Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence.

Posted on September 3, 2015 by David

“Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics.

The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems.

The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes.

Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/26325482

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential.

Posted on August 28, 2015 by David

“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/

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

Posted on August 27, 2015 by David

“The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy.

The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg).

The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased.

CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly.

Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26309534

“Epilepsy is one of the most common diseases of the brain, affecting at least 50 million people globally… Despite development of a number of new antiepileptic drugs, epilepsy could not be significantly reduced and is a challenge to the clinicians… Many plants, known for their anticonvulsant activity are subjected to phytochemical and pharmacological studies. Cannabidiol (CBD) a constituent of the hemp seed exhibits potent anticonvulsant activity… The CBD possess anticonvulsive, anti-epileptic, and antimicrobial properties… The present study was performed to examine the anticonvulsive effects of CBD in pentylenetetrazole-induced chronic epilepsy rat models… The present study demonstrates that CBD protects against pentylenetetrazole-induced chronic seizures, decreases astrocytic hyperplasia, decreases neuronal cell loss and selectively suppresses NMDA1 receptor in the hippocampus… Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537971/

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

Marijuana Use in Epilepsy: The Myth and the Reality.

Posted on August 25, 2015 by David

“Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia.

Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts.

This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD).

Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26299273

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

Sativex® and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.

Posted on August 21, 2015 by David

“Despite the proven efficacy of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects.

The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS.

This was a randomized, double-blind, placebo-controlled, crossover study…

Our findings confirm the clinical benefit of Sativex on MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26289497

Cannabinoids and Epilepsy.

Posted on August 19, 2015 by David

“Cannabis has been used for centuries to treat seizures.

Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies.

In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy.

These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures.

Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/26282273

Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release.

Posted on August 19, 2015 by David

“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders.

Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties.

Its effects against cocaine neurotoxicity, however, has remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms.

In conclusion, CBD protects against seizures in a model of cocaine intoxication.

CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/26283212

HU-444, A Novel, Potent Anti-Inflammatory, Non-Psychotropic Cannabinoid.

Posted on August 15, 2015 by David

“Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas.

In contrast to Δ9-tetrahydrocannabinol (Δ9-THC) it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of TNF-α, a proinflammatory cytokine, and was found to be an oral anti-arthritic therapeutic in murine collagen-induced arthritis in vivo.

However in acidic media it can cyclize to the psychoactive Δ9-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ9-THC-like compound.

In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-a production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ9-THC- like effects in mice.

We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26272937

[Clinical pharmacology of medical cannabinoids in chronic pain].

Posted on August 14, 2015 by David

“In Switzerland, medical cannabinoids can be prescribed under compassionate use after special authorization in justified indications such as refractory pain. Evidence of efficacy in pain is limited and the clinical benefit seems to be modest. Their drug-drug interactions (DDI) profile is poorly documented. Cytochromes P450 (CYP) 2C9 and 3A4 are involved in the metabolism of tetrahydrocannabinol and cannabidiol, which implies possible DDI with CYP450 inhibitor and inducer, such as anticonvulsivants and HIV protease inhibitors, which may be prescribed in patients with neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/26267945

HU-446 and HU-465, derivatives of the non-psychoactive cannabinoid cannabidiol, decrease the activation of encephalitogenic T cells.

Posted on August 12, 2015 by David

“Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS).

Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465)…

These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases. ”

http://www.ncbi.nlm.nih.gov/pubmed/26259697