Can Smoking Tobacco Make Epilepsy Worse or Affect Anticonvulsant Levels?
Obviously smoking is dangerous but there are additional risks for individuals who may be prone to seizures. In women it may be associated with an increased risk of seizures. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090289/
Moreover, it has been shown to reduce the levels of one of the most commonly used seizure medications, lamotrigine (Lamictal).http://www.ncbi.nlm.nih.gov/pubmed/18583161
And there are concerns about nicotine alone. http://jpet.aspetjournals.org/content/291/3/1284
http://www.if-pan.krakow.pl/pjp/pdf/2003/5_799.pdf
Moreover, it has been shown to reduce the levels of one of the most commonly used seizure medications, lamotrigine (Lamictal).http://www.ncbi.nlm.nih.gov/pubmed/18583161
And there are concerns about nicotine alone. http://jpet.aspetjournals.org/content/291/3/1284
http://www.if-pan.krakow.pl/pjp/pdf/2003/5_799.pdf
Marijuana, hemp, delta 9 tetrahydrocannabinol, cannabidiol and seizures
Warning, recent reports of marijuana sold for vaping being associated with seizure activity.
There are obvious and some not so obvious concerns about the use of marijuana (Cannabis sativa) because of its main component, D9-tetrahydrocannabinol (THC) which can induce anxiety and psychotic symptoms http://files.iowamedicalmarijuana.org/science/psych/D'Souza%20%202004.pdf
Memory
http://www.pnas.org/content/early/2012/08/22/1206820109.abstract
http://www.springerlink.com/content/b1x80ux5k8g3mh7x/
Brain Blood Flow and Risk of Stroke
http://www.neurology.org/content/64/3/488.abstract
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2001.tb03652.x/abstract;jsessionid=A2592ED18A04BDA8CC94EA24A24DD795.d04t04?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Emotional Problems
http://www.nejm.org/doi/pdf/10.1056/NEJM197004302821803
Controlling Behavior
http://www.springerlink.com/content/q43136438068hm03/
However, marijauna itself (if not adulterated) most likely does not make seizures/epilepsy worse and may even reduce the risk of having a first seizure.
http://www.flickr.com/photos/22390244@N07/2159512338/
However, heavy users may possibly have withdrawal seizures
https://www.sciencedirect.com/science/article/abs/pii/S1525505012005860
The marijuana plant contains at least 400 different chemicals. Two of the most abundant are delta 9 tetrahydrocannabinol (THC, the psychoactive component responsible for the high) and cannabidiol (CBD). There is little evidence that THC has anticonvulsant properties, however, there is accumulating evidence that CBD has anticonvulsant properties
http://www.gwpharm.com/GW%20Pharmaceuticals%20Announces%20Physician%20Reports%20of%20Epidiolex%20Treatment%20Effect%20in%20Children%20and%20Young%20Adults%20with%20Treatment-Resistant%20Epilepsy%20from%20Physician-Led%20Expanded%20Access%20Treatment%20Program.aspx
Epidiolex (pure FDA approved cannabidiol) if FDA approved for treatment of the Lennox-Gastaut syndrome and Dravet's syndrome, however, initial enthusiasm among epileptologists is waning and the drug has a host of interactions with other drugs and its use is associated with hepatitis when used with valproate:
https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13852
Note: cannabidiol (and thus Marijuana) when studied in vitro inhibits (interferes with) the metabolic processes of the majority of cytochrome P-450 enzymes and thus their ability eliminate (and in rare cases activate) various. This explains various interactions with other drugs such bleeding with wafarin (Coumadin) http://aop.sagepub.com/content/43/7-8/1347.shor
enzyme some examples of substrates
1A2 caffeine, clozapine, methadone, olanzapine, propranolol
2B6 buproprion
2C9 most NSAIDs (eg. Motrin, Advil, Alleve etc), warfarin
2C19 most PPIs (see below), citalopram, phenytoin, phenytoin, warfarin, clopidogrel (activates) and active metabolite of
clobazam (level of this may increase four fold when used with marijuana or cannabidiol
2D6 codeine (activates), dextromethorphan, hydrocodone, oxycodone, risperidone, tamoxifen (activates), tramadol
3A4 acetaminophen, alprazolam, atorvastatin, estrogens, lidocaine, midazolam,quetiapine, sildenafil, vincristine
There are obvious and some not so obvious concerns about the use of marijuana (Cannabis sativa) because of its main component, D9-tetrahydrocannabinol (THC) which can induce anxiety and psychotic symptoms http://files.iowamedicalmarijuana.org/science/psych/D'Souza%20%202004.pdf
Memory
http://www.pnas.org/content/early/2012/08/22/1206820109.abstract
http://www.springerlink.com/content/b1x80ux5k8g3mh7x/
Brain Blood Flow and Risk of Stroke
http://www.neurology.org/content/64/3/488.abstract
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2001.tb03652.x/abstract;jsessionid=A2592ED18A04BDA8CC94EA24A24DD795.d04t04?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Emotional Problems
http://www.nejm.org/doi/pdf/10.1056/NEJM197004302821803
Controlling Behavior
http://www.springerlink.com/content/q43136438068hm03/
However, marijauna itself (if not adulterated) most likely does not make seizures/epilepsy worse and may even reduce the risk of having a first seizure.
