THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

Reduced prevalence of alcoholic gastritis in hospitalized individuals who consume cannabis.

Posted on December 12, 2018 by David Worrell

“Alcoholic gastritis, a superficial erosive disease of the stomach, is a common manifestation of risky alcohol use. In contrast, cannabis which is frequently co-used with alcohol suppresses gastric acidity and might counteract the deleterious effect of alcohol on the gastric mucosa.

RESULTS:

Our study revealed that among risky alcohol users, cannabis co-users have a lower prevalence of alcoholic gastritis compared to non-cannabis users (1,289[1,169-1,421] vs. 1,723[1,583-1,875] per 100,000 hospitalizations for risky alcohol use), resulting in a 25% decreased probability of alcoholic gastritis (aRR:0.75[0.66-0.85]; p-value:<0.0001). Furthermore, dependent cannabis usage resulted in a lower prevalence of alcoholic gastritis when compared to both non-dependent-cannabis users (0.72[0.52-0.99]), and to non-cannabis-users (0.56[0.41-0.76]).

CONCLUSIONS:

We reveal that risky alcohol drinking combined with cannabis use is associated with reduced prevalence of alcohol-associated gastritis in patients. Given increased cannabis legislation globally, understanding if and how the specific ingredients in cannabis plant extract can be used in the treatment of alcoholic gastritis is paramount. In this regard, further molecular mechanistic studies are needed to delineate the mechanisms of our novel findings not only for alcoholic gastritis but also gastritis from other causes.” https://www.ncbi.nlm.nih.gov/pubmed/30536396 https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13930]]>

Cannabis-based products for pediatric epilepsy: A systematic review.

Posted on December 7, 2018 by David Worrell

“Evidence from high-quality randomized controlled trials (RCTs) suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty).” https://www.ncbi.nlm.nih.gov/pubmed/30515765 https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.14608 “Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.” https://www.ncbi.nlm.nih.gov/pubmed/25475762]]>

Exploring cannabis use by patients with multiple sclerosis in a state where cannabis is legal.

Posted on December 7, 2018 by David Worrell

“Studies suggest cannabis may improve symptoms like pain and muscle spasticity in patients with multiple sclerosis (PwMS). As cannabis legalization has impacted the variety of cannabis products available, there appears to be growing numbers of PwMS using cannabis, with this study’s Cannabis users (CUs) reporting use of highly efficacious products with minimal side-effects.” https://www.ncbi.nlm.nih.gov/pubmed/30502644 https://www.msard-journal.com/article/S2211-0348(18)30515-7/fulltext]]>

Emerging drugs for the treatment of Dravet syndrome.

Posted on December 1, 2018 by David Worrell

“Dravet syndrome (DS) is an early-onset genetic developmental epileptic encephalopathy characterized by multiple seizure types which are refractory to antiseizure medication. There is an unmet need for effective and tolerable drugs to control different seizure types in DS types, with the aim of improving quality of life and preventing neurological impairment. Areas covered: Narrative review of efficacy and tolerability of fenfluramine, cannabidiol (CBD), verapamil and modulators of serotonin signaling pathways (lorcaserin or trazodone) in the treatment of DS. Expert Opinion/Commentary: A recent large randomized controlled-trial has shown that CBD is effective in the treatment of DS; preliminary data from the placebo-controlled trial on fenfluramine are also promising. Further studies are definitely required to evaluate the role of verapamil and modulators of serotonin signaling in DS. At present, drugs used to treat seizures in DS treat the symptoms of epilepsy rather than its cause(s). Future research should focus on elucidating the natural history of DS and whether appropriate treatment can have a beneficial impact on its disease course. A multidisciplinary, individualized approach to care of DS patients is required.” https://www.ncbi.nlm.nih.gov/pubmed/30482063 https://www.tandfonline.com/doi/abs/10.1080/14728214.2018.1552937?journalCode=iemd20

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Cannabidiolic Acid-Mediated Interference with AP-1 Transcriptional Activity in MDA-MB-231 Breast Cancer Cells.

Posted on December 1, 2018 by David Worrell

“We reported that cannabidiolic acid (CBDA), a non-psychotropic constituent of fiber-type cannabis plants, down-regulates the mRNA expression of cyclooxygenase-2 (COX-2) in highly aggressive MDA-MB-231 human breast cancer cells. However, the molecular mechanism(s) underlying the CBDA suppression of COX-2 have not yet been elucidated in detail. In MDA-MB-231 cells, COX-2 expression is known to be tightly regulated by the transcriptional activity of activator protein-I (AP-1), which is composed of a heterodimer of c-Fos and c-Jun. AP-1-mediated transcriptional activity was inhibited by CBDA in a dose-dependent manner. The expression of c-fos was maintained at markedly lower levels (0.035) than basal c-jun expression levels (1.0), implicating c- fos as a limiting factor in the regulation of COX-2. Analyses indicated that CBDA abrogated the expression of c-fos mRNA without affecting c-jun. Collectively, these results suggest that CBDA abolishes the expression of COX-2 by interfering with AP-I activity in MDA-MB3-231 cells.” https://www.ncbi.nlm.nih.gov/pubmed/30496661

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Reefer madness or real medicine? A plea for incorporating medicinal cannabis in pharmacy curricula.

Posted on December 1, 2018 by David Worrell

“Over the past twenty years, the acceptance and use of medicinal cannabis has increased in the United States. However, there is still a lack of education and comfort as it relates to the therapeutic uses of botanical cannabis and cannabidiol in pharmacy professional curricula. Professional training programs have failed to keep pace with the evolving national landscape and growing acceptance of this therapy.

