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

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

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

 Publication Cover

“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

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

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

Health-related quality of life across cancer cachexia stages.

“Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL).

However, methods to identify the impact of CC on HRQOL are limited.

Finally, the use of cannabinoids in treating appetite loss was examined,

54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic.

Edmonton Symptom Assessment System (ESAS) score for lack of appetite significantly improved between baseline and follow-up after cannabinoid treatment, with no significant difference in weight.

Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.”

An Integrated Review of Cannabis and Cannabinoids in Adult Oncologic Pain Management.

Pain Management Nursing

“The objective of this paper is to review the available literature regarding the use of cannabis and cannabinoids in adult oncologic pain management.

RESULTS:

The final number of articles included is nine articles. Of the nine studies reviewed, eight reviewed the effect of the cannabinoid THC on cancer pain, and one study reviewed the use of medicinally available whole plant cannabis. The following study types were included: multiple multi-center, randomized, placebo- controlled trials and two prospective observational survey studies.

RESULTS AND CONCLUSIONS:

Of the eight studies that reviewed the effect of the cannabinoid THC, five found THC to be more effective than placebo, one found THC to be more effective than placebo in American patients but ineffective in patients from other countries, and two found THC to be no more effective than placebo. The study that reviewed the effect of the whole plant cannabis found that there was a significant decrease in pain among those patients smoking cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/30527857

https://www.painmanagementnursing.org/article/S1524-9042(18)30209-1/fulltext

Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: A systematic review and meta-analysis.

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“Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that results from motor neuron damage.

Cannabinoids have been proposed as treatments for ALS due to their anti-excitotoxicity, anti-oxidant, and anti-inflammatory effects.

This review provides some evidence for the efficacy of cannabinoids in prolonging survival time in an ALS mouse model. A delay in disease progression is also suggested following cannabinoid treatment”

https://www.ncbi.nlm.nih.gov/pubmed/30520038

https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14639

“The endocannabinoid system in amyotrophic lateral sclerosis. There is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS, in addition to other neurodegenerative conditions. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors, respectively. Cannabinoid agents may also exert anti-oxidant actions by a receptor-independent mechanism. Therefore the ability of cannabinoids to target multiple neurotoxic pathways in different cell populations may increase their therapeutic potential in the treatment of ALS.”  https://www.ncbi.nlm.nih.gov/pubmed/18781981

http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/

Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons.

Behavioural Brain Research

“Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation.”

https://www.ncbi.nlm.nih.gov/pubmed/30508607

https://www.sciencedirect.com/science/article/pii/S0166432818311987?via%3Dihub

Cannabinoid receptor 2 agonist prevents local and systemic inflammatory bone destruction in rheumatoid arthritis.

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“Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the non-inflamed synovium and bone tissues. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis.”

https://www.ncbi.nlm.nih.gov/pubmed/30508319

https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3637