- Bender, A., Hagan, K.E., Kingston, N., The association of folate and depression: a meta-analysis. J. Psychiatric Res. 2017 Dec. 95:9-18
- Oude Voshaar, R.C.,Derks, W.J., Comiis, H.C., Schoevers, R.A., de Borst, M.H., Marijnissen, R.M. Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(oH) vitamin D3 in laterlife depression. Transl Psychiatry. 2014, Apr. 15;4:e383
- Benton, D., Donohue, R.T. The effects of nutrients on mood. Public Health Nutr. 1999 Sep; 2(3A):403-409
Virginia Thornley, M.D., Board-Certified Neurologist, Epileptologist
April 6, 2018
Medical marijuana seems like the shining breakthrough drug the shining pill in armor, the magic pill that seems to cure everything. However, there are always two sides to every coin. One must still proceed with caution. The phytocannabinoids, cannabidiol, and tetrahydrocannabinol exert their effects through the endocannabinoid pathway, the CB1 receptor is most abundantly found in the nervous system. Cannabidiol which has no euphoria acts weakly with the CB1 receptor almost as a reverse agonist blocking the THC from exerting its effect offsetting potent side effects of tetrahydrocannabinol.
The medical benefits are overwhelmingly numerous including ameliorating seizures, spasms from multiple sclerosis, peripheral neuropathy in HIV patients, chronic debilitating pain, post-traumatic stress disorder symptoms and other associated diseases. Despite the stigma of using it, the delay in clinical trials and marked hesitation of the medical community, medical marijuana has landed and there is no going back. Yet even with its numerous health benefits, it is always prudent to take a step back and examine any flaws as with any other new kid on the block or any new agent that comes along even though it’s been around for thousands of years.
Is marijuana safe for medical use? The take on medical marijuana by the FDA
So far from the FDA official website, the FDA does not recognize medical marijuana coming from the botanical plant with any medical indication. The FDA does not recognize it to be safe or beneficial for any type of disease or condition. The FDA will facilitate any companies interested in bringing quality products including science-based research. The full take of the FDA on marijuana can be found here https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421168.htm#use
Long-term effects on the brain
Perusing the scientific literature, it is difficult to find any long-term damage to the brain. There was a report in a heavy marijuana user where there was damage to the corpus callosum, possibly worse with young users (1). This is a small study of 11 heavy marijuana users with 11 age-matched cohorts. Diffusion tensor imaging was used. Previous reports alluded towards poor cognition with heavy marijuana use. This study is aligned with that. It was suggested that there may be increased diffusibility within the white matter tracts of the corpus callosum. Young age is thought to make the corpus more susceptible to white matter damage. The only caveat is this is with heavy use and the substance found in recreational marijuana is going to be a different form compared to medical marijuana extracted from the marijuana plant used for medicinal purposes. It is not clear if this report would carry over to medical marijuana users where the preparation of the product is much different(1).
Effect on schizophrenia spectrum diseases
In a large study of 171 patients, it was found that with heavy use of cannabis, the age of onset of schizophrenia spectrum disorders seems to occur earlier (6). This is one of the reasons why in some dispensaries, it is not sold to patients with a history of schizophrenia. There are some anecdotal reports of some patients having a paranoia with medical marijuana that is reversible once taken off.
Effect on the heart, reports of myocardial infarcts and ST elevations
While the literature suggests low toxicity and most side effects are related to cognition and gastrointestinal problems, there are several cannabis-associated myocardial infarcts in the literature. The dispensaries in the state of Florida use a previous history of a previous myocardial infarct as a contraindication in using medical marijuana. These were synthetic drugs used recreationally. There was one case report where a heavy user suffered from an ST elevation and subsequent myocardial infarct after becoming toxic to marijuana used recreationally. In one study, synthetic cannabis was used, the myocardial happened to a young patient where an atheromatous plaque was excluded as the source. Etiology and mechanism are unclear why infarcts should occur. It is quite possible that because it works on the 5HT receptor for anxiety which can cause vasoconstriction, this may be one mechanism. Other studies are needed to elucidate the mechanism of action.
