Therapeutic potential of cannabis-related drugs.

Posted on July 29, 2015 by David

“In this review, I will consider the dual nature of Cannabis and cannabinoids.

The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.

The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.

As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.

After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/26216862

Cannabinoids for the Treatment of Movement Disorders.

Posted on July 25, 2015 by David

“Use of cannabinoids as medications has a long history.

Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner.

The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time.

Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development.

Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions.

Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective.

As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.”

http://www.ncbi.nlm.nih.gov/pubmed/26206230

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys.

Posted on July 24, 2015 by David

“Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects limit their use. Therapeutic utility might be improved by combining opioids with other drugs to enhance analgesic effects, but only if adverse effects are not similarly changed.

Cannabinoids have been shown to enhance the antinociceptive potency of opioids without increasing other effects; this study examined whether the effectiveness of cannabinoids is altered in morphine-dependent monkeys.

Tolerance developed to the antinociceptive effects of morphine and cross-tolerance developed to cannabinoids under conditions that produced modest physical dependence.

Compared with the doses examined in this study, much smaller doses of opioids have antinociceptive effects when given with cannabinoids; it is possible that tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.”

http://www.ncbi.nlm.nih.gov/pubmed/26202613

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury.

Posted on July 24, 2015 by David

“Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts.

Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury.

Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana.

In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults.

CONCLUSION:

A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury.

THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.”

http://www.ncbi.nlm.nih.gov/pubmed/26202357

Elucidating Cannabinoid Biology in Zebrafish (Danio rerio).

Posted on July 22, 2015 by David

“Although exogenous cannabinoids, like those contained in marijuana, are known to exert their effects by disrupting the endocannabinoid system, a dearth of knowledge exists about the potential toxicological consequences on public health.

Conversely, the endocannabinoid system represents a promising therapeutic target for a plethora of disorders because it functions to endogenously regulate a vast repertoire of physiological functions.

Accordingly, the rapidly expanding field of cannabinoid biology has sought to leverage model organisms in order to provide both toxicological and therapeutic insights about altered endocannabinoid signaling.

The primary goal of this manuscript is to review the existing field of cannabinoid research in the genetically tractable zebrafish model-focusing on the cannabinoid receptor genes, cnr1 and cnr2, and the genes that produce enzymes for synthesis and degradation of the cognate ligands anandamide and 2-arachidonylglycerol.

Consideration is also given to research that has studied the effects of exposure to exogenous phytocannabinoids and synthetic cannabinoids that are known to interact with cannabinoid receptors.

These results are considered in the context of either endocannabinoid gene expression or endocannabinoid gene function, and are integrated with findings from rodent studies.

This provides the framework for a discussion of how zebrafish may be leveraged in the future to provide novel toxicological and therapeutic insights in the field of cannabinoid biology, which has become increasingly significant given recent trends in cannabis legislation.”

http://www.ncbi.nlm.nih.gov/pubmed/26192460

Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis.

Posted on July 22, 2015 by David

“Alpha/beta-hydrolase domain 6 (ABHD6) is a novel 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, that can fine-tune the endocannabinoid signaling in the central nervous system.

Recently we and others have demonstrated the protective effect of ABHD6 inhibition in the animal models of traumatic brain injury and epileptic seizures. In this study, we investigated the role of targeting ABHD6 in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS)…

These results suggest that inhibition of ABHD6 might be used as an ideal strategy for the treatment of MS and other neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26189763

Exploring structural requirements for peripherally acting 1,5-diaryl pyrazole-containing cannabinoid 1 receptor antagonists for the treatment of obesity.

Posted on July 19, 2015 by David

“Peripherally acting cannabinoid 1 (CB1) receptor antagonists are considered as potential therapeutics for the treatment of obesity with desired efficacy and reduced central nervous system side effects.

The prediction accuracy and reliability of the best developed CoMSIA model have been validated using well-established methods. Using the inputs from the best CoMSIA contour maps, several novel highly selective peripherally acting CB1 receptor antagonists have been designed and reported herein.”

http://www.ncbi.nlm.nih.gov/pubmed/26183840

Phytocannabinoids for Cancer Therapeutics: Recent Updates and Future Prospects.

