CBD as the New Medicine in the Pain Provider’s Armamentarium.

“As providers who currently treat some chronic pain patients with CBD oil as part of a multimodal analgesic treatment regimen, we have found great benefit of this new weapon recently being utilized in our armamentarium. As mentioned in the article, the current political climate surrounding CBD is both vague and ever-changing, which can and does impact treatment and subsequent patient outcomes as pain medicine providers. If we want to make cannabis and CBD into a legitimate medicinal treatment, there must be more regulations on CBD oil production and accurate labeling. Patients will continue to seek CBD oil as an additional option to treat their chronic pain as it gains popularity, so it is our duty as providers to protect them and ensure they have safe options of this new medication to choose from.”
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Cannabidiol enhances the passage of lipid nanocapsules across the blood-brain barrier both in vitro and in vivo.

 Molecular Pharmaceutics“Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood-brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with non-psychotropic cannabinoids as pioneering non-immunogenic brain targeting molecules and to the evaluation of their brain targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of CBD to LNCs outperformed by 6-fold the enhancement observed for the G-Technology® (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases) As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/30865462

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01344

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Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit.

 

Image result for Am J Gastroenterol.

“Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients’ perceived benefit of cannabinoids for Gp symptoms.

METHODS:

Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments.

RESULTS:

Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use.

CONCLUSIONS:

A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.”

https://www.ncbi.nlm.nih.gov/pubmed/30865015

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Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects.

 

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“Medically refractory epilepsy remains an area of intense clinical and scientific interest since a significant porportion of patients continue to suffer from debilitating seizures despite available therapies. In this setting, recent studies have focused on assessing the benefits of cannabidiol (CBD)-enriched cannabis, a plant based product without psychoactive properties which has been shown to decrease seizure frequency in animal models. More recently, several randomized controlled and open label trials have studied the effects of Epidiolex, a 99% pure oral CBD extract, on patients with refractory epilepsy. This in turn has led to the FDA approval of and more recently, to the Drug Enforcement Administration’s placement of Epidiolex into schedule V of the Controlled Substances Act (CSA). In this review, we summarize the major findings of several recent large-scale studies using this product with a focus on its adverse effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30854190

“The recent FDA approval of Epidiolex combined with the placement of this compound in schedule V of the CSA (the least restrictive schedule of the CSA) has created a much-needed opportunity for the continued study of high-concentration, regulated CBD as a potential therapy for refractory epilepsy. Although recent RCTs and open-label extended-access programs have already demonstrated significant improvement in seizure frequency and severity with a relatively well-tolerated side effect profile for this compound, continued monitoring of Epidiolex is needed to further asses the long-term safety and efficacy, particularly with regard to immune, cognitive, hormonal, and reproductive function. Furthermore, there have been no large-scale RCTs demonstrating significant seizure reduction with Epidiolex in patients with focal onset seizures. Nonetheless, to date, Epidiolex has proven to be an attractive treatment option for an otherwise devastating group of epileptic syndromes. Future studies expanding our knowledge of this compound will be helpful in better understanding its role in the future of epilepsy treatment.”  https://f1000research.com/articles/8-234/v1

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Promoting cannabis products to pharmaceutical drugs.

European Journal of Pharmaceutical Sciences

“Cannabis sativa is widely used for medical purposes. However, to date, aroma, popular strain name or the content of two phytocannabinoids-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are mostly considered for therapeutic activity. This is despite the hundreds of compounds in this plant and their potential synergistic interactions in mixtures. New, specific and effective cannabis-based drugs must be developed to achieve adequate medical standards for the use of cannabis. To do this, the comprehensive molecular profile of cannabis-based drugs must be defined, and mixtures of compounds should be tested for superior therapeutic activity due to synergistic effects compared to individually isolated cannabis compounds. The biological pathways targeted by these new drugs should also be characterized more accurately. For drug development and design, absorption, distribution, metabolism and elimination versus toxicity (ADME/Tox) must be characterized, and therapeutic doses identified. Promoting the quality and therapeutic activity of herbal or synthetic cannabis products to pharma grade is a pressing need worldwide.”

https://www.ncbi.nlm.nih.gov/pubmed/30851400

https://www.sciencedirect.com/science/article/pii/S0928098719300880?via%3Dihub

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Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells.

