Medical Marijuana Journey, Weeks 2-5: Riding the Drug Interaction Roller-Coaster

We've all heard those miraculous stories about kids who become seizure free after a few doses of medical marijuana...

By the end of her first week on CBD oil (medical marijuana)--which you can read about here, we knew our daughter Awesome was NOT one of those kids.  There were no seizure reductions during her first week of cannabis.  Nor in the next four weeks after that.

 In fact, Awesome had as many big seizures in the first 5 weeks on CBD as she'd had in the previous 21 weeks!  Her little seizure counts were up, too--from daily averages in the single digits and teens, to averages in the teens and 20's.  And during the fifth week on CBD, Awesome had her second highest daily seizure count ever--51.

These results were all the more

discouraging because the seizure increases had taken place with all of our previous seizure control measures still in place:  Awesome was still on her anti-epileptic drug (AED) Vimpat; she was still on her special epilepsy diet; we were still maintaining all of her trigger avoidance routines; and she was still taking all her special supplements.  These were things that, in the past, when combined, had reduced her seizure counts by up to 85%.  But yet, here we were experiencing inflated seizure numbers....

There are probably people for whom trialing medical marijuana is straightforward and simple.  But Awesome hasn't been one of those people.  What we've learned in the first 35 days of this journey is that trialing medical marijuana for epilepsy can be (isn't always, but can be) complex and difficult.

CBD can (doesn't always, but can) change the way prescription drugs--including anti-epileptic drugs--are metabolized. And when drug metabolism changes, the amount of AED in the bloodstream changes.  CBD can cause AED blood levels to decrease---which can lead to increased seizures.  Or CBD can cause AED blood levels to increase, leading to increased AED side effects and-- if blood-levels rise enough--AED toxicity (toxicity is when antiepileptic drugs reach such elevated levels that they start to adversely affect the processes and organs in the body).


Drug interactions are exactly what we got into with Awesome.  Despite starting on a very low CBD dose--half of the recommended "sensitive child" starting dose (which is equivalent to one fourth of the recommended "normal" starting dose) for her weight, Awesome quickly experienced drug interactions between CBD and her AED--Vimpat.  By the end of her first week on CBD, Awesome's Vimpat-- blood levels had risen by 25%.  That's no small amount.  It's the equivalent of having raised her AED dose by 25%.

Perhaps having a higher blood level of Vimpat would have been all well and good if Vimpat actually had been preventing seizures for Awesome.  But, in fact, we'd been suspecting for some time--though we couldn't prove it--that Vimpat was doing the opposite: increasing seizures in a dose-dependent way.  The higher the dose of Vimpat, the more seizures.  And now, as Vimpat blood levels increased, so did her seizures.  Seeming to prove our point.

Her Vimpat-associated side-effects also increased.  Quickly and dramatically.  Nausea, diarrhea, and abdominal pain--the Vimpat side effects that she'd always had trouble with--and that had caused us to have to back off on her Vimpat dose in the beginning....and then titrate more slowly again.  The same side effects that we'd spent the last 7 months trying to minimize and help Awesome learn to live with, came roaring back with a vengeance. As CBD caused Vimpat blood levels to increase, the severity of her side effects increased.

All the medication level changes and the addition of CBD, also had the effect of making Awesome's brain even more unusually reactive.  Every time we titrated CBD, we got a big reactive kick-back complex partial seizure (with secondary generalization) seven days later.

In short, between seizures and side effects, Awesome had a very hard time that first 5 weeks on medical marijuana; she was miserable.

In an attempt to minimize drug interactions, we totally reworked Awesome's medication schedule for a second time during the second week of CBD (we'd already reworked it earlier in order to more evenly space out the CBD doses).  That second week, we flipped the order that we dosed Vimpat and CBD so that CBD was given early in the morning instead of Vimpat.  Standard recommendations--to minimize drug interactions--are that CBD and AED's be given at least 2-3 hrs apart.  We'd always met the minimal requirements; but now we exceeded them in the hope that it would help.  It didn't; things continued to deteriorate.  At the end of the 4th week another blood draw showed that Vimpat blood levels had further increased by 1%, to a total 26% above pre-CBD baseline. Now we did a third much more radical rework of the medication schedule, decreasing CBD and Vimpat doses each, from 3 times a day to two times a day.  This third reworking increased the time between CBD and AED doses to between 4 and 7 hrs. But sadly, again, this provided no relief.  Drug interactions continued, and as CBD built up in Awesome's fat stores--as it was supposed to do--the interactions simply became worse.

By the middle of the fourth week of CBD, Awesome was doing so badly that she was taking to bed for 3 hrs each afternoon, totally exhausted, moaning and crying about how tired she was.  She also complained about how cold she felt during these afternoon periods of exhaustion.  Visibly shivering, she'd put on her winter coat and wrap herself in a warm quilt--though it was the middle of the summer and outside temperatures were in the upper 90's.  It was painful to watch her be this exhausted and distressed.  We had no idea what was causing her exhaustion until a wise friend suggested that the exhaustion was a result--another side effect--of the increased blood-levels of Vimpat.  We looked it up Vimpat side effects and found that exhaustion was indeed one.

