Uncategorized

Cannabidiol: a large study in the U.S., Netherlands, and Poland shows its efficacy in patients with the epileptic disorder Lennox-Gastaut Syndrome

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

March 31, 2018

Introduction

Lennox-Gastaut Syndrome is an epileptic syndrome starting in childhood characterized by a wide spectrum of seizures and slow spike and wave on EEG. The seizures are characterized by the classic mnemonic “a fall, a jerk and a stare” or atonic seizures, myoclonus and complex partial seizures, although there are many other different types. Slow spike and wave generalized epileptiform discharges of 2.5 Hertz or less on electroencephalogram clinch the diagnosis. Patients are often delayed in development. Controlling seizures, because of the sheer complexity, of the different types is often a medical challenge.

Methods of the study

A new study using cannabidiol, which is the non-psychoactive medical component of the cannabis sativa plant, was carried out with the results recently demonstrating value. It covered 24 sites from the U.S., the Netherlands and Poland and studied seizures in patients medically refractory to medications using cannabidiol as an adjunctive add-on agent.  171 patients were enrolled from April 28, 2015, to October 15, 2015, and were randomly assigned to either the placebo control or the group with cannabidiol. 86 received cannabidiol and 85 were in the placebo group. 14 discontinued treatment in the cannabidiol group and 1 in the placebo group. All patients had at least one dose of treatment. Eligible patients ranged from 2-55 years old. Cannabidiol was given at a dose of 20mg/kg.

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Seizure reduction

The results were startling, there was a reduction of seizures by 43.9% in the cannabidiol group and 21% in the control group. 86% patients had side effects in the cannabidiol group and 69% in the control group on placebo. These included somnolence, pyrexia, diarrhea, reduced appetite, and vomiting. 12 stopped in the cannabidiol group due to adverse reactions considered mild to moderate while 1 withdrew from the placebo group. 1 died due to unrelated causes from the cannabidiol group.

Conclusion

Reviewing this study, perhaps one of my critiques of this study is that the dosage was 20mg/kg in a 14-week study which means that within 14 weeks a patient of 50 kg. would have been ramped up to about 1000mg. In real life practice, medications are titrated more gradually over a period of months before maximum efficacy may be seen and in such a gradual way in order to avoid side effects. Although a large percentage of patients had side effects which were mild to moderate, it is quite possible they may have needed a smaller dose and the dosages were increased more than it was necessary to achieve the beneficial effects seen in the study within a short period of time. Nevertheless, the bottom line is that cannabidiol, a product of the Cannabis sativa plant, shows a reduction in seizures in a patient with Lennox-Gastaut syndrome.

This study concluded that there is some efficacy of cannabidiol in Lennox-Gastaut syndrome, one of the most difficult epileptic syndromes to treat, and was found with only very mild to moderate side effects. An open-label study as an extension to this study is currently ongoing.

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Reference

  1. 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.
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ketogenic diet, Uncategorized

Ketogenic diet, modified Atkins diet and what is in them: used in seizure control, can these be a weight loss solution to morbid obesity, a risk factor for cerebrovascular and cardiovascular disease?

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

March 29, 2018

Introduction

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.

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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).

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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.

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Reference

  1. 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)
  2. McDonald, et al, “Ketogenic diets for adults with highly refractory epilepsy,” Epilepsy Currents, 2017, Nov.-Dec., 17 (6):346-350.
  3. 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.

 

 

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Anxiety, Depression, Post-Traumatic Stress Disorder, Uncategorized

Cannabidiol and tetrahydrocannabinol: effectiveness in post-traumatic stress disorder, anxiety and depression

Virginia Thornley, M.D., Neurologist, Epileptologist

March 20, 2018

Post-traumatic stress disorder is the silent disorder that could be affecting the co-worker who sits one cubicle over from you. When one hears of post-traumatic stress disorder, one thinks of traumatizing incidents such as war, abuse or some other devastating event but can occur even in situations such as car accidents or a spouse of many decades suddenly leaving. It is the quiet disorder that if you do not expound on it, nobody really knows about it. Because of the stigma surrounding psychological disorders, often times, help is not sought in a timely manner.

It is often characterized by nightmares waking someone up in the middle of the night or sudden flashbacks when placed in a situation similar to the traumatic event.  Management includes working with a psychiatrist using conventional medications and a psychologist using behavioral therapy. It is not uncommon for a patient to have to go through many different anti-depressants or anxiolytics before one finds the correct drug and titration. But sometimes even the best medications fail to treat someone with Post-traumatic stress disorder adequately. Psychotherapy may be helpful in some patients depending on the patient. In others,  there is less benefit and some dislike the thought of reliving the experience in order to learn coping mechanisms.

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Alternatives include non-pharmacologic measures including relaxation techniques such as doing yoga, Tai Chi or meditation. Exercise can often boost the mood and doing enjoyable activities may help alleviate symptoms without the addition of pharmacologic agents. Doing something one enjoys or taking joy in the simple activities in life such as writing poetry, art therapy, taking up a sport may help alleviate some of the stress. Great tips can be found on Psychiatrist, Dr. Welby’s site found here: https://drmelissawelby.com/exercise-depression-get-started-want-stay-bed/

More and more patients are turning towards alternative measures, finding that conventional medications are not always optimal. Cannabidiol works through the endocannabinoid pathway and modulates its effect through the CB1 receptor which is predominantly found in the nervous system. The CB2 receptor is found mostly in the immune system. In some studies, it was found that cannabidiol may help reduce fearful memory if taken in the conditioning phase so that rather than reacting to the stimulus with fear, the stimulus is then associated with a different reaction and may help mitigate the symptoms of post-traumatic stress disorder through this mechanism (1). In another study, it was found to influence synaptic dendrites and may contribute towards learned memory in the hippocampus.

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Cannabidiol interacts with the 5-HT1A receptor which is an important receptor in mitigating the symptoms of anxiety. Serotonin works through the 5HT1A receptors. Some anxiolytics and anti-depressants work through an increase in serotonin which boosts the mood. Cannabidiol itself is known to have a calming effect with none of the euphoria found in THC alone.   Cannabidiol is non-intoxicating and when combined with low dose tetrahydrocannabinol has great medical effects. One category of medical marijuana known as Sativa is known to help with mood alleviating anxiety and insomnia.

In summary, when medications and therapy are found to be ineffective for post-traumatic stress disorder, anxiety or depression, cannabidiol which is non-intoxicating may be an effective therapeutic option alone or in conjunction with low dose THC and should be considered.

Introduction/Disclaimer

About

https://neurologybuzz.com/

References

  1. Uhernik, et al, “Learning and memory are modulated by cannabidiol when administered during trace fear-conditioning,” Neurobiology of Learned Memory, 2018, Feb., 9, 149:58-76. doi: 10.1016/j.nlm.2018.02.009 (Epub ahead of print)
  2. Lee, et al, “Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorder,” British Journal of Pharmacology, 2017, Oct., 174 (19): 3242-3256. doi: 10.1111/bph.13724. (Epub. 2017 Mar. 9.)
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