Because medical marijuana is used as an adjunctive agent for epilepsy, perhaps off-label since it has not been approved through FDA as an anti-epileptic agent yet, it was found that medical marijuana used in conjunction with Clobazam (Onfi) tended to elevate Onfi at higher levels.
In one small clinical study, in 13 patients, 9 had an increase of about 60 in the Clobazam level and by 300 in Norclobazam level. There was, however, a tremendous reduction of seizures by >50% but Onfi (Clobazam and Norclobazam levels) should be monitored (3) on a routine basis to avoid any untoward toxicity.
Other milder symptoms
In one large study on Lennox-Gastaut syndrome where cannabidiol was titrated to a 20mg/kg over a course of 14 weeks, mild to moderate symptoms were noted including pyrexia, sedation, dizziness, and diarrhea. However, the titration rate was very rapid and the patents who were 50kg were quickly at 1000mg within 14 weeks which does not usually happen in the real world. Medications are usually increased over a longer period of time in slower increments.
While everybody is touting the horn of medical marijuana it is always prudent to stand back and ensure there are no possible risk factors for adverse side effects. The most serious and common seen in the literature appear to be related to schizophrenia spectrum disorders and cannabis associated myocardial infarct. The only caveat is that the literature is peppered with these reports, however, the quality of the recreational drugs are vastly different from medical marijuana which tends to be organic and all natural extracted from the plant in licensed medical dispensaries. The extraction of the medical components is vastly different from the smoked synthetic version of tetrahydrocannabinol. So, is difficult to know if these reports would actually corroborate with use in medical marijuana. The ones with side effects were heavy users of recreational smoked types of marijuana, it is unclear if it was synthetic or organic. As the popularity of medical marijuana progresses, more information will be available regarding the side effect profile.
- Arnone, et al, “Corpus callosum damage in heavy use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics,” Neuroimage, 2008, Jul., 1, 41 (3): 1067-74. “J Addict Med. 2017 Sep/Oct;11(5):405-407. doi: 10.1097/ADM.0000000000000326.
- Volpon, et al, “Multiple cerebral infarcts in a young patient associated with marijuana use, ” Journ. Addic. Med, 2017, Sep./Oct., 11(5):405-407.
- Geffrey, Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy,” Epilepsia, 2015, Aug., 58 (8):1246-1251.
- Stewart, et al, “Obstructive sleep apnea due to laryngospasm links ictal to postictal events in SUDEP cases and offers practical biomarkers for review of past cases and prevention of new ones,” Epilepsia, 2017, Jun., 58(6): e87-90
Shahzade, et al, “Patterns in adolescent cannabis use predict the onset and symptom structure of schizophrenia-spectrum disorder,” Schizophrenia Research, 2018, Feb., 2 pii S090-9964 doi:10. 1016/j. schres. 2018.01.008 (Epub ahead of print)
Orsini, et al, “Prolonged cardiac arrest complicating massive ST-segment elevation myocardial infarct associated with myocardial consumption,” J. Community Hosp. Intern. Med. Perspect, 2016, Sep., 7. 6 (4):31695
Thiele, et al, “Cannabidiol in patients with seizures from Lennox-Gastaut Syndrome (GWPCARE4): a randomized, double-blind placebo-controlled phase 3 trial,” Lancet, 2018, Jan., 390 (10125):1085-1096
Virginia Thornley, M.D., Neurologist, Epileptologist
March 29, 2018
Ketogenic diet has been used for seizure control when physicians started to notice a reduction of seizures in patients with a high ketone laden diet. This fell out of favor in the 1920’s with the onset of newer agents. As a side note, weight loss has been noted in those on a ketogenic diet.
