A Descriptive Review of Cannabis sativa Patents for Cancer Treatment

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“Background: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid.

Objective: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using cannabis to treat cancer.

Methods: The research was carried out in the free and online database Espacenet, using the descriptors “cancer” and “Cannabis or cannabidiol” in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study.

Results: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry.

Conclusion: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.”



The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans


“The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer.

Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2-/-) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (ApcMin/+). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence.

Aging CB2-/- mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2-/- and ApcMin/+CB2-/- mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans.

Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients.”



Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma


“Cannabis has been used for decades as a palliative therapy in the treatment of cancer. This is because of its beneficial effects on the pain and nausea that patients can experience as a result of chemo/radiotherapy. Tetrahydrocannabinol and cannabidiol are the main compounds present in Cannabis sativa, and both exert their actions through a receptor-mediated mechanism and through a non-receptor-mediated mechanism, which modulates the formation of reactive oxygen species. These oxidative stress conditions might trigger lipidic changes, which would compromise cell membrane stability and viability.

In this sense, numerous pieces of evidence describe a potential antitumor effect of cannabinoid compounds in different types of cancer, although controversial results limit their implementation. In order to further investigate the possible mechanism involved in the antitumoral effects of cannabinoids, three extracts isolated from Cannabis sativa strains with high cannabidiol content were analyzed. Cell mortality, cytochrome c oxidase activity and the lipid composition of SH-SY5Y cells were determined in the absence and presence of specific cannabinoid ligands, with and without antioxidant pre-treatment.

The cell mortality induced by the extracts in this study appeared to be related to the inhibition of the cytochrome c oxidase activity and to the THC concentration. This effect on cell viability was similar to that observed with the cannabinoid agonist WIN55,212-2. The effect was partially blocked by the selective CB1 antagonist AM281, and the antioxidant α-tocopherol. Moreover, certain membrane lipids were affected by the extracts, which demonstrated the importance of oxidative stress in the potential antitumoral effects of cannabinoids.”


“In conclusion, cannabinoid extracts from high-CBD strains exhibit differential antitumor effects in human neuroblastoma cells by interfering with mitochondrial respiration and increasing ROS production, lipid peroxidation, and cell apoptosis in such a way that appears to correlate with THC content. However, the contributions of other compounds cannot be excluded. This action of the Cannabis sativa plant extracts used in our study was not only mediated by the cannabinoid receptor’s activity, but also by its effect on the mETC complexes, among others, which promote oxidative stress. Moreover, the use of plant extracts has demonstrated higher antitumoral effects than cannabinoids by themselves.”


UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders

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“Objectives: Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research specifically focuses on CBMPs’ efficacy and safety in headache disorders. This study aims to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population.

Methods: A case series of the UK Medical Cannabis Registry was conducted. Primary outcomes were changes from baseline in PROMs (Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire and Single-Item Sleep Quality Scale (SQS)) at 1-, 3-, and 6-months follow-up. P-values <0.050 were deemed statistically significant.

Results: Ninety-seven patients were identified for inclusion. Improvements in HIT-6, MIDAS, EQ-5D-5L and SQS were observed at 1-, 3-, and 6-months (p < 0.005) follow-up. GAD-7 improved at 1- and 3-months (p < 0.050). Seventeen (17.5%) patients experienced a total of 113 (116.5%) adverse events.

Conclusion: Improvements in headache/migraine-specific PROMs and general health-related quality of life were associated with the initiation of CBMPs in patients with headache disorders. Cautious interpretation of results is necessary, and randomized control trials are required to ascertain causality.”



Cannabidiol’s neuroprotective properties and potential treatment of traumatic brain injuries

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“Cannabidiol (CBD) has numerous pharmacological targets that initiate anti-inflammatory, antioxidative, and antiepileptic properties. These neuroprotective benefits have generated interest in CBD’s therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI).

There are currently no effective broad treatment strategies for combating the damaging mechanisms that follow the primary injury and lead to lasting neurological consequences or death. However, CBD’s effects on different neurotransmitter systems, the blood brain barrier, oxidative stress mechanisms, and the inflammatory response provides mechanistic support for CBD’s clinical utility in TBI.

This review describes the cascades of damage caused by TBI and CBD’s neuroprotective mechanisms to counter them. We also present challenges in the clinical treatment of TBI and discuss important future clinical research directions for integrating CBD in treatment protocols.

The mechanistic evidence provided by pre-clinical research shows great potential for CBD as a much-needed improvement in the clinical treatment of TBI. Upcoming clinical trials sponsored by major professional sport leagues are the first attempts to test the efficacy of CBD in head injury treatment protocols and highlight the need for further clinical research.”


“There is strong mechanistic support that CBD could be an effective pharmacological intervention for TBIs, however the current state of the research field is mostly derived from rodent studies. The upcoming clinical trials will be especially informative for determining CBD’s efficacy as a TBI treatment.”


