The Efficacy of Cannabis on Seizures, As Explained by Dr. Rasmussen

One of the most frightening, life-threatening events that can occur in susceptible patients is developing a seizure that conventional medications cannot prevent or break. It’s called status epilepticus.

Here’s the main problem. During a seizure there is uncontrolled firing of neurons in parts of the brain or globally. During this period of increased brain activity, the involved neurons use a tremendous amount of oxygen. Within minutes the brain can become hypoxic (without oxygen) if the person cannot move air effectively because of the seizure. In a very short time (about three minutes of hypoxia), irreversible brain damage can occur should the seizure continue unabated.

This is truly a medical nightmare for both patient and physician.

STATUS EPILEPTICUS DEFINED

From E Medicine:

Status epilepticus (SE) is a common, life-threatening neurologic disorder that is essentially an acute, prolonged epileptic crisis.. SE can represent an exacerbation of a preexisting seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder. In patients with known epilepsy, the most common cause is a change in medication. Most seizures terminate spontaneously

Pharmacotherapy

Most patients with status epilepticus who are treated aggressively with a benzodiazepine, fosphenytoin, and/or phenobarbital experience complete cessation of their seizures. If status epilepticus does not stop, general anesthesia is indicated.

Medications used in the treatment of status epilepticus include the following:

• Benzodiazepines (eg, lorazepam, diazepam, midazolam): First-line agents

• Anticonvulsant agents (eg, phenytoin, fosphenytoin)

• Barbiturates (eg, phenobarbital, pentobarbital)

• Anesthetics (eg, propofol)[ref](http://emedicine.medscape.com/article/1164462-overview) 06/21/2015[/ref]

In case you missed it the ultimate treatment for this life-threatening condition, when all else fails, is to go under anesthesia as if you were having surgery. That’s because general anesthetics are the most powerful drugs we have to “slow down” brain activity. This is performed to save the brain from hypoxia and to arrest the seizure.

As an anaesthesiologist I have never seen a case go this far but it is done often enough. Yet, it’s as if we need a jackhammer to kill a fly, even if the fly weighs two pounds.

All of the drugs we use for seizure disorders read like a who’s who of drug adverse effects. Perhaps one of the worst, and most familiar, is gingival hyperplasia from phenytoin use. You can recognize an adolescent chronically on phenytoin by their gums which tend to grow right over their teeth.

Yet, doctors who question the use of medical marijuana still reject it claiming they do not know enough of the safety profile of cannabis. That’s said with a straight face. Scientists still languish over “hypothetical harms” in spite of the fact that much of the planet uses the plant regularly, and have been for millennia, without much fanfare.

Meanwhile, to the amazement of people everywhere, a certain preparation of cannabis made national headlines last year. An extract from a strain called Charlotte’s Web was able to dispatch a “status” patients’ seizure with no more effort than it takes to fall off your roof.

Considering the big guns we sometimes need to control seizures, and the risks they entail, this news is very comforting.

I have a friend whose daughter was having dozens of seizures throughout the day. It went on for at least a year before being discovered. These are the type often missed except by the astute teacher with the eye of an Accipiter. Often called absence seizures or the old term petite mal. She was put on three antiseizure medications with little effect. Lucky for her, this was a condition that she eventually outgrew. Not so fluky for many others who must deal with relentless debilitating seizures.

PATHWAY OPENED FOR CLINICAL TRIALS

The US Food and Drug Administration (FDA) has given approval for studies to begin on a medicinal form of marijuana for the treatment of intractable epilepsy in children.

The drug, cannabidiol (Epidiolex, GW Pharmaceuticals) is the largest nonpsychoactive component of the cannabis plant. The product has also been granted orphan drug status for the treatment of children with Dravet syndrome, a rare and severe syndrome of infantile-onset, genetic, drug-resistant epilepsy.

