Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.

“It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP).

Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a major cause of blindness.

THC likely acts via one of the known cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this has never been determined explicitly.

Cannabidiol (CBD) is a second major constituent of cannabis that has been found to be without effect on IOP in most studies.

RESULTS:

We now report that a single topical application of THC lowered IOP substantially (∼28%) for 8 hours in male mice. This effect is due to combined activation of CB1 and GPR18 receptors each of which has been shown to lower ocular pressure when activated. We also found that the effect was sex-dependent, being stronger in male mice, and that mRNA levels of CB1 and GPR18 were higher in males. Far from inactive, CBD was found to have two opposing effects on ocular pressure, one of which involved antagonism of tonic signaling.

CBD prevents THC from lowering ocular pressure.

CONCLUSIONS:

We conclude that THC lowers IOP by activating two receptors-CB1 and GPR18-but in a sex-dependent manner. CBD, contrary to expectation, has two opposing effects on IOP and can interfere with the effects of THC.”

https://www.ncbi.nlm.nih.gov/pubmed/30550613

https://iovs.arvojournals.org/article.aspx?articleid=2718702

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Chemical characterization of leaves, male and female flowers from spontaneous cannabis (Cannabis sativa var. spontanea) growing in Hungary.

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“Cannabis sativa var. spontanea is a spontaneous form of hemp with a low content of psychoactive cannabinoids and can be considered as a valuable source of other phytoconstituents to be used in nutraceuticals or for their health promoting properties.

Chemical data on this hemp variety are rather scarce. In this paper we report a comprehensive phytochemical characterization of leaves, male and female inflorescences of C. sativa var. spontanea growing wild in Hungary.

The results indicated that female inflorescence essential oil contains high amounts of the CB2 agonists (E)-caryophyllene (28.3%) and cannabidiol (CBD) (24.9%), whereas leaves and male inflorescence essential oils contained lower amounts of both compounds. HPLC-MS allowed to quantify CBD and CBD-A in the ethyl acetate extracts from leaves, male and female inflorescences; they were 0.3, 0.8 and 0.9%, and 0.2, 0.3 and 0.4%, respectively. Flavonoids were formed by C-glycosides and glucuronic acids of kaempferol and apigenin, with a total content of 3.8, 6.1 and 7.8 mg/g in methanolic extracts from leaves, male and female inflorescences, respectively.

Based on these results, C. sativa var. spontanea may represent an important source of CB2 agonists and bioflavonoids to be used in nutraceuticals, cosmetics and pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/30548994

https://onlinelibrary.wiley.com/doi/abs/10.1002/cbdv.201800562

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Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study.

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“Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureusHelicobacter pyloriCandida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.”

https://www.ncbi.nlm.nih.gov/pubmed/30544765

https://www.mdpi.com/1420-3049/23/12/3266

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Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

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“Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.

RESULTS:

From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.

CONCLUSIONS:

Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.”

https://www.ncbi.nlm.nih.gov/pubmed/30543451

https://www.liebertpub.com/doi/10.1089/acm.2018.0437

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Cannabinoids: Potential Role in Inflammatory and Neoplastic Skin Diseases.

 

“The endocannabinoid system is a complex and nearly ubiquitous network of endogenous ligands, enzymes, and receptors that can also be stimulated by exogenous compounds such as those derived from the marijuana plant, Cannabis sativa.

Recent data have shown that the endocannabinoid system is fully functional in the skin and is responsible for maintaining many aspects of skin homeostasis, such as proliferation, differentiation, and release of inflammatory mediators. Because of its role in regulating these key processes, the endocannabinoid system has been studied for its modulating effects on both inflammatory disorders of the skin and skin cancer.

Although legal restrictions on marijuana as a Schedule I drug in the USA have made studying cannabinoid compounds unfavorable, an increasing number of studies and clinical trials have focused on the therapeutic uses of cannabinoids. This review seeks to summarize the current, and rapidly expanding field of research on the broad potential uses of cannabinoids in inflammatory and neoplastic diseases of the skin.”

https://www.ncbi.nlm.nih.gov/pubmed/30542832

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Cannabinoids and Pain: New Insights From Old Molecules.

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“Cannabis has been used for medicinal purposes for thousands of years.

The prohibition of cannabis in the middle of the 20th century has arrested cannabis research.

In recent years there is a growing debate about the use of cannabis for medical purposes.

The term ‘medical cannabis’ refers to physician-recommended use of the cannabis plant and its components, called cannabinoids, to treat disease or improve symptoms.

Chronic pain is the most commonly cited reason for using medical cannabis.

Cannabinoids act via cannabinoid receptors, but they also affect the activities of many other receptors, ion channels and enzymes.

Preclinical studies in animals using both pharmacological and genetic approaches have increased our understanding of the mechanisms of cannabinoid-induced analgesia and provided therapeutical strategies for treating pain in humans.

The mechanisms of the analgesic effect of cannabinoids include inhibition of the release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulation of postsynaptic neuron excitability, activation of descending inhibitory pain pathways, and reduction of neural inflammation.