Previously, guidelines have recommended a reduction in saturated fat which was thought to be the cause of the growing morbid obesity epidemic. Currently, it has been found that carbohydrates which are rich and refined may contribute towards the obesity epidemic. Sugar-laden sodas, the white bread which has refined flour, pizza batter made out of refined flour, all these food which are popular in theIt is no Western culture contribute to the morbid obesity as it is looming today.
How current culture sets the perfect stage for morbid obesity
The current western diet is about 50% carbohydrates. In addition, physical activity is at an all-time low compared to other eras. The current culture is designed as a sedentary and carbohydrate-rich eating culture. Everything nowadays is rapid pace. There are drive-through banks, drive-through pharmacies. Rather than having to physically go to a shop or order things in person, many things can be done online or by phone reducing the daily need to exert physical activity. There is less time spent on physical activity compared to 100 years ago. If you go to neighborhoods, sidewalks no longer exist. Unless one lives in an urban environment where you are forced to walk to the bus station or live in cities amenable to walking or biking, the car is the mode of transport. Food is rich in carbohydrate, such hamburger buns, pizza dough, white bread or rolls. It is little wonder that morbid obesity abounds. Food rich in sugar is abundant in grocery store aisles including donuts, cookies, baking packets. The colorful rich in anti-oxidant fresh fruits and vegetables are usually on the sides of the grocery shops, the food that is actually good for you and you need to take time out of your schedule to cook.
Living a healthy diet is not just staying active but also eating the proper diet. Food that is closest to their original source are richest in nutrients. In short, the colorful vegetables you have to cook without any of the processing that takes place are the food richest in nutrients and have high anti-oxidant properties. Anti-oxidation is important in helping to combat a wide variety of diseases. Colorful fruits and vegetables are rich in fiber and more difficult to digest, hence, uses up more calories. Those which are high in refined carbohydrates are easily digested and contributes more towards obesity.
Components of the ketogenic diet and ketogenic diet variants
Ketogenic diet variants include modified Atkins diet, low glycemic index treatment, and medium chain diet. The ketogenic diet consists of 4:1 ratio of fat to carbohydrates shifting metabolism to the use of ketone bodies as a source of energy. A lower ratio is sometimes employed called the modified ketogenic diet with a 3:1 or 2:1 ratio of fat to carbohydrates. In the modified ketogenic diet, the palatability is improved and avoids the gastrointestinal symptoms associated with the ketogenic diet such as nausea. With the modified Atkins diet, carbohydrates are restricted to 10-20 grams a day, or a 1-2:1 ratio of protein to fat plus carbohydrates. In the low glycemic index treatment, carbohydrates are limited to 40-60 grams while 50-60% of the diet is fat and 20-30% is from protein. The medium-chain triglyceride diet employs oils as a supplement such as coconut oil. The palatability of these diets improve patient compliance and lessen the side effects of the ketogenic diet. Some patients also used the diets to incidentally lose weight in addition to treating seizures.
Ketogenic diet and evidence it works in losing weight
The ketogenic diet has a carbohydrate component of about 20-50 grams a day. It is not so much the restriction of the carbohydrates but the quality of carbohydrates that are ingested that causes people to shed pounds. High fiber, wheat, and whole grain carbohydrates portend a healthier diet as opposed to just restricting carbohydrates in general. In some clinical studies, it was found that weight loss was higher in those with a low carbohydrate diet compared to a low-fat diet (1).
Will the high fat cause me to have heart disease?
In one study where ketogenic diet was used in glucose transporter deficiency, a pediatric epileptic syndrome with encephalopathy, 10 patients were followed for 10 years. After 10 years on ketogenic therapies, there was no evidence of increased cardiovascular risk. While it is a small study, it shows evidence that eating a low carbohydrate diet did not appear to contribute towards heart disease. Larger clinical trials are needed (3).
