Tag Archives: cannabis

Polypharmacology Shakes Hands with Complex Aetiopathology.

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“Chronic diseases are due to deviations of fundamental physiological systems, with different pathologies being characterised by similar malfunctioning biological networks.

The ensuing compensatory mechanisms may weaken the body’s dynamic ability to respond to further insults and reduce the efficacy of conventional single target treatments.

The multitarget, systemic, and prohomeostatic actions emerging for plant cannabinoids exemplify what might be needed for future medicines.

Indeed, two combined cannabis extracts were approved as a single medicine (Sativex®), while pure cannabidiol, a multitarget cannabinoid, is emerging as a treatment for paediatric drug-resistant epilepsy.

Using emerging cannabinoid medicines as an example, we revisit the concept of polypharmacology and describe a new empirical model, the ‘therapeutic handshake’, to predict efficacy/safety of compound combinations of either natural or synthetic origin.”

http://www.ncbi.nlm.nih.gov/pubmed/26434643

Targeting the endocannabinoid system to treat anxiety-related disorders.

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“The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders.

The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety.

Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD).

There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue.

In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients.

Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects.

Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks.

In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/26426887

Cannabis – the Israeli perspective.

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“Short overviews are presented on the historical uses of cannabis in the Middle East and on the more recent scientific and medical research on phytocannabinoids and the endocannabinoid system, with emphasis on research contributions from Israel. These are followed by examples of research projects and clinical trials with cannabinoids and by a short report on the regulation of medical marijuana in Israel, which at present is administered to over 22,000 patients.”

http://www.ncbi.nlm.nih.gov/pubmed/26426888

Medical Cannabis Effective for Chronic Pain, Other Indications

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“According to this study:

* Moderate-quality evidence supports the use of cannabinoids for the treatment of chronic pain and for the spasticity related to multiple sclerosis.

* Low-quality evidence suggests that cannabinoids may be effective for chemotherapy-induced nausea and vomiting and other indications.”

http://journals.lww.com/ajnonline/Abstract/2015/10000/Medical_Cannabis_Effective_for_Chronic_Pain,_Other.31.aspx

https://www.researchgate.net/publication/282153137_Medical_Cannabis_Effective_for_Chronic_Pain_Other_Indications

“Medical Cannabis Effective for Chronic Pain, Other Indications. According to this study.” http://www.ncbi.nlm.nih.gov/pubmed/26402288

“Cannabinoids for Medical Use: A Systematic Review and Meta-analysis”  http://jama.jamanetwork.com/article.aspx?articleid=2338251

Endocannabinoids and the Cardiovascular System in Health and Disease.

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“The endocannabinoid system is widely distributed throughout the cardiovascular system.

Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders.

In shock, endocannabinoids released within blood mediate the associated hypotension through CB1 activation. In hypertension, there is evidence for changes in the expression of CB1, and CB1 antagonism reduces blood pressure in obese hypertensive and diabetic patients.

The endocannabinoid system is also upregulated in cardiac pathologies.

This is likely to be cardioprotective, via CB2 and CB1 (lesser extent).

In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids.

Endocannabinoids have positive (CB2) and negative effects (CB1) on the progression of atherosclerosis. However, any negative effects of CB1 may not be consequential, as chronic CB1 antagonism in large scale human trials was not associated with significant reductions in atheroma.

In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB1, CB2, TRPV1 and PPARα.

Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26408169

Endocannabinoids and the Endocrine System in Health and Disease.

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“Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.”

http://www.ncbi.nlm.nih.gov/pubmed/26408166

Cannabis and Endocannabinoid Signaling in Epilepsy.

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“The antiepileptic potential of Cannabis sativa preparations has been historically recognized.

Recent changes in legal restrictions and new well-documented cases reporting remarkably strong beneficial effects have triggered an upsurge in exploiting medical marijuana in patients with refractory epilepsy.

Parallel research efforts in the last decade have uncovered the fundamental role of the endogenous cannabinoid system in controlling neuronal network excitability raising hopes for cannabinoid-based therapeutic approaches.

However, emerging data show that patient responsiveness varies substantially, and that cannabis administration may sometimes even exacerbate seizures. Qualitative and quantitative chemical variability in cannabis products and personal differences in the etiology of seizures, or in the pathological reorganization of epileptic networks, can all contribute to divergent patient responses.

Thus, the consensus view in the neurologist community is that drugs modifying the activity of the endocannabinoid system should first be tested in clinical trials to establish efficacy, safety, dosing, and proper indication in specific forms of epilepsies.

To support translation from anecdote-based practice to evidence-based therapy, the present review first introduces current preclinical and clinical efforts for cannabinoid- or endocannabinoid-based epilepsy treatments.

Next, recent advances in our knowledge of how endocannabinoid signaling limits abnormal network activity as a central component of the synaptic circuit-breaker system will be reviewed to provide a framework for the underlying neurobiological mechanisms of the beneficial and adverse effects.

Finally, accumulating evidence demonstrating robust synapse-specific pathophysiological plasticity of endocannabinoid signaling in epileptic networks will be summarized to gain better understanding of how and when pharmacological interventions may have therapeutic relevance.”

http://www.ncbi.nlm.nih.gov/pubmed/26408165

http://www.thctotalhealthcare.com/category/epilepsy-2/

Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

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“There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS).

These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration.

Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms.

This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.”

http://www.ncbi.nlm.nih.gov/pubmed/26408162

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

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“Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic noncancer pain.

The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among subjects with chronic noncancer pain.

A standardized herbal cannabis product (12.5% THC) was dispensed to eligible subjects for a one-year period; controls were subjects with chronic pain from the same clinics who were not cannabis users.

The primary outcome consisted of serious adverse events (SAEs) and non-serious adverse events (AEs). Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver and endocrine function.

Secondary efficacy parameters included pain and other symptoms, mood, and quality of life.

Two hundred and sixteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. The median daily cannabis dose was 2.5g/d.

There was no difference in risk of SAEs between groups.

Medical cannabis users were at increased risk of non-serious AEs; most were mild to moderate. There were no differences in secondary safety assessments.

Quality-controlled herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program over one year, appears to have a reasonable safety profile.

This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.”

http://www.ncbi.nlm.nih.gov/pubmed/26385201

http://www.thctotalhealthcare.com/category/pain-2/