Medscape Medical News reported an interview with lead author Dr Orrin Devinsky, of New York University School of Medicine. He mentions that this is the first formal study of CBD. The study was inspired by anecdotal reports of “miraculous” benefits using high CBD medicines for intractable seizure disorders or severe epilepsy.

THE AMERICAN EPILEPSY SOCIETY

Recently, a report was issued at the 68th annual meeting of the American Epilepsy Society (AES). After a lengthy review of case reports, open-label trials and informal surveys, they concluded that cannabis extracts high in CBD can be an effective adjunct to traditional medications.

This appears especially true for children with relatively rare disorders, such as infantile spasms, Lennox-Gastaut syndrome (LGS) and Dravet syndrome. And these products appear to be well tolerated.[ref](http://www.medscape.com/viewarticle/837487) 06/22/2015[/ref]

At the meeting, study researcher Dr Shaun Hussain, a pediatric neurologist at UCLA Medical Center, reported the results of an anonymous, online survey of parents treating their children’s seizure disorder with CBD. They had a total of 117 respondents who administered CBD extracts to their kids for an average of nearly 7 months.

Appallingly, over half of the parents surveyed could NOT accurately tell how much CBD their child was getting per day. The better-informed parents reported that each child was receiving on average about 4 mg/kg CBD per day. As such, a 40 kg child would be getting about 160 mg CBD per day. This dose was considerably less, about 1/3rd the CBD, than other study programs used.

Regardless, the conclusions were remarkable.

The study found that of the 53 patients with infantile spasms or LGS, 92% had seizure reduction and 13% had seizure freedom. The only adverse effect reported more often after initiation of CBD was increased appetite. Many patients had improved sleep (53%), alertness (71%), and mood (63%).

Although these survey results “are nothing to scoff at,” they’re not evidence of efficacy, stressed Dr Hussein.

Notice the extraordinary side effects: improved sleep, greater alertness and enhanced mood. Not too shabby for a boutique oil.

MORE EFFICACIOUS?

Is CBD oil better, or more efficacious, than prescription medications? At this point it is too early to tell. Efficacy is how well drug A does in comparison to an equipotent dose of (a different category) drug B. Drug A is said to be more efficacious than drug B if it can quell a greater percentage of seizure activity than drug B. To do that we need formal studies which are underway, not online surveys.

Based on anecdotal reports, high CBD preparations are effective anti-seizure medications. As effective as most pharmaceuticals, and in special cases such as status epilepticus in Dravet syndrome, MORE effective.

Here, the research drug was Epidolex which is a nearly pure CBD pharmaceutical preparation. Note the dose here is much higher: 25 mg/kg body weight. That’s 1,000 mg CBD in a 40 kg patient. Let’s examine this in greater detail shall we?

Yet another study, an open-label, investigator-initiated trial of Epidiolex (25 mg/kg per day) in children and young adults with treatment-resistant epilepsy, was carried out by Orrin Devinsky, MD, also at New York University, and his colleagues.

The researchers collected efficacy data on 58 patients followed for 3 months. Of these patients, almost 40% had a greater than 50% reduction in seizures. For patients with Dravet syndrome, this reduction was just over 50% while for all other patients, it was about 30%.

Seizure freedom at 3 months was also highest for patients with Dravet syndrome (22%) compared with other patients (10%).

“These rates were much higher than we would expect from a placebo response alone,” noted Dr Devinsky…

Researchers followed 40 of the patients to 4 months and found no “drop off” in effectiveness from 3 months, said Dr Devinsky. “There does not appear, from this preliminary snapshot we have in this open-label study, that there is tolerance or loss of effectiveness over time.”

Again, the drug was very well tolerated, said Dr Devinsky. The most common adverse effects, reported by more than 10% of patients, were somnolence (19%) and fatigue (11%).