How obesity relates to other diseases
It is not uncommon to see patients who come into the ER or the doctor’s office with a history of hypertension, diabetes mellitus type II, hypercholesterolemia and obesity all related to one common denominator-obesity. Take away the obesity, the bad cholesterol or the LDL values go down, glucose goes down and hypertension resolves. When these risk factors are reduced early enough in your life, the odds of cerebrovascular disease or strokes and cardiovascular diseases or heart attacks vastly diminish. If, however, obesity is long-standing, while it is definitely good to reduce risk factors, once atherosclerosis is present in the blood vessels, there is no magic pill to reverse that.
Early identification and reduction of obesity as a contributor towards many health problems is key. Ketogenic diet may play a role in weight reduction. A small case series did not show any risk of heart disease while on the ketogenic diet long-term, over a span of 10 years. Larger clinical trials are needed to support this.
- Giugliano, et al, “More sugar? No thank you! The elusive nature of low carbohydrate diets,” Endocrine, 2018, Mar, 19. doi: 10.1007/s12020-018-1580-X (Epub ahead of print)
- McDonald, et al, “Ketogenic diets for adults with highly refractory epilepsy,” Epilepsy Currents, 2017, Nov.-Dec., 17 (6):346-350.
- Heussinger, et al, “10 patients, 10 years-Long-term follow-up of cardiovascular risk factors in Glut1 deficiency treared with ketogenic diet therapies: a prospective , multicenter case series,” Clin. Nut., 2017, Nov, pil:S0261-5614 (17)31399-7.
By Virginia Thornley, M.D., Neurologist
February 15, 2018
Migraines are characterized by recurrent pounding, throbbing pain, occurring on one side of the head. At times, it alternates. At its highest intensity, it is rated a 10/10 on the pain scale. It is often accompanied by nausea, vomiting, sensitivity to bright lights and loud noises. It may or may not be accompanied by visual symptoms which can range from seeing bright lights to seeing sophisticated patterns of color called fortifications that often migrate across your visual fields. The frequency may vary from infrequent to a daily basis. Some patients may have other neurological symptoms that accompany it, however, migraine is a diagnosis of exclusion. In other words, other more serious causes are ruled out before a diagnosis of migraine can be concluded if you also experience other neurological symptoms. It is important to be fully evaluated by a neurologist to exclude other possible neurological etiologies.
Lifestyle changes that help reduce migraine frequency
There are non-pharmacologic measures which may reduce the frequency of migraines. Oftentimes, triggers can be found. Lifestyle changes are the hardest to do but they greatly minimize the frequency of migraines.
Avoidance of caffeine
If large amounts of coffee are consumed, tapering can help ease into complete cessation. A sudden cessation may result in withdrawal effects of caffeine which can involve headaches. Common sources of caffeine include coffee, tea, soda, and chocolate. Avoidance of beverages labeled as decaffeinated as there is still a small amount of caffeine is also beneficial.
There is a lot of myth and misinformation. Many migraineurs say that caffeine alleviates their headaches. Caffeine can help a migraine in the short-term, however, it prolongs a migraine cycle. Refer to a neurologist for questions.
Obtain adequate sleep
Adequate rest at night is important. This may vary from 6-8 hours. A rule of thumb is if one cannot drag themselves out of bed sleep is inadequate. Adequate sleep means waking up refreshed. Sleep requirements vary per individual. Sleep deprivation propagates the migraine cycle. Sleep must be continuous and nocturnal allowing the body to enter the restorative deep wave sleep at stages 3 and 4 of sleep. Even if prolonged sleep occurs if constantly interrupted one will not wake up refreshed since the natural sleep cycle is disrupted and only light sleep stages 1 and 2 will occur. It should be nocturnal, the body is designed to sleep at night when hormones are secreted, daytime sleep will not have the same quality.
Avoidance of food triggers
A food journal provides much useful information. Common culprits include wine, cheese, hot dogs, and fish. Certain red meat may trigger migraine. Food triggers vary per patient and are unique to each individual.
Avoidance of excessive use of over the counter medications
Over the counter medications are easily accessible and consumable. A common pitfall is to overuse these medications. When stopped abruptly, rebound headache may result. It is not infrequent for patients with migraine headaches to have rebound headaches compounding the condition.
