Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea.

Oxford University Press

“There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study.

Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully-blinded parallel groups, placebo-controlled randomized trial of dronabinol in patients with moderate or severe OSA.

These findings support the therapeutic potential of cannabinoids in patients with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved subjective sleepiness and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA”   https://www.ncbi.nlm.nih.gov/pubmed/29121334

“These findings support the therapeutic potential of cannabinoids in patients with obstructive sleep apnea (OSA).” https://academic.oup.com/sleep/article-abstract/doi/10.1093/sleep/zsx184/4600041?redirectedFrom=fulltext

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The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.

Image result for anticancer res. journal

“Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients.

MATERIALS AND METHODS:

Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis.

RESULTS:

Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells.

CONCLUSION:

The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/29061818

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Sativex in the management of multiple sclerosis-related spasticity: An overview of the last decade of clinical evaluation.

Multiple Sclerosis and Related Disorders Home

“Spasticity is a common symptom of multiple sclerosis (MS) affecting about 80% of MS patients. Numerous lines of evidence suggest that spasticity due to its complexity is not adequately managed with conventional anti-spastic therapies. Therefore, in order to improve the outcomes for the majority of MS patients, alternative approaches are needed to be discovered. Over the last years, the use of cannabinoid compounds as a potential treatment for MS-related symptoms has aroused great interest, owing to encouraging preclinical and clinical studies. To date, Sativex, an oromucosal spray containing tetrahydrocannabinol and cannabidiol in approximately 1:1 ratio, is the only commercially available formulation containing cannabinoids used as add-on therapy for treatment of spasticity in adult MS patients who are not responding to conventional antispastic therapies.

METHODS:

Here, by performing a literature search, we provided an overview of the last decade of clinical evaluations as well as post-marketing studies about effectiveness and safety of Sativex in the management of MS-related spasticity.

RESULTS:

Sativex was proven effective in treating spasticity and also in improving the patient’s quality of life. In addition, a low incidence of adverse reactions Sativex-related supports the good safety profile and its tolerability.

CONCLUSION:

This review by recognizing the clinical effectiveness of Sativex in spasticity management, opened a new opportunity for many patients with spasticity resistant to common antispastic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29055461

http://www.msard-journal.com/article/S2211-0348(17)30148-7/fulltext

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Reprint of: survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’.

Complementary Therapies in Clinical Practice

“A majority of women experience some nausea and/or vomiting during pregnancy. This condition can range from mild nausea to extreme nausea and vomiting, with 1-2% of women suffering from the life-threatening condition hyperemesis gravidarum.

Cannabis (Cannabis sativa) may be used therapeutically to mitigate pregnancy-induced nausea and vomiting.

This paper presents the results of a survey of 84 female users of medicinal cannabis, recruited through two compassion societies in British Columbia, Canada. Of the seventy-nine respondents who had experienced pregnancy, 51 (65%) reported using cannabis during their pregnancies. While 59 (77%) of the respondents who had been pregnant had experienced nausea and/or vomiting of pregnancy, 40 (68%) had used cannabis to treat the condition, and of these respondents, 37 (over 92%) rated cannabis as ‘extremely effective’ or ‘effective.’

Our findings support the need for further investigations into cannabis therapy for severe nausea and vomiting during pregnancy.”

https://www.ncbi.nlm.nih.gov/pubmed/19880090

“Marijuana use is common in pregnancy but may not be an independent risk factor for poor neonatal outcomes in term pregnancies.”  http://www.sciencedirect.com/science/article/pii/S000293781500527X

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Activation of cannabinoid receptor type II by AM1241 protects adipose-derived mesenchymal stem cells from oxidative damage and enhances their therapeutic efficacy in myocardial infarction mice via Stat3 activation.

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“The poor survival of cells in ischemic sites diminishes the therapeutic efficacy of stem cell therapy. Previously we and others have reported that Cannabinoid receptor type II (CB2) is protective during heart ischemic injury for its anti-oxidative activity. However, whether CB2 activation could improve the survival and therapeutic efficacy of stem cells in ischemic myocardium and the underlying mechanisms remain elusive.

Here, we showed evidence that CB2 agonist AM1241 treatment could improve the functional survival of adipose-derived mesenchymal stem cells (AD-MSCs) in vitro as well as in vivo. Moreover, AD-MSCs adjuvant with AM1241 improved cardiac function, and inhibited cardiac oxidative stress, apoptosis and fibrosis. To unveil possible mechanisms, AD-MSCs were exposed to hydrogen peroxide/serum deprivation to simulate the ischemic environment in myocardium.

