Epilepsy

Medical Cannabis and Epilepsy

Epilepsy is associated with abnormal electrical activity in the brain, which causes convulsions, loss of consciousness, sensory disturbances and, in some cases, sensitivity to lights, patterns and sounds. Medical cannabis extracts, and the phytocannabinoid cannabidiol (CBD), are now available for prescription in the U.S. for managing seizures associated with treatment-resistant epilepsy, particularly Lennox-Gastaut syndrome and Dravet syndrome.

What is Epilepsy?

Epilepsy is generally divided into four basic types, depending on the type of seizures the patient is having. These include:

1. Generalized epilepsy
2. Focal epilepsy
3. Generalized and focal epilepsy
4. Unknown if generalized or focal epilepsy

There are also different kinds of seizure. Different types of seizure occur with different types of epilepsy. The types of seizures include:

• Simple partial (focal) seizures or ‘auras’: these include stiffness, tingling in the arms and legs, twitching and a rising feeling in the stomach. These types of seizures can be a warning sign of another, more severe seizure.
• Complex partial (focal) seizures: loss of a sense of awareness and making random body movements. People with epilepsy are not able to respond to anyone else during a complex partial seizure, and they will not be able to remember it, either.
• Tonic-clonic seizures (aka “grand mal” seizures): during the tonic stage, the patient loses consciousness, their body goes stiff and they may fall to the floor. During the clonic stage, limbs jerk and flail,  the patient may lose control of their bowel and/or bladder, bite their tongue and/or cheek and have difficulty breathing.
• Tonic seizures: Tonic seizures cause all your muscles to suddenly become stiff.
• Clonic seizures: limbs jerk and flail,  and the patient may lose control of their bowel and/or bladder, bite their tongue and/or cheek and have difficulty breathing.
• Myoclonic seizures: these types of seizures usually only last a few short seconds, and can feel like an electric shock. A myoclonic seizure is where some or all of your body suddenly twitches or jerks. They usually occur after waking up.
• Atonic seizures: Atonic seizures cause all your muscles to suddenly relax. Thei can cause a loss of balance.
• Absences (aka “petit mal” seizures): where the patient loses awareness of their surroundings for a short time. Absence seizures usually occur in the young. The seizures usually only last up to 15 seconds and the patient is unable to remember them. They can happen several times a day.

“Status epilepticus” is the status given to any seizure or series of seizures that lasts a long time, where the person does not regain consciousness. Status epilepticus is a medical emergency and can cause severe brain damage or death.

Approximately 50 million people worldwide have epilepsy, and the Centers for Disease Control estimates about three million adults and 470,000 children in the U.S. with epilepsy.

If you read through all the conditions on this site, you will notice that two things bind almost all of them: stress and the very much related inflammation. Epilepsy is no different, where neuroinflammation leads to a persistent state of neuronal hyperexcitability. As a result, there are lesions found in the nervous system, and there is impaired regulation of the immune system in the injured neuronal tissue.

Brief Summary of Current Treatments for Epilepsy

There are several ways epilepsy is managed. These include:

• Anti-epileptic drugs (AEDs) are the primary treatment: These are often benzodiazepine-based and have sedative effects.
• A low-carbohydrate, high-fat (ketogenic) diet
• Inserting a small electrical device inside the body to help control seizures
• Surgery to remove the small part of the brain causing seizures

How Might Medical Cannabis Help?

The idea that marijuana could help reduce the frequency of seizures has been around since the 1970s. Alongside glaucoma, cancer and multiple sclerosis (MS), epilepsy was one of the first conditions where cannabinoid-based treatments were thought to have therapeutic (in this case, antiseizure) effects.

There is now a considerable body of evidence showing that cannabidiol (CBD) can help reduce the frequency of seizures in people suffering from Dravet syndrome or Lennox-Gastaut syndrome, which are particularly severe and treatment-resistant forms of childhood epilepsy. We now have the Schedule V CBD-based Epidiolex available for prescription in the U.S., which has been shown to be effective in reducing seizures in those with Lennox-Gastaut syndrome or Dravet syndrome.

