Cannabis and epilepsy: The research, the cannabinoid breakdown, and more
By Markita Wilburn, PharmD
Edited by Terri Kroh and Rebekkah Ranallo
Epilepsy is a condition of the brain causing seizures — a neurological condition which affects the nervous system. A patient with this condition may be classified as having a seizure disorder if two or more unprovoked seizures separated by at least 24 hours or after one seizure with a high risk for more has occurred. It is the fourth most common of neurological conditions and affects people of all ages. Most identify a seizure by its repeated involuntary movements, but not all seizures are visible. Seizures can occur in many forms and affect different things in different people.
Epilepsy and Clinical Studies
Over many years, findings of pre-clinical studies reviewing cannabis and anecdotal reports of its use have highlighted substantial anticonvulsant potential. Federal regulations, however, prevent clinical research of the whole plant, so most of these early studies were conducted in California or Washington state — where cannabis has been legal. Recently, rescheduling Cannabidiol (better known as CBD) enabled research opportunities into the mechanism, safety and efficacious impact CBD may have within specific groups of people living with epilepsy. CBD ambitiously showed reduction in both seizure frequency and seizure duration when added to conventional antiepileptic regimens.
What’s more, these findings led to the FDA approving the first plant-based CBD extract, introduced to the pharmaceutical market. Yes! The very first cannabis product hit the US market in November 2018. Comprised mostly of oil and CBD, Epidiolex is an oral solution approved for the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) or Dravet Syndrome in patients two years of age or older. Adverse effects were common in these studies, though mild, beneficial effects such as increased alertness were reported. Most commonly fatigue, diarrhea, suppressed appetite and somnolence were experienced with elevated liver enzymes in some. Diarrhea largely may be in part to the product being more than 98% oil, though CBD increases GI motility, calms gut muscle, optimal for constipation — it may potentiate the opposite.
How can medical marijuana help with epilepsy?
Now, let’s take a moment to break this down. CBD is the non-psychoactive cannabinoid, unlike THC. Specifically for seizure control, we can appreciate CBD for its mind and body calming effect, spastic movement control, anti-inflammatory and neuroprotective properties — all without the psychoactive impact. During a seizure, a burst of excitatory signals temporarily interrupt brain function. What CBD is helpful in doing is regulating cell channels, sorting signals through CB1 or CB2 receptor activation and inhibiting glutamate release (an excitatory big guy in brain communication). CBD modulates brain activity by balancing endocannabinoid levels. Its ability to also avoid euphoric arousal within the Central Nervous System forge a well-tolerated, effective treatment for seizure control.
Not only can we credit cannabis-derived CBD for its impact in seizure control — there is evidence that THC, THCV, CBDV, Delta-8-THC and CBN all have anticonvulsant effects.
THC has been shown to be both anticonvulsant through glutamate inhibition and proconvulsant by inhibiting GABA (another big dog) release. Because of how THC binds mainly to CB1 receptors within the CNS, tolerance to its anticonvulsant effect is common, limiting its clinical use in seizure control. When consumed however, THC should be introduced at low doses to avoid the impact of hitting a plateau within the body, but also not to trigger seizure activity.
THCV showed to reduce seizure incidence significantly.
CBDV may be beneficial in many types of seizures and actually less toxic than conventional antiepileptic medications.
Delta-8-THC, an analogue of THC, showed to abolish seizure activity within 15 to 30 minutes of administration. However, with consistent use tolerance may inhibit its clinical use, just as THC.
Like CBD and CBDV, CBN inhibits the uptake of our natural endocannabinoid, anandamide, also providing antiepileptic activity.
Medical marijuana + antiepileptic medications
Caution should be advised to patients taking other medications as drug-drug interactions have been noted between CBD and commonly used antiepileptic drugs. Patients taking Clozabam seemed to have higher efficacy with Epidiolex when studies were reviewed, however significant changes in blood levels of Clozabam and Topiramate, for example, have been seen with increasing CBD doses. This is when your Maitri Pharmacist can help explain these interactions more specifically to your regimen.