Results delineated that AM1241 blocked the apoptosis, oxidative damage and promoted the paracrine effects of AD-MSCs. Mechanistically, AM1241 activated signal transducers and activators of transcription 3 (Stat3) through the phosphorylation of Akt and ERK1/2. Moreover, the administration of AM630, LY294002, U0126 and AG490 (inhibitors for CB2, Akt, ERK1/2 and Stat3, respectively) could abolish the beneficial actions of AM1241.

Our result support the promise of CB2 activation as an effective strategy to optimize stem cell-based therapy possibly through Stat3 activation.”

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Cannabis for the Treatment of Chronic Pain in the Era of an Opioid Epidemic: A Symposium-Based Review of Sociomedical Science.

Pain Medicine

“This manuscript reviews medical literature published pertaining to the management of chronic pain with medical marijuana therapy (MMJ), with an emphasis on the social, medical, and legal aspects of therapy.

CONCLUSIONS:

Increasing interest in MMJ for chronic pain underscores a need for primary care and pain physicians to better understand the indications and evidence for its use free from cultural bias. Given a lack of full conclusive clinical utility, continued research is needed to better understand how to best utilize MMJ therapy for the treatment of chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29016917

https://academic.oup.com/painmedicine/article-abstract/doi/10.1093/pm/pnx143/3964518/Cannabis-for-the-Treatment-of-Chronic-Pain-in-the?redirectedFrom=fulltext

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Potential of plant-sourced phenols for inflammatory bowel disease.

“Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics.

In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota.

In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help the further development of new preventive/adjuvant regimens for IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28990509

http://www.eurekaselect.com/156267/article

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Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer’s disease.

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“Alzheimer’s disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation.

In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD.

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. In PC12 cells, Aβ-induced tau protein hyperphosphorylation is inhibited by CBD. This inhibition is associated with a downregulation of p-GSK-3β, an inhibitor of Wnt pathway. CBD may also increase Wnt/β-catenin by stimulation of PPARγ, inhibition of Aβ and ubiquitination of amyloid precursor protein.

CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. CBD suppresses, through activation of PPARγ, pro-inflammatory signaling and may be a potential new candidate for AD therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/28981597

https://academic.oup.com/abbs/article-abstract/49/10/853/3978657/Effects-of-cannabidiol-interactions-with-Wnt?redirectedFrom=fulltext

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Photobiomodulation Therapy Improves Acute Inflammatory Response in Mice: the Role of Cannabinoid Receptors/ATP-Sensitive K+ Channel/p38-MAPK Signalling Pathway.

Molecular Neurobiology

“Although photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM.

Here, we reported that PBM (660 nm, 30 mW, 0.06 cm2, 50 J/cm2, plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors. The use of CB1 antagonist AM281 or CB2 antagonist AM630 significantly reversed the anti-inflammatory effect of PBM. Analysis of signalling pathway downstream of cannabinoid receptors activation reveals that anti-inflammatory effects of PBM depend, in great extent, on its ability to activate ATP-dependent K+ channels and p38 mitogen-activated protein kinase. Moreover, PBM therapy significantly reduced the levels of pro-inflammatory cytokine IL-6 in both paw and spinal cord, and restored the reduction of the level of anti-inflammatory cytokine IL-10 in spinal cord after carrageenan injection. Unlike the potent cannabinoid receptor agonist (WIN 55212-2), PBM did not exert any CNS-mediated effects in the tetrad assay. Finally, PBM does not reduce inflammation and noxious thermal response induced by LPS and zymosan, a TLR4 and TLR2/dectin-1 ligand, respectively.

Thus, cannabinoid receptors and, possibly, the endocannabinoid system, represent an important site of action of PBM that opens the possibility of complementary and nonpsychotropic therapeutic interventions in clinical practice.”

https://www.ncbi.nlm.nih.gov/pubmed/28980210

https://link.springer.com/article/10.1007%2Fs12035-017-0792-z

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Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy.

European Respiratory Society

“Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.

Primary vagal ganglia neurons, tissue bioassay, in vivoelectrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents. FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels.

These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.”

https://www.ncbi.nlm.nih.gov/pubmed/28931663

http://erj.ersjournals.com/content/50/3/1700782

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