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O'Shaughnessy's • Winter 2015/16 7
Cannabis in the Treatment of Pediatric Epilepsy
By Bonni Goldstein, MD
The author documents the progress of more than 100 patients using CBD-rich cannabis oil to treat seizure disorders. I have been a medical cannabis physician seeing adult tion they are going to give their child. They cannot give oil, the added expense of testing every bottle becomes pro- patients in California for the past six years. Occasionally untested preparations of CBD. In the world of western hibitive. I would be approached by parents who knew of my back- medicine we have a sense, as consumers, of being pro- ground and asked me to monitor their children's use of tected when we walk into a pharmacy and pick up a medi- Realm of Caring developed a dosing protocol for children cannabis. (As a doctor who trained in pediatrics and prac- cation. We rely on the pharmacist and the companies that on Charlotte's Web that parents are following. For most ticed pediatrics and emergency medicine for 12 years, I make and distribute drugs to produce a clean, consistent epilepsy patients, starting dose is 0.5 milligrams per pound have considerable experience taking care of children.) product that contains exactly what the label says it does.
per day, divided into three doses to be given at eight-hour In the summer of 2013 I evaluated a few adolescents for Unfortunately, the state of California hasn't done much intervals (ideally). Thus a 40-pound child would start at 20 use of cannabis: a teenage boy with cancer; a teenage girl to regulate who can produce and distribute marijuana as milligrams per day divided into three doses. (In pediatric who went through a horrific trauma and was suffering with medicine. It is definitely a "buyer-beware" situation. I in- medicine, everything is based on weight because children PTSD, anxiety and depression and had failed all conven- sist they only use tested preparations, and I explain to them can outgrow their dose as they gain weight.) tional treatment; a teenage boy with Tourette Syndrome; how to read the results of a cannabis lab test report.
After starting on CBD oil, the children are observed for another teenager with epilepsy.
For various reasons my edict sometimes gets ignored. I one or two weeks. Patients whose seizures are less fre- The nature of my practice changed dramatically after had one family that had obtained medication from a local quent —for example only three seizures a month— may Dr. Sanjay Gupta's documentary aired on CNN in August cannabis dispensary. It had not been tested and I insisted be observed for a longer period without increasing the 2013. Parents of children with intractable epilepsy wanted that before giving another dose, they have it evaluated by dose. Most of the patients I see have daily seizures, which to know about CBD and cannabis as a possible treatment. a cannabis testing facility. The test results showed that the enables parents to tell quite quickly if there is any benefit They learned about my background on the Internet and oil contained 9% rubbing alcohol! Not all oils are contami- from the oil. Parents are asked to keep a diary or calendar asked if I'd be willing to treat their children. Many of the nated but the only way to be sure is to have the oil tested of seizures and improvements and to check in every one parents are connected on a pediatric epilepsy Facebook prior to use.
page, through which most of my current patients found The oil made from Charlotte's Web has a CBD-to-THC If the child is doing well, after a week or two the dose is my practice.
ratio of about 25-to-1. The Stanley brothers authorized titrated up by increments of 0.5 milligrams per pound per Epilepsy is not a rare disorder. In the United States, ac- Ray Mirzabegian of Los Angeles to grow Charlotte's Web day. It appears from the data collected in Colorado that the cording to the Centers for Disease Control, some 2.3 mil- plants and produce oil for distribution in California. As of therapeutic range is 2 – 6 mg per pound per day for many lion adults and 468,000 children (under 17) have epilepsy. November, 2014, Mirzabegian was providing oil for 81pa- of the children that respond well to CBD treatment. Epilepsy in children is often a genetic or congenital con- tients. Another 1175 were on his waiting list. Some patients do need higher doses to achieve good re- dition. Epilepsy can result at any time in life from head Some of my patients learned online about other Califor- sults. One little boy was still having about 20 seizures a trauma, infections, or tumors. nia collectives providing CBD-rich oil from a strain called month on three anti-epileptic drugs. With Charlotte's Web "ACDC," which has a similar CBD:THC ratio to Char- oil he became seizure free for six months at a dose of 7.5 About one-third of epilepsy cases are "in- lotte's Web and is equally effective. But in my experience, milligrams per pound per day, and he has been weaned off tractable" —meaning available pharmaceu- its producers have not been meticulous and patients have almost all of the seizure medications.
