Neuroblastoma Cells are Killed by CBD Making it a Possible Future Cancer Treatment
Neuroblastoma responds very well to CBD treatment in the lab: after 48 hrs, 90% of neuroblastoma cells are dead, making CBD a promising future treatment for this type of cancer.
Neuroblastoma is the type of cancer that forms in neural tissue, including adrenal glands, neck, abdomen and spine. This disease is also especially devastating as it primarily afflicts children between the ages of 0 and 4 years. Despite the many forms of aggressive therapy, such as chemotherapy, radiation, surgery, immunotherapy and stem cell transplantation approaches, neuroblastoma patients in the later stages of the disease have poor prognosis. Less-toxic, more effective approaches are therefore in high demand, and Cannabis may be just the answer.
Studies on the anti-cancer effects of cannabinoids have been conducted for over three decades now, but the results have not been made readily available to the general public. In a wide range of models, from cancer cell lines cultured in a lab, to animal models with human tumours (xenograft models) to genetically engineered mouse models, it has been demonstrated that cannabinoids exert anti-cancer and anti-proliferative action in a variety of cancer types. The mechanism of their action is complex, as it involves not only binding and signaling through the cannabinoid receptors CB1 and CB2, but also other types of receptors such as 5HT1A and those known to be involved in signaling cascades involved in cancer progression, such as peroxisome proliferator-activated receptor gamma (PPARg).
Studies on therapeutic benefits of cannabinoids in pediatric cancers are particularly lacking, which is why a group of investigators recently set out to determine the effects of cannabinoids THC and CBD in neuroblastoma in both in vitro (in neuroblastoma cells grown in dishes in the lab) and in vivo (using a mouse xenograft model). They added THC and CBD to cell dishes containing neuroblastoma cells and measured the viability of cells remaining after 24 and 48 hrs. Reductions in viable cells would suggest that the compounds are capable of killing cancer cells, which is a finding that would support the anti-cancer effects of cannabinoids.
Indeed, both THC and CBD treatments resulted in reduction in viable neuroblastoma cells, although the effect of THC was not statistically significant. CBD killed most of the neuroblastoma cells after 24 hrs (about 85%) and the result was even more significant after 48 hrs (more than 90%). Similar results were observed in tumour growth transplanted into mice. They treated mice by injecting THC and CBD for 14 days at 20 mg/kg daily, thus making them systemically available. CBD resulted in a significant blunting of the tumour size, about one third of that of the control untreated counterparts.
The effectiveness of THC in tumor reductions was much less, which led the authors to conclude that CBD showed superior therapeutic potential in this model system. One limitation of this study was that the researchers did not assess the effect of combined THC and CBD treatments, a formulation that exists as Sativex ®, since the interplay between these two cannabinoids may exert even greater therapeutic benefits.
The medicinal potential of cannabis doesn’t stop at THC and CBD, however. Often times the predecessors of cannabinoids in the fresh plant are forgotten. These include the acid forms tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). When the fresh plant is exposed to heat, the acid forms undergo a change in structure, yielding the neutral forms THC and CBD.
Recent study conducted in Spain examined the potential of acid forms of cannabinoids in activation of PPARg. They found that indeed, THCA and CBDA are much more potent in activating this receptor compared to their neutral forms, and the most potent one was THCA. Targeting PPARg has been suggested to be neuroprotective and to have anti-cancer effects, and thus additional studies using cannabis extracts prepared without heating are an attractive starting point.