Tag Archives: CBD

Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control.

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“Chronic GPR18 activation by its agonist abnormal cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol; abn-cbd) improves myocardial redox status and function in healthy rats.

Here, we investigated the ability of abn-cbd to alleviate diabetes-evoked cardiovascular pathology and the contribution of GPR18 to this effect.

Collectively, the current findings present evidence for abn-cbd alleviation of diabetes-evoked cardiovascular anomalies likely via GPR18 dependent restoration of cardiac adiponectin-Akt-eNOS signaling and the diminution of myocardial oxidative stress.”

https://www.ncbi.nlm.nih.gov/pubmed/29274332

http://www.sciencedirect.com/science/article/pii/S0014299917308336

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

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 SAGE Journals

“Clostridium difficile toxin A is responsible for colonic damage observed in infected patients.

Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

RESULTS:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

CONCLUSIONS:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/29238589

“In the last decade, cannabinoids extracted from the marijuana plant (Cannabis sativa) and synthetic cannabinoids have shown numerous beneficial effects on gastrointestinal (GI) functions. Non-psychotropic phytocannabinoid cannabidiol (CBD) is one of the most interesting compounds, since it exerts a wide range of beneficial pharmacological actions on GI functions, ranging from antioxidant to antinflammatory activities. CBD has been shown to act as a non-competitive negative allosteric modulator of CB1 receptors. Notably, CBD is able to restore in vitro intestinal permeability increased by ethylenediaminetetraacetic acid (EDTA) or pro-inflammatory stimuli.

Conclusion

Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Clostridium difficile-Toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.

In the present study, we showed that Cannabidiol, a non-psychotropic component of Cannabis sativa significantly inhibit the apoptosis rate in TcdA-exposed cells and restores barrier function by a significant RhoA GTP rescue.

We also provide evidence that the effects of Cannabidiol are mediated by CB-1 receptor.

Given the absence of any significant toxic effect in humans, cannabidiol may ideally represent an effective adjuvant treatment for Clostridium difficile-associated colitis.”   http://journals.sagepub.com/doi/10.1177/2050640617698622

Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

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“Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties.

The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.

After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms and were more likely to have been rated as improved and as not severely unwell by the treating clinician.

These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.”

https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2017.17030325

“Cannabis ingredient holds promise as antipsychotic medicine” https://www.reuters.com/article/us-health-cannabis-psychosis/cannabis-ingredient-holds-promise-as-antipsychotic-medicine-idUSKBN1E90P6

“Cannabis extract could provide ‘new class of treatment’ for psychosis.” http://www.independent.co.uk/news/health/cannabis-extract-marijuana-psychosis-treatment-mental-health-cbd-thc-cannabidiol-kcl-a8111386.html

Anticonvulsant Effects of Cannabidiol in Dravet Syndrome

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“The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. The importance of this study is that, unlike most other antiseizure medication trials, it assesses a treatment in a specific epilepsy syndrome with a known genetic basis. CBD resulted in a significant decrease of convulsive seizures and seizures of all types in Dravet syndrome, a pharmacoresistant epilepsy known to be associated with high mortality rates.” http://epilepsycurrents.org/doi/10.5698/1535-7597.17.5.281?code=amep-site

Cannabinoids for epilepsy: What do we know and where do we go?

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Epilepsia

“Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients.

The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use.

Nevertheless, recent randomized, placebo-controlled trials with cannabidiol support its efficacy in Dravet and Lennox-Gastaut syndromes.

Further placebo-controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.”

https://www.ncbi.nlm.nih.gov/pubmed/29214639

http://onlinelibrary.wiley.com/doi/10.1111/epi.13973/abstract 

LH-21 and Abn-CBD improve β-cell function in isolated human and mouse islets through GPR55-dependent and -independent signalling.

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Diabetes, Obesity and Metabolism

“CB1 and GPR55 are GPCRs expressed by islet β-cells. Pharmacological compounds have been used to investigate their function, but off-target effects of ligands have been reported.

This study examined the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and islets from GPR55-/- mice were used to determine signalling via GPR55.

RESULTS:

Abn-CBD potentiated glucose-stimulated insulin secretion and elevated [Ca2+ ]i in human islets and islets from both GPR55+/+ and GPR55-/- mice. LH-21 also increased insulin secretion and [Ca2+ ]i in human islets and GPR55+/+ mouse islets, but concentrations of LH-21 up to 0.1 μM were ineffective in islets from GPR55-/- mice. Neither ligand affected basal insulin secretion or islet cAMP levels. Abn-CBD and LH-21 reduced cytokine-induced apoptosis in human islets and GPR55+/+ mouse islets, and these effects were suppressed following GPR55 deletion. They also increased β-cell proliferation: the effects of Abn-CBD were preserved in islets from GPR55-/- mice, while those of LH-21 were abolished. Abn-CBD and LH-21 increased AKT phosphorylation in mouse and human islets.

