“The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.”
Tag Archives: therapies
Dramatic response to Laetrile and cannabidiol (CBD) oil in a patient with metastatic low grade serous ovarian carcinoma.
“Complimentary alternative medicine use is common in women with gynecologic cancers. Cannabinoid receptors are potential therapeutic targets in ovarian cancer. Communication with patients is critical regarding use of alternative therapies.” https://www.ncbi.nlm.nih.gov/pubmed/31193514
In this case report, we present the case of a female patient who demonstrated disease response after declining standard therapy and taking a combination of Laetrile and CBD oil. Previous clinical trials in humans have demonstrated no therapeutic effect in cancer patients taking Laetrile. However, basic science studies have identified cannabinoid receptors in ovarian cancer as potential therapeutic targets for cannabinoid use in treating malignancy.
In this case report, we highlight a dramatic response to combination Laetrile and CBD oil in a patient with widely metastatic Low grade serous ovarian cancer (LGSOC).
Laetrile is a semi-synthetic version of amygdaline, a chemical compound found in plants and fruit seeds. Both Laetrile and amygdaline contain cyanide within a common structural component. Theoretically, Laetrile has anti-cancer effects when cyanide is released via enzymatic degradation. However, a Cochrane review published in 2015 found no randomized or quasi randomized control trials supporting the use of Laetrile in cancer patients. Further, they argued that due to the risk of cyanide poisoning, Laetrile use should be discouraged in patients seeking the compound for alternative cancer therapy. Concerns for toxicity in combination with inability to demonstrate clinical efficacy led to an effective ban on the substance by the FDA in the 1980s. Nevertheless, the substance remains available for purchase in variable formulations commercially.
Cannabidiol (CBD) is a compound naturally derived from the cannabis plant.
The anti-cancer effects of CBD have been evaluated predominantly in the laboratory setting. Interestingly, ovarian cancer cell lines express GPR55, a target that is inhibited indirectly by CBD and that plays a role in prostate and ovarian cancer cell proliferation. Mouse model studies have also demonstrated cannabinoids inhibit tumor cell growth and induce apoptosis in gliomas, lymphomas, prostate, breast, lung, skin, and pancreatic cancer cells.”
https://www.sciencedirect.com/science/article/pii/S2352578919300517?via%3Dihub
Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain.
“Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient’s last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous cannabinoid system has shown great promise and efficacy in alleviating CIPN in preclinical and clinical studies. In this review, we will discuss the mechanisms through which the platinum, taxane, and vinca alkaloid classes of chemotherapeutics may produce CIPN and the potential therapeutic effect of drugs targeting the endocannabinoid system in preclinical and clinical studies, in addition to cannabinoid compounds diffuse mechanisms of action in alleviation of CIPN.”
https://www.ncbi.nlm.nih.gov/pubmed/31127530
https://link.springer.com/article/10.1007%2Fs40265-019-01132-x
Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures.
“There can be a fine line between therapeutic intervention and substance abuse, and this point is clearly exemplified in herbal cannabis and its products. Therapies involving cannabis have been the treatment of last resort for some cases of refractory epilepsy, and this has been among the strongest medical justifications for legalization of marijuana. In order to circumvent the narcotic effects of Δ9-tetrahydrocannabinol (THC), many studies have concentrated on its less intoxicating isomer cannabidiol (CBD). However, CBD, like all natural cannabinoids, is a controlled substance in most countries, and its conversion into THC can be easily performed using common chemicals. We describe here the anticonvulsant properties of 8,9-dihydrocannibidiol (H2CBD), a fully synthetic analogue of CBD that is prepared from inexpensive, non-cannabis derived precursors. H2CBD was found to have effectiveness comparable to CBD both for decreasing the number and reducing the severity of pentylenetetrazole-induced seizures in rats. Finally, H2CBD cannot be converted by any reasonable synthetic route into THC, and thus has the potential to act as a safe, noncontroversial drug for seizure mitigation.”
Supplementation of Cannabis sativa L. leaf powder accelerates functional recovery and ameliorates haemoglobin level following an induced injury to sciatic nerve in mouse model.
“Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss.
Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury.
A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress.
The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group.
This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.”
Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia.
“Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology.
Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity.
Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.”
https://www.ncbi.nlm.nih.gov/pubmed/31052404
https://www.mdpi.com/1422-0067/20/9/2163
“Marijuana Relieves Chronic Pain, Research Shows” https://www.webmd.com/pain-management/news/20100830/marijuana-relieves-chronic-pain-research-show#1
Endocannabinoid System in Spinocerebellar Ataxia Type-3 and Other Autosomal-Dominant Cerebellar Ataxias: Potential Role in Pathogenesis and Expected Relevance as Neuroprotective Targets.
Cannabidiol enhances the passage of lipid nanocapsules across the blood-brain barrier both in vitro and in vivo.
“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
“Cannabidiol could help deliver medications to the brain. Cannabidiol (CBD), a non-psychoactive compound in cannabis, is being touted as beneficial for many health conditions, ranging from anxiety to epilepsy. Although much more research is needed to verify these claims, scientists have now shown that CBD could have a different use as a ‘Trojan horse’: helping slip medications across the blood-brain barrier (BBB) and into mouse brains.” https://www.sciencedaily.com/releases/2019/04/190417102739.htm
Dronabinol for the Treatment of Paraneoplastic Night Sweats in Cancer Patients: A Report of Five Cases.
“Night sweats significantly impact the quality of life for cancer patients and are often resistant to treatment.
Cannabinoids have been shown to modulate cytokine activity and produce hypothermia in animal models, suggesting that they may be a promising candidate for palliation of night sweats in patients with oncologic disease.
A retrospective record search identified five cancer patients who had tried oral dronabinol for palliation of their night sweats between 2013 and 2016 and subjectively reported on its efficacy.
RESULTS:
Treatment of five patients with advanced cancer with synthetic orally administered dronabinol resulted in the successful management of persistent symptomatic paraneoplastic night sweats.
CONCLUSION:
Dronabinol and/or medicinal cannabis are promising therapies for palliation of night sweats in cancer patients.”
Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer.
“Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New therapeutic approaches and diagnostic tools for identification, stratification, and treatment of patients at higher risk of resistance and recurrence are therefore warranted.
Here, we unveil a mechanism controlling the oncogenic activity of HER2: heteromerization with the cannabinoid receptor CB2R. We show that HER2 physically interacts with CB2R in breast cancer cells, and that the expression of these heteromers correlates with poor patient prognosis.
The cannabinoid Δ9-tetrahydrocannabinol (THC) disrupts HER2-CB2R complexes by selectively binding to CB2R, which leads to (i) the inactivation of HER2 through disruption of HER2-HER2 homodimers, and (ii) the subsequent degradation of HER2 by the proteasome via the E3 ligase c-CBL. This in turn triggers antitumor responses in vitro and in vivo. Selective targeting of CB2R transmembrane region 5 mimicked THC effects.
Together, these findings define HER2-CB2R heteromers as new potential targets for antitumor therapies and biomarkers with prognostic value in HER2-positive breast cancer.”
https://www.ncbi.nlm.nih.gov/pubmed/30733293
https://www.pnas.org/content/early/2019/02/06/1815034116