The “critical take-home message” from this study, stressed Dr Devinsky, “is that these are early promising results, but we need controlled trials to know how to move forward.[ref](http://www.medscape.com/viewarticle/837487) 06/22/2015[/ref]

The effect of adding CBD to patients taking anti-epilepsy drugs was investigated in an observational study of patients enrolled in an expanded access, compassionate use of CBD program.

These patients were also taking Epidolex which is a purified 98% oil-based CBD extract. Here, the dose was 10-20 mg/kg of Epidolex per day.[ref](http://www.medscape.com/viewarticle/837487) 06/22/2015[/ref]

So your average 40 kg child might be receiving 400-800 mg of medication per day. Contrast this to parents giving their children only 160 mg per day of CBD for their seizures (part two), and achieving excellent results.

This efficacious “low dose” CBD may be important if we find that the higher doses interfere too greatly with the metabolism of other drugs the patient may be taking.

CBD INTERFERES WITH DRUG METABOLISM

An important finding was that many of the patients witnessed an increase in their serum levels of two key anti-seizure medications: Valproic acid and clobazam.

Patients were on a background regimen of at least one to four medications in addition to CBD,” noted researcher Daniel Friedman, MD, assistant professor, New York University School of Medicine.

They found that levels of CBD were also elevated in addition to valproic acid and clobazam. About ¼ of the study participants on clobazam and about 1/3 of those on valproic acid needed their dose reduced.

If you or one of your children are on CBD, and you are taking other pharmaceuticals, be sure to have your serum levels checked of those other medications if any can become toxic at higher levels. Check in one month after starting CBD. If your source is through an artisanal preparation be aware that it is not the same thing as Epidolex.

Ben Whalley, professor, neuropharmacology, School of Pharmacy, University of Reading, United Kingdom, pointed out that artisanal preparations contain about 500 different chemical compounds, and many have high amounts of tetrahydrocannabinol, the psychoactive element of the marijuana plant.

In contrast, he said, preparations such as Epidiolex that are approved for clinical trials are 98% CBD and are specifically formulated as a conventional medicine.[ref]IBID[/ref]

MORE POSITIVE RESULTS

At Children’s hospital in San Diego, California, Dr Jeffrey Gold reports a case of a boy with Doose syndrome. It’s another rare disease which can morph into status epilepticus. This syndrome can eventually lead to learning problems and profound developmental delays if seizures are not controlled.

After juggling their child’s medication doses and still not happy with the results, the parents informally began daily CBD treatment from an unknown boutique source. Again they found that the CBD may have increased the patient’s levels of valproic acid.

Now comes the interesting part:

After valproate levels were lowered, the parents reported that their son had become seizure-free over about 4 months. Another EEG verified that the boy “was completely normal — honestly to our surprise,” said Dr Gold.

Although resolution of seizures and normalization of EEG have been reported before in Doose syndrome, and this can happen spontaneously or as a result of medication change, “it was very interesting that it happened shortly after the CBD was used, and then the valproate acid was normalized,” noted Dr. Gold.

Parents of children with seizure disorders should stay in the loop with their physician and be sure to tell him or her that you started giving your child CBD.

It looks as if CBD can interfere with the liver’s metabolism of many drugs not just anti-seizure medicines. This can become very important depending on the pharmaceutical being taken.

In summary, we have excellent early reports of CBD being an effective anti-seizure medication at varying doses. Furthermore, it appears that CBD may interfere with the metabolism of many drugs including anti-seizure medicines which could lead to toxicity mandating the checking of serum levels.

CBD’s most promising role may be in the treatment of several orphan diseases for which conventional anti-seizure medication has little impact.

Dr Hussein’s closing remarks were in reference to the titanic levels of bureaucratic red tape, and the frustration researchers must endure while cannabis still holds its absurd schedule 1 classification.

“It’s a tragedy that we’re being held back by bureaucracy when these patients, parents, and practitioners are so desperate,” commented Dr Hussein.

About    |   Terms & Conditions   |  Contact   |   F&Q

Privacy Preference Center