reported occasional inconsistencies. One week I had nu- In Colorado one patient has gone as high as 8 milligrams tical drugs do not control the seizures. merous phone calls from parents reporting that their chil- per pound per day. dren were acting "high." This is just not acceptable. Doctors using GW Pharmaceuticals' Epidiolex report- Many patients who get seizure relief from pharmaceuti- Parents ask if they should test every bottle. This is dif- edly have gone as high as 24 milligrams per kilogram per cal anticonvulsants suffer intolerable side effects. About ficult because in addition to paying out of pocket for the day in an FDA-approved context.
one-third of epilepsy cases are "intractable"—meaning continued on next page available pharmaceutical drugs do not control the seizures. Between August 2013 and April 2014, I became the About Epilepsy
medical cannabis consultant to 93 children with intrac- table epilepsy. Their parents had, in the past, authorized Epilepsy is a condition of recurrent, unprovoked sei- sciousness. After this type of seizure, the patient typically various interventions —surgery, vagus-nerve-stimulator zures. The seizures may result from a hereditary tendency enters a state of confusion and fatigue lasting 30 minutes implant, the ketagenic diet. Some had left the country for or a brain injury, but often the cause is unknown. Many or longer. Also known as a "grand mal" seizure.
stem-cell treatment. These are families that are desperately use the term "seizure disorder" instead because "epilepsy" Partial seizures begin with an abnormal electrical dis-
seems more serious or stigmatized. However, almost all charge restricted to one region of the brain. My first pediatric epilepsy patient was a 14-year-old girl seizure disorders are epilepsy. A person with epilepsy has Simple partial seizure: An episode of altered sensation, with Lennox-Gastaut Syndrome. Her parents had learned had two or more unprovoked seizures, regardless of sei- cognitive function, or motor activity during which the about CBD and signed up to be on the waiting list of zure type. patient is fully alert. Patients usually call these seizures Realm of Caring, the Colorado non-profit run by the Stan- An estimated 65 million people worldwide are afflicted "auras" and symptoms vary depending on the brain region ley Brothers, whose "Charlotte Web" strain was shown to with epilepsy —some 2.2 million in the U.S. When sei- involved.
be very effective in the case featured by Dr. Gupta.
zures cannot be eliminated by medication, epilepsy is said Complex partial seizure: An episode altered behavior, Procedures
to be "refractory" or "intractable" or "treatment-resistant" sensation or motor activity during which alertness and Prior to coming into my office, parents are required to or "catastrophic." Approximately one-third of all epilepsy responsiveness are also compromised. The motor activity fax over their child's medical records for review. They fill cases are refractory. may consist of repetitive automatic movements of the face out a questionnaire and sign an informed consent form. Many types of epilepsy have been defined in terms of age or limbs, or "automatisms." Often patients are unaware of We talk about which medications they've tried, what has of onset, seizure types and where they arise in the brain, these seizures.
helped and what has not helped. Is there is a typical pat- EEG findings, family history, and neurological history, A partial seizure can develop into a tonic-clonic or tern to the child's seizures? Do they occur more when the among other factors. "grand mal" seizure.
child is awake or asleep? What kinds of seizures does the Seizures are characterized as "generalized" or "partial." child have? How are the medications and seizures affect- Generalized seizures begin with a widespread, exces-
Types of epilepsy
ing their child's development? Have they tried cannabis sive electrical discharge involving most or all of the brain. Temporal Lobe Epilepsy Absence Seizure: A brief space-out —an episode usually Frontal Lobe Epilepsy After this evaluation, I decide if the patient qualifies for lasting a few seconds, sometimes associated with auto- Parietal Lobe Epilepsy medical cannabis based on California law and if I think the matic movements of the hands or mouth, formerly called Occipital Lobe Epilepsy child may benefit from medical cannabis. If the answers to "petit mal" seizures.
