Monthly Archives: February 2018
Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.
“Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures.
Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population.
Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy.
Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil.
The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam.
Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant.
In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.”
“In this retrospective study, we report that artisanal CBD is helpful in the treatment of medically refractory seizures.”
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Chronic High Doses of Cannabinoids Promote Hippocampal Neurogenesis
“Hippocampal neurogenesis is suppressed following chronic administration of the major drugs of abuse (including opiates, alcohol, nicotine, and cocaine). However, CB1-knockout mice display significantly decreased hippocampal neurogenesis, suggesting that CB1 receptors activated by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis. Cannabinoids can regulate the proliferation of hippocampal NS/PCs by acting on CB1 receptors. They found that both the synthetic cannabinoid HU210 and the endocannabinoid anandamide profoundly promote embryonic hippocampal NS/PC proliferation. Chronic, but not acute, HU210 significantly increases the number of newborn hippocampal neurons in adult rats by promoting NS/PC proliferation. A significant increase was observed in the hipoppocampal newborn neurons of mice following twice-daily HU210 injection for 10 days. This suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.” “Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.” https://www.jci.org/articles/view/25509 http://www.science20.com/science_why_not/blog/chronic_high_doses_cannabinoids_promote_hippocampal_neurogenesis]]>
Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.
“Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury. This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO). Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R. Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production.” https://aggregator.leafscience.org/role-for-neuronal-nitric-oxide-synthase-in-cannabinoid-induced-neurogenesis/
“Nitric oxide negatively regulates mammalian adult neurogenesis.” http://www.pnas.org/content/100/16/9566.long
“Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO.” http://jpet.aspetjournals.org/content/jpet/319/1/150.full.pdf]]>Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.
“Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important.
The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications.
Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes.
Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro.
A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions.
The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors.
The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity.
These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors.”
https://www.ncbi.nlm.nih.gov/pubmed/29427593
https://www.sciencedirect.com/science/article/pii/S0367326X17317598
