“Objective: To investigate the effects of Δ9-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a Δ9-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells. Methods: Δ9-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer (A549) cells. The effects on cell proliferation, apoptosis, and phosphorylation profiles were examined. The effects of Δ9-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model. Apoptosis and targeted phosphorylation were verified by immunohistochemistry. Results: Δ9-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The Δ9-tetrahydrocannabinol- and cannabinol-treated cells had lower levels of phosphorylated protein kinase B [AKT (S473)], glycogen synthase kinase 3 alpha/beta, and endothelial nitric oxide synthase compared to the controls. The study of xenograft mice revealed that tumors treated with 15 mg/kg Δ9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control mice. The tumor progression rates in mice treated with 15 mg/kg Δ9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group. Conclusions: These findings indicate that Δ9-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways, which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.”
“Background: Cannabis is classified as a Schedule 5 substance under the Narcotics Act B.E. 2522. Among with various modulatory effects of cannabinoids on body functions, two major cannabinoids are known to be used as medicines. They are a psychoactive delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). Currently, THC and CBD are advised to be used for treatment of a variety of medical conditions. Such as cell growth inhibition, anti-inflammatory effects and tumor regression. Although, potential benefit can be found in the medical condition above mentioned. The use of cannabis in some disease states such as cancer remain to be clinically evaluated in both efficacy and safety aspects through systematic research before being generalized for routine use.
Objective: The purpose of this study to investigate the In vitro effects of cannabis extracts on 10 types of human cancer cell line.
Methods: Two cannabis extracts (high THC level and high CBD level) were kept in sterile bottles, in refrigerator, until further use when it was dissolved in DMSO to give a stock solution, filtered and stored at 4 °C. The small percentage of DMSO present in the wells (maximal 0.1%) was found not to affect the experiment. The anti-proliferative activities of cannabis extract on cancer cell lines was determined by MTT assay.
Results: To evaluate the anti-proliferative activity of the cannabis extracts on 10 types of cancer cell line (lung cancer, breast cancer, colorectal cancer, gastric cancer, cervical cancer, ovarian cancer, liver cancer, pancreatic cancer, cholangiocarcinoma cancer, lymphoma cancer), the cells were treated with different concentrations of high THC level and high CBD level for 72h and cell viability was determined using MTT assay.
The results showed that all of cancer cell lines viability significantly reduced in concentration and time dependent manner following treatment with the extract. The IC50 of the high THC level values ranging from 10.80 ±1.03 to 54.60±1.27 μg/mL, and exhibited very strong activity against RBE with IC50 values of 10.80±1.03 μg/mL. The IC50 of the high CBD level values ranging from 6.00±1.16 to 26.00±1.37 μg/mL, and exhibited very strong activity against NCI-N87 with IC50 values of 6.00±1.16 μg/mL.
Conclusions: The results suggest that high THC level and high CBD level is a potent human cancer cells proliferation. Further investigations are needed to elucidate the mechanism of anticancer actions.”
“Background: Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers.
Methods: We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age-standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis.
Results: Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR = 0.61, 95%CI:0.40-0.93, p = 0.021) and prostate cancer (HR = 0.82, 95%CI:0.73-0.93, p = 0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC = 0.42, 95%CI:0.19-0.94, p = 0.034; HRBCa = 0.43, 95%CI:0.21-0.86, p = 0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma.
Conclusions: Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.”
“Cannabis, also known as marijuana, is the most used substance derived from Cannabis Sativa which can be used for recreational or medical purposes. Some evidence also suggested that cannabinoids might induce apoptosis of cancer cells and inhibit oncogenesis, indicating a potential treatment effect”
“Objective: As medical cannabis use increases in North America, establishing its safety profile is a priority. The objective of this study was to assess rates of emergency department (ED) visits and hospitalizations due to poisoning by cannabis, and cannabis-related mental health disorders among medically authorized cannabis patients in Ontario, Canada, between 2014 and 2017.
Methods: This is a retrospective cohort study of patients who received medical cannabis authorization in Ontario, Canada, using data collected in participating cannabis clinics. Outcomes included ED visit/hospitalization with a main diagnosis code for: cannabis/cannabinoid poisoning; and mental/behavioral disorders due to cannabis use. Cox proportional hazard regressions were utilized to analyze the data.
Results: From 29,153 patients who received medical authorization, 23,091 satisfied the inclusion criteria. During a median follow-up of 240 days, 14 patients visited the ED or were hospitalized for cannabis poisoning-with an incidence rate of 8.06 per 10,000 person-years (95% CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioral disorders due to cannabis use-with an incidence rate of 15.0 per 10,000 person-years (95% CI: 10.2-22.0). Predictors of cannabis-related mental and behavioral disorders include prior substance use disorders, other mental disorders, age, diabetes, and chronic obstructive pulmonary disease.