Primary Generalized Epilepsy these two questions are yes, the child is approved and re- Atypical Absence Seizure: A staring episode that usu- Idiopathic Partial Epilepsy ceives a letter of recommendation to use medical cannabis. ally lasts longer than 10 seconds and occurs in children Symptomatic Generalized Epilepsy The parents receive caregiver letters. who have other types of seizure, lower than average intel- Progressive Myoclonic Epilepsy I educate the parents about what we know so far about ligence and difficult to control epilepsy. CBD and the endocannabinoid system. It's important that Myoclonic Seizure: A brief jerk or series of jerks that they understand that although clinical trials are lacking, may involve a small part of the body such as a finger, hand Benign Rolandic Epilepsy there's a scientific basis for what we're doing. or foot, or the shoulders or upper arms.
Juvenile Myoclonic Epilepsy I explain that I have very high standards for the medica- Atonic Seizure: A sudden loss of muscle tone through- out most or all of the body which may cause the head to Lennox-Gastaut Syndrome Bonni Goldstein, MD, sees patients in an office in Lawn- drop suddenly, objects to fall from the hands, or the person Childhood Absence Epilepsy dale (Los Angeles County) and is the director of the Can- to fall to the ground.
Benign Occipital Epilepsy na-Centers chain of clinics, with five offices in California. Clonic Seizure: Rhythmic jerking movements of body Mitochondrial Disorders She graduated from the Robert Wood Johnson Medical parts such as the arms or legs.
Landau-Kleffner Syndrome School in New Jersey and did her internship, residency Tonic Seizure: A stiffening of the body and/or limb, often Rasmussen Syndrome and Chief Residency at Childrens Hospital Los Ange- resulting in a fall if the patient is standing. Hypothalamic Hamartoma & Epilepsy les. She worked in Critical Care Transport and Pediat- Tonic-Clonic Seizure: Whole body stiffening with si- ric Emergency Medicine for 12 years before becoming a multaneous rhythmic jerking of the arms and legs, usually Source: NYU Langone Medical Center Comprehensive medical cannabis specialist. lasting at least one minute and also incuding loss of con- Epilepsy Center




Treating Pediatric Epilepsy from previous page
THC free preparation
week, she improved and seizures reduced again. Parents The chances of achieving freedom from sei- Concentrated oil is the formulation easiest for the par- reported that after this difficult week, she was much more ent giving a dose. When you're giving close to four mil- alert and responsive. And now the hope is that seizure re- zures diminishes sharply with each drug tried. ligrams per pound per day to a 50-pound child, you're giv- duction due to CBD will resume. ing up to 200 milligrams. If the oil only has 15 milligrams who have failed all other options that they may get some per milliliter, you're giving that child a lot of oil. In large control over their seizures and possibly lead a normal life.
quantities, even healthful olive oil or coconut oil can cause In June 2014 I reported on what I had learned about can- The side effects of the anti-epilepsy drugs described by nabis in the treatment of pediatric epilepsy at events put my patients and their families include lethargy and somno- on by the Realm of Caring Foundation and the Epilepsy lence, loss of focus, learning and memory problems, loss of Many people think that seizure reduction is Foundation of Los Angeles. I reviewed the charts of the speech, loss of social skills and motor skills, incontinence, the goal of treatment, but it's only part of the 93 patients that I approved to use CBD oil for epilepsy and insomnia, anorexia, and failure to thrive. Felbamate can who had been on the oil for at least three months. cause aplastic anemia and or liver failure. Vigabatrin can Twelve of the children were on oil from Realm of Car- cause permanent loss of vision.
ing Foundation (Charlotte's Web oil). Nine of the 12 had Parents have reported that their child seemed to be tol- Many people think that seizure reduction is the goal of reduction in severity and frequency of seizures, and some erating the first one or two drugs, but then they'll add an- treatment, but it's only part of the goal. The effects of the were in the process of weaning off other medications. other drug and they stop talking and stop walking, it just conventional anti-epileptic drugs (AEDs) can be debilitat- Forty-one children were on AC/DC oil and the success shuts them down.
