“Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis.
Tag Archives: CBD
Molecular Targets of the Phytocannabinoids: A Complex Picture.
“For centuries, hashish and marihuana, both derived from the Indian hemp Cannabis sativa L., have been used for their medicinal, as well as, their psychotropic effects.
These effects are associated with the phytocannabinoids which are oxygen containing C21 aromatic hydrocarbons found in Cannabis sativa L.
To date, over 120 phytocannabinoids have been isolated from Cannabis.
For many years, it was assumed that the beneficial effects of the phytocannabinoids were mediated by the cannabinoid receptors, CB1 and CB2. However, today we know that the picture is much more complex, with the same phytocannabinoid acting at multiple targets.
This contribution focuses on the molecular pharmacology of the phytocannabinoids, including Δ9-THC and CBD, from the prospective of the targets at which these important compounds act.”
Phytochemistry of Cannabis sativa L.
“Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ9-tetrahydrocannabinol (Δ9-THC). The plant’s behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ9-THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ9-THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer’s, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant. This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.” https://www.ncbi.nlm.nih.gov/pubmed/28120229]]>
Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.
“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.” https://www.ncbi.nlm.nih.gov/pubmed/28110213]]>
A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.
“Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns.” https://www.ncbi.nlm.nih.gov/pubmed/28102593]]>
Targeting Cutaneous Cannabinoid Signaling in Inflammation – A “High”-way to Heal?
“The endocannabinoid system (ECS) is a recently emerging complex regulator of multiple physiological processes. It comprises several endogenous ligands (e.g. N-arachidonoylethanolamine, a.k.a. anandamide [AEA], 2-arachidonoylglycerol [2-AG], palmitoylethanolamide [PEA], etc.), a number of endocannabinoid (eCB)-responsive receptors (e.g. CB1 and CB2, etc.), as well as enzymes and transporters involved in the synthesis and degradation of the eCBs.
Among many other tissues and organs, various members of the ECS were shown to be expressed in the skin as well. Indeed, AEA, 2-AG, CB1 and CB2 together with the major eCB-metabolizing enzymes (e.g. fatty acid amide hydrolase [FAAH], which cleaves AEA to ethanolamine and pro-inflammatory arachidonic acid) were found in various cutaneous cell types. Importantly, the eCB-tone and cannabinoid signaling in general appear to play a key role in regulating several fundamental aspects of cutaneous homeostasis, including proliferation and differentiation of epidermal keratinocytes, hair growth, sebaceous lipid production, melanogenesis, fibroblast activity, etc.
Moreover, appropriate eCB-signaling through CB1 and CB2 receptors was found to be crucially important in keeping cutaneous inflammatory processes under control.
Collectively, these findings (together with many other recently published data) implied keratinocytes to be “non-classical” immune competent cells, playing a central role in initiation and regulation of cutaneous immune processes, and the “c(ut)annabinoid” system is now proven to be one of their master regulators.
Another recently emerging, fascinating possibility to manage cutaneous inflammation through the cannabinoid signaling is the administration of phytocannabinoids (pCB). Cannabis sativa contains over 100 different pCBs, the vast majority of which have no psychotropic activity, and usually possess a “favorable” side-effect profile, which makes these substances particularly interesting drug candidates in treating several inflammation-accompanied diseases.
With respect to the skin, we have recently shown that one of the best studied pCBs, (−)-cannabidiol (CBD), may have great potential in managing acne, an inflammation-accompanied, extremely prevalent cutaneous disease.
Collectively, in light of the above results, both increase/restoration of the homeostatic cutaneous eCB-tone by FAAH-inhibitors and topical administration of non-psychotropic pCBs hold out the promise to exert remarkable anti-inflammatory actions, making them very exciting drug candidates, deserving full clinical exploration as potent, yet safe novel class of anti-inflammatory agents.”
http://www.ebiomedicine.com/article/S2352-3964(17)30003-8/fulltext]]>Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.
“Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability.
Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.” https://www.ncbi.nlm.nih.gov/pubmed/28088032]]>Pharmacology of cannabinoids in the treatment of epilepsy.
