Monthly Archives: November 2016

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation.

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“Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts.

To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer.

A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns.

RESULTS:

There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial.

CONCLUSION:

Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.”

https://www.ncbi.nlm.nih.gov/pubmed/27530738

Targeting the Endocannabinoid System in Psychiatric Illness.

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“Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning.

The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis.

The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder.

Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, Δ-tetrahydrocannabinol vs cannabidiol) as well as study design.

The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.”

 https://www.ncbi.nlm.nih.gov/pubmed/27811555

Endogenous cannabinoid system alterations and their role in epileptogenesis after brain injury in rat.

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“Post-traumatic epilepsy (PTE) is one of the most common complications resulting from brain injury, however, antiepileptic drugs usually fail to prevent it.

Several lines of evidence have demonstrated that the endogenous cannabinoid system (ECS) plays a pivotal role during epileptogenesis in several animal models.

A recent study has shown that a cannabinoid type 1 (CB1) receptor antagonist could suppress long-term neuron hyperexcitability after brain injury, but the underlying mechanisms remain largely unknown.

In this study, we first analyzed the dynamic expression of different components of the ECS at various time points after brain injury in rats. Then, we conducted a 12-month-long session of behavioral monitoring after the brain injury, and based on the results, the rats were divided into a PTE group and a non-PTE group. Finally, the changes in the ECS between the two groups were compared.

We found that the ECS exhibited a biphasic alteration after brain injury; the expression of the CB1 receptor and 2-arachidonoylglycerol (2-AG) in the PTE group was significantly higher than that of the non-PTE group 12 months after traumatic brain injury.

Our preliminary results indicated that the ECS might be involved in post-traumatic epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27810514

Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids.

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“For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.

OBJECTIVE:

The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2.

CONCLUSION:

Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.”

https://www.ncbi.nlm.nih.gov/pubmed/27805543

 

Cannabinoids, inflammation, and fibrosis.

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“Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs).

As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis.

A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented.

The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed.

The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances.

Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents.

Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.”

https://www.ncbi.nlm.nih.gov/pubmed/27435265

Opioids Out, Cannabis In

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“Negotiating the Unknowns in Patient Care for Chronic Pain”

“With the current nationwide epidemic of opioid abuse, dependence, and fatalities, clinicians are being asked by federal agencies and professional societies to control their prescribing of narcotic medications for pain. Federal guidelines emphasize tapering, discontinuing, and limiting initiation of these drugs except in provision of end-of-life care. Reducing reliance on opioids, however, is a massive task. According to one estimate, more than 650 000 opioid prescriptions are dispensed each day in the United States. Unless the nation develops an increased tolerance to chronic pain, reduction in opioid prescribing leaves a vacuum that will be filled with other therapies.”

http://jamanetwork.com/journals/jama/article-abstract/2576617

WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals.

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“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis.

Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown.

RESULTS:

WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells.

CONCLUSION:

WIN can inhibit the EMT of GC cells through the downregulation of COX-2.”

https://www.ncbi.nlm.nih.gov/pubmed/27802436

The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats.

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“An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration.

The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults.

We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes.

Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27520083

Exocannabinoids effect on in vitro bovine oocyte maturation via activation of AKT and ERK1/2.

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“Endocannabinoids are known to mediate practically all reproductive events in mammals; however, little is known about their role in oocyte maturation. Through RT-PCR and immunocytochemistry, this study confirms the presence of CB1 and CB2 cannabinoidreceptors in bovine oocytes and shows how exposure to the exogenous cannabinoids HU-210 and THC during their in vitro maturation (IVM) activates the phosphorylation of AKT and ERK1/2 proteins associated with the resumption of meiosis. Although supplementation with HU-210 or THC during IVM did not increase blastocyst yields, the expression of interferon tau (IFNτ) and gap junction alpha-1 protein (GJA1) was enhanced at the blastocyst stage. Our data suggest that cannabinoid agonists may be useful IVM supplements as their presence during oocyte maturation upregulates the expression in blastocysts of key genes for embryo quality.”

https://www.ncbi.nlm.nih.gov/pubmed/27798282