CONCLUSIONS:

This study demonstrated that Abn-CBD and LH-21 improve human and mouse islet β-cell function and viability. Use of islets from GPR55-/- mice suggests that designation of Abn-CBD and LH-21 as GPR55 agonist and CB1 antagonist, should be revised.”

https://www.ncbi.nlm.nih.gov/pubmed/29205751

http://onlinelibrary.wiley.com/doi/10.1111/dom.13180/abstract

Therapeutic use of Δ9-THC and cannabidiol: evaluation of a new extraction procedure for the preparation of cannabis-based olive oil.

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“Since 2013 Cannabis-based preparations, containing the two main cannabinoids of interest, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD), can be used for therapeutic purposes, such as palliative care, neurodegenerative disorder treatment and other therapies.

The preparations may consist of a drug partition in sachets, capsules or through the extraction in certified olive oil.

OBJECTIVE:

the aims of the study were: a) to develop and validate a new liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the identification and quantification of THC and CBD in olive oil; b) to evaluate the extraction efficiency and reproducibility of a new commercial extractor on the market.

METHODS:

the olive oil was simply diluted three consecutive times, using organic solvents with increasing polarity index (n-hexane → isopropanol → methanol). The sample was then direct injected into LC-MS/MS system, operating in Multiple Reaction Monitoring Mode, in positive polarization. The method was then fully validated.

RESULTS:

The method assessed to be linear over the range 0.1-10 ng/µL for both THC and CBD. Imprecision and accuracy were within 12.2% and 16.9% respectively; matrix effects proved to be negligible; THC concentration in oil is stable up to two months at room temperature, whenever kept in the dark. CBD provided a degradation of 30% within ten weeks. The method was then applied to olive oil after sample preparation, in order to evaluate the efficiency of extraction of a new generation instrument. Temperature of extraction is the most relevant factor to be optimized. Indeed, a difference of 2 °C (from 94.5°C to 96.5°C, the highest temperature reached in the experiments) of the heating phase, increases the percentage of extraction from 54.2% to 64.0% for THC and from 58.2% to 67.0% for CBD. The amount of THC acid and CBD acid that are decarboxylated during the procedure must be check out in the future.

CONCLUSION:

the developed method was simple and fast. The extraction procedure proved to be highly reproducible and applicable routinely to cannabis preparations.”

https://www.ncbi.nlm.nih.gov/pubmed/29189144

http://www.eurekaselect.com/157854/article

“Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil Preparations.”  https://www.ncbi.nlm.nih.gov/pubmed/29202510

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges.

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“It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.].

These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS), a recently emerging regulator of several physiological processes.

The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc.

Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis) or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption.

Thus, the objective of the current article is (i) to summarize the most recent findings of the field; (ii) to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii) to identify open questions and key challenges; and (iv) to suggest promising future directions for cannabinoid-based drug development.”   https://www.ncbi.nlm.nih.gov/pubmed/29176975

“Although, many open questions await to be answered, pharmacological modulation of the (endo)cannabinoid signaling, and restoration of the homeostatic eCB tone of the tissues augur to be very promising future directions in the management of several pathological inflammation-accompanied diseases.”   https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full

Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings.

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European Journal of Pain

“Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review.

Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice.

Cannabis-based medications available for humans mainly comprise Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and nabilone.

During the last 10 years, six controlled studies assessing analgesic effects of cannabinoid-based drugs in human experimental settings were reported. An effect on nociceptive processing could be translated to the human setting in functional magnetic resonance imaging studies that pointed at a reduced connectivity within the pain matrix of the brain. However, cannabinoid-based drugs heterogeneously influenced the perception of experimentally induced pain including a reduction in only the affective but not the sensory perception of pain, only moderate analgesic effects, or occasional hyperalgesic effects. This extends to the clinical setting.

While controlled studies showed a lack of robust analgesic effects, cannabis was nearly always associated with analgesia in open-label or retrospective reports, possibly indicating an effect on well-being or mood, rather than on sensory pain. Thus, while preclinical evidence supports cannabinoid-based analgesics, human evidence presently provides only reluctant support for a broad clinical use of cannabinoid-based medications in pain therapy.

SIGNIFICANCE:

Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.”

https://www.ncbi.nlm.nih.gov/pubmed/29160600

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1148/abstract?systemMessage=Wiley+Online+Library+usage+report+download+page+will+be+unavailable+on+Friday+24th+November+2017+at+21%3A00+EST+%2F+02.00+GMT+%2F+10%3A00+SGT+%28Saturday+25th+Nov+for+SGT+

Multiple sclerosis symptoms and spasticity management: new data.

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“Spasticity, perceived by patients as muscle rigidity and spasms, is a common symptom in multiple sclerosis (MS). It is associated with functional impairment that can exacerbate other MS symptoms and reduce quality of life.

Pharmacological treatment options are limited and frequently ineffective. Treatment adherence is a key issue to address in these patients.

The efficacy and safety of 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray for treatment of MS spasticity were demonstrated in four Phase III trials.

Observational studies and registry data subsequently confirmed the effectiveness and tolerability of THC:CBD oromucosal spray under everyday practice conditions.

Among patients who respond to treatment, THC:CBD oromucosal spray has been shown to produce positive improvements in gait parameters and to normalize muscle fibers.”

https://www.ncbi.nlm.nih.gov/pubmed/29143581
https://www.futuremedicine.com/doi/10.2217/nmt-2017-0034