One of the other reasons why CBD may help is because many people with epilepsy find the drugs (benzodiazepines in particular) ineffective and/or find the side effects intolerable. Cytochrome P450 (CYP450), CYP2C9, CYP3A, CYP2C19 and CYP2D6 are all enzymes responsible for the metabolism of many anti-epileptic drugs (AEDs), such as Clobazam. Many of those with epilepsy have mutations in the genes that code for these enzymes, meaning that the anti-epileptic drugs (AEDs) they are being given are not effective and can even be harmful.

Side effects of antiseizure medications include addiction, drowsiness, fatigue, tremors, headache, vomiting, being in a “fog” and death in cases of overdose. CBD could help reduce or replace the need for such drugs, with the added benefit of having far fewer adverse side effects. CBD use could also help reduce needing further, more invasive treatments.

Cannabinoids

Phytocannabinoids (plant cannabinoids) other than CBD that display anti-seizure properties include:

• Cannabidivarin (CBDV or CBDv) = has displayed antiseizure and anticonvulsant properties 
• Cannabidiolic acid (CBDA or CBDa) = may combine with CBD to increase its anticonvulsant, antiseizure, antispasmodic and anti-inflammatory properties
• Tetrahydrocannabidiolic acid (THCA or THCa) = reduces pain and inflammation, and may also have antiseizure properties
• Cannabichromene (CBC) = CBC has neuroprotective effects that may help protect against any inflammation and brain damage caused by seizures
• Cannabigerol (CBG) = also has antioxidant and neuroprotective properties
• Cannabinol (CBN) = has sedative effects that can aid sleep

CBD displays significant antiseizure activity.

Cannabinoid Ratios

THC:CBD:

• 0.1
• 1:20
• 1:25
• 1:30

Terpenes and Terpenoids

• Linalool
• Myrcene
• Beta-caryophyllene

These terpenes have relaxing and pain-relieving properties that can help provide relief from some of the side-effects of seizures.

Flavonoids

• Quercetin
• Kaempferol
• Catechin

Flavonoids have anti-inflammatory properties.

Effective Ways of Taking Medical Cannabis for Epilepsy

Routes of Administration

• Sublingual
• Ingestion
• Suppository

Special Formulations

Artisanal CBD products are generally best avoided, as their THC content may induce seizures. Small amounts of THC may be helpful for some for its sedative and analgesic properties, and may also reduce the amount of CBD needed for therapeutic effects such as managing chronic pain and helping overcome addiction to sedatives.

Products rich in CBD with some CBC, CBDV, THCA and CBDA could be most helpful. Some terpenes like beta-caryophyllene, linalool and myrcene have displayed anti-inflammatory and sedative effects that could help manage seizures, but there is little definitive evidence.

Flavonoids like quercetin, kaempferol and catechin may also have neuroprotective and anti-seizure properties that could help manage epilepsy, but there are only studies on rodents so far.

Dosing guidelines for Epidiolex can be found here. To quote:

“EPIDIOLEX is to be administered orally. Seizures may benefit from a dosage increase up to a maximum recommended 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.”

High doses of CBD are needed for its sedative effects. As medical cannabis products contain other cannabinoids as well as CBD, the dosing regiment may differ. However, the guidelines for Epidiolex may still be useful for some patients figuring out their ideal dosage.

Dosing Methods

• Tinctures (most often recommended due to their being easy to measure and their relatively quick onset of 30-60 minutes, usually within 45 minutes)
• Edibles can help with potency and long-lasting effects, but their slow onset is not always ideal.

Pros and Cons of Medical Marijuana for Epilepsy

Potential Pros

• CBD desensitizes the TRPV1 receptor (also called the vanilloid receptor, responsible for detecting pain and heat), reducing neuronal excitability.
• CBD acts as an anti-inflammatory as “cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses.”
• High concentrations of CBD block calcium ion channels and antagonize GPR55, CB1 and CB2 receptors, lending to CBD’s anti-convulsant properties. “An effect on adenosine reuptake and antagonism of G protein-coupled receptor 55 (GPR55) has been recently suggested to play an important role in CBD anti-seizure activity.”
• The sedative and anti-inflammatory effects of high doses of CBD may help reduce neuronal excitability and help manage other issues like insomnia, anxiety and chronic pain.
• Those with epilepsy display lower levels of anandamide in their cerebrospinal fluid. Cannabinoids like CBD may help enhance anandamide signaling.