Medical marijuana + epilepsy
For roughly 30% of people living with epilepsy, conventional treatments alone do not work to control seizures. Most patients looking to manage epilepsy with medical marijuana should focus on CBD-dominant strains. Other cannabinoids such as THC and THCV also have noted potential in seizure control. Though psychoactive, high THC cultivars with presence of linalool, a mildly psychoactive terpene, are becoming popular for seizure control when looking for something more relaxing of both mind and body before bed. Linalool — a strong anticonvulsant, relaxing and extremely beneficial in seizure control. THCV, non-psychoactive, has potential to reduce seizure incidence, similar to that of CBD.
I recommend the following combinations of cannabinoid and terpene profiles when looking to manage epilepsy or seizure activity. If further information is needed to determine the best Medical Marijuana products for your epileptic condition, please do not hesitate to contact one of your Maitri Pharmacists.
Strains high in CBD are ideal for reducing seizure frequency and seizure duration
Strains with higher concentrations of Linalool is helpful for reducing anxiety, with calming and anticonvulsant properties
High CBD + low THC + Linalool = ideal for overall seizure control
High CBD + low THC = ↓ seizure frequency & ↓ seizure duration
Delta-8-THC + THC = notable anticonvulsant potential
THC + THCV + Linalool = evening relaxation with anticonvulsant potential
THC:CBD 1:1 ratio ideal for muscle spasticity
Commonly recommended strains currently in stock for patients with epilepsy or seizure disorders are Harle-Tsu 1:4 RSO, Blue Dream CBD Dry Leaf, Dosi-Do Disposable Pen, Papaya x Fire OG Live Resin Cartridge, Birthday Cake Live Crumble, Mint Chocolate Chip Live Resin Sauce.
TIps
Always start CBD or THC low and slow, then assess seizure response. Increase the dose every 1 to 2 weeks. Patients may not see the full effects of dose changes for 3 weeks, so it is best to keep changes to a minimum to allow these changes to acclimate.
Complete a Seizure Action Plan
Keep a Seizure Diary of seizure type, number of seizures per day, length and severity of each seizure
Notate other issues such as behavioral disturbances, changes in mood, bowel excretion and/or sleep patterns
Track dose changes
Track triggers
Be sure to record daily and summarize weekly. This will help to optimize the most effective therapeutic regimen for seizure control.
REFERENCES
1.) Epilepsy Foundation
2.) Rosenburg, E. C., Tsien, R. W., Whalley, B.J. & Devinsky, O. Cannabinoids and Epilepsy. Retrieved October 2020, from Springer. Published online 18 August 2015.
3.) Critical Review and Invited Commentary. Devinsky, O., Cilio, M.R., Cross, H., et al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other necropsychiatric disorders. International League Against Epilepsy 2013;1-12.
4.) https://www.nejm.org/doi/full/10.1056/NEJMoa1611618
5.) https://www.nejm.org/doi/10.1056/NEJMoa1714631
6.) Wallace, M.J., Blair, R. E., Falenski, K. W., et al. The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model ofTemporal Lope Epilepsy. 2003, The Journal of Pharmacology and Experimental Therapeutics. Vol 307 No 1.
7.) Detyniecki, Kamil & Hirsch, Lawrence. Marijuana Use In Epilepsy: The Myth and The Reality. Current Neurol Neurosci Rep (2015) 15:65
8.) Rosenburg, Pabitra, P & Whalley, B.J. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. Published in final edited form as: Epilepsy Behav. 2017 May ; 70(Pt B): 319–327. doi:10.1016/j.yebeh.2016.11.006.
9.) Gaston, T.E., Bebin, E. M., Cutter, G. R., et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia, **(*):1–7, 2017 doi: 10.1111/epi.13852
10.) dos Santos, R.G., Hallak, J.E.C., Leite, J.P., et al. Phytocannabinoids and Epilepsy. Journal of Clinical Pharmacy and Therapeutics, 2014