Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus.

antioxidants-logo “Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed.

RESULTS:

Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis.

CONCLUSION:

The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.”

https://www.ncbi.nlm.nih.gov/pubmed/31941059

https://www.mdpi.com/2076-3921/9/1/71

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Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity.

ijms-logo“Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2-/- and Cnr1-/-/Cnr2-/- bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1-/- DCs. In vitro stimulated Cnr2-/- DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2-/- DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2-/- DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31940843

https://www.mdpi.com/1422-0067/21/2/475

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Nose-to-brain Delivery of Natural Compounds for the Treatment of Central Nervous System Disorders.

“Several natural compounds have demonstrated potential for the treatment of central nervous system disorders such as ischemic cerebrovascular disease, glioblastoma, neuropathic pain, neurodegenerative diseases, multiple sclerosis and migraine.

This is due to their well-known antioxidant, anti-inflammatory, neuroprotective, anti-tumor, anti-ischemic and analgesic properties. Nevertheless, many of these molecules have poor aqueous solubility, low bioavailability and extensive gastrointestinal and/or hepatic first-pass metabolism, leading to a quick elimination as well as low serum and tissue concentrations.

Thus, the intranasal route emerged as a viable alternative to oral or parenteral administration, by enabling a direct transport into the brain through the olfactory and trigeminal nerves. With this approach, the blood-brain barrier is circumvented and peripheral exposure is reduced, thereby minimizing possible adverse effects.

OBJECTIVE:

Herein, brain-targeting strategies for the nose-to-brain delivery of natural compounds, including flavonoids, cannabinoids, essential oils and terpenes, will be reviewed and discussed. Brain and plasma pharmacokinetics of these molecules will be analyzed and related to their physicochemical characteristics and formulation properties.

CONCLUSION:

Natural compounds constitute relevant alternatives for the treatment of brain diseases but often require loading into nanocarrier systems to reach the central nervous system in sufficient concentrations. Future challenges lie in a deeper characterization of their therapeutic mechanisms and in the development of effective, safe and brain-targeted delivery systems for their intranasal administration.”

https://www.ncbi.nlm.nih.gov/pubmed/31939728

http://www.eurekaselect.com/178321/article

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Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report.

Image result for cureus journal“Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety.

Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects.

In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.”

https://www.ncbi.nlm.nih.gov/pubmed/31938604

https://www.cureus.com/articles/23602-cannabidiol-cbd-for-treatment-of-neurofibromatosis-related-pain-and-concomitant-mood-disorder-a-case-report

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Use of cannabinoids in cancer patients: A Society of Gynecologic Oncology (SGO) clinical practice statement.

Gynecologic Oncology“Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) affect the human endocannabinoid system.

Cannabinoids reduce chemotherapy induced nausea or vomiting (CINV) and neuropathic pain.

Each state has its own regulations for medical and recreational cannabis use.

Effects of cannabinoids on chemotherapy, immunotherapy, and tumor growth remain under investigation.

Providers should focus indications, alternatives, risks and benefits of medical cannabis use to make appropriate referrals.”

https://www.ncbi.nlm.nih.gov/pubmed/31932107

https://www.gynecologiconcology-online.net/article/S0090-8258(19)31805-0/fulltext

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Activation of cannabinoid receptor type 2 reduces lung ischemia reperfusion injury through PI3K/Akt pathway.

Image result for int j clin exp pathol“Cannabinoid receptor-2 activation plays a protective role against ischemic reperfusion injury (IRI) in various organs, and exerts a protective effect against paraquat-induced acute lung injury, while the role of CB2 in lung IRI remains unclear.

Hence, the present study was designed to explore the role of CB2 in lung IRI, and whether the PI3K pathway was involved.

The study suggested that activation of CB2 receptor plays a protective role against IR-induced lung injury through reducing inflammation in mice.

The PI3K/Akt pathway might be involved in the protective effect of CB2 receptors in lung IRI.”

https://www.ncbi.nlm.nih.gov/pubmed/31933805

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Involvement of endocannabinoid system, inflammation and apoptosis in diabetes induced liver injury: Role of 5-HT3 receptor antagonist.

International Immunopharmacology“Confident relationships between diabetes and liver damage have previously been established.

This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or without tropisetron treatment.

These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.”

https://www.ncbi.nlm.nih.gov/pubmed/31926479

https://www.sciencedirect.com/science/article/pii/S1567576919322684?via%3Dihub

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Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer’s Disease Lymphoblast Alterations.

“Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative disorder marked by progressive impairment of cognitive ability. Patients with AD display neuropathological lesions including senile plaques, neurofibrillary tangles, and neuronal loss.

There are no disease-modifying drugs currently available. With the number of affected individuals increasing dramatically throughout the world, there is obvious urgent need for effective treatment strategy for AD.

The multifactorial nature of AD encouraged the development of multifunctional compounds, able to interact with several putative targets. Here, we have evaluated the effects of two in-house designed cannabinoid receptors (CB) agonists showing inhibitory actions on β-secretase-1 (BACE-1) (NP137) and BACE-1/butyrylcholinesterase (BuChE) (NP148), on cellular models of AD, including immortalized lymphocytes from late-onset AD patients.

We report here that NP137 and NP148 showed neuroprotective effects in amyloid-β-treated primary cortical neurons, and NP137 in particular rescued the cognitive deficit of TgAPP mice. The latter compound was able to blunt the abnormal cell response to serum addition or withdrawal of lymphoblasts derived from AD patients.

It is suggested that NP137 could be a good drug candidate for future treatment of AD.”

https://www.ncbi.nlm.nih.gov/pubmed/31898159

https://link.springer.com/article/10.1007%2Fs12035-019-01813-4

“The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.” http://www.ncbi.nlm.nih.gov/pubmed/25147120

“These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.” http://www.ncbi.nlm.nih.gov/pubmed/25024327

“In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD” http://www.ncbi.nlm.nih.gov/pubmed/25147120

“Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.ncbi.nlm.nih.gov/pubmed/15728830

“Based on the complex pathology of AD, a preventative, multimodal drug approach targeting a combination of pathological AD symptoms appears ideal. Importantly, cannabinoids show anti-inflammatory, neuroprotective and antioxidant properties and have immunosuppressive effects.” http://www.ncbi.nlm.nih.gov/pubmed/22448595

“CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD therapy.” http://www.ncbi.nlm.nih.gov/pubmed/27471947

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Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases.

Image result for clinical and translational gastroenterology“In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant’s ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/31899693

https://journals.lww.com/ctg/Abstract/latest/Cannabinoids_and_Opioids_in_the_Treatment_of.99898.aspx

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β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

molecules-logo “Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs.

Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis (Cannabis sativa) activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence.

Therefore, we investigated the effect of β-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain.

BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31892132

https://www.mdpi.com/1420-3049/25/1/106

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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