Cannabidiol Loaded Extracellular Vesicles Sensitize Triple-Negative Breast Cancer to Doxorubicin in both in-vitro and in vivo Models Running Title: Formulation and anti-cancer potential of CBD loaded hUCMSC-derived Extracellular Vesicles in TNBC

International Journal of Pharmaceutics“Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1±1.02 nm, zeta potential of -30.26±0.12 mV, entrapment efficiency of 92.3±2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74±2.44% and 53.99±1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Ourin-vitrostudies demonstrated that CBD either alone or in EVs form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P<0.05). Flow cytometry and migration studies revealed that CBD EVs either alone or in combination with DOX induced G1 phase cell cycle arrest and decreased migration of MDA-MB-231 cells, respectively. CBD EVs and DOX combination significantly reduced tumor burden (***P<0.001) in MDA-MB-231 xenograft tumor model. Western blotting and immunocytochemical analysis demonstrated that CBD EVs and DOX combination decreased the expression of proteins involved in inflammation, metastasis and increased the expression of proteins involved in apoptosis. CBD EVs and DOX combination will have profound clinical significance in not only decreasing the side effects but also increasing the therapeutic efficacy of DOX in TNBC.”

https://pubmed.ncbi.nlm.nih.gov/34324983/

https://www.sciencedirect.com/science/article/abs/pii/S0378517321007493?via%3Dihub

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KY Hemp-induced Modulation of Ovarian Cancer Cell Metastasis

“Our laboratory is interested in searching for a new plant-based therapeutics to treat ovarian cancer.

We are interested in studying anti-cancer effects of KY grown hemp as a potential candidate drug.

Marijuana and hemp belong to the same genus and species. However, they are different in cannabidiol (CBD) and tetrahydrocannabinol (THC) content.

Both CBD and THC are therapeutically beneficial. Hemp is harmless and non-addictive.

Major objective of this study is to investigate whether KY hemp extract can modulate the metastasis of ovarian cancer.

Based on the data here we conclude that KY hemp has significant anti-metastatic properties against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.667.7

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Searching for a New Anti-Cancer Drug: Investigation of KY Hemp-Induced Apoptosis in Ovarian Cancer Cells

“Marijuana (cannabis sativa) is a schedule 1 drug that has been recently approved by some states in the US for its therapeutic benefit.

Although there are a few reports about its anti-cancer potential, currently it has been used mainly for treatment-resistant epilepsy and to alleviate pain.

Hemp, which belongs to the same genus and species as marijuana, shows similar therapeutic benefits without addictive potential.

Our laboratory is interested in examining for unconventional therapies for ovarian cancer.

The main objective of the current study is to investigate hemp-induced modulation of A2780 ovarian cancer cell apoptosis.

Based on the data here we conclude that KY hemp has anti-cancer potential against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.616.1

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Cannabis Improves Stuttering: Case Report and Interview with the Patient

View details for Cannabis and Cannabinoid Research cover image“Introduction: Speech dysfluency, often referred to as stuttering, is a frequent speech disorder encountered in about 5% of children. Although in the majority of people affected, symptoms improve in adulthood, in some patients, stuttering persists and significantly impairs everyday functioning and quality of life. Treatment for stuttering includes speech therapy, cognitive behavioral therapy, and relaxation techniques. However, a substantial number of patients do not benefit sufficiently from these treatment strategies or are even treatment resistant. 

Methods: We present the case of a 20-year-old male with treatment-resistant stuttering, who markedly improved after treatment with medicinal cannabis. 

Results: Besides improved speech fluency as assessed by several phoniatric tests, we observed remission of (social) anxiety, improved mood, and reduced stress, resulting in an overall improvement of quality of life after cannabis therapy. The patient, in addition, reported improved attention, concentration, and sleep, increased self-confidence, and better social life. No side effects occurred. Over a time period of more than a year, treatment was equally effective. In an interview, the patient describes his personal view and the influence of cannabis-based treatment on his life. 

Conclusions: Medicinal cannabis could be effective in treatment of refractory stuttering, but these preliminary data have to be confirmed in controlled studies.”

https://pubmed.ncbi.nlm.nih.gov/34314602/

https://www.liebertpub.com/doi/10.1089/can.2021.0060

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Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland

SpringerLink“Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland.

