Phytocannabinoids and epilepsy.

“Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly.

Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs.

The present review summarizes studies on the anticonvulsant properties of phytocannabinoids.

Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration…

 

Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25475762

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

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

“Cannabis has been used to treat disease since ancient times. Δ9 -Tetrahydrocannabinol (Δ9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis.

Cannabis and Δ9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9 -THC limit tolerability.

CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models.

The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors.

CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.

More recent anecdotal reports of high-ratio CBD:Δ9 -THC medical marijuana have claimed efficacy, but studies were not controlled.

CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy.”

http://www.ncbi.nlm.nih.gov/pubmed/24854329

The case for medical marijuana in epilepsy.

“Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte’s mother started adjunctive therapy with a high concentration cannabidiol/Δ9 -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte’s Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte’s seizure frequency from nearly 50 convulsive seizures per day to now 2-3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her other antiepileptic drugs. We briefly review some of the history, preclinical and clinical data, and controversies surrounding the use of medical marijuana for the treatment of epilepsy, and make a case that the desire to isolate and treat with pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior to therapy with whole plant extracts. Much more needs to be learned about the mechanisms of antiepileptic activity of the phytocannabinoids and other constituents of Cannabis sativa.”

http://www.ncbi.nlm.nih.gov/pubmed/24854149

“Marijuana stops child’s severe seizures”  http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/

http://www.thctotalhealthcare.com/category/dravet-syndome/

Marijuana Effectively Reduces Seizures in Epilepsy Patients

marijuanas

“Medicinal uses of marijuana have been a matter for heated debate for quite some time now. A review by American Academy of neurology collated all available information on marijuana use for brain disease treatment and concluded that except for treating symptoms of multiple sclerosis, there is no hard evidence in favor of medical usage of marijuana.

But now some articles have been published in the journal Epilepsia that contradicts the earlier review. One of these articles is a case study of a family living in Denver, CO. The child in the family suffers from a severe form of epilepsy known as Dravet Syndrome and used to have frequent seizures, as many as 50 convulsions a day. But the child was given “Charlotte’s Web”- a marijuana strain with high levels of cannabidiol (CBD) and tetrahydrocannabinol (THC). Reportedly, the seizures decreased considerably and now the child suffers from only 2 or 3 seizures each month.

According to the author of the article, Dr. Edward Maa, “As medical professionals it is important that we further the evidence of whether CBD in cannabis is an effective antiepileptic therapy.””

http://www.newsonwellness.com/2014/05/marijuana-effectively-reduces-seizures-epilepsy-patients/

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

Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.

“The aim of this study was to characterize the influence of WIN 55,212-2 (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model…

These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.”

http://www.ncbi.nlm.nih.gov/pubmed/24549572

Cannabidiol Relieves Psychosis in Schizophrenia, Why is it Illegal?

“A molecule in cannabis (CBD) has shown to relieve anxiety and symptoms of psychosis in people diagnosed with schizophrenia, though many patients are denied or discouraged from this medicine with fewer side effects than pharmaceutical products because the DEA has deemed the cannabis plant to be “illegal”. The U.S. government needs to answer “why?” this medicine warrents time in prison when nobody is being harmed.

 Investigators concluded, “Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications. … The results … potentially represent a completely new mechanism in the treatment of schizophrenia.”

 “Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?

1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”

2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”

3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”

4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”

5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”

6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”

7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”

8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”

9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”

10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”

11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”

12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”

In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.

What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?” 

Read more: http://rinf.com/alt-news/latest-news/cannabidiol-relieves-psychosis-in-schizophrenia-why-is-it-illegal/17827/

An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats.

Abstract

“The effects of cannabidiol (CBD) on electrically evoked kindled seizures were studied in conscious, unrestrained rats with chronically implanted cortical and limbic electrodes, and the results were compared with those of delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin (PHT), and ethosuximide (ESM). All drugs were anticonvulsant, but there were marked differences in their effects on afterdischarge (AD) threshold, duration, and amplitude. CBD, like PHT and delta 9-THC, elevated the AD threshold; in contrast, ESM decreased the threshold but suppressed AD spread. CBD, however, also resembled ESM inasmuch as both drugs decreased AD duration and amplitude. Electrophysiologically, the antiseizure effects of CBD were a combination of those of PHT and ESM. The combination of effects may account for the observation that CBD was the most efficacious of the drugs tested against limbic ADs and convulsions. Other properties of CBD were also noted: For example, compared with delta 9-THC, it is a much more selective anticonvulsant vis-à-vis motor toxicity. CBD also lacks the CNS excitatory effects produced by delta 9-THC, PHT, and ESM. These characteristics, combined with its apparently unique set of electrophysiological properties, support the suggestion that CBD has therapeutic potential as an antiepileptic.”

http://www.ncbi.nlm.nih.gov/pubmed/477630

Cannabidiol–antiepileptic drug comparisons and interactions in experimentally induced seizures in rats.

Abstract

“A comparison of the anticonvulsant and neurotoxic effects of cannabidiol (CBD), delta 9tetrahydrocannabinol, cannabinol and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, chlordiazepoxide, clonazepam, ethosuximide and trimethadione) was made in rats. Median effective potencies (ED 50 values) for maximal electroshock, audiogenic seizures and TD50 values for a rotor rod neurotoxicity test were calculated. Additionally, the interactive effects of CBD and the antiepileptic drugs against maximal electroshock and audiogenic seizures were studied. Each drug was given orally at peak effect time. CBD was an effective and relatively potent anticonvulsant in both maximal electroshock and audiogenic seizure tests. The anticonvulsant potency of phenytoin was significantly increased when combined with phenobarbital, CBD and phenobarbital plus CBD. Additionally, CBD reliably reduced the anticonvulsant potencies of chlordiazepoxide, clonazepam, trimethadione and ethosuximide. These data indicate that CBD is an effective anticonvulsant with a specificity more comparable to drugs clinically effective in major than minor seizures. Furthermore, it appears that CBD enhances the anticonvulsant effects of the former and reduces the effects of the latter types of antiepileptic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/850145

Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo

“CBD is the major nonpsychoactive component of Cannabis sativa whose structure was first described by Mechoulam and Shvo (1963); CBD has recently attracted renewed interest for its therapeutic potential in a number of disease states. CBD has been proposed to possess anticonvulsive, neuroprotective, and anti-inflammatory properties in humans.”

 “Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the antiepileptiform and antiseizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model…. These findings suggest that CBD acts, potentially in a CB1 receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.”

“In conclusion, our data in separate in vitro models of epileptiform activity and, in particular, the beneficial reductions in seizure severity caused by CBD in an in vivo animal model of generalized seizures suggests that earlier, small-scale clinical trials for CBD in untreated epilepsy warrant urgent renewed investigation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819831/

Marijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature.

Abstract

“Although more data are needed, animal studies and clinical experience suggest that marijuana or its active constituents may have a place in the treatment of partial epilepsy. Here we present the case of a 45-year-old man with cerebral palsy and epilepsy who showed marked improvement with the use of marijuana. This case supports other anecdotal data suggesting that marijuana use may be a beneficial adjunctive treatment in some patients with epilepsy. Although challenging because of current federal regulations, further studies are needed to examine the role of marijuana in the treatment of this disorder.”

http://www.ncbi.nlm.nih.gov/pubmed/17609644