Cannabinoid Ligands and Alcohol Addiction: A Promising Therapeutic Tool or a Humbug?

“The vast therapeutic potential of cannabinoids of both synthetic and plant-derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies.

In addition, some observations indicate that cannabinoid receptor antagonists may be useful for the treatment of alcohol dependence and addiction, which is a major health concern worldwide.

While the synergism between alcohol and cannabinoid agonists (in various forms) creates undesirable side effects when the two are consumed together, the administration of CB1 antagonists leads to a significant reduction in alcohol consumption.

Furthermore, cannabinoid antagonists also mitigate alcohol withdrawal symptoms.

Herein, we present an overview of studies focusing on the effects of cannabinoid ligands (agonists and antagonists) during acute or chronic consumption of ethanol.”

http://www.ncbi.nlm.nih.gov/pubmed/26353844

Cannabidiol and sodium nitroprusside: two novel neuromodulatory pharmacological interventions to treat and prevent psychosis.

“Since most patients with schizophrenia do not respond properly to treatment, scientific effort has been driven to the development of new compounds acting on pharmacological targets beyond the dopaminergic system.

Therefore, the aim is to review basic and clinical research findings from studies evaluating the effects of cannabidiol (CBD), an inhibitor of the reuptake and metabolism of anandamide and several other effects on nervous system, and sodium nitroprusside, a nitric oxide donor, on the prevention and treatment of psychosis.

Animal and human research supports that CBD and sodium nitroprusside might be effective in the prevention and treatment of psychosis in general and especially in schizophrenia.

The evidence available to date shows that CBD and sodium nitroprusside act in pathways associated with psychotic symptoms and that they may be important agents in the management of prodromal psychotic states and psychosis.

This underscores the relevance of further research on the effects of these agents and others that mediate the activity of the cannabinoid system and of nitric oxide, as well as comparative studies of their antipsychotic effects and those of other antipsychotic drugs currently used to treat schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/26350340

Cannabidiol as a Potential Treatment for Anxiety Disorders.

“Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders.

The purpose of the current review is to determine CBD’s potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies.

We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing.

Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations.

Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.”

http://www.ncbi.nlm.nih.gov/pubmed/26341731

A pharmacological basis of herbal medicines for epilepsy.

“Epilepsy is the most common chronic neurological disease, affecting about 1% of the world’s population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs).

Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures.

Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals.

Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs.

Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays.

To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids.

Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs.

Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites.

Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy.

Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development.

In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/26074183

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

Cannabinoids in the Treatment of Neurological Disorders

“The force of the recent explosion of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology.

Paradoxically, for 10 millennia this plant has been an integral part of human cultivation, where it was used for its fibers long before its pharmacological properties.

With regard to the latter, cannabis was well known to healers from China and India thousands of years ago; Greek and Roman doctors during classic times; Arab doctors during the Middle Ages; Victorian and Continental physicians in the nineteenth century; American doctors during the early twentieth century; and English doctors until 1971 when a variety of nonevidence-based remedies were removed from the British Pharmaceutical Codex.

The clinical data on cannabis therapeutics are meager and the vast majority are formed by surveys or small studies that are underpowered and/or suffer from multiple methodological flaws, often by virtue of limited research funding for nonaddiction-focused studies. Thus, we know relatively little about the clinical efficacy of cannabinoids for the various neurological disorders for which historical nonscientific and medical literature have advocated its use.

The relative scarcity of proven cannabis-based therapies is not due to data that show that cannabinoids are ineffective or unsafe, but rather reflects a poverty of medical interest and a failure by pharmaceutical companies arising from regulatory restrictions compounded by limits for patent rights on plant cannabinoid-containing preparations that have been used medicinally for millennia, as is the case for most natural products.

We are pleased to have gathered many of the world’s experts together on the basic biology of cannabinoids, as well as their potential role in treating neurologic and psychiatric disorders…

We hope that this issue of Neurotherapeutics will serve to mark the bounds of verifiable scientific knowledge of cannabinoids in the treatment of neuropsychiatric and neurological disorders. At the same time, our contributors have also helped identify areas for future research, as well as the strategies needed to move our base of knowledge forward.

We hope that this volume will help to accelerate the pace of the appropriately focused and productive research and double-blind placebo-controlled randomized trials to the point at which the care of patients is informed by valid data and not just anecdote.”

http://link.springer.com/article/10.1007/s13311-015-0388-0/fulltext.html

The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.

“One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”

http://www.ncbi.nlm.nih.gov/pubmed/16616335

“Marijuana has been used in medicine for many centuries, and nowadays there is a renaissance in the study of the therapeutic effects of cannabinoids. One of the most active areas of research in the cannabinoid field is the study of the potential antitumoral application of these drugs. Our results unravel the mechanism of cannabinoid antitumoral action by demonstrating the proapoptotic role of the stress protein p8 via its downstream targets ATF-4, CHOP, and TRB3.

The identification of this pathway may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of potential antitumoral therapies with cannabinoids.

Our results also support that cannabinoid treatment does not activate this pathway in nontransformed cells, in line with the belief that cannabinoid proapoptotic action is selective for tumor versus nontumor cells, and that cannabinoids act in a synergic fashion with ER stress inducers as well as with other antitumoral agents.

The identification of the p8-regulated pathway described here may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of a potential cannabinoid-based antitumoral therapy.”

http://www.sciencedirect.com/science/article/pii/S1535610806000857

Medical Marijuana: Reducing Spasticity in Multiple Sclerosis Patients

 

“Medical marijuana is a justifiable treatment for spasticity in patients with MS.

Interviews indicate that many patients choose marijuana over other medicines because they experience minimal side effects and rapid improvements in motor functioning…

Compared to the steroids, tranquilizers, and sedatives usually prescribed for MS patients, marijuana is remarkably safe and benign…

There is a lack of evidence for long-term risks associated with marijuana use. The short-term risks are minimal and short-lived.

Studies verify the positive relationship between medical marijuana use and reduced spasticity.

Voters are realizing the cruelty associated with robbing a terminally or chronically ill patient from the medicine that most relieves their pain.

MS is a chronic disease that can lead to severe pain and disability if untreated. For these reasons, medical marijuana should be available to patients who understand the risks associated with its use.

Until medical research develops an equally effective oral drug, marijuana will remain a reasonable option for patients suffering from MS.”

http://www.vanderbilt.edu/AnS/psychology/health_psychology/medicalmarijuana.htm

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

Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease.

“Parkinson’s disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain.

Symptomatic therapies are available but no treatment slows or prevents the loss of neurons.

Neuroinflammation has been implicated in its pathogenesis.

To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients.

Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated.

The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death.

Furthermore, the addition of DFU (25mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects.

Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits.

The results expand the current understanding of the role that this signalling system has and its potential influence in PD.”

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential.

“The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia.

Anandamide signaling in the central nervous system may be particularly important.

Δ9-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects.

CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties.

Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.”

http://www.ncbi.nlm.nih.gov/pubmed/26311150

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