Potential Cons

• CBD desensitizes the enzyme CYP450, which could interfere with the metabolism of many anti-epileptic drugs (AEDs).
• CBD may not be suitable for all types of epilepsy and may, in some cases, make seizures worse. This may be the case with the cannabinoids THC and THCV (or some of their analogs). However, for some, low doses of THCA (and perhaps low doses of THC as well, with many studies showing positive results) may help increase CBD’s efficacy and have anti-seizure effects of their own. Lower doses of CBD may be required when other cannabinoids are added, helping reduce the chances of GI upset.

Useful Anecdotal Information

Billy Caldwell and the Fight for Medical Cannabis in the UK | The Independent

CBD Oil Hailed A Miracle Drug For Children With Severe Epilepsy

Scientific Data Overview and Studies

• Total Studies = 143
• Positive Studies = 125
• Inconclusive Studies = 15
• Negative Studies = 3
• 82 Meta-Analyses (69 positive, 11 inconclusive, 2 negative); 33 Animal Studies (31 positive, 1 inconclusive, 1 negative); 3 Double-Blind Human Trials (all positive); 19 Human Trials (16 positive, 3 inconclusive); 4 Lab Studies (all positive)
• 96 studies include CBD (87 positive, 9 inconclusive); 26 studies include THC (21 positive, 5 inconclusive); 4 studies include CBC (3 positive, 1 inconclusive); 3 studies include CBG (2 positive, 1 inconclusive); 3 studies include CBN (2 positive, 1 inconclusive); 1 study includes THCV (inconclusive); 3 studies include CBDA (all positive); 2 studies include THCA (1 positive, 1 inconclusive).
• No. of Leafwell Patients (2022) = 481 (epilepsy or seizures)
• Possible Overall Efficacy: High

Quotes from Studies

“Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet and Lennox-Gastaut syndrome. In these studies, CBD was superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes.” Source: Perucca, Emilio,

J Epilepsy Res. 2017 Dec 31;7(2):61-76. doi: 10.14581/jer.17012. eCollection 2017 Dec.

“Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%.”

McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, McDonald K, Zhang G, Sharma R, Whitney R, Sinopoli K, Snead OC 3rd. ‘A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.’ Ann Clin Transl Neurol. 2018 Aug 1;5(9):1077-1088. doi: 10.1002/acn3.621. PMID: 30250864; PMCID: PMC6144444.

“This study indicates that highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain. This effect may underlie its efficacy. This study provides Class III evidence for CBD’s normalizing effect on rs-FC in TRE.”

Nenert R, Allendorfer JB, Bebin EM, Gaston TE, Grayson LE, Houston JT, Szaflarski JP. ‘Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy.’ Epilepsy Behav. 2020 Nov;112:107297. doi: 10.1016/j.yebeh.2020.107297. Epub 2020 Jul 31. PMID: 32745959.

Conclusion

There is a large body of evidence showing that several phytocannabinoids found in cannabis have antiseizure properties when carefully dosed. Medical cannabis preparations could be of great use for those with treatment-resistant forms of epilepsy such as Lennox-Gastaut syndrome and Dravet syndrome.

Medical cannabis could also help with other kinds of epilepsy, treatment-resistant or not, as many find the side effects of current AEDs intolerable. CBD represents an excellent, well-tolerated alternative to current prescription medications. However, artisanal, hemp-based CBD products are not necessarily recommended for epilepsy, as they may increase the risk and frequency of seizures. Pharmaceutical-grade CBD and medical cannabis products may be better suited.

More research is also needed on other phytocannabinoids, terpenes and flavonoids for their potential antiseizure effects.

Related Articles

Using Cannabis for a Child with Epilepsy

How CBD Can Help Treat Epilepsy

Lennox-Gastaut Syndrome

Dravet Syndrome

What is Epidiolex?

CBD and the Brain: The Impact of Cannabidiol on Brain Health

Seizures and Seizure Disorders

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