Tag Archives: cannabis

From cannabis to cannabidiol to treat epilepsy, where are we?

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“Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions).

Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy.

Among this wide class, the most studied is cannabidiol (CBD) considering its lack of psychotropic effects and its anticonvulsant properties.

Several preclinical studies have tried to understand the mechanism of action of CBD, which still remains largely not understood.

CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures; beneficial effects were reported also in animal models of epileptogenesis and chronic models of epilepsy,

There is indeed sufficient supporting data for clinical development and important antiepileptic effects and the currently ongoing clinical studies will permit the real usefulness of CBD and possibly other cannabinoids.

Undoubtedly, several issues also need to be addressed in the next future (e.g. better pharmacokinetic profiling). Finally, shading light on the mechanism of action and the study of other cannabinoids might represent an advantage for future developments.”

http://www.ncbi.nlm.nih.gov/pubmed/27587196

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study.

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“Cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes.

RESULTS:

Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = -1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = -44.51 points; P < 0.01]), adiponectin (ETD = -5.9 × 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = -6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (-898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated.

CONCLUSIONS:

THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/27573936

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit.

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“Epidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial.

We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.

Patients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects.

Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.”

http://www.ncbi.nlm.nih.gov/pubmed/27568641

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model.

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“Previous reports have demonstrated that the combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) botanical extracts, which are the components of an already approved cannabis-based medicine, reduce the Alzheimer-like phenotype of AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage.

Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in AβPP/PS1 mice at advanced stages of the disease but are not effective in modifying the Aβ processing or in reducing the glial reactivity associated with aberrant Aβ deposition as occurs when administered at early stages of the disease.

The present study also demonstrates that natural cannabinoids do not affect cognitive impairment associated with healthy aging in wild-type mice.

The positive effects induced by Δ9-THC and CBD in aged AβPP/PS1 mice are associated with reduced GluR2/3 and increased levels of GABA-A Ra1 in cannabinoid-treated animals when compared with animals treated with vehicle alone.”

http://www.ncbi.nlm.nih.gov/pubmed/27567873

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease.

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“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.

Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.

After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.

Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.

In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.

PURPOSE:

The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/27561826

Severe motor and vocal tics controlled with Sativex®.

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“A single case report on cannabinoid treatment for treatment-resistant Tourette syndrome (TS).

METHOD:

Our subject received 10.8 mg Tetrahydocannabinol and 10 mg cannabidiol daily, in the form of two oro-mucosal sprays of ‘Sativex®‘, twice daily. Assessment was pre-treatment and at week one, two, and four during treatment. He completed the Yale Global Tic Severity Scale as a subjective measure, and was videoed at each stage. The videos were objectively rated by two assessors, blind to the stage of treatment, using the Original Rush Videotape Rating Scale.

RESULTS:

Both subjective and objective measures demonstrated marked improvement in the frequency and severity of motor and vocal tics post-treatment. There was good interrater reliability of results.

CONCLUSIONS:

Our results support previous research suggesting that cannabinoids are a safe and effective treatment for TS and should be considered in treatment-resistant cases.

Further studies are needed to substantiate our findings.”

http://www.ncbi.nlm.nih.gov/pubmed/27558217

Cannabis and a lower BMI in psychosis: What is the role of AKT1?

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“Cannabis use has been associated with favorable outcomes on metabolic risk factors.

In this study we investigated whether this effect is mediated by the AKT1 gene, as activation of the related enzyme by cannabis may cause metabolic changes.

In conclusion, cannabis use is likely to be associated with a lower BMI in patients with a psychotic disorder.

Moreover, AKT1 risk alleles may increase the incidence of cannabis use in patients with a psychotic disorder, but AKT1 does not appear to mediate the effect of cannabis on BMI.”

http://www.ncbi.nlm.nih.gov/pubmed/27554198

Cannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention.

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“There is substantial evidence from studies in humans and animal models for a role of the endocannabinoid system in the control of emotional states. Several studies have shown an association between exposure to trauma and substance use. Specifically, it has been shown that there is increased prevalence of cannabis use in post-traumatic stress disorder (PTSD) patients and vice versa.

Clinical studies suggest that PTSD patients may cope with their symptoms by using cannabis. This treatment-seeking strategy may explain the high prevalence of cannabis use among individuals with PTSD.

Preliminary studies in humans also suggest that treatment with cannabinoids may decrease PTSD symptoms including sleep quality, frequency of nightmares, and hyperarousal.

Studies in animal models have shown that cannabinoids can prevent the effects of stress on emotional function and memory processes, facilitate fear extinction, and have an anti-anxiety-like effect in a variety of tasks.

Moreover, cannabinoids administered shortly after exposure to a traumatic event were found to prevent the development of PTSD-like phenotype.

In this article, we review the existing literature on the use of cannabinoids for treating and preventing PTSD in humans and animal models.

There is a need for large-scale clinical trials examining the potential decrease in PTSD symptomatology with the use of cannabis.

In animal models, there is a need for a better understanding of the mechanism of action and efficacy of cannabis. Nevertheless, the end result of the current clinical and preclinical data is that cannabinoid agents may offer therapeutic benefits for PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/27551883

Cannabinoid type 1 receptor antagonism ameliorates harmaline-induced essential tremor in rat.

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“Essential tremor (ET) is a neurological disorder with unknown etiology. Its symptoms include cerebellar motor disturbances, cognitive and personality changes, hearing and olfactory deficits. Excitotoxic cerebellar climbing fibre hyperactivity may underlie essential tremor and has been emulated in rodents by systemic harmaline administration.

Cannabinoid receptor agonists can cause motor disturbances although there are also anecdotal reports of therapeutic benefits of cannabis in motor disorders. We set out to establish the effects of cannabinoid type 1 receptor agonism and antagonism in an established rodent model of ET using a battery of accepted behaviour assays in order to determine risk and therapeutic potential of endocannabinoid system modulation in ET.

Overall, harmaline induced robust tremor that was typically worsened across the measured behavioural domains by CB type 1 (CB1 ) receptor agonism but ameliorated by cannabinoid type 1 receptor antagonism.

CONCLUSIONS AND IMPLICATIONS:

These results provide the first evidence of effects of endocannabinoid system modulation on motor function in the harmaline model of essential tremor and suggest that CB1 receptor manipulation warrants clinical investigation as a therapeutic approach to protection against behavioural disturbances associated with essential tremor.”

http://www.ncbi.nlm.nih.gov/pubmed/27545646

Cannabinoids and the gut: new developments and emerging concepts.

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“Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease.”

https://www.ncbi.nlm.nih.gov/pubmed/20117132/