ing —lethargy, developmental delay, liver damage and rate was very similar —31 out of 41 reporting reduction in more. The ultimate goal for pediatric epilepsy patients is frequency of seizures. One child in this group was seizure Endocannabinoids and Epilepsy
freedom from seizure and the side effects of the AEDs. free. Epilepsy —like any given medical problem— will re- Interestingly, many parents whose children are having suc- Ten children were using other CBD-rich oils, obtained main "treatment resistant" if the prescribed medications cess with CBD oil to treat epilepsy are also reporting that from small collectives. Six experienced seizure reduction. are not targeting the appropriate metabolic system(s). their children have improved sleep, improved appetite, Twenty-two of the families had not started oil and were There is ample evidence that the endocannabinoid system more alertness, and developmental progression. It is these waiting for Charlotte's Web to become available. plays an important role in modulating excitatory signals other beneficial effects that make CBD a wonderful option Eight patients had started taking CBD-rich oil from other in the brain. for children suffering with seizures. sources but had stopped, six for financial reasons. To cite but a few examples, in 2008 Hungarian research- ers compared tissue from epileptic patients who had de- Some patients do not show up as seizure- cided to undergo brain surgery to tissue from the brains of CBD has not been shown to be a pro-convulsant in 21 reduction statistics because the frequency of people who died naturally. Controlling for age and health preclinical and laboratory studies (see below). If a patient status, they found that the level of endocannabinoids in using CBD has an increase in seizure activity, it is likely seizures hasn't gone down —but severity and tissue removed from the epileptics was 60% lower than in from an interaction with other AEDs that the patient is tak- recovery time have gone down. brain tissue from the cadavers. The strong implication is that a lack of endocannabinoids is associated with loss of Drug interactions are very complex. Each patient is on a On average, the patients had been put on 10 anticonvul- neurotransmitter control.
different drug regimen and/or special diet. There are many sants over the course of their young lives. At present they In 2010 Andrea Romigi and colleagues at the Univer- variables: the patient's metabolism, the other medications, were on between one and four AEDs. Only one out of the sity of Rome tested spinal fluid from patients with newly the patient's endocannabinoid system, and the profile of 93 patients was not taking pharmaceuticals at the time I diagnosed temporal-lobe epilepsy and found lower-than- the particular cannabis product. collated my data. normal endocannabinoid levels. These studies and others CBD is an inhibitor of the P450 enzyme system, and A point worth repeating: some patients do not show up suggest that some types of epilepsy are associated with an affects the rate at which other drugs are metabolized. Un- as seizure-reduction statistics because the frequency of "endocannabinoid deficiency syndrome." (The concept fortunately, research is lacking on how CBD interacts with seizures hasn't gone down —but severity and recovery of an endocannabinoid deficiency syndrome underlying most of the other anti-epilepsy drugs in the liver but there time have gone down. Parents may report, "When he has many disorders was introduced by Ethan Russo, MD, him- are researchers who have started looking at these very im- a seizure he's not wiped out for three hours." Each case is self a pediatric neurologist.) portant reactions. Because CBD can enhance endocannabinoid tone with- A reassuring fact has been reported by G.W. Pharma- out inducing psychoactivity, it became a compound of ceuticals, the British company that makes Epidiolex and Report to the Society of Cannabis Clinicians
interest to far-sighted medical researchers. In the 1970s also makes Sativex, which is 50% CBD and has been ap- In September 2014 I described my work with pediatric and ‘80s, in addition to animal studies, there were several proved for use in 27 countries to treat pain and spasticity epilepsy patients to colleagues in the Society of Cannabis small, promising studies in Brazil of CBD as a treatment from Multiple Sclerosis. Sativex has been used for 30,000 Clinicians at a meeting in San Francisco. I had by then for people with seizure disorders.
patient-years by people taking concommitant drugs and seen some 200 children with almost every type of Epilepsy A 1978 paper co-authored by Raphael Mechoulam de- there have been no confirmed adverse consequences due diagnosis .
scribed the treatment of nine patients —four with CBD to drug-drug interactions.
