The Link – Epilepsy, Endocannabinoids and Phyto-cannabinoids?
By James Tindall, PhD
Research is demonstrating that cannabidiol (CBD) and other cannabis compounds can help patients with seizure disorders. Often, it can be best to combine CBD with conventional anti-epileptic medications. While doctors may not tell you this, pharmacists will.
• More than 5 million Americans suffer from epilepsy.
• CBD is helping many patients – this includes children with seizure disorders.
• Generally, patients must experiment with various cannabis products to find the best remedy for their condition – we have found that CBD oil is one of the better initial treatments.
• The unheated form of THC (THCA), and linalool, an aromatic terpene present in many varieties of cannabis, are potent anti-convulsant compounds.
We were helping a child from Nebraska who was having siezures every day. At the young age of 9, this was a tragedy to the parents who didn’t know where to turn since current medications seemed ineffectual. He was having convulsions, 1-3 times each day, even though he was being treated with two anti-seizure medications – lamotrigine (Lamictal) and valproic acid. The parents had tried other medications that included: carbamazepine, Levetiracetam, phenobarbital, and zonisamide – all without success.
The compound THCA was added to his medication at 0.05mg/kg/day (0.05 ppm) and his parents immediately noticed a reduction in the frequency of seizures. The THCA dosage was increased to 2.2mg/kg/day (2.2 ppm). With the increased dosage, no immediate benefit was noticed, but the young boy was kept on the higher rate. After 3 months there was about 40% reduction in seizure frequency and also the siezures were shorter – they then discontinued the use of Diastat. Although various ratios of THCA:THC were tried, there was no additional improvement. However, THCA was able to make a significant difference in quality of life. This is just one of the many success stories out there.
What really is epilepsy and what can we do about it? Epilepsy is complex; it is termed a medical, economic, and social issue and affects 5.1 million people in the U.S. as of 2013; the number has grown since then but has not been further quantified. Both indirect and direct costs of epilepsy in the U.S. is estimated to be about $16 billion yearly. Life can be complicated for those with epilepsy and their families especially given the type and frequency of seizures, as well as the effects of anti-seizure medications.
In epilepsy, the brain can become overly excited and or nerves in the brain can begin to fire in an abnormal way – this creates a seizure due to an abrupt imbalance between the triggers of excitatory signals and inhibitory signals – the excitatory forces take over. The excitation spreads to surrounding cells. As the excitation spreads, the surrounding cells all start firing in the same abnormal way. Thus, the increased excitation of nerve cells or decreased inhibition of nerve cells can lead to a seizure because balance and or homeostasis is interrupted. The real problem is that there is no known cause for why this occurs for most who suffer from epilepsy, whether from trauma, infections, inborn metabolic errors, drugs (or withdrawal from drugs), and inherited conditions.
There are currently no effective treatments for the underlying causes of seizures, as well as none that reliably prevent the development of seizures, such as those after head traumas. Most of the medications on the market simply limit, but do not prevent seizure intensity or frequency. Almost 1/3 of epileptic patients fail to become seizure free after trying multiple anti-epileptic drugs. Thus far, during the last 30 years, about 20 seizure medications have been developed, but have not been effective. It may be due to biochemical individuality, but so far, we have not found a reliable medication that works long term. Thus, people in the trenches are turning to cannabis as an alternative that is considered safe with no incidence of fatalities due to the lack of cannabinoid receptors in the brainstem.
The most common side effects reported among patients using cannabis for seizure control are fatigue, decreased appetite, and abnormal drowsiness (somnolence). These symptoms all disappear when cannabis use is discontinued. Current drugs also have side effects, more serious, and that can cause death.
It should be noted that if you are using anti-eleptic medication/drug (AED) there can be a drug interaction with CBD. Cannabidiol and cannabinoids are metabolized by the Cytochrome P-450 system in the liver. Thus, competition for these enzymes can affect the serum levels of AEDs. This means that patients using both cannabis, as well as an AED should be monitored. Dosage rates will also likely need to be adjusted.
I have discussed the endocannabinoid system in other posts so, how does it work in epilepsy?
As previously mentioned, the role of the endocannabinoid system is to maintain homeostasis, which makes it more clear why cannabis could work with seizures. As a matter of fact, studies on rats have demonstrated that the endocannabinoid system is a significant part of the brain’s response to seizure disorders. Also, cannabinoid receptors are particularly dense in the central nervous system (CNS), which helps scientists to develop theories.
Let’s look at an example. There are cannabinoid receptors in the hippocampus – the part of the brain that deals with emotions and memory encoding. Any abnormal changes in cells within the hippocampus are one of the causes of medial temporal lobe epilepsy – one of the most common forms of epilepsy.
In the above type of epilepsy, hippocampal cells create an excitatory feedback loop that cause seizures. The nice part of this is that cannabinoids appear to be protective of the normal hippocampal cells that could make the abnormal cells less active. Other studies have shown that the endocannabinoid 2-AG is significantly increased compared to controls – anandamide and 2-AG are both synthesized on demand when seizures occur, which activates CB1 receptors. Additionally, in studies done on rats with refractory seizures, it was noted that THC completely terminated those seizures without causing sedation, while maximal levels of phenobarbital or phenytoin were unable to do the same. This would appear to indicate that phytocannabinoids could offer advantages in treating refractory seizures compared to currently prescribed anti-convulsants. Thus, human clinical observations are promising for the use of cannabis as an anti-epileptic medication, whether alone or as adjunctive therapy.
It is also interesting to note that research indicates that whole-plant usage is generally more effective than any single isolated constituent – likely due to the entourage effect. Cannabis contains many cannabinoids, THC and CBD being only two of over 100 potential other compounds. Additionally, the plant contains terpenes that are medically active chemicals that give the plant its fragrance. Thus, there is so much interdependence that it will take a while for scientists to sort out causes, effects, and specific solutions. In summary, CBD appears to be the major source in cannabis that is proven as an anti-convulsant, but THC has been shown to reduce seizure frequency and intensity, while THCA also appears to have anti-seizure properties. One of the main problems is dosing rates. However, rates at around 2-50 ppm for adults has been shown to work, i.e., 2-50 mg/Kg as well as ratios of 10:1 CBD:THC. The good thing is that if using only CBD type products without AEDs, there is lots of room to experiment, of course this mean always starting at a low dose rate and often, split the dose rate to twice per day: ½ in the morning and the rest at night. Or, doses can be divided into 8-hour portions, as well as increasing dosage rates each 1-2 weeks depending on results. Research also suggests that therapeutic rates range from 4-9 mg/kg/day (4-9 ppm).
More research will be able to identify how well CBD’s work with epilepsy. In the meantime, they may be worth trying if other medications continue to fail.
