Author Archives: David Worrell

THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

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“The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013.

RESULTS:

In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months’ observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT.

CONCLUSIONS:

While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26901343

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

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“A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.

…no evidence of addiction, abuse or misuse.

The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.”

http://www.ncbi.nlm.nih.gov/pubmed/26901342

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze.

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“Previous studies have shown that cannabinoidergic system is involved in anxiety.

The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat.

It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system.

It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.”

http://www.ncbi.nlm.nih.gov/pubmed/26904171

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

Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents. Non-psychoactive cannabinoids, ‘entourage’ compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects.

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“There is good evidence that plant-derived and synthetic cannabinoids possess neuroprotective properties.

These compounds, as a result of effects upon CB(1) cannabinoid receptors, reduce the release of glutamate, and in addition reduce the influx of calcium following NMDA receptor activation.

The major obstacle to the therapeutic utilization of such compounds are their psychotropic effects, which are also brought about by actions on CB(1) receptors. However, synthesis of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, which also have neuroprotective properties, are increased under conditions of severe inflammation and ischemia, raising the possibility that compounds that prevent their metabolism may be of therapeutic utility without having the drawback of producing psychotropic effects.

In this review, the evidence indicating neuroprotective actions of plant-derived, synthetic and endogenous cannabinoids is presented. In addition, the pharmacological properties of endogenous anandamide-related compounds that are not active upon cannabinoid receptors, but which are also produced during conditions of severe inflammation and ischemia and may contribute to a neuroprotective action are reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/12505646

Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways.

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“In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation.

This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism.

These findings indicate a protective role of CB1 receptors in airway inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/26896777

Medical marijuana laws and adolescent marijuana use in the USA from 1991 to 2014: results from annual, repeated cross-sectional surveys.

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The Lancet Psychiatry

“Our findings, consistent with previous evidence, suggest that passage of state medical marijuana laws does not increase adolescent use of marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26303557

http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00217-5/fulltext

Prevalence of marijuana use does not differentially increase among youth after states pass medical marijuana laws: Commentary on and reanalysis of US National Survey on Drug Use in Households data 2002-2011.

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“There is considerable interest in the effects of medical marijuana laws (MML) on marijuana use in the USA, particularly among youth. The article by Stolzenberg et al. (2015) “The effect of medical cannabis laws on juvenile cannabis use” concludes that “implementation of medical cannabis laws increase juvenile cannabis use”. This result is opposite to the findings of other studies that analysed the same US National Survey on Drug Use in Households data as well as opposite to studies analysing other national data which show no increase or even a decrease in youth marijuana use after the passage of MML. We provide a replication of the Stolzenberg et al. results and demonstrate how the comparison they are making is actually driven by differences between states with and without MML rather than being driven by pre and post-MML changes within states. We show that Stolzenberg et al. do not properly control for the fact that states that pass MML during 2002-2011 tend to already have higher past-month marijuana use before passing the MML in the first place. We further show that when within-state changes are properly considered and pre-MML prevalence is properly controlled, there is no evidence of a differential increase in past-month marijuana use in youth that can be attributed to state MML.”

http://www.ncbi.nlm.nih.gov/pubmed/26895950

Endocannabinoid system in the brain…and elsewhere.

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“The endocannabinoid system is a complex system with endogenous ligands, synthesis and transport processes, specific receptors (CB1 and CB2) and intracellular degrading enzymes.

It is widely distributed in the central nervous system, but also in peripheral organs.

In the brain, endocannabinoids and CB1 receptors are almost ubiquitous and play a role in synaptic plasticity: they modulate, through an inhibitory retrograde action, the release of classical neurotransmitters such as amines, acetylcholine or amino acids.

They may exert a neuroprotective effect, but are also involved in appetite and alcohol/drug dependence.

At the periphery, they are present (and overexpressed in case of abdominal obesity) in various organs involved in energy control and metabolic regulation.

Furthermore, CB2 receptors are also present in the brain, although less numerous than CB1 receptors.

They could attenuate pain and also be neuroprotective.

Selective agonists, antagonists and inverse agonists of CB1 and CB2 receptors are currently developed and open new interesting therapeutic perspectives.”

http://www.ncbi.nlm.nih.gov/pubmed/18669206

The endocannabinoid system: novel pathway for cardiometabolic Risk-factor reduction.

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“Although rimonabant has been approved for use in several countries, the Food and Drug Administration has expressed concern about the potential for adverse neurologic and psychiatric effects, considering the widespread distribution of CB1 receptors in the brain. While more research is clearly needed, the clinical evidence shows that CB1-receptor blockade with rimonabant improves multiple cardiovascular and metabolic variables, including body weight and waist circumference, HDL-C, triglycerides, and glucose metabolism. Furthermore, these effects, which are probably mediated by both peripheral and central actions in the ECS, appear to be greater than the improvements that would be expected from weight loss alone. There are multiple ongoing and planned studies with rimonabant as well as several other CB-receptor blockers (e.g., taranabant, CP-945,598). While diet and exercise are the cornerstones of cardiometabolic risk-factor reduction, improved pharmacotherapies are urgently needed. The ECS has provided us with new insights and a promising new avenue for the management of obesity and its associated cardiometabolic risk factors.”

http://www.ncbi.nlm.nih.gov/pubmed/18047036

The endocannabinoid system: potential for reducing cardiometabolic risk.

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“The endocannabinoid system (ECS) affects multiple metabolic pathways in the brain and other organs. The transmembrane CB receptors were cloned in the early 1990s, followed shortly thereafter by the discovery of endogenous ligands, now known as endocannabinoids.

Three general types of cannabimimetic compounds have been described: herbal CBs, which occur uniquely in the cannabis plant (Cannabis sativa); endogenous CBs (or endocannabinoids), which are produced in the brain and peripheral tissues; and synthetic CBs, which are functionally similar compounds synthesized in the laboratory.

Obesity is associated with increased risk for insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, atherogenic dyslipidemia, and cardiovascular disease. Recent studies indicate that the body protects itself from weight loss by lowering energy expenditure. Both energy consumption and energy expenditure are regulated by hormones from a number of organs that act on the brain, as well as neural signals emanating from the brain itself.

Lifestyle modification is the initial intervention for obesity, with emphasis on reducing calorie intake and increasing physical activity; pharmacotherapy may be indicated for certain cardiovascular and metabolic risk factors.

This review focuses on the link between the biology of the cannabinoid receptor type 1 (CB1 receptor) system and body-weight regulation, as well as clinical data from studies of the first CB1 receptor antagonist…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905146/