Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary.

Image result for Nutrition and Metabolic Insights“Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level.

The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard.

Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States.

This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.” https://www.ncbi.nlm.nih.gov/pubmed/31308686

https://journals.sagepub.com/doi/10.1177/1178638819847480

S-Adenosyl-L-Methionine (SAMe), Cannabidiol (CBD), and Kratom in Psychiatric Disorders: Clinical and Mechanistic Considerations.

Brain, Behavior, and Immunity“Given the limitations of prescription antidepressants, many individuals have turned to natural remedies for the management of their mood disorders.

We review three selected natural remedies that may be of potential use as treatments for depressive disorders and other psychiatric or neurological conditions.

The best studied and best supported of these three remedies is S-adenosyl-L-methionine (SAMe), a methyl donor with a wide range of physiological functions in the human organism.

With the increasing legalization of cannabis-related products, cannabidiol (CBD) has gained popularity for various potential indications and has even obtained approval in the United States and Canada for certain neurological conditions.

Kratom, while potentially useful for certain individuals with psychiatric disorders, is perhaps the most controversial of the three remedies, in view of its greater potential for abuse and dependence.

For each remedy, we will review indications, doses and delivery systems, potential anti-inflammatory and immunomodulatory action, adverse effects, and will provide recommendations for clinicians who may be considering prescribing these remedies in their practice.” https://www.ncbi.nlm.nih.gov/pubmed/31301401

https://www.sciencedirect.com/science/article/pii/S0889159119302788?via%3Dihub

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

Image result for jama network

“This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment.”   https://www.ncbi.nlm.nih.gov/pubmed/31305874
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737918
“nabiximols: An herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains a standardized extract of tetrahydrocannabinol (THC), the non-psychoactive cannabinoid cannabidiol (CBD), other minor cannabinoids, flavonoids, and terpenes from two cannabis plant varieties.” https://www.cancer.gov/publications/dictionaries/cancer-drug/def/nabiximols
“Cannabis treatment counters addiction: First study of its kind. Trial shows cannabis replacement therapy can be effective” https://www.sciencedaily.com/releases/2019/07/190715114247.htm

Biological bases for a possible effect of cannabidiol in Parkinson’s disease.

 SciELO - Scientific Electronic Library Online“Current pharmacotherapy of Parkinson’s disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients’ quality of life with fewer side effects are needed, but not yet available.

Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD.

RESULTS:

Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms.

CONCLUSIONS:

Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.”

https://www.ncbi.nlm.nih.gov/pubmed/31314869

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462019005012104&tlng=en

The protective mechanism of cannabidiol in cardiac injury: A systematic review of non-clinical studies.

“Cardiac disease is accounted as the leading cause of worldwide morbidity and mortality, mainly in association with induction of inflammation and oxidative stress. The disease is characterized by the overproduction of reactive oxygen and/or nitrogen species (ROS/RNS), and reduced antioxidant capacity.

Cannabidiol (CBD) is a non-psychoactive ingredient of marijuana that reported to be safe and well tolerated in patients. Due to its pleiotropic effect, CBD has been shown to exert cytoprotective effects. This study intended to clarify the mechanisms and the potential role of CBD regarding cardiac injuries treatment.

RESULTS:

Our findings obviously demonstrate that CBD has multi-functional protective assets to improve cardiac injuries; preliminary through scavenging of free radicals, and reduction of oxidative stress, apoptosis, and inflammation.

CONCLUSION:

CBD can protect against cardiac injuries, mainly through its anti-oxidant, anti-inflammatory, and anti-apoptotic effects on the basis of non-clinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31291873

http://www.eurekaselect.com/173374/article

“Cytoprotection is a process by which chemical compounds provide protection to cells against harmful agents.” https://en.wikipedia.org/wiki/Cytoprotection

Strong reasons make strong actions: medical cannabis and cancer—a call for collective action

Logo of curroncol“Call it cannabis, not marijuana or weed.

It has been more than 17 years since the Canadian prohibitory regulations on the use of medical cannabis began to ease and more than 17 weeks (more than 6 months by the time of publication) since the Cannabis Act (Bill C-45) became law. Cannabis use for medical purposes has been part of the historical record and medical writings for millennia. However, it is only in the last 30 years that the workings of the human endocannabinoid system have been described and its receptors discovered. Amazing as all of those developments have been, the challenge of reintegrating cannabis into the science of modern medicine—and particularly care for patients with cancer—is a need whose time has come.

Surveys inform us that patients with cancer are using cannabis to manage symptoms related to cancer and cancer treatment. More concerning is that their use is for a medical need occurring outside the confines of modern cancer care, with patients accessing their cannabis from friends and family, and often from casual or unlicensed suppliers. Beliefs in the benefits of cannabis—for its yet unfounded therapeutic potential—are commonly held or supported by poor-quality evidence. Patients and their caregivers are inundated with media stories about a budding industry and its mergers and acquisitions while it grows to meet a need for what is regarded by some as overlooked and undertreated ailments. How should oncologists and the oncology team, trusted as the informed and compassionate advocates for their patients, reconcile the overwhelming public attention being given to this product—growing more, creating new routes of administration, and reaching for new uses—with the work needed to further the science of cannabis as it pertains to cancer care?