PERSPECTIVE:

In this manuscript, the current landscape of pharmacy professional involvement in the dispensing and administration of medicinal cannabis throughout the United States is described. A concern exists that there is a knowledge gap among pharmacists and pharmacy students, as demonstrated by recent survey results, related to the pharmacology, dosing, administration, adverse effects, drug interactions, and monitoring of both medicinal and recreational cannabis use.

IMPLICATIONS:

While cannabis use is still considered illegal by the federal government, it is imperative pharmacy educators prepare the next generation of pharmacists to be knowledgeable on the safe and effective use and communication tactics related to cannabis. As a therapy garnering national attention with growing support for use, education on this topic must be included in pharmacy curricula and pharmacy continuing education.” https://www.ncbi.nlm.nih.gov/pubmed/30497617 https://www.sciencedirect.com/science/article/abs/pii/S1877129717304860?via%3Dihub]]>

Stilbenoids and cannabinoids from the leaves of Cannabis sativa f. sativa with potential reverse cholesterol transport activity.

Posted on December 1, 2018 by David Worrell

“Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α’-dihydro-3′,4,5′-trihydroxy-4′-methoxy-3-isopentenylstilbene (HM1), α,α’-dihydro-3,4′,5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α’-dihydro-3′,4,5′-trihydroxy-4′-methoxy-2′,3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α’-dihydro-3,4′,5-trihydroxy-4,5′-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa. These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death. The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9. The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1. In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.” https://www.ncbi.nlm.nih.gov/pubmed/30500001 https://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C8FO01896K#!divAbstract]]>

Oral Ingestion of Cannabis sativa: Risks, Benefits, and Effects on Malaria-Infected Hosts.

Posted on December 1, 2018 by David Worrell

“The emergence of a multidrug-resistant strain of Plasmodium falciparum (Pf Pailin) raises concern about malaria control strategies. Unfortunately, the role(s) of natural plants/remedies in curtailing malaria catastrophe remains uncertain. The claims of potential antimalarial activity of Cannabis sativa in vivo have not been well established nor the consequences defined. This study was, therefore, designed to evaluate the effects of whole cannabis consumption on malaria-infected host. Methods: Thirty mice were inoculated with dose of 1×10⁷ chloroquine-resistant Plasmodium berghei ANKA-infected erythrocyte and divided into six treatment groups. Cannabis diet formulations were prepared based on weighted percentages of dried cannabis and standard mice diet and the study animals were fed ad libitum. Chemosuppression of parasitemia, survival rates, parasite clearance, and recrudescence time were evaluated. Histopathological studies were performed on the prefrontal cortex (PFC) and hippocampus of the animals after 14 days’ consumption of cannabis diet formulation by naive mice. Results: There was a significant difference (p<0.05) in the day-4 chemosuppression of parasitemia between the animals that were fed C. sativa and chloroquine relative to the untreated controls. There was also a significant difference in the survival rate (p<0.05) of animals fed C. sativa diet (40%, 20%, 10%, and 1%) in contrast to control animals on standard mice diet. A parasite clearance time of 2.18±0.4 was recorded in the chloroquine treatment group, whereas recrudescence in chloroquine group occurred on day 7. There were slight histomorphological changes in the PFC and cell densities of the dentate gyrus of the hippocampus of animals that were fed C. sativa. Conclusions: C. sativa displayed mild antimalarial activity in vivo. There was evident reduction in symptomatic manifestation of malaria disease, though unrelated to levels of parasitemia. This disease tolerance status may be beneficial, but may also constitute a transmission burden through asymptomatic carriage of parasites by habitual cannabis users.” https://www.ncbi.nlm.nih.gov/pubmed/30498786 https://www.liebertpub.com/doi/10.1089/can.2018.0043]]>

Peripubertal cannabidiol treatment rescued behavioral and neurochemical abnormalities in MAM model of schizophrenia.

Posted on December 1, 2018 by David Worrell

“In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.” https://www.ncbi.nlm.nih.gov/pubmed/30496751 https://www.sciencedirect.com/science/article/pii/S0028390818308761?via%3Dihub

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The Role of CB2 Receptor in the Recovery of Mice after Traumatic Brain Injury.

Posted on December 1, 2018 by David Worrell

“Cannabis is one of the most widely used plant drugs in the world today. In spite of the large number of scientific reports on medical marijuana there still exists much controversy surrounding its use and the potential for abuse due to the undesirable psychotropic effects. However, recent developments in medicinal chemistry of novel non-psychoactive synthetic cannabinoids have indicated that it is possible to separate some of the therapeutic effects from the psychoactivity. We have previously shown that treatment with the endocannabinoid 2-AG that binds to both CB1 and CB2 receptors 1 hr after traumatic brain injury in mice attenuates neurological deficits, edema formation, infarct volume, blood-brain barrier permeability, neuronal cell loss at the CA3 hippocampal region and neuroinflammation. Recently, we synthesized a set of camphor-resorcinol derivatives, which represent a novel series of CB2 receptor selective ligands. Most of the novel compounds exhibited potent binding and agonistic properties at the CB2 receptors, with very low affinity for the CB1 receptor, and some were highly anti-inflammatory. This selective binding correlated with their intrinsic activities. HU-910 and HU-914 were selected in the present study to evaluate their potential effect in the pathophysiology of traumatic brain injury (TBI). In mice and rats, subjected to closed head injury and treated with these novel compounds, we showed enhanced neurobehavioral recovery, inhibition of TNF-alpha production, increased synaptogenesis and partial recovery of the cortical spinal tract. We propose these CB2 agonists as potential drugs for development of novel therapeutic modality to TBI.” https://www.ncbi.nlm.nih.gov/pubmed/30489198 https://www.liebertpub.com/doi/10.1089/neu.2018.6063

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