Recent meta-analyses of clinical trials that have examined the use of medical cannabis in chronic pain present a moderate amount of evidence that cannabis/cannabinoids exhibit analgesic activity, especially in neuropathic pain.

The main limitations of these studies are short treatment duration, small numbers of patients, heterogeneous patient populations, examination of different cannabinoids, different doses, the use of different efficacy endpoints, as well as modest observable effects.

Adverse effects in the short-term medical use of cannabis are generally mild to moderate, well tolerated and transient. However, there are scant data regarding the long-term safety of medical cannabis use.

Larger well-designed studies of longer duration are mandatory to determine the long-term efficacy and long-term safety of cannabis/cannabinoids and to provide definitive answers to physicians and patients regarding the risk and benefits of its use in the treatment of pain.

In conclusion, the evidence from current research supports the use of medical cannabis in the treatment of chronic pain in adults. Careful follow-up and monitoring of patients using cannabis/cannabinoids are mandatory.”

https://www.ncbi.nlm.nih.gov/pubmed/30542280

https://www.frontiersin.org/articles/10.3389/fphar.2018.01259/full

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What does the ecological and epidemiological evidence indicate about the potential for cannabinoids to reduce opioid use and harms? A comprehensive review.

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“Pre-clinical research supports that cannabinoids reduce opioid dose requirements, but few studies have tested this in humans. This review evaluates ecological and epidemiological studies that have been cited as evidence that medical cannabis use may reduce opioid use and opioid-related harms. Medline and Embase were searched for relevant articles. Data were extracted on study setting, analyses approach, covariates, and outcomes. Eleven ecological and 14 epidemiological studies were found. In ecological studies, states that allow medical cannabis laws have reported a slower rate of increase in opioid overdose deaths compared with states without such laws. These differences have increased over time and persisted after controlling for state sociodemographic characteristics and use of prescription monitoring programmes. Few studies have controlled for other potential confounders such as opioid dependence treatment and imprisonment rates. Some epidemiological studies provide evidence that cannabis availability may reduce opioid use, but are limited by selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects of cannabis. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and harms, although important methodological weaknesses were identified. Well-designed clinical studies may provide more conclusive evidence on whether cannabinoids can reduce opioid use and related harm.”

https://www.ncbi.nlm.nih.gov/pubmed/30522342

https://www.tandfonline.com/doi/abs/10.1080/09540261.2018.1509842?journalCode=iirp20

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Cannabis-related cognitive impairment: a prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study.

 

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“In patients with cancer, the use of medical cannabis has increased significantly during the recent years. There is evidence that cannabis consumption may affect cognitive performance; however, this potential effect has not been investigated prospectively in patients with cancer to date.

We aimed to evaluate the effect of cannabis consumption on cognitive abilities as well as on symptom relief in patients with cancer during chemotherapy treatment.

RESULTS:

Improvement in executive functioning was demonstrated in the case group. In aspects of symptoms, improvement in fatigue, appetite and sleep disorder was demonstrated after cannabis consumption. Patients consuming cannabis did not differ from the control group in cognitive functioning over 3 months of use. No significant cognitive decline was observed in either group over time.

CONCLUSION:

These preliminary findings suggest that the short-term use of cannabis during chemotherapy treatment improved disease-related symptoms and did not affect cognitive skills in patients with cancer.”

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An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers.

Image result for frontiers in behavioral neuroscience “The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection.

The aim of this study was to investigate whether activities other than running can increase circulating eCBs.

Nine healthy female volunteers (mean 61 years) were recruited from a local choir. Circulating eCBs, haemodynamics, mood and hunger ratings were measured before and immediately after 30 min of dance, reading, singing or cycling in a fasted state.

Singing increased plasma levels of anandamide (AEA) by 42% (P < 0.05), palmitoylethanolamine (PEA) by 53% (P < 0.01) and oleoylethanolamine (OEA) by 34% (P < 0.05) and improved positive mood and emotions (P < 0.01), without affecting hunger scores.

Dancing did not affect eCB levels or hunger ratings, but decreased negative mood and emotions (P < 0.01).

Cycling increased OEA levels by 26% (P < 0.05) and tended to decrease how hungry volunteers felt, without affecting mood.

Reading increased OEA levels by 28% (P < 0.01) and increased the desire to eat.

Plasma AEA levels were positively correlated with how full participants felt (P < 0.05). Plasma OEA levels were positively correlated with positive mood and emotions (P < 0.01). All three ethanolamines were positively correlated with heart rate (HR; P < 0.0001).

These data suggest that activities other than running can increase plasma eCBs associated with changes in mood or appetite. Increases in eCBs may underlie the rewarding and pleasurable effects of singing and exercise and ultimately some of the long-term beneficial effects on mental health, cognition and memory.”

https://www.ncbi.nlm.nih.gov/pubmed/30534062

https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00269/full

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Cannabinoid 2 receptor attenuates inflammation during skin wound healing by inhibiting M1 macrophages rather than activating M2 macrophages.

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“The anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation.

Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation.

However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.

In summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation.

These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30534003

https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-018-0201-z

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