“The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA). It has long been known that ∆9-THC has partial agonist activity at the endocannabinoid receptors CB1 and CB2, though it also binds to other targets which may modulate neuronal excitability and neuroinflammation. The actions of Δ9-THCV and Δ9-THCA are less well understood. In contrast to ∆9-THC, CBD has low affinity for CB1 and CB2 receptors and other targets have been investigated to explain its anticonvulsant properties including TRPV1, voltage gated potassium and sodium channels, and GPR55, among others. We describe the absorption, distribution, metabolism, and excretion of each of the above mentioned compounds. Cannabinoids as a whole are very lipophilic, resulting in decreased bioavailability, which presents challenges in optimal drug delivery. Finally, we discuss the limited drug-drug interaction data available on THC and CBD. As cannabinoids and cannabis-based products are studied for efficacy as anticonvulsants, more investigation is needed regarding the specific targets of action, optimal drug delivery, and potential drug-drug interactions.” https://www.ncbi.nlm.nih.gov/pubmed/28087250]]>
Medical Cannabis in the Palliation of Malignant Wounds—A Case Report
“Anecdotal accounts of the use of topical extracts from the cannabis plant being used on open wounds date back to antiquity. In modern times, cannabinoid therapies have demonstrated efficacy as analgesic agents in both pharmaceutical and botanical formats. Medical cannabis (MC), also known as medical marijuana,… The endogenous cannabinoid system, consisting of cannabinoid receptors and their endogenous ligands, is ubiquitous throughout the human body. Available research shows that cancer cells express higher levels of the cannabinoid receptors, CB1 and CB2, relative to their noncancer counterparts, while also demonstrating an overall state of upregulation. Human in vitro studies, using nonmelanoma skin lines, have demonstrated direct induction of tumor cell apoptosis and inhibition of tumor-related angiogenesis, both by way of activation of cannabinoid receptors.
The analgesic outcomes observed in this case are supported by the results of a recent systematic review and meta-analysis of cannabinoids for medical use. Unlike intact skin, which is polar and hydrophilic, wounds lack epithelial coverage and are nonpolar and lipophilic. Therefore, lipophilic compounds such as the THC and CBD cannabinoids may be readily absorbed through cutaneous wounds.
Before the use of topical MC oil, the patient’s wound was growing rapidly. Yet, after a few weeks, a modest regression of his malignant wound was observed while the patient used topical MC. This secondary outcome suggests that topical MC may promote antineoplastic activity as per the findings of Casanova et al.
In summary, this is the first case report to demonstrate the potential for MC to provide effective pain and symptom management in the setting of malignant wounds. The rapid onset of analgesia after topical placement suggests that the effects were mediated through absorption of the THC and CBD cannabinoids that subsequently interacted with peripheral nociceptors, immune cells, and cancer cells. The postapplication analgesia may be because of the gastrointestinal absorption of ingested residual MC oil. This case suggests that MC delivered in vaporized and topical oil formats warrants further investigation in human malignancy, including randomized controlled trials capable of establishing long-term efficacy, optimal dosage, schedules of administration, mixture composition, and safety.”
http://www.jpsmjournal.com/article/S0885-3924(16)30328-1/fulltext “Can Cannabis Oil Help Heal Wounds?” http://www.livescience.com/57500-can-medical-cannabis-help-heal-wounds.html “Oral cancer patient, 44, claims cannabis oil helped to shrink a hole in his cheek that was caused by the disease” http://www.dailymail.co.uk/health/article-4124752/Oral-cancer-patient-44-claims-cannabis-oil-helped-shrink-hole-cheek-caused-disease.html“Miracle plant: Can medical marijuana heal wounds?” http://www.nydailynews.com/life-style/medical-marijuana-heal-wounds-article-1.3384572
“Cannabis Oil Shows Potential To Heal Cancer Wounds Fast” http://www.healthaim.com/cannabis-oil-shows-potential-heal-cancer-wounds-fast/71395]]>Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells.
“Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer’s disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy.
In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform.
By comparing the expression profiles between GMSCs treated with CBD (CBD-GMSCs) and control GMSCs (CTR-GMSCs), we found that CBD led to the downregulation of genes linked to AD, including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In parallel, immunocytochemistry analysis has shown that CBD inhibited the expression of GSK3β, a central player in AD pathogenesis, by promoting PI3K/Akt signalling.
In order to understand through which receptor CBD exerted these effects, we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/GSK3β axis.
In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD.”