Why CBD for Lennox-Gastaut Syndrome?
What is Lennox-Gastaut syndrome?
Lennox-Gastaut syndrome (LGS) is a rare form of childhood-onset epilepsy that represents less than 2% of new cases of epilepsy. However, due to its intractable nature, it represents around 15% of total epilepsy cases because it is simply so difficult to manage.
Doctors and institutions are not in complete agreement on the exact definition of LGS, but nearly all characterizations of the disease include three parts: multiple types of seizure, slow-wave (<2.5 Hz) electroencephalogram pattern, and mental/developmental delay. Around ¾ of cases are symptomatic of a range of other conditions, from autism to prenatal brain injury and many others. The remaining quarter of cases are idiopathic: they have no known cause.
Cause(s) of Lennox-Gastaut Syndrome
LGS presents in several different ways during the first 2 to 6 years of life, depending on other conditions and overall health before, during, and after birth.
- 75% of Lennox-Gastaut syndrome cases result from another condition.
- Autism, encephalitis, meningitis, perinatal asphyxiation, traumatic brain injuries, and metabolic deficiencies can all lead to the manifestation of LGS.
- 25% of Lennox-Gastaut cases result idiopathically; that is, without any medically apparent cause.
- Many researchers posit that a deficiency of the endocannabinoid system causes the dysfunctional conditions that lead to the presence of LGS; this may be why CBD is so effective when nearly all other AEDs (anti-epilepsy drugs) fail to significantly relieve LGS across the board.
Diagnosis and Characteristics of Lennox-Gastaut Syndrome
While different institutions and resources define Lennox-Gastaut Syndrome by slightly different metrics, there are several distinct characteristics that overlap and define the consensus on this rare disorder.
- LGS by definition cause several different types of seizure in children:
- Myoclonic, Tonic-Clonic, Tonic, and several other more severe types of seizures are typical with LGS
- LGS seizures by definition have a specific slow spike-wave EEG pattern:
- Slow spike-wave patterns very near to 2.5 Hz. are characteristic of LGS, interspersed with
- LGS by definition results in intellectual/developmental disability
- Children with Lennox-Gastaut syndrome have difficulty developing neurotypically due to the constant barrage of ictal assault.
Current Treatment Options and Best Practices for LGS
Current AED’s work by modulating the ratio and overall expression of excitatory neurotransmitters. However, the brain is much more complex than simply a set of chemical on-off switches. The endocannabinoid system, present in nearly every part of the brain, controls how sensitive neurons are to transmission from nearby neurons. It also controls the strength of the signals that a neuron is able to send.
When this intricate balance fails to be maintained, many neuropsychological conditions may appear. LGS seems to be a severe result of imbalance in the expression of the endocannabinoid system that controls how sensitive neurons are to signalling. This leads to the myriad of different seizure types present in LGS. Due to the severe nature of even relatively mild cases of LGS, children usually must wear helmets to protect their heads from sudden drop seizures or other unpredictable motor activity.
Why CBD Improves Cases of Lennox-Gastaut Syndrome
As mentioned above, CBD and other phytocannabinoids act on the endocannabinoid system to relieve the symptoms of LGS. Namely, CBD helps through its activity on the CB1 receptor. CB1 receptors are the most numerous receptors in the brain, more than all other receptors combined. Cannabinoid receptors are inhibitory in nature, so when they are activated, the activity of the cell in which they reside is reduced. THC directly activates these receptors, reducing the potential that a neuron will fire by inhibiting its cellular activity. This is also how it produces the high.
CBD works by negatively modulating cannabinoid receptors. At first, this may seem confusing: wouldn’t that INCREASE the activity of the cell rather than decreasing it?!
Well, yes, sort of.
At first, CBD inhibits the inhibitory receptor: this is the biological equivalent of a double negative, 1dis – 2inhibiting the activity of the cell in which the CB1 receptor is located. However, the body’s natural response to negative activity is to compensate with positive feedback: in the presence of CBD, the brain actually creates MORE of the inhibitory CB1 receptors. This produces the end net result of raising the excitatory threshold of neurons, by increasing their resting level of inhibition (resting inhibition is correlated to the quantity of cannabinoid receptors).
In essence, CBD indirectly increases the natural process by which your brain inhibits unwanted activity like seizures: the endocannabinoid system (ECS). By increasing the inhibitory presence of the ECS, CBD increases the threshold amount of excitation required to elicit a neuronal response.
Similarly, THC in tandem with CBD is an even more potent anti-epileptic remedy. This makes sense, because CBD increases the amount of CB1 receptors available for THC to activate, thereby inhibiting neuronal activity more than it would have without the presence of CBD. THC takes advantage of the effect of CBD to increase the expression of CB1 receptors. This is an example of the entourage effect in action.