“Bones and Joints” The Role of Cannabidiol (CBD) in Musculoskeletal Health

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“Cannabis has a rich history as a therapeutic tool with wide ranging applications.

The efficacy of cannabidiol (CBD), the non-psychoactive component of cannabis, has been well demonstrated for pain management. Further, recent orthopedic studies have demonstrated positive effects of CBD on wound healing, inflammation, bone marrow density, and fracture healing.

Despite the growing interest in CBD, there is a paucity of research on its impact on fracture risk and bone density in human clinical trials and the existing literature has significant limitations. As the rate of cannabis consumption increases, further research is essential to delineate the therapeutic qualities of CBD and its long-term effects on fracture healing and bone metabolism in order to optimize patient outcomes.”


“Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts”


The Endocannabinoid System and Physical Exercise


“The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions.

Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endogenous cannabinoids.

Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time.

A runner’s high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon.

The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects.

This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.”


“PE is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with many health benefits, one of them being the activation of endogenous cannabinoids to reduce stress and anxiety and improve wellness.”


“Exercise activates the endocannabinoid system”


Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial

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“Background: Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU.

Methods: A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14).

Results: None of the subjects exhibited allergic reactions or side effects. Their vital signs and blood parameters were stable before and after the 7-day CBD intervention. CBD and TA significantly reduced ulcer size more than placebo at all time points. The erythematous size reduction was higher in the CBD intervention than the placebo on day 2, while TA reduced the erythematous size at all time points. The pain score in the CBD group was lower compared with placebo on day 5, whereas TA reduced pain more than placebo on day 4, 5, and 7. The subjects receiving CBD reported higher satisfaction than placebo. However, the OHIP-14 scores were comparable among the interventions.

Conclusions: Topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without side effects. CBD exerted anti-inflammatory effects in the early stage and an analgesic effect in the late RAU stage. Thus, topical 0.1% CBD might be more appropriate for RAU patients who decline to take topical steroids, except for cases where CBD is contraindicated.”


“This clinical study demonstrated that topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without any reported local (signs of allergic and anaphylactic reactions) or systemic (vital sign and blood test alteration) side effects. Furthermore, in the RCT, topical CBD exerted an anti-inflammatory effect by reducing the erythematous border size in the early stage and decreased pain intensity in the late stage of RAU. Thus, CBD may be appropriate for RAU patients who choose not to take topical steroids, except for cases where CBD is contraindicated, such as being allergic to CBD, a history of drug or alcohol addiction, and a history of mood disorders.”


Management of Chronic Anal Fissure with a Novel Topical Hemp-Herbal-Based Ointment: A Pilot Study

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“Introduction: Anal fissure (AF) is a common anorectal disease. Although several pharmacological treatments are available, many patients still require surgical interventions. In this study, we aimed to evaluate the efficacy of an ointment based on a multifunctional blend of herbal ingredients including hemp (ProctoFiz) for chronic AF.

Methods: A single-arm, questionnaire-based prospective study was conducted in a large tertiary center to evaluate the outcomes of patients suffering from chronic AF treated with topical ProctoFiz.

Results: Ninety-two patients were included in the study, 54 (58.7%) were females with a median age of 39 (range 17-78). 32 patients (34.7%) suffered from recurrent AF before enrolling in the study, and 5 patients (5.4%) underwent previous surgical interventions for AF. Three patients (3.2%) were lost to follow-up, leaving 89 patients for analysis. Eighty patients (89.9%) reported significant improvement of symptoms after 1 week using ProctoFiz, and 79 patients reported continued improvement after 1 month of treatment. The mean pain Visual Analog Score (VAS) declined by 6.6 points (8.9 vs. 2.3; 95% CI: 7.20 to -5.99, p < 0.0001) following 1 week of treatment, with continuous improvement to a mean of 0.64 after 1 month. Negative impact on quality of life significantly decreased from a mean of 8.8 to 0.38 following a month of treatment (p < 0.0001), with significant reduction in the number of patients suffering from bleeding following bowel movements (64.1-2.5%; p = 0.0001).

Conclusion: Hemp-based topical treatment of AF is feasible and significantly improves AF-correlated symptoms.”


Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation

Journal of Integrative Medicine

“Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient’s life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects.

Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells. Cannabinoids promote atypical protein kinase C, deactivate fatty acid amide hydrolase enzymes, and activate transient receptor potential vanilloid 1 (TRPV1) and TRPV2 to induce pro-apoptotic signaling pathways without increasing endogenous cannabinoids. In previous in vivo studies, endocannabinoids, chemically classified as amide formations of oleic and palmitic acids, have been shown to increase the pro-apoptotic activity of human cancer cells and inhibit cell migration and angiogenesis.

This review focuses on the biological synthesis and pharmacology of endogenous cannabinoids for the enhancement of cancer cell apoptosis, which have potential as a novel therapy for GBM.”


“As discussed above, endocannabinoids could prove to be a viable alternative treatment for GBM.”