We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy.

Improvements were reported in 59 (66%) study participants.

The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).

Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young.

What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders.

What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting.

• The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.”

https://pubmed.ncbi.nlm.nih.gov/34309706/

“For two thirds of participants treated with standardized THC or CBD preparations, the caregiver reported an improvement in their condition and well-being. Medical cannabis could be a promising and useful therapy for children and adolescents with neurological conditions.”

https://link.springer.com/article/10.1007%2Fs00431-021-04202-z

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Use of complementary therapies for chronic pain management in patients with reported Ehlers-Danlos syndrome or hypermobility spectrum disorders

American Journal of Medical Genetics Part A“Ehlers-Danlos Syndromes (EDS) and related Hypermobility Spectrum Disorders (HSD) are debilitating connective tissue disorders that feature a prominent pain component for which there are limited therapeutic options for pain management.

Consequently, many patients try various non-prescribed treatments, including complementary and alternative therapies that have not been well studied in the EDS/HSD patient population. We surveyed over 500 individuals through the EDS Society who reported having been diagnosed with EDS or HSD to ascertain what complementary and alternative therapies were used and their reported effectiveness in alleviating pain and improving quality of life.

Specifically, we focused on the use of traditional Chinese therapies, herbal medications, and marijuana.

The most commonly reported therapies, used by 70-92% of participants, were non-steroidal anti-inflammatory drugs, acetaminophen, opioids, and physical therapy.

Therapies rated by participants as most efficacious were opioids, physical therapy, and marijuana with 10-24% of those using these therapies rating them as extremely helpful.

Patient-initiated complementary therapy use in EDS/HSD patients is widespread at 56%. Complementary therapies were largely utilized by EDS/HSD patients with higher reported pain levels. Providers caring for EDS/HSD patients should be aware of these data showing broad usage of predominantly non-prescribed therapies and be prepared to consider such usage in working collaboratively with these patients to develop comprehensive treatment plans to manage their chronic pain complications.”

https://pubmed.ncbi.nlm.nih.gov/32909698/

https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.61837

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Treating pain related to Ehlers-Danlos syndrome with medical cannabis

BMJ Journals“We present the case of an 18-year-old woman who suffered from complications of Ehlers-Danlos syndrome (EDS). Her pain was poorly controlled despite being on a myriad of analgesic medications at the time.

On initiating cannabinoid-based treatment, her pain was drastically reduced, immediately enhancing the patient’s quality of life. As the patient continued to self-administer, she was able to eliminate her opioid requirement.

Considering the recent legalisation, we underline the need for physicians to be educated regarding the use of cannabinoids. In this case, specifically for chronic pain stemming from hypermobile EDS. Furthermore, we review the various impediments preventing ease of access to this potentially beneficial treatment.”

https://pubmed.ncbi.nlm.nih.gov/34301703/

https://casereports.bmj.com/content/14/7/e242568

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Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

molecules-logo“In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite.

The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion.

The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers.

The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers.

In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.”

https://pubmed.ncbi.nlm.nih.gov/34205169/

https://www.mdpi.com/1420-3049/26/11/3389

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Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

ijms-logo“Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative.

Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs).

Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.”

https://pubmed.ncbi.nlm.nih.gov/34298921/

https://www.mdpi.com/1422-0067/22/14/7302

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Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?

BMJ Journals - Northern Devon Healthcare NHS Trust“Central pain after stroke due to brainstem infarction is very rare. Treatment is difficult and specific guidelines are lacking. This is the report of a 61-year-old female patient who, after a posterolateral left medulla oblongata insult with incomplete Wallenberg syndrome, subsequently developed a burning and tingling pain in the contralateral leg and a burning and shooting pain in the ipsilateral face in trigeminal branches 1 and 2. More than 3 years of therapy with amitriptyline, gabapentin, pregabalin and various grade II and III opioids was ineffective or showed intolerable side effects. The administration of tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio improved the pain situation and quality of life quickly and permanently. The encouraging results in the present case may suggest that treatment with medical cannabis should be considered in similar cases when standard therapies are insufficient.”

https://pubmed.ncbi.nlm.nih.gov/34230048/

https://casereports.bmj.com/content/14/7/e243072

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