Monthly Archives: January 2019

Marijuana Consumption in Liver Transplant Recipients.

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“Marijuana is legalized for either medical or recreational use in over half of the United States and in Canada, but many transplant centers will not list patients who are using marijuana. However, the effect of marijuana on transplant outcomes remains unclear. Thus, we performed a retrospective analysis of all adult (≥18 years old) liver transplant patients treated at our center between 2007 and 2017. After adjustment, current tobacco users were over three times as likely to die within 5 years, compared to never users, but no difference was seen between current/former and never marijuana users. No significant differences in inpatient respiratory complications, reintubation, or >24 hours intubation was seen. Overall, pre-transplant marijuana use, past or current, does not appear to impact liver transplant outcomes; however, tobacco smoking remains detrimental.”

https://www.ncbi.nlm.nih.gov/pubmed/30693668

https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/lt.25417

Diet-Induced Obesity in Cannabinoid-2 Receptor Knockout Mice and Cannabinoid Receptor 1/2 Double-Knockout Mice.

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“Evidence suggests that cannabinoid-1 receptor (CB1R) activation is associated with increased food intake and body weight gain. Human epidemiological studies, however, show decreased prevalence of obesity in cannabis users.

Given the overlapping and complementary functions of the cannabinoid receptors (CB1R and CB2R), mice lacking CB2R and mice lacking both CB1R and CB2R were studied.

These results indicate that lacking both CB1R and CB2R protected mice from diet-induced obesity, possibly through the prominent role of CB1R in obesity or through an interactive effect of both receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/30699233

https://onlinelibrary.wiley.com/doi/abs/10.1002/oby.22403

The annual cannabis holiday and fatal traffic crashes.

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“Prior evidence suggests the potential for population-wide effects of the annual cannabis celebration on April 20th (‘4/20’), but evidence to date is limited. Across all years we found little evidence to distinguish excess drivers involved in fatal crashes on 4/20 from routine daily variations. There is little evidence to suggest population-wide effects of the annual cannabis holiday on the number of drivers involved in fatal traffic crashes.” https://www.ncbi.nlm.nih.gov/pubmed/30696698

Cannabidiol as a novel candidate alcohol use disorder pharmacotherapy: a systematic review.

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“There is substantial interest in the therapeutic potential of cannabidiol (CBD), a non-psychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy.” https://www.ncbi.nlm.nih.gov/pubmed/30698831
https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13964

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain

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“A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.

A growing body of scientific literature demonstrates reproducible efficacy of cannabis in the treatment of several medical conditions, including chronic neuropathic pain. Clinical trials of oral, smoked, and vaporized cannabis and cannabinoids have all demonstrated analgesic benefit of medicinal cannabis in the treatment of this costly and disabling condition. A recent meta-analysis of individual patient data from five randomized controlled trials of inhaled cannabis demonstrated pain relief comparable to gabapentin. Treatment guidelines for neuropathic pain recommend consideration of cannabinoids as third-line agents.

As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/30944870

https://www.liebertpub.com/doi/10.1089/can.2018.0027

“New study analyzes cost effectiveness of smoked cannabis to treat chronic neuropathic pain” https://www.eurekalert.org/pub_releases/2019-01/mali-nsa012919.php

Decarbonylation: a metabolic pathway of cannabidiol in humans.

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“Cannabidiol (CBD) is a non-psychoactive cannabinoid, which is of growing medical interest. We investigated the phase I metabolism of CBD and cannabidivarin (CBDV) using in vitro experiments with human liver microsomes in order to discover so far not considered metabolites. Within these experiments, we came across decarbonylation of CBD and CBDV. Further investigations were focused on observed decarbonylated CBD (DCBD). DCBD appears to be an important supplementary human metabolite that might be helpful for the analytical confirmation of a CBD uptake and might improve the interpretation of the consumption of CBD containing products. Results of this study indicate a prolonged detectability of DCBD in comparison to CBD after oral CBD ingestion.”
https://www.ncbi.nlm.nih.gov/pubmed/30698361

Cannabinoid Ligands Targeting TRP Channels.