http://www.flickr.com/photos/22390244@N07/2159512338/
However, heavy users may possibly have withdrawal seizures
https://www.sciencedirect.com/science/article/abs/pii/S1525505012005860
The marijuana plant contains at least 400 different chemicals. Two of the most abundant are delta 9 tetrahydrocannabinol (THC, the psychoactive component responsible for the high) and cannabidiol (CBD). There is little evidence that THC has anticonvulsant properties, however, there is accumulating evidence that CBD has anticonvulsant properties
http://www.gwpharm.com/GW%20Pharmaceuticals%20Announces%20Physician%20Reports%20of%20Epidiolex%20Treatment%20Effect%20in%20Children%20and%20Young%20Adults%20with%20Treatment-Resistant%20Epilepsy%20from%20Physician-Led%20Expanded%20Access%20Treatment%20Program.aspx
Epidiolex (pure FDA approved cannabidiol) if FDA approved for treatment of the Lennox-Gastaut syndrome and Dravet's syndrome, however, initial enthusiasm among epileptologists is waning and the drug has a host of interactions with other drugs and its use is associated with hepatitis when used with valproate:
https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13852
Note: cannabidiol (and thus Marijuana) when studied in vitro inhibits (interferes with) the metabolic processes of the majority of cytochrome P-450 enzymes and thus their ability eliminate (and in rare cases activate) various. This explains various interactions with other drugs such bleeding with wafarin (Coumadin) http://aop.sagepub.com/content/43/7-8/1347.shor
enzyme some examples of substrates
1A2 caffeine, clozapine, methadone, olanzapine, propranolol
2B6 buproprion
2C9 most NSAIDs (eg. Motrin, Advil, Alleve etc), warfarin
2C19 most PPIs (see below), citalopram, phenytoin, phenytoin, warfarin, clopidogrel (activates) and active metabolite of
clobazam (level of this may increase four fold when used with marijuana or cannabidiol
2D6 codeine (activates), dextromethorphan, hydrocodone, oxycodone, risperidone, tamoxifen (activates), tramadol
3A4 acetaminophen, alprazolam, atorvastatin, estrogens, lidocaine, midazolam,quetiapine, sildenafil, vincristine
Can Proton Pump Inhibitors (PPIs: Prilosec, Protonix, Nexium, Prevacid, AcipHex, etc) Cause Seizures?
Recent concern about about association between chronic use of PPIs and dementia (google)
For a lay overview of PPIs see review from New York Times June 25th 2012
http://well.blogs.nytimes.com/2012/06/25/combating-acid-reflux-may-bring-host-of-ills/
Proton pump inhibitors are unlikely to cause seizures. However, in occasional patients the chronic use (usually more than a year) of one of these drugs can interfere with the absorption of magnesium and patients have been reported to have seizures due to low magnesium.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2008.03194.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Low magnesium can result in a kaliuresis (increased excretion of potassium) resulting in a low enough level of potassium to cause cardiac arrhythmias (irregular beating of the heart) which can lead to convulsive syncope (fainting spells that can masquerade as grand mal seizures).
http://www.ajkd.org/article/S0272-6386(09)01600-X/abstract
Fortunately complications such as these are extremely rare but what is more of a concern is the effect of these drugs on bone health. With a few exceptions the majority of anticonvulsants increase the risk of osteoporosis (particularly when used in conjunction with antidepressants and or tobacco. PPIs can add to this burden not only by interfering with calcium absorption through induction of hypochlorhydria (reducing stomach acid) but also by reducing bone resorption (direct effect on bone metabolsim) through interference with osteoclastic (the cells that remodel bones).
http://jama.jamanetwork.com/article.aspx?articleid=204783
One theoretical concern about PPIs for which there is very little objective information is that they can interfere with one of the enzymes (cytochrome P-450 2C19) responsible for the metabolism (primarily in the liver) of several of the "older" anticonvulsants:
diazepam (Valium)
mephenytoin (Mesantoin)
mephobarbita (Mebaral)
phenobarbital (Luminal)
phenytoin (Dilantin)
primidone (Mysoline)
and elevate the level in the blood possibly causing symptoms; alternatively if the PPI is stopped the levels may fall possibly making it easier to have a seizure.
