Combinations of Cannabidiol and Δ9-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain

Posted on by
biomedicines-logo

“Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios.

We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data suggest that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant.

We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model.”

https://pubmed.ncbi.nlm.nih.gov/36289810/

https://www.mdpi.com/2227-9059/10/10/2548/htm

Use of Cannabis and Cannabinoids for Treatment of Cancer

Posted on by
cancers-logo

“The endocannabinoid system (ECS) is an ancient homeostasis mechanism operating from embryonic stages to adulthood. It controls the growth and development of many cells and cell lineages. Dysregulation of the components of the ECS may result in uncontrolled proliferation, adhesion, invasion, inhibition of apoptosis and increased vascularization, leading to the development of various malignancies. Cancer is the disease of uncontrolled cell division.

In this review, we will discuss whether the changes to the ECS are a cause or a consequence of malignization and whether different tissues react differently to changes in the ECS. We will discuss the potential use of cannabinoids for treatment of cancer, focusing on primary outcome/care-tumor shrinkage and eradication, as well as secondary outcome/palliative care-improvement of life quality, including pain, appetite, sleep, and many more factors. Finally, we will complete this review with the chapter on sex- and gender-specific differences in ECS and response to cannabinoids, and equality of the access to treatments with cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36291926/

“Cancer is a disease which affects approximately 40% of people in their lifetime. Chemotherapy, the primary choice for treatment of cancer, is often ineffective or/and presents itself with many debilitating side effects, including loss of appetite, nausea, insomnia, and anxiety. Components of cannabis extracts, including cannabinoids and terpenes, may present an alternative for controlling side effects and may be used for tumor shrinkage together with chemodrugs.

Cannabinoids act on so called endocannabinoid system (ECS) that operates in our body to maintain homeostasis. ECS promotes healthy development of tissues and regulates many processes in our organism and when disbalanced may lead to disease, including cancer. In this review, we will discuss the role of the ECS in relation with carcinogenesis and use of cannabis extracts and their components for primary and secondary care of cancer.

Knowledge about the use of cannabinoids for cancer therapy may prolong the life of many cancer patients.

Here, we showed substantial preclinical and clinical evidence of the potential of cannabinoids and cannabis extracts in primary and palliative care of cancer.”

https://www.mdpi.com/2072-6694/14/20/5142/htm

The Synthetic Cannabinoid URB447 Exerts Antitumor and Antimetastatic Effect in Melanoma and Colon Cancer

Posted on by
pharmaceuticals-logo

“The endocannabinoid system is widespread through the body and carries out a wide variety of functions. However, its involvement in other pathologies, such as cancer, still needs further attention. We aim to investigate the role of CB2 receptor during melanoma and colorectal cancer (CRC) aggressiveness and metastatic growth in the liver. We used the synthetic cannabinoid URB447, a known CB2 agonist and CB1 antagonist drug, and studied prometastatic ability of mouse B16 melanoma and MCA38 CRC cells, by means of proliferation, apoptosis, cell cycle, migration and matrix degradation in vitro upon URB447 treatment. We reported a dose-dependent viability decrease in both tumor types. This result is partly mediated by apoptotic cell death and cell cycle arrest in G1/G0 phase, as observed through flow cytometry. Melanoma and CRC cell migration was affected in a dose-dependent fashion as observed through scratch assay, whereas the secretion of matrix degrading proteins metalloprotease 2 (MMP2) and 9 (MMP9) in tumor cells did not significantly change. Moreover, daily treatment of tumor bearing mice with URB447 decreased the development of liver metastasis in a melanoma model in vivo. This proof of concept study points out to the synthetic cannabinoid URB447 as a potential candidate for deeper studies to confirm its potential as antitumor therapy and liver metastasis treatment for CRC and melanoma.”

https://pubmed.ncbi.nlm.nih.gov/36297277/

https://www.mdpi.com/1424-8247/15/10/1166/htm

Effect of Cannabidiolic Acid, N- Trans-Caffeoyltyramine and Cannabisin B from Hemp Seeds on microRNA Expression in Human Neural Cells