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“Many diseases involve Transient receptor potential (TRP) channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels. The TRP vanilloid (TRPV), TRP ankyrin (TRPA), and TRP melastatin (TRPM) subfamilies were all found to contain channels that can be modulated by several endogenous, phytogenic, and synthetic cannabinoids. To date, six TRP channels from the three subfamilies mentioned above have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing data regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be “ionotropic cannabinoid receptors.””

https://www.ncbi.nlm.nih.gov/pubmed/30697147

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00487/full

[Endogenous Cannabinoid System of the Brain as the Target for Influences at Neurodegenerate Diseases]

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“The review represents the analysis of works about role of endogenous cannabinoid (EC) system in the neuro- degenerate diseases (ND), in which the cellular death and disturbances of neuronal functions of the hippo- campus, neocortex and striatum are observed. Here, the diseases.ofAlzheimer, of Parkinson, of Hangtington, and the temporal lobe epilepsy are considered. In recent years the fundamental role of EC system in regu- lation of neuroexcitability, energy metabolism, inflammatory and many other processes has been opened in ND pathogenesis. It points to possibility of development of therapeutic approaches which use the prepara- tions for activation of EC system. In the review various mechanisms of cellular survival and their reparations provided to EC system during action of pathological factors are stated.”

https://www.ncbi.nlm.nih.gov/pubmed/30695519

Cannabisin F from Hemp (Cannabis sativa) Seed Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia as SIRT1 Modulator.

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“Hemp seed (Fructus cannabis) is rich in lignanamides, and initial biological screening tests showed their potential anti-inflammatory and anti-oxidative capacity.

This study investigated the possible effects and underlying mechanism of cannabisin F, a hempseed lignanamide, against inflammatory response and oxidative stress in lipopolysaccharide (LPS)-stimulated BV2 microglia cells.

Cannabisin F suppressed the production and the mRNA levels of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in a concentration-dependent manner in LPS-stimulated BV2 microglia cell. Furthermore, cannabisin F enhanced SIRT1 expression and blocked LPS-induced NF-κB (Nuclear factor kappa B) signaling pathway activation by inhibiting phosphorylation of IκBα (Inhibit proteins of nuclear factor kappaB) and NF-κB p65. And the SIRT1 inhibitor EX527 significantly inhibited the effect of cannabisin F on pro-inflammatory cytokines production, suggesting that the anti-inflammatory effects of cannabisin F are SIRT1-dependent. In addition, cannabisin F reduced the production of cellular reactive oxygen species (ROS) and promoted the expression of Nrf2 (Nuclear factor erythroid-2 related factor 2) and HO-1 (Heme Oxygenase-1), suggesting that the anti-oxidative effects of cannabisin F are related to Nrf2 signaling pathway.

Collectively, these results suggest that the neuro-protection effect of cannabisin F against LPS-induced inflammatory response and oxidative stress in BV2 microglia cells involves the SIRT1/NF-κB and Nrf2 pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/30691004

https://www.mdpi.com/1422-0067/20/3/507

Pills to pot: observational analyses of cannabis substitution among medical cannabis users with chronic pain.

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“Chronic pain is common, costly and challenging to treat. Many individuals with chronic pain have turned to cannabis as an alternative form of pain management.

We report results from an ongoing, online survey of medical cannabis users with chronic pain nationwide about how cannabis affects pain management, health, and pain medication use. We also examined whether and how these parameters were affected by concomitant recreational use, and duration of use (novice: <1 year vs. experienced: ≥1 year). 1,321 participants (59% female, 54% ≥50 years old) completed the survey.

Consistent with other observational studies, ∼80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. Medical only users were older (52 vs. 47, p<0.0001), less likely to drink alcohol (66% vs. 79%, p<0.0001), and more likely to be currently taking opioids (21% vs. 11%, p<0.0001) than users with a combined recreational + medical history. Compared to novice users, experienced users were more likely to be male (64% vs. 58%, p<0.0001), take no concomitant pain medications (43% vs. 30%), and report improved health (74% vs. 67%, p=0.004) with use.

Given that chronic pain is the most common reason for obtaining a medical cannabis license, these results highlight clinically important differences among the changing population of medical cannabis users. More research is needed to better understand effective pain management regimens for medical cannabis users.

PERSPECTIVE: This article presents results that confirm previous clinical studies suggesting that cannabis may be an effective analgesic and potential opioid substitute. Participants reported improved pain, health, and fewer side effects as rationale for substituting. This article highlights how use duration and intentions for use affect reported treatment and substitution effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30690169

https://www.jpain.org/article/S1526-5900(18)30735-1/fulltext