THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

Impact of recreational and medicinal marijuana on surgical patients: A review.

Posted on November 26, 2018 by David Worrell

“As medicinal and recreational marijuana use broadens across the United States, knowledge of its effects on the body will become increasingly important to all health care providers, including surgeons.

DATA SOURCES:

We performed a literature review of Pubmed for articles discussing the basic science related to cannabinoids, as well as articles regarding cannabinoid medications, and cannabis use in surgical patients.

CONCLUSIONS:

The primary components in the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), have been made available in numerous forms and formulations to treat multiple medical conditions, and recreational access to marijuana is increasing. Of particular importance to the surgeon may be their effects on prolonging intestinal motility, decreasing inflammation, increasing hunger, mitigating pain, and reducing nausea and vomiting. Perioperative use of medicinal or recreational marijuana will become increasingly prevalent, and the surgeon should be aware of the positive and negative effects of these cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30471810 https://www.americanjournalofsurgery.com/article/S0002-9610(18)31123-1/fulltext]]>

Cannabinoids for Treating Cardiovascular Disorders: Putting Together a Complex Puzzle.

Posted on November 24, 2018 by David Worrell

“Cannabinoids have been increasingly gaining attention for their therapeutic potential in treating various cardiovascular disorders. These disorders include myocardial infarction, hypertension, atherosclerosis, arrhythmias, and metabolic disorders. The aim of this review is to cover the main actions of cannabinoids on the cardiovascular system by examining the most recent advances in this field and major literature reviews. It is well recognized that the actions of cannabinoids are mediated by either cannabinoid 1 or cannabinoid 2 receptors (CB₂Rs). Endocannabinoids produce a triphasic response on blood pressure, while synthetic cannabinoids show a tissue-specific and species-specific response. Blocking cannabinoid 1 receptors have been shown to be effective against cardiometabolic disorders, although this should be done peripherally. Blocking CB₂Rs may be a useful way to treat atherosclerosis by affecting immune cells. The activation of CB₂Rs was reported to be useful in animal studies of myocardial infarction and cardiac arrhythmia. Although cannabinoids show promising effects in animal models, this does not always translate into human studies, and therefore, extensive clinical studies are needed to truly establish their utility in treating cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pubmed/30464888

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Activating Cannabinoid Receptor 2 Protects Against Diabetic Cardiomyopathy Through Autophagy Induction.

Posted on November 24, 2018 by David Worrell

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“Cannabinoid receptor 2 (CB₂) has been reported to produce a cardio-protective effect in cardiovascular diseases such as myocardial infarction. Here in this study, we investigated the role of CB₂ in diabetic cardiomyopathy (DCM) and its underlying mechanisms. In conclusion, we initially demonstrated that activating CB₂ produced a cardio-protective effect in DCM as well as cardiomyocytes under HG challenge through inducing the AMPK-mTOR-p70S6K signaling-mediated autophagy.” https://www.ncbi.nlm.nih.gov/pubmed/30459625 “Taken together, in this study, we initially showed that activating CB₂ produced a cardio-protective effect in DCM as well as cardiomyocytes under HG challenge through the induction of the AMPK-mTOR-p70S6K signaling-mediated autophagy process. We believe that the findings of this study might enhance our knowledge on the understanding of the pathogenesis and progression of DCM and provide a novel insight in the development of therapeutic strategies against DCM.” https://www.frontiersin.org/articles/10.3389/fphar.2018.01292/full

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Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-γ receptors.

Posted on November 24, 2018 by David Worrell

“Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats’ brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated.

KEY RESULTS:

Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF.

CONCLUSION:

This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR–γ seems to be CB2R-dependent.” https://www.ncbi.nlm.nih.gov/pubmed/30469079 https://www.sciencedirect.com/science/article/pii/S0753332218370033?via%3Dihub “β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/18574142

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Naturally occurring compounds as pancreatic cancer therapeutics.

Posted on November 24, 2018 by David Worrell

“Naturally occurring small molecule compounds have long been in the spotlight of pancreatic cancer research as potential therapeutics to prevent cancer progression and sensitize chemoresistant tumors. The hope is that terminal pancreatic cancer patients receiving aggressive chemotherapy can benefit from an increase in treatment efficacy without adding further toxicity by way of utilizing natural compounds. While preclinical studies on a number of natural compounds, such as resveratrol, curcumin, rapalogs and cannabinoids, show promising preclinical results, little has translated into clinical practice, though a number of other compounds hold clinical potential. Nevertheless, recent advances in compound formulation may increase the clinical utility of these compounds.” https://www.ncbi.nlm.nih.gov/pubmed/30459936 “The combination of natural products and standard of care chemotherapy has the potential to increase quality of life and lifespan in pancreatic cancer patients, even though a number of hurdles need to be overcome for routine clinical use.” http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26234&path[]=81769

“Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes. In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivo due to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway.” http://cancerres.aacrjournals.org/content/66/13/6748

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IMPACT OF NEUROIMMUNE ACTIVATION INDUCED BY ALCOHOL OR DRUG ABUSE ON ADOLESCENT BRAIN DEVELOPMENT.

