Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor.

Posted on June 19, 2016 by David

“Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor.

In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments was studied.

The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions.”

http://www.ncbi.nlm.nih.gov/pubmed/27317835

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

Posted on June 11, 2016 by David

“There is growing pressure for states and the federal government to legalize the use of cannabis products for medical purposes in the United States.

Sixteen states have legalized (or decriminalized possession of) products high in cannabidiol (CBD) and with restricted Δ⁹ -tetrahydrocannabinol (Δ⁹ -THC) content. In most of these states, the intent is for use in refractory epileptic seizures in children, but in a few states, the indications are broader.

The objectives of this review are to provide an overview of the pharmacology and toxicology of CBD; to summarize some of the regulatory, safety, and cultural issues relevant to the further exploitation of its antiepileptic or other pharmacologic activities; and to assess the current status and prospects for clinical development of CBD and CBD-rich preparations for medical use in the United States.

Unlike Δ⁹ -THC, CBD elicits its pharmacologic effects without exerting any significant intrinsic activity on the cannabinoid receptors (CB₁ and CB₂ ), whose activation results in the psychotropic effects characteristic of Δ⁹ -THC, and CBD possesses several pharmacologic activities that give it a high potential for therapeutic use.

CBD exhibits antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.

In combination with Δ⁹ -THC, CBD has received regulatory approvals in several European countries and is currently under study in U.S. Food and Drug Administration-registered trials in the United States.

A number of states have passed legislation to allow for the use of CBD-rich, limited Δ⁹ -THC-content preparations of cannabis for certain pathologic conditions. CBD is currently being studied in several clinical trials and is at different stages of clinical development for various medical indications.

Judging from clinical findings reported so far, CBD and CBD-enriched preparations have great potential utility, but uncertainties regarding sourcing, long-term safety, abuse potential, and regulatory dilemmas remain.”

http://www.ncbi.nlm.nih.gov/pubmed/27285147

Neuroprotection by Cannabinoids in Huntington’s Disease

Posted on May 18, 2016 by David

“A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington’s Disease.”

“Huntington’s disease (HD) is a progressive neurodegenerative disorder, related to an abnormal expansion of CAG triplets in the huntingtin gene, characterized by motor, cognitive and behavioral abnormalities, without known effective symptomatic treatment and without known disease slowing strategy. The most severe neuropathological lesions observed in HD take place in the striatum, one brain area important in motor control and rich in cannabinoid receptors (CBR). CBR are subdivided in two classes: CB1R are located in neurons and play a role in neuronal function; CB2R in brain are located mostly in microglia and modulate neuroinflammation.

CBR disappear early in the course of HD, before there is a massive drop out of cells in the striatum. Cannabinoid transmission is also an early event in brains of animal models of HD. In R6/2 mice, which carry large CAG expansions and develop an early and severe HD phenotype the suppression of the CB1R gene further accelerate the development of a severe clinical syndrome and the characteristic brain inclusions and abnormalities of synaptic density. R6/2 treated mice treated with cannabinoids improve their clinical phenotype, their brain lesions, the synaptic density and the levels of BNDF, a neurotrophic factor which enhances survival and resistance of striatal neurons.

Preliminary studies of cannabinoids in patients with HD have shown that these compounds are safe in these patients.”

https://clinicaltrials.gov/show/NCT01502046

Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.

Posted on May 8, 2016 by David

“Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson’s disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.

Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/27155397

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

Posted on April 26, 2016 by David

“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749

Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability.

Posted on April 21, 2016 by David

“Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models.

Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure.

Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability.

Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and “drug likeness”, while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group.

Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations.

Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/27096053

An update on peroxisome proliferator-activated receptor (PPAR) activation by cannabinoids.

Posted on April 16, 2016 by David

“Some cannabinoids activate the different isoforms of peroxisome proliferator-activated receptors (PPARs; α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies.

Activation of all isoforms, but primarily PPARα and γ, mediate some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti-inflammatory, metabolic, anti-tumoral, gastrointestinal and cardiovascular effects of some cannabinoids, often in conjunction with activation of the more traditional target sites of action such as CB₁ , CB₂ and TRPV1.

PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport. Cannabinoids may be chaperoned to the PPARs by fatty acid binding proteins (FABPs).

The aim of this review is to update the evidence supporting PPAR activation by cannabinoids, and review the physiological responses to cannabinoids that are mediated, and not mediated, by PPAR activation.”

http://www.ncbi.nlm.nih.gov/pubmed/27077495

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices.

Posted on March 20, 2016 by David

“In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND).

Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood.

Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB₁R-related mechanism.

Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments.”

http://www.ncbi.nlm.nih.gov/pubmed/26993829

http://www.thctotalhealthcare.com/category/hivaids/

Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: a Dietary Phytocannabinoid of Pharmaceutical Promise.

Posted on March 12, 2016 by David

“β-Caryophyllene (BCP) is natural bicyclic sesquiterpene abundantly found in essential oils from various spices, fruits and medicinal as well as ornamental plants. It is approved by United States Food and Drug Administration and European agencies as food additive, taste enhancer and flavoring agent and termed as a phytocannabinoid.

Various pharmacological activities such as cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidant, anti-inflammatory, antimicrobial and immune-modulator have been reported in experimental studies. It has shown potent therapeutic promise in neuropathic pain, neurodegenerative and metabolic diseases.

CONCLUSION:

The present review provides a comprehensive insight of pharmacological and therapeutic potential of BCP, its molecular mechanism and signaling pathways in different pathological conditions. The review also examines the possibility of its further development as a novel candidate for various pathologies considering the polypharmacological and multifaceted therapeutic properties potential along with favorable oral bioavailability, lipophilicity and physicochemical properties.”

http://www.ncbi.nlm.nih.gov/pubmed/26965491

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

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.

Posted on February 23, 2016 by David

“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