Posted on by
cimb-logo

“Given the increasing interest in bioactive dietary components that can modulate gene expression enhancing human health, three metabolites isolated from hemp seeds-cannabidiolic acid, N–trans-caffeoyltyramine, and cannabisin B-were examined for their ability to change the expression levels of microRNAs in human neural cells. To this end, cultured SH-SY5Y cells were treated with the three compounds and their microRNA content was characterized by next-generation small RNA sequencing. As a result, 31 microRNAs underwent major expression changes, being at least doubled or halved by the treatments. A computational analysis of the biological pathways affected by these microRNAs then showed that some are implicated in neural functions, such as axon guidance, hippocampal signaling, and neurotrophin signaling. Of these, miR-708-5p, miR-181a-5p, miR-190a-5p, miR-199a-5p, and miR-143-3p are known to be involved in Alzheimer’s disease and their expression changes are expected to ameliorate neural function. Overall, these results provide new insights into the mechanism of action of hemp seed metabolites and encourage further studies to gain a better understanding of their biological effects on the central nervous system.”

https://pubmed.ncbi.nlm.nih.gov/36286061/

https://www.mdpi.com/1467-3045/44/10/347/htm

Cannabis sativa in Phytotherapy : Reappraisal of therapeutic potential and regulatory aspects

Posted on by
Generic placeholder image

“Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids.

Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer.

However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to the resurgence of interest in the clinical application of its constituents, particularly cannabinoids.

This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.”

https://pubmed.ncbi.nlm.nih.gov/36281862/

https://www.eurekaselect.com/article/127142

Cannabis Use Is Inversely Associated with Metabolic Disorders in Hepatitis C-Infected Patients (ANRS CO22 Hepather Cohort)

Posted on by
jcm-logo

“Background and aims: Hepatitis C virus (HCV) infection is associated with the onset of metabolic disorders which constitute risk factors for liver disease progression. Their impact may persist after the HCV infection has been cured. Cannabis use is associated with a lower risk of obesity and diabetes in both general and HCV populations. The associations between cannabis use and both dyslipidemia and hypertension have not yet been studied in persons with chronic HCV infection.

Methods: Using cross-sectional data from the French ANRS CO22 Hepather cohort, we used regression models to test for an inverse relationship between cannabis use and (i) dyslipidemia, (ii) hypertension, and (iii) the total number of metabolic disorders.

Results: Among the 6364 participants in the study population, both former and current cannabis use were associated with a lower risk of hypertension and fewer metabolic disorders. These results were independent of central obesity. Cannabis use was not associated with dyslipidemia.

Conclusions: In people chronically infected with HCV, cannabis use was associated with a lower risk of hypertension and a lower number of metabolic disorders. Post-HCV cure studies are needed to confirm these findings using longitudinal data and to test whether they translate into reduced mortality in this population.”

https://pubmed.ncbi.nlm.nih.gov/36294456/

“In a large cohort of people with chronic HCV infection living in France, current or former cannabis use was associated with a lower risk of hypertension and a lower number of metabolic disorders.”

https://www.mdpi.com/2077-0383/11/20/6135/htm

Cannabidiol as a modulator of α7 nicotinic receptors

Posted on by
SpringerLink

“Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor (α7 nAChR) is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. By high-resolution single-channel recordings and confocal microscopy, we here reveal how CBD modulates α7 nAChR ionotropic and metabotropic functions. CBD leads to a profound concentration-dependent decrease of α7 nAChR single-channel activity with an IC50 in the sub-micromolar range. The inhibition of α7 nAChR activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 nAChR conformational states. CBD modulation is complex as it also leads to the later appearance of atypical, low-frequency α7 nAChR channel openings. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 nAChR activation, thus decreasing cell calcium responses. The modulation of α7 nAChR is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.”

https://pubmed.ncbi.nlm.nih.gov/36282426/

https://link.springer.com/article/10.1007/s00018-022-04600-y

“Targeting α7 nicotinic acetylcholine receptors for chronic pain”

https://pubmed.ncbi.nlm.nih.gov/36245927/

Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic

Posted on by
Frontiers - Crunchbase Company Profile & Funding

“Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation. 

Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12. 

Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F1-125 = 7.67; p = 0.006; ηp 2 = 0.06; F1-125 = 6.58; p = 0.01; ηp 2 = 0.05; F1-125 = 4.28; p = 0.04; ηp 2 = 0.03, respectively) after the end of the treatment. 

Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.”

https://pubmed.ncbi.nlm.nih.gov/36263136/

“This observational and clinical trial study combination follow-up showed that the beneficial effects on anxiety, emotional exhaustion/burnout, and depressive symptoms observed among frontline health care professionals working with patients with COVID-19 after 28 days of daily CBD administration were maintained for up to a month after the treatment discontinuation. This study meets the recently highlighted need for extensive real-world studies on CBD’s potential medicinal use. Future double-blind placebo-controlled clinical trials are needed to assess the CBD long-term effects and confirm the present findings.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.856846/full

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

Posted on by
Frontiers - Crunchbase Company Profile & Funding

“Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson’s disease.”

https://pubmed.ncbi.nlm.nih.gov/36278152/

“Cannabis has therapeutic promise in PD. However, there is a need to move beyond whole plant extracts and generate safe, reproducible medicines for patients. This paper identified promising minimal essential mixtures of cannabinoids based on a step-wise, strategic approach to reducing the complexity of the plant secondary metabolome. The sequential use of in silico, in vitro, and medium throughput in vivo experimental systems has generated refined, de-risked, mixtures that can now be tested in additional, higher-cost, preclinical model systems of PD.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.907579/full

Efficacy and mechanism of the antinociceptive effects of cannabidiol on acute orofacial nociception induced by Complete Freund’s Adjuvant in male Mus musculus mice

Posted on by
Archives of Oral Biology

“Objectives: The objectives were to investigate the efficacy and mechanisms of cannabidiol on orofacial nociception induced by Complete Freund’s Adjuvant (CFA) in male Mus musculus mice.

Design: For the study of efficacy, mice were divided into seven groups: sham; inflammation; and cannabidiol 0.5, 1, 3, 5, and 10 mg. For the study of mechanisms of cannabidiol, mice were divided into six groups: sham, inflammation, calcitonin gene-related peptide (CGRP) antagonist with and without cannabidiol, and vanilloid receptor 1 antagonist with and without cannabidiol. Spontaneous pain-like behaviors, trigeminal nociception, and trigeminal modulating activity were investigated.

Results: CFA injected in the right masseter muscle significantly induced spontaneous pain-like behaviors and the trigeminal nociceptive pathway. This effect was inhibited by injection of 1, 3, 5, and 10 mg of cannabidiol. The 50 % inhibitory concentration of cannabidiol on antinociception was found to be 3 mg/kg. In addition, there was no difference in spontaneous pain-like behaviors with vanilloid receptor 1 antagonist injected before treatment with cannabidiol compared to saline control. Reduced c-fos expression was observed in the trigeminal nucleus caudalis and periaqueductal gray in the group injected with CGRP antagonist before treatment with cannabidiol.

Conclusion: The antinociceptive effects of cannabidiol induced by acute orofacial nociception is mediated by vanilloid receptor 1 but not by CGRP. Cannabidiol can act with peripheral nonpeptidergic neurons and can be used as an alternative drug or as a synergistic medication in pain treatment.”

https://pubmed.ncbi.nlm.nih.gov/36265395/

“Our results may imply that cannabidiol can be used as an alternative drug or as synergistic medication in orofacial pain treatment.”

https://www.sciencedirect.com/science/article/abs/pii/S0003996922002278?via%3Dihub