Dosing and what to do in the event of a seizure
There are several factors that contribute to epilepsy. The mechanisms underlying the anti-epileptic effects of CBD is not well defined. We know that CBD helps to reduce anxiety and inflammation which has been associated with some episodes. CBD is legal in all 50 states because it is derived from hemp that only contains 0.3% THC and does not produce a “high”. The evidence of CBD benefit to treat epileptic children is so promising that the FDA recently approved an isolated CBD pharmaceutical product, trademarked as Epidiolex. Isolated CBD can also be found over the counter but many prefer full spectrum products meaning it contain the many other beneficial cannabinoids found in hemp. Cannabis contains over 100 different cannabinoids and like other botanicals, benefit is achieved from the synergy of the many compounds found in a plant. This synergy is often referred to as “the entourage effect,” which describes the combined effect of all cannabinoids working together to relieve symptoms. A lot of great research is going on involving the benefits of the other cannabinoids. More on this later.
Trial dosages of CBD
Human studies were done with patients 2 years and older, diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS), two severe forms of epilepsy.
In many studies, CBD was added to a baseline anti-epileptic drug (AED). Many found improved quality of life, along with improvements in behavior, alertness, language, communication, motor skills and sleep (3,4).
A 2016 study reported an 89% reduction of seizure frequency in epileptic children that were not responding to medication, vagal nerve stimulation, or ketogenic way of eating. The CBD to THC ratio was 20:1. Dosage was 1-20 mg/kg/day (2).
The FDA approved the following dosage of isolated CBD:
Minimum: 5mg CBD per kg body weight and day
Maximum: 25mg of CBD per kg body weight and day
Starting dosage is 2.5 mg/kg twice daily (5 mg/kg/day). (1kg= 2.205 lbs)
After one week, the dosage can be increased to a maintenance dosage of 5 mg/kg twice daily (10 mg/kg/day).
Patients who are tolerating CBD at 5 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase to a maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day), in weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated.
For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day. Administration of the 20 mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions. (11)
A 2015 study increased the dose to 50 mg/kg/day, as allowed by the US Food and Drug Administration. The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy after 12 weeks of use. One-third of the patients had treatment resistant epilepsy. Overall, the median monthly frequency of motor seizures decreased by 36.5% (1).
Conversion of mg/kg to mg/lb
1kg = 2.2 lbs
Starting dose (2.5 mg/kg) is about 1 mg/lb given twice daily.
Research indicates dosage can go up to (50 mg/kg) about 25 mg/lb/day.
Let’s use a 100 lb person for example.
Starting dose 1st week (2.5 mg/kg) twice a day: ~50 mg twice a day
2nd week increased to (5 mg/kg) twice a day: ~ 100 mg twice a day
3rd week increase by 2.5 mg/kg to (7.5 mg/kg): ~150 mg twice a day
A review of research indicates the average dose of CBD was 200–300 mg/day.
If needed, dosages are increased by 2.5 mg/kg each week.
Maximum recommended maintenance dose (10 mg/kg): ~225 mg twice a day
Reported effects
Effects of CBD on childhood epilepsy and comparison between its side effects and those of medicines
The most common adverse effect of CBD was drowsiness. Most reported adverse effects were mild, for example diarrhea, fatigue, and decreased appetite. Nonetheless, more serious effects reported in a small percentage of patients was status epilepticus (epileptic seizures following one another without recovery of consciousness between them). It is interesting that CBD had this severe adverse effect, status epilepticus, because animal studies have not shown any proconvulsant effects of CBD. (8,9) The authors did not find any relationship between status epilepticus and reduced doses of AED or CBD.
Devinsky et al. also reported thrombocytopenia (low platelet count) in 5 patients (3%). This condition is associated with easy bruising or prolonged bleeding. CBD also did not affect kidney function. Ten patients (6%) showed elevated liver enzymes and this elevation was significant in one patient (< 1%). The observation has been made that elevations in liver enzymes associated with CBD treatment occur much more frequently among patients co-medicated with valproate. (10)
CBD and medications:
CBD is metabolized by the liver, and can inhibit cytochrome P450, especially CYP 2C and CYP 3A, which aids metabolism of several anti-epileptic drugs (5,6). Therefore, if a patient with epilepsy takes CBD with an enzyme-inducing AED, such as carbamazepine or phenytoin, the AED can reduce serum CBD levels. Whereas, if the patient takes clobazam (CLB) with CBD, CBD can raise the serum level of nor-oclobazam, the active metabolite of CLB. (7) The half-life of CBD in humans is estimated to be between 18 and 32 hours.