My patients are concurrently being treated by a pediatri- (200 milligrams/day) and five with placebo. Two of the A journal article from 1977 suggested that CBD potenti- cian and a neurologist and may be seeing other specialists four CBD patients were seizure-free during the test period ated the effects of phenytoin (Dilantin) and phenobarbital, such as geneticists. Almost all have been categorized as and suffered no toxic side effects. None on placebo report- but reduced the anticonvulsant potency of Librium, Clon- "refractory" or "intractable" cases, meaning anti-epileptic ed improvement.
azepam, Trimethadione, and Ethosuximide. drugs have not eliminated their seizures. Almost all have In 1980 J.M. Cunha et al treated 16 refractory tonic- Laboratory testing has shown that some but not all pa- been on multiple medications with no improvement. clonic seizure patients. Eight received 200-300 milligrams tients on CBD oil can have decreased Depakote levels A study published in the New England Journal of Medi- of CBD per day. Of these, three became seizure free, four and decreased felbamate levels with CBD. It appears that cine in 2000 showed that the chances of achieving free- had seizure reduction, and one was unchanged. In the pla- CBD interacts to increase Onfi (clobazam) levels. dom from seizures diminishes sharply with each drug cebo group, one patient had seizure reduction, seven were Some parents using THCA
tried. Whereas 47% responded to the first-line drug they unchanged. THCA is the raw, unheated, non-psychoactive phytocan- were treated with, the response to a second drug —either "It seemed very promising," said Mechoulam looking nabinoid that converts to THC when heated. THCA has substituted or added— went down to 13%. The third drug back decades later, "but unfortunately, nothing has been been shown to be a significant anti-inflammatory. There helped only 4% of patients. done ever since. To the best of my knowledge, nobody has are tested THCA preparations that have become available The burdens of refractory epilepsy include poor quality done any work on cannabidiol in the clinic on epilepsy, and have been claimed to have anticonvulsant properties. of life, the debilitating side-effects of medications, cogni- and I just wonder why?" There are at least five patients in my practice who added tive decline, physical injuries from falling, psychosocial At the 2005 meeting of the International Association for THCA to the CBD treatment regimen and had improved dysfunction, a restricted lifestyle —adults can't drive, Cannnabinoid Medicine, Italian researchers led by A. Pel- seizure reduction. which makes living in our society very difficult— and in- liccia described an open study ("modulating administra- Treating pediatric epilepsy patients is very complicated. creased mortality: the idea that you're going to drop dead tion and titration schedules on a case-by-case basis, ac- Treatment varies case-by-case, day-by-day and week-by- any day now. cording to clinical response") in which 18 children with week. Weaning a child off an anti-epileptic drug involves SUDEP —Sudden Unexpected Death in Epilepsy— has intractable epilepsy were treated with a low dose of CBD an act of faith on the part of the parents who have to deal been explained to my patients by their neurologists. Those in corn oil.
with the withdrawal symptoms. For example, one of my who are teenagers and young adults live with this possibil- The results were very promising. No patients discontin- patients achieved an 80% reduction in seizures. When the ity. One patient in her early twenties said to me, "I could ued due to side effects. Most obtained seizure reduction parents started to wean one of the AEDs that she was on, have a seizure tonight and not wake up tomorrow." of 25% or more. And, according to Pelliccia: "in all CBD- she had an increase in number of seizures. After about one With cannabis medicine you can offer hope that patients continued on next page slides summarizing dr. goldsTein's unpublished resulTs Los Angeles and the Realm of Caring Foundation in June. whose cannabis use she has been monitoring have experi-
were part of her presentation to the Epilepsy Foundation of Approximately two-thirds of the pediatric epilepsy patients enced seizure reduction.
O'Shaughnessy's • Winter 2015/16 9
Treating Pediatric Epilepsy from previous page
treated children, a clear improvement of consciousness and spasticity (whenever present) was observed.
Compound Species Studies Dose Anticonvulsant No effect Proconvulsant
"However, only nine out of these are currently on treat- ment, since the parents of the remaining children, although 0.25-200 mg/kg 61% appreciating the improvement of their offspring, not only concerning the fits but also the awareness and the mus- 1-400 mg/kg 81% cular tone, preferred to discontinue due to the economic overcharge induced by the treatment (approximately 300 Euros per month)." This heartbreaking situation —parents unable to afford a helpful medication— is one I have encountered in my practice. As noted, the issue of affordability should not be summary of preclinical evidence was presented by University of Reading pharmacologist Ben Walley at the October, 2013,
ignored by clinicians. conference on Cannabidiols and Epilepsy at NYU. "Studies" refers to the separate conditions, models, and designs reviewed.
