Monday, January 18, 2016

Medicalcannabis for epilepsy - is it really safe??

To understand the perspective, author is a Pediatric Neurologist and Epileptologist with experience of treating many children with drug resistant epilepsy in India and Australia.  

Why this blog?

In recent days, there has been tremendous publicity given to medical cannabis being “very effective in controlling seizures and epilepsy”. This is contrary to what is the available evidence shows, misleading many patients and families to resort to indigenous even illegal means to procure and take (give to one's near and dear ones) cannabis in the belief that it is the magical cure! Is it really effective and safe? This is a million dollar questions yet to be answered, worse you any not have clear answer for years to come. 

What is the real issue?

Question one should ask is not is it effective? but is it really safe? effective but at what cost? how is it effective? Available data shows that cannabis increases the blood levels of Clobazam and Valproate. Two most commonly taken anti seizure medications among patients with epilepsy. In some cases, the Clobazam blood level was increased up to 600% That is similar to raising the dose of Clobazam 6 times (for argument sake). So it comes at a steep cost! and along with associated adverse effects. Another important aspect to note is short term (12 weeks/16 weeks) effectiveness in controlling seizures that recent studies suggested for Cannabis are not long lasting (seizures come back), the same effect seen every time a new medication is added to the existing regime in  any patient with drug resistant epilepsy. Third factor is placebo effect. It is unbelievably high proportion of 25-35% of patients who have placebo effect (in any RCT comparing placebo versus a new anti seizure medication). So, the water is really murky and muddy ideal for those with vested interests to fish (recreational marijuana lobby, those who are growing cannabis and pharma companies)

Which cannabis molecule is effective?

The answer is we dont know yet. Cannabis is not a single chemical molecule, rather a mixture of many different agents with different safety concerns and long term effects. as of now there is no quality control of anything produced on the grey market, no way of knowing what and how much these contain? If we assume even one of these is effective in controlling epilepsy, the unsuspecting patient is taking the crude plant extract containing all other unwanted substances that may be harmful. Its like taking an antiseizure medication mixed with a known toxin (poison). It is poroven in studies that the medium/solvent used in the cannabis preparation is responsible for the adverse events. The only way out is to do more research to really understand which molecules are effective in controlling seizures so that these can be purified and produced as against those unwanted/harmful substances that can be removed from the final product. It takes some time. For those parents who promote cannabis in compassionate basis saying that they cannot wait any longer as their kids are running out of time (because severe epilepsy), my advice is that it is better not do any further harm to the child by administering potentially harmful agents that we do not know effective or not!
 
what about claims of dramatic effectiveness of cannabis in epilepsy?

Behind every success claim there are at least 20-30 patients that go unreported (or not pupublicized enough) because it was not effective, or it had to be ceased as there were problems, even worse there were cases of cannabis over dosage reported in Colorado, US! Again it is all about whipping up the frenzy, isn't it? This is exactly the problem if you go by lay press and anecdotal reports rather than waiting for the robust scientific evidence!

What about cannabis side effects (adverse effects)?

Many concerning short term and long term side effects are known to occur with intake of cannabis. The side effect profile depends largely on the actual molecule. As there is no way of knowing the actual composition of the unregulated products available in the market, there is no way of predicting side effect profile. Sleepiness, irritability and hallucinations. Long term side effects include memory and cognition problems, risk of addiction, schizophrenia in young people, psychosis, anxiety, etc. 

Can cannabis itself cause seizures?

Yes, of course. Some of the cannabis molecules are known to cause seizures (proconvulsants). In the Lancet Neurology study, 11% of patients who took cannabis had convulsions and 6% had status epilepticus (long seizures) without any other reasons being identified. It is concerning that such a high proportion of patients developed convulsive seizures or long seizures. 

Why drug trials on cannabis should not enroll children?

There is a dictum in medical science, if there are no randomized controlled trials (robust clinical research study) available on adults utilizing a particular medication, there cannot be an RCT commenced that enroll children for the same medication treatment. This is a prudent approach, as more often than not, there are unanticipated adverse effects that can occur with any trial medication, adults can handle many adverse effects better than children, because of higher safety margin. Another important point is that adults can articulate subjective sensations (cognitive and behavioral side effects) better than children. So it is all about safety. 

When there is no safety data on cannabis available or the available data points to serious concern, children should not be included in such drug trials. Cannabis with its potential side effects like hallucinations, psychosis, schizophrenia and many other cognitive and behavior related effects can never be tested in children without first being tested adequately in adults, period. The scariest thing is to enroll severely developmentally disabled kids like patients with Dravet’s syndrome and LGS in such trials, how are they supposed to articulate their mood and cognition related effects. It is unethical and unfair. For such kids with severe epilepsy and development delay, who do you think take decisions about commencing or ceasing the medications? Naturally, the next of the kin, parents and family. 

Keeping this in mind, how is it to fair to conclude a study (Recent open lebel trial on Cannabidiol, Lancet Neurology, 23 Dec 2015) “might be safe” just based on the fact that only 3% patients discontinued medications though 30% patients had severe adverse events!! Parents who are desperate to try and control their kid’s epilepsy and who is looking for a “magic medication” (and seeing one in cannabis), how are they expected to discontinue the same? It is natural for the family to think that the effects may be transient and to wait it out rather than to cease the “magic medication” that is doing some good (?!) to their kids. Credit cannabis for the good and blame the disease for the bad should not be the approach taken by medical community.
 

  

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