Posted on July 17, 2015 by David

“Phytocannabinoids (pCBs) are lipid-soluble phytochemicals present in the plant, Cannabis sativa L. and non-cannabis plants which have a long history in traditional and recreational medicine.

The plant and constituents were central in the discovery of the endocannabinoid system, the most new target for drug discovery.

The endocannabinoid system includes two G protein-coupled receptors; the cannabinoid receptors-1 and -2 (CB1 and CB2) for marijuana’s psychoactive principle ∆(9)-tetrahydrocannabinol (∆9-THC), their endogenous small lipid ligands; namely anandamide (AEA) and 2-arachidonoylglycerol (2-AG), also known as endocannabinoids and the proteins for endocannabinoid biosynthesis and degradation such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

The endocannabinoid system has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during pathological conditions including cancer.

Targeting the CB1 receptors become a concern because of adverse psychotropic reactions. Hence, targeting the CB2 receptors or the endocannabinoid metabolizing enzyme by phytocannabinoids obtained from non-cannabis plant lacking psychotropic adverse reactions has garnered interest in drug discovery.

These pCBs derived from plants beyond cannabis appear safe and effective with a wider access and availability.

In recent years, several pCBs derived other than non-cannabinoid plants have been reported to bind to and functionally interact with cannabinoid receptors and appear promising candidate for drug development in cancer therapeutics.

Several of them also target the endocannabinoid metabolizing enzymes that control endocannabinoid levels. In this article, we summarize, critically discuss the updates and future prospects of the pCBs as novel and promising candidates for cancer therapeutics.”

http://www.ncbi.nlm.nih.gov/pubmed/26179998

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

Endocannabinoid 2-arachidonylglycerol protects primary cultured neurons against homocysteine-induced impairments in rat caudate nucleus through CB1 receptor.

Posted on July 17, 2015 by David

“Homocysteine (Hcy) is a high risk factor for Alzheimer’s disease (AD). Caudate nucleus (CN), the major component of basal ganglia in the brain, is also involved in many neurological disorders.

2-Arachidonoylglycerol (2-AG), the true natural ligand for cannabinoid type-1 (CB1) receptors and the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in the hippocampus and CN.

In the present work, we explored that 2-AG significantly protects CN neurons in culture against Hcy-induced response.

2-AG is capable of inhibiting elevation of Hcy-induced cyclooxygenase-2 expression associated with nuclear factor-kappaB/p38MAPK/ERK1/2 signaling pathway through CB1 receptors-dependent way in primary cultured CN neurons.

Our study reveals the therapeutic potential for 2-AG for the treatment of neurodegenerative diseases, such as AD.”

http://www.ncbi.nlm.nih.gov/pubmed/25007951

Effect of Homocysteine on Voltage-Gated Sodium Channel Currents in Primary Cultured Rat Caudate Nucleus Neurons and Its Modulation by 2-Arachidonylglycerol.

Posted on July 17, 2015 by David

“Homocysteine (Hcy) is an important risk factor for Alzheimer’s disease (AD) and other neurodegenerative diseases. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders.

2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects from many stimuli in the central nervous system (CNS).

Furthermore, it has been reported that voltage-gated sodium channels (VGSCs) are the common targets of many neuronal damages and drugs.

However, it is still not clear whether VGSCs are involved in the neurotoxicity of Hcy and the neuroprotective effect of 2-AG in CN neurons. In the present study, whole-cell patch clamp recording was used to invest the action of Hcy on sodium currents in primary cultured rat CN neurons and its modulation by 2-AG.

The results showed that in cultured CN neurons, pathological concentration of Hcy (100 μM) significantly increased the voltage-gated sodium currents (I Na) and produced a hyperpolarizing shift in the activation-voltage curve of I Na.

The further data demonstrated 2-AG is capable of suppressing elevation of Hcy-induced increase in I Na and hyperpolarizing shift of activation curves most partly through CB1 receptor-dependent way.

Our study provides a better understanding of Hcy-associated neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26179279