Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats- Effect of an acute dose of WIN55212-2
A recent study has exposed an age-dependent mechanism within the dopaminergic system that relies on cannabinoid receptor 1 (CB1). Adult and adolescent dopamine levels were examined in the presence of a CB1 agonist and increased levels of extracellular dopamine were found in adolescents. This study reveals the different effects cannabis-based medicine has depended on the age of the patient and warrants future research to ensure cannabis has the desired therapeutic effect on patients.
Dr Caplan Discussion Points:
This adds a helpful layer of insight to the way an animal model of dopamine changes over time, as well as its interaction with exogenous cannabinoids. This sheds light on the natural evolution of the dopamine control system (irrespective of how it interacts with endocannabinoids), and it also points to how cannabinoids may be involved.
This helps to educate the discussion about how psychosis and cannabis use may interact. There is a long-held understanding that dopamine abnormalities in the specific parts of the brain (mesolimbic and prefrontal brain regions) exist in schizophrenia. More recently, research has also strongly suggested that other neurotransmitters, including glutamate, GABA, acetylcholine, and serotonin are also involved in schizophrenia (and, coincidentally, there is also interaction with these other neurotransmitters from various components of cannabis). Nonetheless, this study simply suggests that, by nature, basal dopamine levels increase during adolescence. Also, the study points out that some cannabinoids boost basal levels too. It seems logical to suggest that excessive dopamine may create a problematic force of additional tipping toward illness, within individuals for whom a congenital predisposition toward illness exists.
“Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.
“From the results of this study, the key findings include, observation that a non-cannabinoid derivative of cannabis can enhance radiotherapy treatment outcomes in-vitro and in-vivo as highlighted in Figures 2, 4. Secondly, the sustained delivery of the cannabis derivative FBL-03G from smart radiotherapy biomaterials (SRBs) results in tumor growth inhibition of both locally treated and distant untreated tumors, with and without radiotherapy. The use of smart radiotherapy biomaterials (SRBs) (8, 23) was recently proposed as a novel approach to deliver cannabinoids, allowing for prolonged exposure of tumor cells to these cannabis derivatives, which is expected to be more effective (10). The FBL-03G payload used in this study is a flavonoid non- cannabinoid derivative of cannabis, and the potential to inhibit both local and metastatic tumor progression is remarkable, especially for pancreatic cancer, with a dismal 5-year survival rate of 8% (1).”
“While the results indicate that sustained exposure of tumor cells to FBL-03G can boost both local and metastatic tumor cell kill, the mechanism of such action needs to be further investigated. One hypothesis is that, FBL-03G can serve as an immunotherapy agent, inhibiting growth of locally treated and untreated tumors, representing metastasis. Metastasis accounts for most of all cancer-associated suffering and death, and questionably presents the most daunting challenge in cancer management. Henceforth, the observed significant increase in survival is promising, especially for pancreatic cancer which is often recalcitrant to treatments. Another hypothesis is that sustained delivery allows FBL-03G to reach the untreated tumor over a prolonged period as well. Either way, the FBL-03G results reveal a new potential non-cannabinoid cannabis derivative with major potential for consideration in further investigations in the treatment of pancreatic cancer, where new therapy options are urgently needed.”
Dr Caplan’s Take:
This article is one in a growing collection of impressive data that highlights a critical area of Medicine that has hidden from the scientific community for decades. The goal of the review is NOT to hail praise on cannabis as a panacea, nor even a sole treatment option, for pancreatic cancer. Rather, it highlights that it seems to be working effectively, both in living tumor cells in the lab and in animal models with live tumor cells. For a devastating illness that currently carries a grim prognosis, the proposition here is to learn more.
The milestones between pioneering scientific study and effective medication are many and there is much work to be done. Studies must be reviewed, criticized, replicated, integrated, before pioneering products can be developed, produced, tested, scaled, brought to market, marketed, sold, and consumed. The process is long, but at least there is a seed of hope at the beginning!