevents Excitotoxic Damage in the Rat Striatum: Possible Involvement of CB1 Receptors Regulation.

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Molecular Neurobiology

“The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system.

Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its production via the kynurenine pathway (KP), quinolinic acid (QUIN) can act as an excitotoxin through the selective overactivation of NMDAr, thus participating in the onset and development of neurological disorders.

In this work, we evaluated whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by URB597, and the consequent increase in the endogenous levels of anandamide, can prevent the excitotoxic damage induced by QUIN. URB597 (0.3 mg/kg/day × 7 days, administered before, during and after the striatal lesion) exerted protective effects on the QUIN-induced motor (asymmetric behavior) and biochemical (lipid peroxidation and protein carbonylation) alterations in rats.

URB597 also preserved the structural integrity of the striatum and prevented the neuronal loss (assessed as microtubule-associated protein-2 and glutamate decarboxylase localization) induced by QUIN (1 μL intrastriatal, 240 nmol/μL), while modified the early localization patterns of CBr1 (CB1) and NMDAr subunit 1 (NR1).

Altogether, these findings support the concept that the pharmacological manipulation of the endocannabinoid system plays a neuroprotective role against excitotoxic insults in the central nervous system.”

 https://www.ncbi.nlm.nih.gov/pubmed/29802570
https://link.springer.com/article/10.1007%2Fs12035-018-1129-2