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!
Forget CBD; flavonoids found in cannabis have been found to be 30 times more effective painkillers than aspirin, targeting inflammation at the source and making them great alternatives for pain killers. If produced on a larger scale, they could help get away from the opioid crisis.
Title:Preferences for Medical Marijuana over Prescription Medications Among Persons Living with Chronic Conditions: Alternative, Complementary, and Tapering Uses
In a survey of 30 patients using medical cannabis for a range of diseases including rheumatoid arthritis, cancer, hepatitis C, PTSD, among others, patients reported an array of benefits they have reaped from cannabis use. Patients successfully used cannabis in several ways: as an alternative to prescription medication, complementarily with prescription medicine, and to gradually replace use of prescription medication.
Benefits described by participants included the effects of cannabis lasting longer than that of opioids, lower risk of addiction, fewer side-effects. Patients also saw their sleep, anxiety, appetite, and adverse reactions improve with the use of medical cannabis. Larger, more controlled studies may suggest cannabis more affirmatively as an alternative or complementary therapy with prescription medications.
Title: Novel approaches in clinical development of cannabinoid drugs
A pamphlet has recently been published that highlights new approaches in the clinical development of cannabinoid-based therapies. The pamphlet begins with a look into how current cannabinoids affect patients based on gender, stress, physiological variations, and also delves into how cannabis works on the body in general.
A novel therapy that features an oral version of tetrahydrocannabinol (THC) and a synthetic activator of cannabinoid-receptor-1 (CB1) is explored in this piece and frames it to be a promising future therapy. The pharmacological properties of these two novel therapies were optimized during development after various analysis techniques, forming medications that the authors hope to see in future clinical trials.
Although the authors remain hopeful that their cannabis-based therapies will reach clinical trials soon, trials featuring cannabinoids are difficult to test in a formal setting because of a dire lack of funding. The federal government still lists cannabis as a Schedule I substance, under the Controlled Substances Act, meaning that the federal government does not support the idea that cannabis has any medical use. Considering the legal status of cannabis, only privately-funded studies are able to take place, and unfortunately, that leaves cannabis research in an area of complete bias and prohibitively underfunded. Considering the massive literature supporting a myriad of novel therapeutic benefits, this is a costly reality to the health and well-being of millions.
Title: Neuroanatomical alterations in people with high and low cannabis dependence
A recent article has been published revealing some volumetric alterations in specific brain regions in people who report dependence on cannabis. Magnetic resonance imaging revealed that the volume of certain regions, including the hippocampus, the cerebellum, and the caudate, in cannabis dependent users, were all reduced in size, relative to recreational cannabis users who did not use cannabis chronically. Future research will likely focus on the effects of the structural alterations on patients’ reward, stress, and addiction-relevant circuitry to examine the possible relevance of cannabis dependance on those circuits.
There are certainly possibilities that suggest this volume difference could be of concern, but there are also a great number of explanations (more than likely) whereby this is related to another variable that we have not yet fully appreciated.
Currently, cannabis use is thought to have a little-to-no risk of addiction (beyond any “normal” product of medical value, such as coffee or eyeglasses), because it does not act directly on the reward circuit. Opioids have a high risk of addiction, and therefore a concerning safety profile, in part because of the direct effect of the opioid system on the reward pathway of the central and peripheral nervous systems. While the endocannabinoid system has been observed to act directly up the reward circuit, it does so in subtle, soft ways, making it an ideal adjunct therapy for opioids to help with pain management. Current research provides inconsistent results and appropriately emphasizes a need for more testing to validate the possibility of cannabis as a recommended pain medication.
Smoking cannabis brings toxins and unhealthy combustion byproducts into the body. With temps in the ~2000’F range for flame, burning flower incinerates a large portion of the product being consumed. As the distance from the point of flame grows, temperatures are lower, and cannabinoids are vaporizing, in addition to being burned by the flame. Over time, as heating technology has improved, there is no longer a need for blasting temperatures way beyond what the material can safely sustain before turning to tar and ash.
Beyond developed habits of consumption, social familiarity, and simplicity of use, one of the reasons many enjoy combustion is the other effects of heat. As with any human contact with extreme heat, blood rushes to the source of heat, and this may present a platform, through which cannabinoids may enter the bloodstream more quickly. The extravagant heat is also aerosolizing many more cannabis compounds than vaporization temperatures typically support, so the effect of flame is often felt to be more intense.
Vaporizing cannabis, however, is less likely to introduce mutations in the polyphenol compounds found in abundance within cannabis, and some of the mutations create terrible molecules known to be caustic and destructive.
If the medical rationale for vaporizing (over combustion) is not convincing, please consider the financial argument: Though purchasing a vaporizer may be costly, it’s a smart investment that could save money in the long run. Learn more by watching this video:
Benjamin Caplan, MDCannabis: Vaporizing vs Smoking