When G.W. Pharmaceuticals got approval from the Brit- In none of the 21 projects involving CBD or CBDV did researchers see a proconvulsant effect.
ish government to develop cannabis-based extracts for clinical trials in 1998, the company began funding lab studies to establish the safety of cannabidiol and other so- called "minor" cannabinoids. G.W. provided purified CBD and CBD extracts to many labs, where scientists studied the effects on cell lines and mice, and the mechanism of In 2013 one of the G.W.-supported researchers, Ben Wal- ley of the University of Reading, reviewed the preclinical data (see graphic at top of page) and found no evidence — zero—that CBD acts as a pro-convulsant. To a physician helping patients figure out appropriate dosing levels, this is important information. G.W.'s interest in CBD and other possibly beneficial cannabinoids inspired U.S. activists to study the contents of marijuana being grown for distribution by dispensaries. O'Shaughnessy's reported in 2010 that about one in 700 varieties being tested by analytic chemistry labs in Cali- fornia and Colorado contained four percent or more CBD. A few plant breeders crossed these "CBD-rich" strains to create increasingly high CBD-to-THC ratios. By 2013 there were enough epilepsy patients using CBD to inspire a data-collection effort by Stanford University neurologists B.E. Porter and C. Jacobsen that was pub- cbd acTs in ways similar To various anTi-epilepsy drugs listed at left. In this chart developed by AJ Hill and colleagues, +
lished in Epilepsy & Behavior in December 2013. signs indicate the relative strength of the interactions (row at top) that have been observed in the lab. "This is a slide that
They looked at results from 19 Colorado patients using parents find very useful," according to Goldstein. "Instead of having to take all these different drugs, they can get many of
the benefits with one medication."
oil from Charlotte's Web. Thirteen were Dravet's patients, four had Doose syndrome, and one each had Lennox- There are only a few suppliers of oil that seem to be consis- Other patients are using lower-than-ideal doses because Gastaut syndrome and idiopathic epilepsy (meaning of un- tent bottle to bottle. There have been instances of CBD oil they're at their limits financially certain origin). The average number of anti-epileptic drugs products having similar CBD content but having different CBD use by Diagnosis
tried before CBD was 12.
effects, as they are prepared from different CBD strains. Lennox-Gastaut Syndrome: Of 10 patients with LGS, Sixteen of 19 families reported a reduction in their Having a producer who makes oil from one specific strain ages two to 14, the parents all reported > 25% seizure child's seizure frequency while taking CBD-rich cannabis. increases the likelihood of obtaining consistent medication reduction. Parents also reported that their children were Two reported complete seizure freedom. Eight reported a from month to month. Certain terpenes (essential oils in more alert, more interactive, happier, and had quicker re- greater than 80% reduction in seizure frequency. (Interest- the cannabis plant) are known to have beneficial medici- covery from seizure. Eight of the 10 were able to wean ingly, this corresponds to what Walley found in reviewing nal effects. Beta caryophyllene, a terpene that binds to the AEDs, two got off the ketogenic diet. There were no re- the animal studies.) Six patients in the Stanford survey ex- CB2 receptor, is a potent anti-inflammatory that appears ports of negative side effects.
perienced a 25-60% reduction. to work synergistically with CBD. Both Charlotte's Web There were eight Dravet patients, ages four to 20. Four Beneficial effects included increased alertness, bet- and AC/DC strains contain high amounts of this terpene.
of reported 75-90% seizure reduction. One reports 35% ter mood and improved sleep. Adverse effects included Anybody who is making oil should know that parents reduction. Three report no change. All parents report im- drowsiness and fatigue (which may have been brought on get it tested and share the lab results on websites. Some proved alertness, behaviors, memory, ability to learn, bet- in part by AEDs. The authors didn't specify which child of these parents will get it tested at two or three different ter speech, improved social and motor skills, improved was on which pharmaceuticals.) labs so they know what is in the oil that they are giving to appetite and sleep. One parent reported "better sense of Also in December 2013, Drs. Margaret Gedde and Ed- their child. humor." Half have been able to wean AEDs. There were ward Maa, at a meeting of the American Epilepsy Society Having a reliable supply, one that is available and won't no reports of negative side effects.
