Sunday, December 18, 2011

Ask a Doc:Epilepsy and Medical Marijuana

Epilepsy Warriors - Ask A Doc - Epilepsy and Medical Marijuana

This week I’ve had a number of questions about the use of medical marijuana for epilepsy.  It’s not a common question, so I did some research. 

Obviously, talking about illicit substances can cause a significant amount of emotion...its a hot topic...  But we cannot hide from the topic since its an active area of published research. Your typical kids "Mary or Jane" can look it up in the school libary.

Some background ... Many medications are "controlled"  by government regulations.  Some chemicals can be used therapeutically but if bought and sold by lay-people they are illicit.  Besides marijuana, other "controlled" substances are  commonly used as medications. Ophthalmologists use cocaine  for examination. Amphetamine is commonly prescribed for ADHD. Narcotics are essential for pain control.  Gamma hydroxybutyrate  is used for narcolepsy. What would I use to treat methanol poisoning in a child? IV Ethanol ... Don't try to buy phenobarbital or lorazepam on the street...

However, we should focus on the data supporting or refuting the use of cannabinoids for a therapeutic end.... in this case seizures.

The National Library of Medicine sponsors a free search engine (pubmed) that lists medical articles published by peer-reviewed journals. The peer review process is meant to ensure a certain amount of academic integrity.

Let me roll-up the papers that I have found:

Basically, almost all research in this area has been done on rodents. There were 2 small studies of adults published in 1979 in 1980 a total of 16  individuals that appeared to show some promise with the use of cannabanoids for generalized epilepsy.   Despite the apparent positive response, this is not very strong data.

Regardless of the therapeutic modality, I would not recommend treatment based on studies performed on 16 individuals, especially when the research was performed by one group and has not been replicated.

More importantly,  there is no therapeutic data information for people under 18. For children the effects of calmly available cannabinoids on neurodevelopment are highly likely to be negative.

 To shed little a light on this hot and smokey topic, allow me to refer readers to 3 recent articles that review the topic of cannabinoids in epilepsy.

 Dr. Smith writes this matter than I can  ”Since the action of cannabinoids is complex, and there is a dearth of clinical trial data, it is currently unclear whether cannabinoids might be both efficacious and safe in the treatment of epilepsy.

While I respect an individual’s claims (no pot-shots from me),  any reports of a positive effect must be kept in that category: interesting anecdote. 

But, science moves forward with anecdote. The research possibilities may be promising, I  would not recommend the use of this substance to prevent seizures.  I look forward to more research producing medications that may use bring out a therapeutic use for the cannabinoid receptor.

I hope I added some insight and a little needed levity,

Dr. Rotenberg

Curr Opin Investig Drugs. 2005 Jul;6(7):680-5.
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Cannabinoids have long been recognized as having the potential for both anticonvulsant and proconvulsant effects. The increased understanding of the cannabinoid receptors and their endogenous ligands over the last decade has provided a potential mechanism of action for these apparently paradoxical effects. Although the anticonvulsant effects of cannabinoids appear to be mediated by their action at presynaptic cannabinoid receptors, which inhibit the release of excitatory neurotransmitters such as glutamate, it is clear that they are also capable of producing proconvulsant effects through the activation of cannabinoid receptors on terminals releasing inhibitory neurotransmitters, such as gamma-amino-butyric acid. In the brain, the activation of cannabinoid receptors is carefully controlled by the rapid synthesis and degradation of endocannabinoids in a way that targets the endogenous ligands to specific sets of cannabinoid receptors. The potential problem in delivering a cannabinoid drug to treat epilepsy is the inability to control its actions at different cannabinoid receptors regulating the release of different neurotransmitters. Since the action of cannabinoids is complex, and there is a dearth of clinical trial data, it is currently unclear whether cannabinoids might be both efficacious and safe in the treatment of epilepsy.
PMID: 16044663 [PubMed - indexed for MEDLINE]
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Publication Types, MeSH Terms, Substances

Epilepsia. 2009 Jul;50(7):1657-69. Epub 2009 Jul 1.
Department of Anatomy and Neurobiology, University of California, Irvine, California, USA.
There are essentially two potential treatment options for any acquired disorder: symptomatic or prophylactic. For acquired epilepsies that follow a variety of different brain insults, there remains a complete lack of prophylactic treatment options, whereas at the same time these epilepsies are notoriously resistant, once they have emerged, to symptomatic treatments with antiepileptic drugs. The development of prophylactic strategies is logistically challenging, both for basic researchers and clinicians. Nevertheless, cannabinoid-targeting drugs provide a very interesting example of a system within the central nervous system (CNS) that can have very different acute and long-term effects on hyperexcitability and seizures. In this review, we outline research on cannabinoids suggesting that although cannabinoid antagonists are acutely proconvulsant, they may have beneficial effects on long-term hyperexcitability following brain insults of multiple etiologies, making them promising candidates for further investigation as prophylactics against acquired epilepsy. We then discuss some of the implications of this finding on future attempts at prophylactic treatments, specifically, the very short window within which prevention may be possible, the possibility that traditional anticonvulsants may interfere with prophylactic strategies, and the importance of moving beyond anticonvulsants-even to proconvulsants-to find the ideal preventative strategy for acquired epilepsy.
PMID: 19552655 [PubMed - indexed for MEDLINE] PMCID: PMC2894282 Free PMC Article
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Cannabinoids: Defending the Epileptic Brain
Robyn Wallace, Ph.D.

Full article here...

...Can we target therapy to the critical circuits in the forebrain? Smoking marijuana is obviously is not an appropriate therapy; in addition to the psychoactive effects, the inhalation of smoke poses obvious health risks. To this end, drug companies have already isolated the active ingredients in cannabis and produced them in the form of a pill or a spray. However, most synthetic cannabinoids still have psychoactive effects and are undesirable for therapeutics. It may be more beneficial to target cannabinoid transport or degradation systems to increase the levels of endogenous cannabinoids. Enhancing the cannabinoid system may prove to be an effective treatment for epilepsy, especially in cases in which standard drugs fail to control seizures.

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