Posted on November 24, 2018 by David Worrell

“Evidence obtained in recent decades has demonstrated that the brain still matures in adolescence. Changes in neural connectivity occur in different regions, including cortical and subcortical structures, which undergo modifications in white and gray matter densities. These alterations concomitantly occur in some neurotransmitter systems and hormone secretion, which markedly influence the refinement of certain brain areas and neural circuits. The immaturity of the adolescent brain makes it more vulnerable to the effects of alcohol and drug abuse, whose use can trigger long-term behavioral dysfunction. This article reviews the action of alcohol and drug abuse (cannabis, cocaine, opioids, amphetamines, anabolic androgenic steroids) in the adolescent brain, and their impact on both cognition and behavioral dysfunction, including predisposition to drug abuse in later life. It also discusses recent evidence that indicates the role of the neuroimmune system response and neuroinflammation as mechanisms that participate in many actions of ethanol and drug abuse in adolescence, including the neurotoxicity and alterations in neurocircuitry that contribute to the dysfunctional behaviors associated with addiction. The new data suggest the therapeutic potential of anti-inflammatory targets to prevent the long-term consequences of drug abuse in adolescence.” https://www.ncbi.nlm.nih.gov/pubmed/30468786 https://www.sciencedirect.com/science/article/pii/S073657481830251X?via%3Dihub

“Cannabinoids as novel anti-inflammatory drugs.” https://www.ncbi.nlm.nih.gov/pubmed/20191092

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Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation.

Posted on November 24, 2018 by David Worrell

“New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia. Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult. In the present study, we examined NSCs exposed to IL-1β in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury. Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult.”

https://www.ncbi.nlm.nih.gov/pubmed/30465881

https://www.sciencedirect.com/science/article/pii/S0889159118303246?via%3Dihub

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A meta-analysis of the crash risk of cannabis-positive drivers in culpability studies-Avoiding interpretational bias.

Posted on November 24, 2018 by David Worrell

“Culpability studies, a common study design in the cannabis crash risk literature, typically report odds-ratios (OR) indicating the raised risks of a culpable accident. This parameter is of unclear policy relevance, and is frequently misinterpreted as an estimate of the increased crash risk, a practice that introduces a substantial “interpretational bias”.

RESULTS:

The model outperforms the culpability OR in bootstrap analyses. Used on actual study data, the average increase in crash risk is estimated at 1.28 (1.16-1.40). The pooled increased risk of a culpable crash is estimated as 1.42 (95% credibility interval 1.11-1.75), which is similar to pooled estimates using traditional ORs (1.46, 95% CI: 1.24-1.72). The attributable risk fraction of cannabis impaired driving is estimated to lie below 2% for all but two of the included studies.

CONCLUSIONS:

Culpability ORs exaggerate risk increases and parameter uncertainty when misinterpreted as total crash ORs. The increased crash risk associated with THC-positive drivers in culpability studies is low.” https://www.ncbi.nlm.nih.gov/pubmed/30468948 https://www.sciencedirect.com/science/article/pii/S0001457518304706?via%3Dihub]]>

Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage.

Posted on November 24, 2018 by David Worrell

“Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection.

RESULTS:

HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated.

CONCLUSIONS:

cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone.” https://www.ncbi.nlm.nih.gov/pubmed/30468796 https://www.sciencedirect.com/science/article/pii/S0028390818308554?via%3Dihub]]>

Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US.

Posted on November 23, 2018 by David Worrell

“Purified cannabidiol is a new antiepileptic drug that has recently been approved for use in patients with Lennox-Gastaut and Dravet syndromes, but most published studies have not extended beyond 12-16 weeks.

The objective of this study was to evaluate the long-term safety, tolerability, and efficacy of cannabidiol in children with epilepsy.

Twenty-six children were enrolled. Most had genetic epilepsies with daily or weekly seizures and multiple seizure types. All were refractory to prior antiepileptic drugs (range 4-11, mean 7), and were taking two antiepileptic drugs on average. Duration of therapy ranged from 4 to 53 months (mean 21 months). Adverse events were reported in 21 patients (80.8%), including reduced appetite in ten (38.4%), diarrhea in nine (34.6%), and weight loss in eight (30.7%). Four (15.4%) had changes in antiepileptic drug concentrations and three had elevated aspartate aminotransferase and alanine aminotransferase levels when cannabidiol was administered together with valproate. Serious adverse events, reported in six patients (23.1%), included status epilepticus in three, catatonia in two, and hypoalbuminemia in one. Fifteen patients (57.7%) discontinued cannabidiol for lack of efficacy, one because of status epilepticus, and one for severe weight loss. The retention rate declined rapidly in the first 6 months and more gradually thereafter. At 24 months, the number of patients continuing cannabidiol as adjunctive therapy was nine of the original 26 (34.6%). Of these patients, seven (26.9%) had a sustained > 50% reduction in motor seizures, including three (11.5%) who remain seizure free.

CONCLUSION:

Over a 4-year period, cannabidiol was effective in 26.9% of children with otherwise refractory epilepsy. It was well tolerated in about 20% of patients, but 80.8% had adverse events, including 23.1% with serious adverse events. Decreased appetite and diarrhea were frequent along with weight loss that became evident only later in the treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/30460546

https://link.springer.com/article/10.1007%2Fs40263-018-0589-2

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