The metabolism of two of the "newer" anticonvulsants involves the same enzyme.
One of these is lacosamide (Vimpat) but it is primarily cleared by the kidney and thus cytochrome P-450 2C19 in the liver plays a relatively insignificant role and it is unlikely that there is any significant interaction
On the other hand the interaction involving clobazam (Frisium, Onfi, Urbanyl) and desmethylclobazam (active metabolite of clobazam) may be more significant. When the metabolism of a single 10 mg dose of clobazam in volunteers taking omeprazole (Prilosec) is compared to the metabolism in volunteers not taking a PPI the amount of clobazam and desmethylclobazam (the active metabolite of clobazam) in the blood were respectively 28% and 37% higher when there was pretreatment with omeprazole. However, these increases were felt not to be "clinically meaningful" in that they did not appear to cause any significant adverse effects. Nevertheless if omeprazole were suddenly stopped in a patient taking clobazam the subsequent reduction in the amount of drug in the blood might make it easier to have a seizure. http://www.ncbi.nlm.nih.gov/pubmed/22422635
For a lay overview of PPIs see review from New York Times June 25th 2012
http://well.blogs.nytimes.com/2012/06/25/combating-acid-reflux-may-bring-host-of-ills/
Proton pump inhibitors are unlikely to cause seizures. However, in occasional patients the chronic use (usually more than a year) of one of these drugs can interfere with the absorption of magnesium and patients have been reported to have seizures due to low magnesium.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2008.03194.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Low magnesium can result in a kaliuresis (increased excretion of potassium) resulting in a low enough level of potassium to cause cardiac arrhythmias (irregular beating of the heart) which can lead to convulsive syncope (fainting spells that can masquerade as grand mal seizures).
http://www.ajkd.org/article/S0272-6386(09)01600-X/abstract
Fortunately complications such as these are extremely rare but what is more of a concern is the effect of these drugs on bone health. With a few exceptions the majority of anticonvulsants increase the risk of osteoporosis (particularly when used in conjunction with antidepressants and or tobacco. PPIs can add to this burden not only by interfering with calcium absorption through induction of hypochlorhydria (reducing stomach acid) but also by reducing bone resorption (direct effect on bone metabolsim) through interference with osteoclastic (the cells that remodel bones).
http://jama.jamanetwork.com/article.aspx?articleid=204783
One theoretical concern about PPIs for which there is very little objective information is that they can interfere with one of the enzymes (cytochrome P-450 2C19) responsible for the metabolism (primarily in the liver) of several of the "older" anticonvulsants:
diazepam (Valium)
mephenytoin (Mesantoin)
mephobarbita (Mebaral)
phenobarbital (Luminal)
phenytoin (Dilantin)
primidone (Mysoline)
and elevate the level in the blood possibly causing symptoms; alternatively if the PPI is stopped the levels may fall possibly making it easier to have a seizure.
The metabolism of two of the "newer" anticonvulsants involves the same enzyme.
One of these is lacosamide (Vimpat) but it is primarily cleared by the kidney and thus cytochrome P-450 2C19 in the liver plays a relatively insignificant role and it is unlikely that there is any significant interaction
On the other hand the interaction involving clobazam (Frisium, Onfi, Urbanyl) and desmethylclobazam (active metabolite of clobazam) may be more significant. When the metabolism of a single 10 mg dose of clobazam in volunteers taking omeprazole (Prilosec) is compared to the metabolism in volunteers not taking a PPI the amount of clobazam and desmethylclobazam (the active metabolite of clobazam) in the blood were respectively 28% and 37% higher when there was pretreatment with omeprazole. However, these increases were felt not to be "clinically meaningful" in that they did not appear to cause any significant adverse effects. Nevertheless if omeprazole were suddenly stopped in a patient taking clobazam the subsequent reduction in the amount of drug in the blood might make it easier to have a seizure. http://www.ncbi.nlm.nih.gov/pubmed/22422635