Magnesium is known to help with migraine. Intravenous magnesium is often used in the hospital setting in status migrainosus which is a continuous extremely painful migraine which sometimes lasts up to weeks. Magnesium is a mineral found naturally in food. Oral magnesium oxide at specific doses is helpful in preventing the migraine cycle.
Riboflavin is found naturally in the diet. It can prevent the migraine cycle at specific doses.
Other lifestyle changes
Other lifestyle changes include keeping hydrated especially during hot weather, eating 3 meals a day and avoiding hunger. Some triggers are unique to individuals. Avoiding stress helps with migraines. A zen-like environment is optimal.
Medications are often prescribed for the management of frequent migraine headaches. They are divided into 2 classes, preventative and abortive agents. However, even the best medications will not work effectively if triggers or aggravating factors are still present as mentioned above in daily life.
By Virginia Thornley, M.D., Neurologist, Epileptologist
February 16, 2018
Epilepsy is a condition involving 2 or more seizures. A seizure occurs when the electrical impulses in the brain do not cease and as a result, become recurrent resulting in excess cerebral activity. Typically, it occurs in the grey matter of the cortex, although seizures can be seen in white matter diseases such as in multiple sclerosis. Manifestations depend on the area involved. Etiologies are vast and are due to underlying structural abnormalities in the brain which may arise due to autoimmune processes, neoplastic causes (cancer), infectious diseases, traumatic etiologies or drug-induced causes. At times, there is no structural damage and may be genetic in predisposition. The seizures are similar in nature because the same underlying part of the brain is activated causing the same type of seizure. Different clinical manifestations signify a different or new area involved. If a seizure spreads to the entire brain it manifests as convulsions with clinical symptoms of loss of consciousness and whole body rhythmic jerking.
What to avoid if you have seizures
Sleep deprivation causes seizures to occur. When the brain is well rested it performs at maximal capacity. When it performs at suboptimal conditions such as sleep deprivation or fatigue, neurological conditions become more manifest.
Missing meals can give rise to seizures. When you miss a meal your blood glucose or sugar is lower. This low level of sugar also known as hypoglycemia can cause seizures to occur.
Certain medications can reduce the threshold of seizures including ciprofloxacine, certain cephalosporins and tramadol. Some psychotropic agents such as clozapine and chlorpromazine can lower the seizure threshold. It is best to avoid these agents and ensure your physicians know all your conditions. Amphetamines can also cause seizures and lower the seizure threshold.
Drugs of abuse
Some drugs are notorious for causing seizures such as cocaine. Cocaine can cause the blood vessels to constrict leading to strokes which can result in brain damage and seizures can result. Alcohol, if consumed by those with a genetic predisposition, can give rise to seizures. Excessive alcohol abuse can give rise to alcohol-induced seizures.
Other lifestyle changes
Because loss of consciousness may be involved, potential harm can occur. Avoiding heights such as ladders, cliffs, the edges of train platforms or subway platforms can help avert harm. Using the back burner while cooking help prevents burns. Avoiding driving for at least 1 year of seizure freedom can prevent accidents, some states require only 6 months. Avoiding the operation of heavy equipment such as forklifts, cranes can prevent accidents. Avoidance of swimming alone may prevent drowning, same is true with avoidance of taking baths alone.
It is an excellent idea to get a medics alert bracelet especially for young patients who may have a seizure late at night in public. After a seizure, patients may appear incoherent, disoriented and confused. It is also good to keep a list of medications.
Keeping everything clear around the patient can prevent injury.
An excellent resource for information and support is the Epilepsy Foundation. They provide a wealth of non-medical services including support and assistance in job-related issues. Some branches even have summer camps for children.
Avoiding heights such as ladders, cliffs, the edges of train platforms or subway platforms can help avert harm. Using the back burner while cooking help prevents burns. Avoiding driving for at least 1 year of seizure freedom can prevent accidents, some states require only 6 months.