In any case, assessment of the data suggested that changes in serum levels of AEDs during CBD administration were generally minor, except for clobazam and N-desmethylclobazam levels. (10) In fact, occurrence of sedation because of the interaction with clobazam often led to a decrease in clobazam dose. (4)
General guidelines for what to do if you are with someone having a seizure:
Witnessing someone with epilepsy having a seizure can be truly frightening. But most seizures aren’t an emergency. They stop on their own with no permanent ill effects.
There isn’t much you can do to stop a seizure once it starts. But there are simple steps you can take to protect someone from harm during a seizure. It’s worth knowing some basic first aid — and when it’s time to call 911.
Types of Seizures, Degrees of Danger
Some are more dangerous than others. There are two main types:
Focal onset seizures start in a single part of the brain. This can involve uncontrolled arm movement or facial twitching. The person may appear to be awake and aware but with a vacant stare. And afterward, they may not remember a thing.
Generalized seizures involve multiple areas of the brain at once. People are rarely aware of what’s happening. The most well-known type falls in this group: the generalized tonic-clonic seizure, also known as a grand mal seizure. These are frightening to watch and can be an emergency.
First aid:
Keep other people out of the way.
Clear hard or sharp objects away.
Don’t try to hold them down or stop movements.
Place them on their side, to help keep the airway clear.
Look at your watch at the start of the seizure, so you can time its length.
Don’t put anything in their mouth.
Stay calm, speak softly, and assure them that they will be ok.
When to Call 911
Get medical help when:
It’s a person’s first seizure.
The seizure lasts longer than 5 minutes.
Another seizure begins soon after the first.
The person doesn’t “wake up” after the movements have stopped.
The person was injured during the seizure.
If you’re concerned that something else may be wrong, or the person has another medical condition such as heart disease or diabetes, call a doctor.
Epileptic Pets and CBD
Many pet owners are reporting less frequency and severity of epileptic seizures with the use of CBD. Some report that their dog no longer has seizures after 3 months use. Dr. Stephanie McGrath, an assistant professor and veterinarian at the Colorado State University Veterinary Teaching Hospital is researching CBD as a treatment for epileptic dogs. In reference to the first double blind, placebo-controlled safety study, she states: “We haven’t seen anything that’s been adversely affecting our dogs.” The main side effect has been diarrhea with high doses of 75-150 mg every 12 hours for 6 weeks via transdermal cream, microencapsulated oil beads, and oral CBD infused oil. CBD infused oil was found to the best absorbed. (12) Their most recent study found that 5 mg/kg helped to significantly reduce the frequency of seizures in epileptic dogs. A larger animal study has recently been granted.
Some dog owners are using a gradual 3 tier increase approach until they see that the dog is feeling better. Starting with Tier 1, they observe for a week and then decide whether to move on to Tier 2 or stay on Tier 1. The trick is to get the initial low dosage based on weight and then incrementally increase the daily amount over the course of several weeks.
The 3-tier dosage plan for dogs:
Tier 1 (low dosage): 0.05 mg x lb / twice daily
Tier 2 (medium dosage): 0.125 mg x lb / twice daily
Tier 3 (high dosage): 0.25 mg x lb / twice daily
Canvas Boutique and Dispensary carries high milligram CBD products. Click the following link for quality products: NuLeaf, Receptra Pro, and pet formulas.
Sources:
Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270–8.
Tzadok, Michal et al. CBD-enriched medical cannabis for intractable pediatric epilepsy. Seizure – European Journal of Epilepsy, Volume 35, 41 – 44
Koo, Chung Mo, and Hoon-Chul Kang. “Could Cannabidiol Be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?” Journal of Epilepsy Research1 (2017): 16–20. PMC. Web. 31 July 2018.
Longo DL, Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med. 2015;373:1048–58.
Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86–95.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol. 2003;2:347–56.
Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. 2015;56:1246–51.
Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. 2014;55:791–802.
Hill AJ, Hill TD, Whalley B. Endocannabinoids: molecular, pharmacological, behavioral and clinical features.Bentham science publishers; Oak Park, IL: 2013. The development of cannabinoid based therapies for epilepsy; pp. 164–204.
Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used anti-epileptic drugs. Epilepsia. 2017;581586–92.
FDA Epidiolex factsheet: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf
Bartner, Lisa R.; McGrath, Stephanie; et al. Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dog. Volume 82, Number 3, July 2018, pp. 178-183(6)
Other reviews of research:
About the author:
Dr Tiffanie A Jones is a medically trained naturopathic doctor. A graduate of Bastyr University in Seattle, WA. Her mission is to offer science-based, holistic approaches to improve vitality and quality of life. Some of her research includes how CBD can help with ailments such as depression, anxiety, pain management and more. She visits with clients is St Louis, MO. For more information please visit: www.DrTiffanieJones.com