Finally, 26 days into the CBD trial, we felt something had to change.  We wrote an email to Awesome's epileptologist and told him that unless we heard from him with an objection or a different plan, that we were planning to reduce Awesome's Vimpat dose from 200 mg a day to 175 mg a day.  We heard nothing back and so we did--we reduced Awesome's Vimpat dose by 12.5%.  The relief was immediate.  There were no more afternoon periods of exhaustion and feeling very cold.  This was confirmation to us that Vimpat had indeed been the culprit where the 3 hr periods of exhaustion were concerned.   Awesome's other symptoms, however, remained: increased seizures, nausea, abdominal pain, and diarrhea.

At the beginning of July, five weeks after starting her CBD trial, Awesome entered our local Children's Hospital for a 48 hr VEEG (video EEG).  This VEEG had been scheduled since May--before Awesome had started CBD.

Awesome's brain was especially reactive for the few days before the VEEG and her seizure counts were high.  She was very anxious about going to the hospital--so anxious that on the day of the VEEG Awesome awoke 5 hrs earlier than usual and couldn't go back to sleep.  By the time we arrived at the hospital, checked in, and were waiting for someone from the Epilepsy Monitoring Unit (EMU) to come down and escort us to the unit, Awesome was having an absence seizure every few minutes.  We were praying that she wouldn't have a big seizure that would necessitate Diastat--and so ruin her VEEG.  They needed to see the seizures she was having and record them on both EEG and synced video.  It was the whole reason for the hospitalization.  Diastat--had we have had to use it--would have quieted her reactive brain and suppressed the seizures.

On the EMU, the technician glued electrodes all over Awesome's head, wired her for sound (electrical waves, actually), turned on the synced video camera, and then, while Awesome was confined to a hospital bed like a bug pinned to a board, proceeded to watch her seizure activity for 48 hrs. Awesome was found to be having seizure activity literally every few minutes.  Very short absence seizures with eye-rolls mostly--and lots more subclinical seizure activity (that we couldn't see).  She was having so many seizures that the nurses--who were trained to come running into the room when the seizure button was pushed (it was our job to watch Awesome and push the button every time she had a seizure) to assess the seizing child--turned off the alarm to their desk.  We were given a second alarm to press if there was a big seizure (a complex partial or tonic-clonic) that warranted their attention.

Awesome's epileptologist came in to speak to us the next morning after having reviewed the previous day and night's VEEG.  He said that Vimpat was doing nothing positive for Awesome. She should come off it.   We were to begin a slow wean of Vimpat, but continue to use CBD oil.  There was a question about exactly what kind of seizures Awesome was having--as there always has been about her little seizures (they're just weird and hard to classify even for our very excellent, very experienced epileptologist).  While clinically they look like typical absence seizures, on EEG they definitely aren't. The long-standing confusion continued for that hospitalization.  The epileptologist thought--as he has for some time--that the seizures were likely focal seizures that simply generalized very quickly, but wasn't 100% sure.  He asked us to try an experiment to prove that they weren't generalized by having Awesome trial Ethosuximide (Zarontin) using a loading dose in the hospital (he hoped to see a change in the EEG while we were still there). (FWIW, over the next two days in the hospital, there would be, it turned out, no change in the EEG, which suggests that Ethosuximide will likely not work for Awesome).
Awesome's doctor asked us to continue trialing Ethosuximide at home until we had an answer as to whether it was or wasn't doing anything to reduce her little seizures.  He doubted that it would work, but wanted us to try it, even if it was a long shot.

Unconventionally, we were not going to be given a new medication to cover Awesome's big seizures, but we would only have CBD to cover those.  The reason--without going into detail-- has to do with the way that Awesome has failed the medications that she's failed--which perhaps I'll explain in another blogpost.  Suffice it to say right now, that the epileptologist had good reason to avoid aromatic AED's and was starting also to suspect--after 3 sodium channel blocking AED's had not only failed to stop seizures, but seemed to increase seizures, that perhaps sodium channel blocking AED's were simply problematic for Awesome--as they are, he said, for some people.

The epileptologist also told us that--while he understood that it was good to go slow with medical marijuana--we needed to get going with it.  He, like we wants to know if medical marijuana is going to work for Awesome.  Getting Vimpat out of the way is also designed to help make that determination easier.

We were told that if things weren't "substantially better" with Awesome by early fall that he'll give us a referral to another epileptologist who will take us through the pre-surgery evaluation process--which will finally prove whether Awesome's little seizures are focal--as her big seizures are.

By the end of Awesome's hospital stay, our heads were spinning.  A second, on-call epileptologist who came in to review Awesome's data the second and third mornings, told us that he didn't think Awesome would find any relief from her seizures until she has surgery--that he believes her seizures are focal.  He told us that the likelihood that any AED will stop her seizure is, at this point,about 5%--and that likelihood diminishes further with each failed AED trial.

The day after we left the hospital, we did as the epileptologist asked us.  We titrated up to the next higher dose of CBD; and we began the Vimpat wean.  The next 6-8 weeks would be taken up with weaning Vimpat and the instability that that would bring....  But that's a story for another blogpost, which you can read here, "Medical Marijuana Journey,Weeks 6-12: Distracted."