Biomedicine & Pharmacotherapy

“Insulin resistance and β-cell dysfunction are the main defects in Type 2 Diabetes Mellitus (T2DM), and β-cell dysfunction and apoptosis is the critical determinant in the progression of T2DM. G-protein coupled receptor 55 (GPR55) is an orphan G-protein coupled receptor, which is activated by endocannabinoids and lipid transmitters. Recently, GPR55 was shown to regulate glucose and energy homeostasis, however its role in β-cell apoptosis was not studied. Therefore, in this study, we investigated the novel effect of GPR55 agonists, O-1602 and abnormal cannabidiol (Abn-CBD), on endoplasmic reticulum (ER) stress-induced apoptosis in mouse pancreatic β-cell lines, MIN6 and Beta-TC-6, and its underlying mechanisms. Our results showed that O-1602 and Abn-CBD reduced ER stress-induced apoptosis in MIN6 and Beta-TC-6 cells. This was through the phosphorylation of 3′-5′-cyclic adenosine monophosphate response element-binding protein (CREB) in β-cells, hence activating CREB downstream anti-apoptotic genes, Bcl-2 and Bcl-xL. Moreover, O-1602 and Abn-CBD directly activated kinases, CaMKIV, Erk1/2 and PKA, to induce CREB phosphorylation. Therefore, our results indicated that GPR55 agonists protected from β-cell apoptosis through CREB activation, thus up-regulating anti-apoptotic genes. In conclusion, our study provided a novel protective effect of GPR55 agonists on ER stress-induced apoptosis in β-cells and its underlying mechanisms mediating this protection, therefore we suggested that GPR55 might be a therapeutic target for T2DM.”

https://www.ncbi.nlm.nih.gov/pubmed/30841431

https://www.sciencedirect.com/science/article/pii/S0753332218375668?via%3Dihub

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The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder.

 Related image“Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs’ therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD’s promise, further investigation and validation of CBD’s efficacy, across preclinical and clinical trials will be necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/30837904

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00063/full

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Striking lung cancer response to self-administration of cannabidiol: A case report and literature review.

SAGE Journals

“In spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitroand in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice.

We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa. Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer.

The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30815264

https://journals.sagepub.com/doi/10.1177/2050313X19832160

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Lung alveolar tissue destruction and protein citrullination in diesel exhaust exposed mouse lungs.

Basic &amp; Clinical Pharmacology &amp; Toxicology banner

“Humanity faces an increasing impact of air pollution worldwide, including threats to human health. Air pollutants prompt and promote chronic inflammation, tumourigenesis, autoimmune and other destructive processes in the human body.

Post-translational modification of proteins, e.g. citrullination, results from damaging attacks of pollutants, including smoking, air pollution and others, rendering host tissues immunogenic. Citrullinated proteins and citrullinating enzymes, deiminases, are more prevalent in patients with COPD and correlate with ongoing inflammation and oxidative stress.

In this study, we installed an in-house-designed diesel exhaust delivery and cannabidiol vaporization system where mice were exposed to relevant, urban traffic-related levels of diesel exhaust for 14 days and assessed integrity of alveolar tissue, gene expression shifts and changes in protein content in the lungs and other tissues of exposed mice. Systemic presence of modified proteins was also tested.

The protective effect of phytocannabinoids was investigated as well.

Data obtained in our study show subacute effects of diesel exhaust on mouse lung integrity and protein content. Emphysematous changes are documented in exposed mouse lungs. In parallel, increased levels of citrulline were detected in the alveolar lung tissue and peripheral blood of exposed mice.

Pretreatment with vaporized cannabidiol ameliorated some damaging effects.

Results reported hereby provide new insights into subacute lung tissue changes that follow diesel exhaust exposure and suggest possible dietary and/or other therapeutic interventions for maintaining lung health and healthy ageing.”

https://www.ncbi.nlm.nih.gov/pubmed/30801928

https://onlinelibrary.wiley.com/doi/abs/10.1111/bcpt.13213

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Intractable Generalized Epilepsy: Therapeutic Approaches.

 

“PURPOSE OF REVIEW:

To summarize recent developments in therapeutic options, both medical and surgical, for patients with drug-resistant generalized epilepsy syndromes, which continue to be a multifaceted challenge for patients and physicians.

RECENT FINDINGS:

Newer generation pharmaceutical options are now available, such as brivaracetam, rufinamide, lacosamide, perampanel, and cannabidiol. Less restrictive dietary options appear to be nearly as effective as classic ketogenic diet for amelioration of seizures. The latest implantable devices include responsive neurostimulation and deep brain stimulation. Corpus callosotomy is an effective treatment for some seizure types, and newer and less invasive approaches are being explored. Resective surgical options have demonstrated success in carefully selected patients despite generalized electrographic findings on electroencephalogram. The current literature reflects a widening range of clinical experience with newer anticonvulsant medications including cannabinoids, dietary therapies, surgical approaches, and neurostimulation devices for patients with intractable generalized epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/30806817

https://link.springer.com/article/10.1007%2Fs11910-019-0933-z

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