The onus is on us, the community of cancer care providers, to act.

Therapeutic and clinical developments in oncology are resulting in improvements in the survival of many patients. Costly immunologic therapies are promising and are being implemented for a variety of cancers. New science about the microbiome, about cancer detection, and about targeted therapies are being researched. And yet, contrasted against those celebrations of scientific ingenuity are the glaring gaps in the work pertaining to cannabis to settle unsubstantiated claims and anecdotal observations of this elixir for the ages. As clinicians and scientists, we must work to generate the needed evidence-based outcomes and to document or dispel the potential interactions and sequelae between cannabis and prescribed cancer treatments. “There are in fact two things, science and opinion, the former begets knowledge, the latter ignorance”.

The frameworks to lead this charge are ours to create. The current legal framework is focused on issues of access and control to regulate production, distribution, and sale. The medical framework for cannabis research is more tenuous, concentrated in silos of expertise as a result of the previous prohibitory environment. The study of cannabis is ripe for development, but even intra-institutional endeavors require help. The machinery of science requires some assembly and repurposing to address the new challenges.

If the current and future oncology landscape is a challenge for those working in cancer care, we must remember that patients deserve our compassion as they attempt to navigate this emotional journey with or without cannabis. More importantly, they need our support and deserve to see us take leadership in cannabis research. Oncologists who have expertise in both the clinical and scientific worlds must inform the necessary work. We must be the architects of its design, building bridges to industry and patients, while engaging our academic institutions.

“Coming together is a beginning, staying together is progress, and working together is success”.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588059/

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

 “Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray’s competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients.

Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved.

People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.”

https://www.ncbi.nlm.nih.gov/pubmed/31286317

https://link.springer.com/article/10.1007%2Fs10461-019-02585-7

Isolation, Synthesis And Structure Determination Of Cannabidiol Derivatives And Their Cytotoxic Activities.

Publication Cover

“In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (1) with acid catalyst POCl3 afforded a new derivative 6 along with six known molecules 2  57 and, 8. The structure of 6 was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data. All the compounds (2  8) were evaluated for their cytotoxic potential against a panel of eight cancer cell lines. Compounds 457, and 8showed pronounced in vitro cytotoxic activity with IC50 values ranging from 5.6 to 60 μM. Out of the active molecules, compounds 4, and 7 were found to be comparable to that of the parent molecule 1 on the inhibition of almost all the tested cancer cell lines.”

https://www.ncbi.nlm.nih.gov/pubmed/31282748

https://www.tandfonline.com/doi/abs/10.1080/14786419.2019.1638381?journalCode=gnpl20

Employment and Marijuana Use Among Washington State Adolescents Before and After Legalization of Retail Marijuana

 Journal of Adolescent Health Home“The purpose of the study was to describe associations between employment and marijuana use among adolescents 2 years before passage of 2012 ballot initiative and 2 years after the implementation of retail recreational marijuana sales took place in Washington.

Working adolescents in all grades had higher prevalence of recent marijuana use compared with nonworking adolescents.

Working youth were more likely to use marijuana before and after Washington’s legalization of retail marijuana.”

https://www.jahonline.org/article/S1054-139X(19)30020-5/fulltext

“Study shows working teens more likely to try marijuana. Employed adolescents are more likely to use marijuana than those who don’t work, according to a study recently published in the Journal of Adolescent Health.”
“Teens with jobs are more likely to use cannabis than those who aren’t employed: study” https://www.thegrowthop.com/cannabis-news/teens-with-jobs-are-more-likely-to-use-cannabis-than-those-who-arent-employed-study

Association of Marijuana Laws With Teen Marijuana Use

Image result for jama pediatrics

“In the United States, 33 states and the District of Columbia have passed medical marijuana laws (MMLs), while 10 states and the District of Columbia have legalized the recreational use of marijuana.

A 2018 meta-analysis concluded that the results from previous studies do not lend support to the hypothesis that MMLs increase marijuana use among youth, while the evidence on the effects of recreational marijuana laws (RMLs) is mixed.

Here, we report estimates of the association between the legalization of marijuana and its use, simultaneously considering both MMLs and RMLs.

Consistent with the results of previous researchers, there was no evidence that the legalization of medical marijuana encourages marijuana use among youth.

Moreover, the estimates reported in the Table showed that marijuana use among youth may actually decline after legalization for recreational purposes.

This latter result is consistent with findings by Dilley et al and with the argument that it is more difficult for teenagers to obtain marijuana as drug dealers are replaced by licensed dispensaries that require proof of age.”

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2737637?guestAccessKey=5e4e41eb-ec96-4641-86f9-b5c89cc7cc48&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=070819

“New JAMA study shows legalizing pot might discourage teen use”  https://www.cnbc.com/2019/07/08/new-jama-study-shows-legalizing-pot-might-discourage-teen-use.html

“Recreational marijuana legalization tied to decline in teens using pot, study says”  https://www.cnn.com/2019/07/08/health/recreational-marijuana-laws-teens-study/index.html

“Recreational marijuana legalization tied to decline in teens using pot, study says”  https://wtvr.com/2019/07/08/recreational-marijuana-legalization-tied-to-decline-in-teens-using-pot-study-says/