Monthly Archives: July 2019

Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts.

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“Herein, we report the antioxidant activity of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in pure and mixed solutions at different ratios, as well as of six different Cannabis sativa extracts containing various proportions of CBD and THC by using spectrophotometric (reducing power assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), hypochlorous acid (HOCl) scavenging assays) and electrochemical methods (cyclic voltammetry and differential pulse voltammetry).

The isolated cannabinoids, the different stoichiometric ratios of CBD and THC, and the natural extracts proved to have remarkable antioxidant properties in all the methods employed in this work.

The antioxidant activity of CBD and THC was compared against that of the well-defined antioxidants such as ascorbic acid (AA), resveratrol (Resv) and (-)-epigallocatechin-3-gallate (EGCG). Clear evidence of the synergistic and antagonistic effects between CBD and THC regarding to their antioxidant activities was observed.

Moreover, a good correlation was obtained between the optical and electrochemical methods, which proved that the reported experimental procedures can easily be adapted to determine the antioxidant activity of extracts from various Cannabis sativa species and related compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31318364

https://pubs.rsc.org/en/content/articlelanding/2019/AN/C9AN00890J#!divAbstract

Graphical abstract: Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts

Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms.

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molecules-logo“Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders.

In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed.

CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- and stress-induced reinstatement of cocaine and priming-induced reinstatement of METH seeking behaviours. CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP and prevented priming-induced reinstatement of METH CPP.

Observational studies suggest that CBD may reduce problems related with crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015). The potential mechanisms involved in the protective effects of CBD on addiction to psychostimulant drugs include the prevention of drug-induced neuroadaptations (neurotransmitter and intracellular signalling pathways changes), the erasure of aberrant drug-memories, the reversion of cognitive deficits induced by psychostimulant drugs and the alleviation of mental disorders comorbid with psychostimulant abuse. Further, preclinical studies and future clinical trials are necessary to fully evaluate the potential of CBD as an intervention for cocaine and methamphetamine addictive disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31315244

https://www.mdpi.com/1420-3049/24/14/2583

Allostatic load and the cannabinoid system: implications for the treatment of physiological abnormalities in post-traumatic stress disorder (PTSD).

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Image result for cns spectrums“It is becoming clear that post-traumatic stress disorder (PTSD) is not simply a psychiatric disorder, but one that involves pervasive physiological impairments as well. These physiological disturbances deserve attention in any attempt at integrative treatment of PTSD that requires a focus beyond the PTSD symptoms themselves. The physiological disturbances in PTSD range over many systems, but a common thread thought to underlie them is that the chronic effects of PTSD involve problems with allostatic control mechanisms that result in an excess in what has been termed “allostatic load” (AL).

A pharmacological approach to reducing AL would be valuable, but, because of the large range of physiological issues involved – including metabolic, inflammatory, and cardiovascular systems – it is unclear whether there exists a simple comprehensive way to address the AL landscape. In this paper, we propose that the cannabinoid system may offer just such an approach, and we outline evidence for the potential utility of cannabinoids in reducing many of the chronic physiological abnormalities seen in PTSD which are thought to be related to excess AL.” https://www.ncbi.nlm.nih.gov/pubmed/31303187
https://www.cambridge.org/core/journals/cns-spectrums/article/allostatic-load-and-the-cannabinoid-system-implications-for-the-treatment-of-physiological-abnormalities-in-posttraumatic-stress-disorder-ptsd/F85D2588638C20BE9DD86DEC2F768242

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

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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.

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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.

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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.

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 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

Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review.

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Journal of Pharmacy and Pharmacology banner“Osteoporosis is a skeletal disease with decreased bone mass and alteration in microarchitecture of bone tissue, and these changes put patients in risk of bone fracture. As a common symptom of osteoporosis and complication of osteoporotic fracture, chronic pain is a headache for clinicians. Nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors and opioid drugs can temporarily reduce osteoporotic pain but have relevant side effects, such as addiction, tolerability and safety. The review summarized the recent advancements in the study of CB receptors in osteoporosis and osteoporotic pain and related mechanisms.

KEY FINDINGS:

Recent studies indicated the two nociceptive receptors, cannabinoid receptor (CB) and transient receptor potential vanilloid type 1 (TRPV1) channel, are co-expressed in bone cells and play important role in the metabolism of bone cells, suggesting that dualtargeting these 2 receptors/channel may provide a novel approach for osteoporotic pain. In addition, both CB receptor and TRPV1 channel are found to be expressed in the glial cells which play vital role in mediating inflammation, chronic pain and metabolism of bone cells, suggesting a role of glial cells inosteoporotic pain.

SUMMARY:

Multiple-targeting against glial cells, CB receptors and TRPV1 channel may be one effective therapeutic strategy for osteoporotic pain in the future, following the elucidation of the complicated mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/31294469

https://onlinelibrary.wiley.com/doi/full/10.1111/jphp.13135

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

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“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

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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/