Israeli scientists have recently found that cannabinoids are effective at helping mitigate the rapid multiplication of neuroblastoma. In a new study, published in Current Oncology, researchers discovered that cannabidiol (CBD) and tetrahydrocannabinol (THC) show anti-tumor effects, while CBD was found to be the more active of the two.
In the animal component of the study, tumors were induced in mice through subcutaneous injection. After allowing for the tumors to grow to an average size of 400 mm3, the researchers then injected the mice with either 20 mg/kg THC or 20 mg/kg CBD, or they left the mice untreated, for 14 days.
Previous preclinical studies have shown CBD to inhibit the progression of many types of cancer, including glioblastoma, breast, lung prostate, and colon cancers. The non-psychoactive cannabinoid has shown effective for inhibiting tumor cell viability, invasion, metastasis, and angiogenesis, as well as for inducing cancer cell death.
While cannabis remains classified federally as a Schedule I substance – a category for substances that possess no therapeutic value — the U.S. National Cancer Institute has acknowledged the anti-cancer properties of cannabinoids like CBD. Because CBD is devoid of psychoactive effects, it may be a more suitable treatment option for cancers that affect children, such as neuroblastoma. In related news, investigators from Nottingham University’s world-leading Children’s Brain Tumor Research Centre recently announced a new study to investigate CBD’s effects on brain tumors in children.
Both compounds displayed anti-tumor activity by reducing tumor cell viability and effectively impeding tumor growth, although CBD’s effects were more significant. Additionally, treatment with CBD also reduced invasiveness of neuroblastoma cells and induced cancer cell death.
CBD also helped “exert a chemopreventive effect in a mouse model of colon cancer ,” adds the U.S. Cancer Institute. Along with prevention, CBD has shown to alleviate nausea from chemotherapy. The institute reports, “ animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appe t ite and increase food intake.”
The U.S. National Cancer Institute confirms that medical cannabis is a highly effective treatment, describing in detail how the plant properties can prevent tumors like neuroblastoma. “Cannabinoids appear to kill tumor cells but do not affect their non-transformed counterparts and may even protect them from cell death,” according to the institute.
The often-inherited cancer type affecting children gets worse as they age. “Infants have a better chance than older children of remaining free of neuroblastoma after treatment,” according to St. Jude’s, the only National Cancer Institute-designated Comprehensive Cancer Center for children only.
Neuroblastoma Causes, Symptoms & Treatments
“Because CBD is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of NBL.”
As with any severe and rare cancer, surgery and chemotherapy are often initial treatments, but medical cannabis also proves to be beneficial. A 2016 Current Oncology study tested the non-psychoactive cannabinoid cannabidiol (CBD) on neuroblastoma cells in culture, showing how its properties helped cancer. “Our results demonstrate the anti-tumourigenic action of CBD on NBL cells,” reports the medical journal.
“Results from blood tests, a bone marrow biopsy and spinal tap proved Landon no longer had leukemia, not even the microscopic kind,” reports Newsweek.
Neuroblastoma is a form of cancer most associated with children, with 90% of cases diagnosed in children under the age of 5 according to the American Cancer Society. The rare condition is often inherited and is caused by a specific type of nerve cell, called a neuroblast, having a mutation that leads to abnormal growth, reports St. Jude’s Children’s Hospital. Symptoms of pediatric neuroblastoma include a painful mass on the neck, feelings of agitation, stomach pain, decreased appetite, weight loss, and weak legs.
We used an mtt assay to assess the effect of thc and cbd on the viability of the SK-N-SH, NUB-6, IMR-32, and LAN-1 nbl cell lines [ Figure 1(A) ]. In vitro, after 24 hours of treatment, cbd and thc had already effectively reduced the viability of nbl cell lines in a dose- (0–50 μg/mL) and time-dependent manner, with cbd having the better effect. Better response to treatment was observed in the SK-N-SH and NUB-6 cell lines, as demonstrated by a 50% reduction in cell viability at lower cbd or thc concentrations (5 μg/mL and 15 μg/mL for SK-N-SH and NUB-6 respectively, compared with >20 μg/mL for IMR-32 and LAN-1). The same trend was found, and even enhanced, after treatment with thc and cbd for 48 hours [ Figure 1(A) ]. More importantly, the response after treatment of SK-N-SH cells with cbd (10 μg/mL) was better than the response after treatment with the same concentration of thc [ Figure 1(B) , p = 0.0004 for 24 and 48 hours of treatment].
Unless otherwise specified, results are shown as means or medians ± standard deviation. A Kruskal–Wallis test, followed by a post hoc Mann–Whitney test, was used to evaluate significant differences in the viability of cell lines, the growth rate of xenografts, and the counts of positive cleaved caspase 3 cells for the various treatment groups. A p value less than 0.05 was considered statistically significant. All analyses were performed using the IBM SPSS Statistics software application (version 21: IBM, Armonk, NY, U.S.A.).
Annexin V Assay
Cannabidiol (CBD) suppresses tumour growth in a mouse xenograft model and increases cleaved caspase-3 staining in treated xenografts. (A) Growth rate of SK-N-SH cell–derived tumour xenografts treated for 14 days with intraperitoneal injections of ethanol-vehicle (n = 12, closed triangles), 20 mg/kg Δ 9 -tetrahydrocannabinol (n = 12, closed squares), 20 mg/kg CBD (n = 12, closed circles) and untreated controls (n = 12, open squares). Data represents tumour volume during 14 days of treatment. a p < 0.05 and b p < 0.01 for CBD compared with ethanol treatment (Mann–Whitney U-test). (B) Activated caspase-3 immunostaining in SK-NS-H cell–derived tumour xenografts treated with CBD 20 mg/kg or ethanol vehicle for 14 days. (C) Counts of cleaved caspase-3 immunoreactive cells in 18×10 lens fields from xenografts of CBD- and ethanol-treated mice. a p < 0.0001 compared with ethanol.
To further define the in vivo effect of cbd treatment with respect to apoptosis induction, we analyzed tissue obtained from tumour xenografts. Tumours were excised after the last day of treatment, and paraffin-embedded sections were analyzed immunohistochemically with the apoptosis indicator cleaved caspase 3. Cells positive for cleaved caspase 3 were detected with significantly greater frequency in sections of xenografts from cbd -treated mice [ Figure 5(B) ] than in sections from ethanol-treated mice [p < 0.001, Figure 5(C) ].
Δ 9 -Tetrahydrocannabinol was supplied by Prof. Raphael Mechoulam, Institute for Drug Research, Medical Faculty, The Hebrew University, Ein Kerem Campus, Jerusalem, Israel. Cannabidiol was supplied by THC Pharm GmbH, Frankfurt, Germany.