“Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents.
In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.”
“Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs.
In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERα-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy.
In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation.
In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone.
Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERα- breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.”
“The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth.
Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties.
To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL.
Expression levels of CNR1&2 were determined in 107 CLL patients by real-time PCR and analyzed with regard to prognostic markers and survival.
In contrast to other tumor entities, our data suggest a limited usability of cannabinoids for CLL therapy. Nonetheless, we could define CNR1 mRNA expression as novel prognostic marker.”
“Endocannabinoids (eCBs) are endogenous lipids able to activate cannabinoid receptors, the primary molecular targets of the cannabis (Cannabis sativa) active principle Δ(9)-tetrahydrocannabinol. During the last 20 years, several N-acylethanolamines and acylesters have been shown to act as eCBs, and a complex array of receptors, metabolic enzymes, and transporters (that altogether form the so-called eCB system) has been shown to finely tune their manifold biological activities. It appears now urgent to develop methods and protocols that allow to assay in a specific and quantitative manner the distinct components of the eCB system, and that can properly localize them within the cell. A brief overview of eCBs and of the proteins that bind, transport, and metabolize these lipids is presented here, in order to put in a better perspective the relevance of methodologies that help to disclose molecular details of eCB signaling in health and disease. Proper methodological approaches form also the basis for a more rationale and effective drug design and therapeutic strategy to combat human disorders.”
“The therapeutic properties of cannabinoids are well-known since ancient years.
Growing evidence exist on endocannabinoid system (ECS) modulation related with human tumorigenesis.
Taking into account the substantial role of ECS on immune cell regulation, the present review is aimed to summarize the emerging evidence concerning cannabinoid receptor (CBR) expression and cannabinoid ligand effects on haematological malignancies.
Most of cannabinoid actions, mainly CB2R-mediated against haematopoietic malignant cells, seems promising, as inhibition of cell proliferation and apoptosis and paraptosis induction have been documented.
Cannabinoid ligands appear to activate rudimentary pathways for cell survival, such as ERK, JNK, p38 MAPK, and to induce caspase synthesis, in vitro. Such data are strongly recommended to be confirmed by in vivo experiments with emphasis on cannabinoid ligands’ bioavailability and phytocannabinoid psychotropic properties.
The preliminary antitumoral ECS effects and their relative lack of important side effects render ECS a promising therapeutic target for the treatment of haematological malignancies.”
“The endocannabinoid system (ECS) is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1cannabinoid receptor (CB 1). In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB 1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons). Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB 1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB 1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile.”
“Since ancient times, plants have been used for therapeutic purposes.
Cannabis sativa has been widely used as a medicinal herb by Ayurveda and traditional Chinese medicine for centuries.
According to our in vitro and in vivo experimental models, cannabinoids are able to modulate fibrosis.
The exact mechanism underlying this effect requires further investigation, but it seems to go beyond their anti-inflammatory and immunomodulatory properties.
Based on the above observations, we aimed to investigate the role of cannabinoids in systemic sclerosis (SSc), an autoimmune disease characterized by diffuse fibrosis.
Since preclinical data on cannabinoids show their capability to modulate fibrosis, inflammation and vasodilatation, these molecules could be ideal drugs for targeting SSc.”
“Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoid forms can be used.
Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas, and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of “cannavaping,” defined as the “vaping” of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids.
The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively.
Conversely, “therapeutic cannavaping” could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.”
“Male lower urinary tract symptoms (LUTS) are prevalent in the general population, especially in those of advanced age, and are characterized by notable diversity in etiology and presentation, and have been proven to cause various degrees of impairment on quality of life.
The prostate has traditionally been regarded as the core cause of male LUTS. As a result, medical treatment aims to provide symptomatic relief and effective management of progression of male LUTS due to benign prostatic enlargement.
Anti-inflammatory agents, vitamin D3-receptor analogs, and cannabinoids represent treatment modalities currently under investigation for use in LUTS patients.
Furthermore, luteinizing hormone-releasing hormone antagonists, transient receptor-potential channel blockers, purinergic neurotransmission antagonists, Rho-kinase inhibitors, and inhibitors of endothelin-converting enzymes could have therapeutic potential in LUTS management, but still remain in the experimental setting.
This article reviews new strategies for the medical treatment of male LUTS, which are dictated by the potential role of the bladder and the risk of benign prostatic hyperplasia progression. Moreover, combination treatments and therapies currently under investigation are also presented.”
“Modulation of the CB2 receptor is an interesting approach for pain and inflammation, arthritis, addictions, neuroprotection, and cancer, among other possible therapeutic applications, and is devoid of central side effects.