” Flower Power”: Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients


“In November 2018, the UK’s Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration (“oils”) and dried flowers for inhalation (“flos”). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; p < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; p < 0.001) and interference (T = 7.19; p < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; p < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.”


“Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos was associated with a robust improvement in patient-reported pain scores, general mood, anxiety, sleep, and overall HRQoL in a treatment-resistant clinical population.”


Herbal Cannabis Use Is Not Associated with Changes in Levels of Endocannabinoids and Metabolic Profile Alterations among Older Adults


“Activation of the endocannabinoid system has various cardiovascular and metabolic expressions, including increased lipogenesis, decreased blood pressure, increased heart rate, and changes in cholesterol levels. There is a scarcity of data on the metabolic effects of exogenous cannabis in older adults; therefore, we aimed to assess the effect of exogenous cannabis on endocannabinoid levels and the association with changes in 24 h ambulatory blood pressure and lipid levels. We conducted a prospective study of patients aged 60 years or more with hypertension treated with a new prescription of herbal cannabis. We assessed changes in endocannabinoids, blood pressure, and metabolic parameters prior to and following three months of cannabis use. Fifteen patients with a mean age of 69.47 ± 5.83 years (53.3% male) underwent complete evaluations. Changes in 2-arachidonoylglycerol, an endocannabinoid, were significantly positively correlated with changes in triglycerides. Changes in arachidonic acid levels were significantly positively correlated with changes in C-reactive protein and with changes in mean diastolic blood pressure. Exogenous consumption of cannabidiol was negatively correlated with endogenous levels of palmitoylethanolamide and oleoylethanolamide. On average, cannabis treatment for 3 months does not result in a significant change in the levels of endogenous cannabinoids and thus has a safe metabolic risk profile.”


“The endocannabinoid system is a complex cell-signaling system that has numerous effects on the human body, including on the heart, blood vessels, and metabolism. In this study, we aimed to assess the effects of exogenous herbal medical cannabis use on the components of the endocannabinoid system among older adults with a diagnosis of hypertension. Medical cannabis is a product containing cannabinoids used for medical purposes. Herbal cannabis contains many types of cannabinoids, the most well-known of which are Δ9-tetrahydrocannabinol and cannabidiol. We followed people aged 60 years and older and conducted a number of tests, including endocannabinoids levels, before they started using cannabis and following three months of daily cannabis treatment. Fifteen patients (53.3% male; mean age, 69.5 years) underwent complete evaluations. We found positive correlations between the components of the endocannabinoid system and blood lipids, markers of inflammation, and blood pressure. On average, cannabis treatment for 3 months does not result in a significant change in the levels of endogenous cannabinoids and thus has a safe metabolic risk profile. This study provides additional evidence for the safety of medical cannabis use among older adults.”


The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases


“The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.”


“The cannabinoid system has the potential to ameliorate different underlying mechanism involved in the progression of aging-related diseases. Additionally, ECS may represent a promising approach not only for the treatment, but also for the alleviation of age-related disorder-associated symptoms and/or for increasing the efficacy of existing drugs. Moreover, our findings show that cannabinoids may be able to modulate various mechanisms rather than targeting a single dysregulated pathway in age-related diseases. Natural as well as synthetic cannabinoids ameliorate the balance between neurodegeneration and neuroinflammation in neurodegenerative diseases. In addition, they may play an important role in modulating the complex physio-pathology of MS and may be used as immune modulators, neuroprotectors, or remyelination promoters. The modulation of pro-inflammatory cytokines through the endogenous cannabinoid system may have beneficial effects on MS, AD, PD, aging-related musculoskeletal changes, and CVDs. On the other hand, it is clearly now that targeting the ECS with various natural or synthetic compounds may have the theoretical potential of an improved control of cancer progression.”


