Tetrahydrocannabivarin (THCv) reduces Default Mode Network and increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

“The cannabinoid CB1 Neutral Antagonist Tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity but without the depressogenic side-effects of inverse antagonists such as Rimonabant.

Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the Default Mode network and increases connectivity in the Cognitive Control network and Dorsal Visual Stream network.

This effect profile suggests possible therapeutic activity of THCv for obesity where functional connectivity has been found to be altered in these regions.”

http://www.ncbi.nlm.nih.gov/pubmed/26362774

Assessment of Israeli Physicians’ Knowledge, Experience and Attitudes towards Medical Cannabis: A Pilot Study.

“Cannabis has been used throughout history for different purposes but was outlawed in the United States in 1937; many countries followed suit. Although recently reintroduced as a medical treatment in several countries, the use of cannabis in Israel is permitted for some medical purposes but is still controversial, eliciting heated public and professional debate. The few published studies on physicians’ attitudes to medical cannabis found them to be generally unsupportive.

OBJECTIVES:

To examine, for the first time, the experience, knowledge and attitudes of Israeli physicians towards medical cannabis (MC)…

Physicians generally agreed that MC treatment could be helpful for chronic and for terminally ill patients. Oncologists and pain specialists did not agree unanimously that MC can undermine mental health, whereas other physicians did. Physicians who recommended MC in the past (once or more) agreed, more than physicians who did not, with the statement “MC treatment in Israel is accessible to patients who need it”.

CONCLUSIONS:

In contrast to other studies we found partial acceptance of MC as a therapeutic agent. Further in-depth studies are needed to address regulatory and educational needs.”

http://www.ncbi.nlm.nih.gov/pubmed/26357721

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

High Times for Painful Blues: The Endocannabinoid System in Pain-Depression Comorbidity.

“Depression and pain are two of the most debilitating disorders worldwide and have an estimated cooccurrence of up to 80%. Comorbidity of these disorders is more difficult to treat, associated with significant disability and impaired health-related quality of life than either condition alone, resulting in enormous social and economic cost.

Several neural substrates have been identified as potential mediators in the association between depression and pain, including neuroanatomical reorganization, monoamine and neurotrophin depletion, dysregulation of the hypothalamo-pituitary-adrenal axis, and neuroinflammation.

However, the past decade has seen mounting evidence supporting a role for the endogenous cannabinoid (endocannabinoid) system in affective and nociceptive processing, and thus, alterations in this system may play a key role in reciprocal interactions between depression and pain.

This review will provide an overview of the preclinical evidence supporting an interaction between depression and pain and the evidence supporting a role for the endocannabinoid system in this interaction.”

http://www.ncbi.nlm.nih.gov/pubmed/26342110

“The plant Cannabis sativa has been used as a medicine throughout the world for several thousand years, with reports of its use in treating painful symptoms appearing as early as 2600 BC. The principal psychoactive ingredient of Cannabis sativa, delta-9-tetrahydrocannabinol (Δ9-THC), was first identified in 1964, and subsequent studies to understand its mechanism of action led to the discovery of the endogenous cannabinoid (endocannabinoid) system… Because of the distribution of the endocannabinoid system throughout spinal and supraspinal regions, it is in a prime position to regulate neurophysiological activities such as affective and nociceptive processing… evidence suggests a prominent role for the endocannabinoid system in the interaction between depression and pain,” http://ijnp.oxfordjournals.org/content/early/2015/09/04/ijnp.pyv095.long

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

Issues and promise in clinical studies of botanicals with anticonvulsant potential.

“Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy.Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine.

Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products.

The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. ”

http://www.ncbi.nlm.nih.gov/pubmed/26341963

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

The complete chloroplast genomes of Cannabis sativa and Humulus lupulus.

“Cannabis and Humulus are sister genera comprising the entirety of the Cannabaceae sensu stricto, including C. sativa L. (marijuana, hemp), and H. lupulus L. (hops) as two economically important crops.

These two plants have been used by humans for many purposes including as a fiber, food, medicine, or inebriant in the case of C. sativa, and as a flavoring component in beer brewing in the case of H. lupulus.

In this study, we report the complete chloroplast genomes for two distinct hemp varieties of C. sativa, Italian “Carmagnola” and Russian “Dagestani”, and one Czech variety of H. lupulus “Saazer”.

Both C. sativa genomes are 153 871 bp in length, while the H. lupulus genome is 153 751 bp. The genomes from the two C. sativa varieties differ in 16 single nucleotide polymorphisms (SNPs), while the H. lupulus genome differs in 1722 SNPs from both C. sativa cultivars.”

http://www.ncbi.nlm.nih.gov/pubmed/26329384

Clinical perspectives on medical marijuana (cannabis) for neurologic disorders.

“The American Academy of Neurology published an evidence-based systematic review of randomized controlled trials using marijuana (Cannabis sativa) or cannabinoids in neurologic disorders.

Several cannabinoids showed effectiveness or probable effectiveness for spasticity, central pain, and painful spasms in multiple sclerosis.

The review justifies insurance coverage for dronabinol and nabilone for these indications.

Many insurance companies already cover these medications for other indications.

It is unlikely that the review will alter coverage for herbal marijuana.

Currently, no payers cover the costs of herbal medical marijuana because it is illegal under federal law and in most states.

Cannabinoid preparations currently available by prescription may have a role in other neurologic conditions, but quality scientific evidence is lacking at this time.”

http://www.ncbi.nlm.nih.gov/pubmed/26336632