reported very promising results from 11 patients who had be "out of stock," is also crucial. Patients who start CBD Of nine patients with other genetic syndromes, ages two used oil from Charlotte's Web for three months. All the oil treatment may wean their children off other medica- to 17 years, one was seizure free. Four reported 75-90% children experienced at least 20% seizure reduction. Nine tions. It could be catastrophic if a child is weaned off their reduction in frequency. Three reported 50% reduction. had at least 75% reduction. Eight had at least 98% reduc- anti-epileptic drugs and the CBD oil supplier did not con- One reported no change. Most reported improved alert- tion. And five had 100% reduction. (Gedde notes that the tinue to provide the oil that had been working. ness, better sleep and appetite. One parent reported side patients in the study "were selected by the provider of the effect of fatigue. Six of nine weaned at least one AED.
Affordability is a major concern for most families. They Of four patients with Infantile Spasms (West's Syn- CBD's Anticonvulsant Mechanism of Action
are paying anywhere from $150/month for a small child drome), ages nine to 18 months, one was seizure free, two CBD does not act directly on the CB1 receptor. It works and up to $1800/ month for an adult-sized teenager.
had 80-90% reduction, one reported no effect from CBD. by multiple actions —what has been termed "polypharma- One oil provider in Southern California is trying to be All parents reported improved development and better eye cology," exerting various effects within different parts of consistent with concentrated oil made from AC/DC plants. contact. All reported no negative side effects. Significant the brain that might defuse seizures. I explain it in com- Their oil costs nine cents per mg, which is relatively af- development takes place in the first year of life. Many parison to the AEDs that parents are all familiar with. fordable. Other CBD-rich oils used by my patients cost parents state that development is arrested when their very CBD blocks NMDA receptors, which are involved in ex- between 17 cents and 33 cents per milligram. young child has frequent seizures. With reduction of sei- citation. Felbamate acts similarly.
Realm of Caring is subsidized by the Stanley Brothers zures with CBD, development can continue to move for- CBD binds to GABA receptors, enhancing the inhibition Social Enterprises so they can make their oil available for ward. of excitation —as do Felbamate, Depakote, Tegratol, Onfi, five cents a milligram. Tuberous Sclerosis: one patient soon after starting CBD and Phenobarbital.
I have had five patients who have had to discontinue was able to wean off Onfi, reduce trileptal, and had 75% CBD stabilizes ion channels —as do Banzel, Lamictal, treatment because they could not afford the oil. These pa- fewer seizures. She improved in that she began trying to Dilantin, Keppra, and Trileptal.
tients have remained on AEDs and are on the waiting list vocalize and interact with her caregivers.
CBD modulates calcium release in neurons, blocking the for more affordable oil from Realm of Caring. uptake of endocannabinoids in order to normalize endo- cannabinoid tone. P.S. 3/22/15: As of December 2014 there was no longer a waiting list for the CBD-rich oil made from the Charlotte's
CBD counters inflammatory reactions that appear to in- Web strain by the Realm of Caring Foundation. Good quality CBD rich oil from the ACDC strain has also become read- crease neuronal excitability and impair cell survival. This ily available in Southern California. I have seen an additional 100+ pediatric patients with refractory epilepsy since is why the National Football League is reviewing a pro- reviewing my files for this article and will be reporting on their results after three months of treatment and observation. posal that CBD be provided to players suffering head in- Interestingly, a few patients who have reported excellent results have found, after 9 months or so, an increase of sei- juries. CBD is neuroprotective; it reduces oxidative stress zures or lethargy that appears to be unrelated to any other cause. Parents in Colorado also noticed this phenomena and and glutamate toxicity. found that stopping CBD for a few days, then restarting at a slightly lower dose (10-15% less) completely resolved the issues. It might be that there may be a point at which the endocannabinoid system is "full" and does not need as much The question of where to get their oil and what to use is cannabinoid medicine. This makes sense as the endocannabinoids are produced "on demand" in response to a trigger. a family decision. It's hard to find consistent CBD grow- Presumably by taking a break from the CBD oil or decreasing the dose, the endocannabinoid system can reset itself. ers in Southern California at this time [September 2014]. Research into this phenomenon is greatly needed. —B.G.

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