Cannabinoids and terpenes for diabetes mellitus and its complications: from mechanisms to new therapies

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“The number of people diagnosed with diabetes mellitus and its complications is markedly increasing worldwide, leading to a worldwide epidemic across all age groups, from children to older adults. Diabetes is associated with premature aging. In recent years, it has been found that peripheral overactivation of the endocannabinoid system (ECS), and in particular cannabinoid receptor 1 (CB1R) signaling, plays a crucial role in the progression of insulin resistance, diabetes (especially type 2), and its aging-related comorbidities such as atherosclerosis, nephropathy, neuropathy, and retinopathy. Therefore, it is suggested that peripheral blockade of CB1R may ameliorate diabetes and diabetes-related comorbidities. The use of synthetic CB1R antagonists such as rimonabant has been prohibited because of their psychiatric side effects. In contrast, phytocannabinoids such as cannabidiol (CBD) and tetrahydrocannabivarin (THCV), produced by cannabis, exhibit antagonistic activity on CB1R signaling and do not show any adverse side effects such as psychoactive effects, depression, or anxiety, thereby serving as potential candidates for the treatment of diabetes and its complications. In addition to these phytocannabinoids, cannabis also produces a substantial number of other phytocannabinoids, terpenes, and flavonoids with therapeutic potential against insulin resistance, diabetes, and its complications. In this review, the pathogenesis of diabetes, its complications, and the potential to use cannabinoids, terpenes, and flavonoids for its treatment are discussed.”


“Cannabis components (phytocannabinoids and terpenes) may exert antagonistic activity on CB1R signaling without causing deleterious side effects. Hence, phytocannabinoids and terpenes may be excellent potential candidates for the treatment of diabetes and its complications.”


Antimicrobial and Cytotoxic Effects of Cannabinoids: An Updated Review with Future Perspectives and Current Challenges


“The development of new antibiotics is urgently needed to combat the threat of bacterial resistance. New classes of compounds that have novel properties are urgently needed for the development of effective antimicrobial agents.

The extract of Cannabis sativa L. has been used to treat multiple ailments since ancient times. Its bioactivity is largely attributed to the cannabinoids found in its plant. Researchers are currently searching for new anti-infective agents that can treat various infections. Although its phytocannabinoid ingredients have a wide range of medical benefits beyond the treatment of infections, they are primarily associated to psychotropic effects.

Different cannabinoids have been demonstrated to be helpful against harmful bacteria, including Gram-positive bacteria. Moreover, combination therapy involving the use of different antibiotics has shown synergism and broad-spectrum activity. The purpose of this review is to gather current data on the actions of Cannabis sativa (C. sativa) extracts and its primary constituents such as terpenes and cannabinoids towards pathogens in order to determine their antimicrobial properties and cytotoxic effects together with current challenges and future perspectives in biomedical application.”


“C. sativa is a plant with an untapped potential. This versatile plant can be used for various purposes. Given its complex metabolic profile and excessive use as a recreational substance, its therapeutic benefits should not be ignored or overshadowed. Due to the limited effectiveness of antibiotics against MDR bacteria, the use of these drugs can be limited. This is why the discovery of an antimicrobial agent that can be used by plants has been regarded as a great step in the development of anti-infectives [8]. Multiple cannabinoids have been shown to have potent antimicrobial properties against Gram-positive pathogens, such as MRSA. In vitro studies have shown that cannabinoids can be useful in the removal of harmful microbes from the environment. Combination therapy with antibiotics that have different modes of action has shown broad-spectrum activities and synergism. There is also evidence that compounds found in C. sativa can have antimicrobial properties. This suggests that further investigations are needed to understand their potential. As the development of antibiotic resistance continues, cannabinoids have the potential to become a new source of treatment for bacterial infections.”


Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials


“Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached.

Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, Scopus, ClinicalTrials.

Results: out of 974 papers found with electronic search, six studies have been included into the systematic review, and five of them, for a grand total of 208 patients, were included into the meta-analysis.

Conclusions: cannabinoid supplementation as adjuvant therapy may increase the chances of success for standard therapy of Crohn’s Disease during the induction period; no statement on its potential usage during maintenance period can be derived from retrieved evidence. Its usage in Ulcerative Colitis is not to be recommended. If ever, low-dose treatment may be more effective than higher dosage. Mean CDAI reduction was found stronger in patients treated with cannabinoids (mean CDAI reduction = 36.63, CI 95% 12.27-61.19) than placebo. In future studies, it is advisable to include disease activity levels, as well as patient-level information such as genetic and behavioral patterns.”



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


“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.”



Use of Cannabis and Cannabinoids for Treatment of Cancer


“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.”


“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.”


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


“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.”



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


“Given the increasing interest in bioactive dietary components that can modulate gene expression enhancing human health, three metabolites isolated from hemp seeds-cannabidiolic acid, Ntrans-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.”