Conclusions: The results suggest that the incidence of cannabis poisoning or cannabis-related mental and behavioral disorders was low among patients who were authorized to use cannabis for medical care. Identified predictors can help to target patients with potential risk of the studied outcomes.”
“Aflatoxin B1 is a carcinogenic mycotoxin that frequently contaminates crops worldwide.
Current research indicates that the use of natural extracts to combat mycotoxin contamination may represent an eco-friendly, sustainable strategy to ensure food safety. Although Cannabis sativa L. has long been known for its psychoactive cannabinoids, it is also rich in many other bioactive molecules.
This study examines extracts from various organs of Cannabis sativa L. to determine their ability to limit aflatoxin production and growth of Aspergillus flavus.
The results indicate that flower extract is most effective for limiting the synthesis of aflatoxin B1, leading to an almost-complete inhibition of toxin production at a concentration of 0.225 mg dry matter per gram of culture medium. Since flower extract is rich in phenolic compounds, its total antioxidant ability and radical-scavenging capacity are determined.
Compared with other anti-aflatoxigenic extracts, the anti-oxidative potential of Cannabis sativa L. flower extract appears moderate, suggesting that its anti-mycotoxin effect may be related to other bioactive compounds.”
“Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns.
Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors.
In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways.
Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.”
“The antineoplastic role of cannabinoids in malignancy of the immune system, as well as in many other tumors, i.e., osteosarcoma, is well documented. Cannabinoids derive from the Cannabis plant, and interact with the cannabinoid receptors CB1 and CB2, principally expressed in the central nervous system and in peripheral and immune cells, respectively. These receptors, together with their specific ligands (endocannabinoids) and the enzymes involved in their own synthesis and degradation, constitute the endocannabinoid system (ECS). ECS is involved in many biological functions, such as pain management, regulation of appetite, control of bone metabolism, and, noteworthily, it modulates both inflammatory processes and immune response. Several authors proposed ECS as anticancer target for different neoplasms; in particular, a proper stimulation of CB2 receptors is responsible for counteracting tumor growth and progression. We demonstrate the involvement of ECS in this neoplasm and highlight the possibility to target it to arrest growth and progression of B-ALL
Our findings describe the involvement of CB2 receptors in the pathogenesis of B-ALL, and also propose its stimulation as an innovative and effective anticancer strategy. In particular, this approach is a “molecular target therapy approach”, since the selective triggering of cannabinoid modulates both gene and protein expression. We identified a specific anti-tumoral signature playing a key role in the development and maintenance of tumors, speculating a protective effect of CB2 selective stimulation. Certainly, further investigations are needed to better understand the molecular and biochemical mechanisms underlying the observed interactions, but our study seems to already highlight a good and beneficial therapeutic perspective to ameliorate the outcome for high-risk B-ALL patients.”
“Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial.
In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested.
We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001).
Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed.”
“We, for the first time, show that application of TRSV in combination with CBD constitutes a very promising anti-aging and regenerative regimen that can potentially be used for treatment or/and prevention of appearance of aging spots and treating cutaneous wounds. Moreover, we found pCBs alone appeared to be highly efficacious as an anti-aging treatment. Further work should study and test pCBs alone, as well as TRSV in combination with CBD as anti-aging remedies.”
“Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination.
Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain.
Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630.
Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.”
“The present findings indicate that intrathecal delivery of the phytocannabinoids THC and CBD reduces the mechanical and cold allodynia associated with a nerve injury induced model of neuropathic pain. Interestingly, THC and CBD acted synergistically to reduce allodynia, leading to a substantial increase in their anti-allodynic potency. In addition, both THC and CBD were devoid of the cannabis-like side-effects associated with the systemic delivery of THC-containing cannabinoids. These findings indicate that spinal delivery of the primary phytocannabinoids of the plant Cannabis sativa has potential in the treatment of chronic neuropathic pain.”
“Introduction: Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS).
Objectives: We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain.
Methods: A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time.
Results: More than half (n = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (p = 0.034), and pain intensity scores verged on significance (p = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%).
Conclusion: This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.”
“This is a clinically relevant finding considering that this patient cohort comprises refractory cases where relief has not been obtained with existing medications, including opioids, NSAIDs, and steroids.”
“Background: The synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson’s disease (PD) patients in comparison to placebo.
Objectives: To characterize the effects of nabilone on different sleep outcomes in PD patients.
Methods: We performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).
Results: After open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).
Conclusions: This post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.”
