THC blocks the process that starts a seizure and even at a low dose, the effects last 7 weeks.
Seizures are associated with hyperexcitability of neurons in the area of the brain called the hippocampus. The exact mechanisms and neurotransmitters involved in starting this hyperexcitability are a topic of intense investigation, and it looks like TRPV1 is a culprit. This is important in relation to cannabis medicine because activating the CB1 receptor, via THC, closes the TRPV1 ion channel. Cannabinoids activate the CB1 receptor. And THIS action reduces neuronal excitement, therefore stopping or preventing the seizure.
How Does TRPV1 Activation Lead to a Seizure?
Researchers have recently publishing data showing the interplay between TRPV1 and CB1 activation, and another neurotransmitter, nitric oxide. They performed the studies in vivo on anesthetized rats with a synthetic THC compound.
When TRPV1 is activated, its ion channels open, allowing calcium ions into the neuron. The excess calcium causes nitric oxide to be produced and this leads to hyperexcitability of neurons and then seizure.
Activation of CB1 receptor with a THC-like compound prevented opening of TRPV1 channel and stopped the whole process in its tracks. This data is in line with previously published study showing that CB1 mediated inhibition of NO production was protective against neurotoxicity.
How Much THC Do You Need to Stop a Seizure?
Another important question arises regarding the dose of THC that would be beneficial. A group of researchers have recently highlighted that the therapeutic window of THC may actually be a very low dose. They injected 0.002mg/kg of THC into mice that sustained different kinds of neuronal insults: seizures, carbon monoxide-induced hypoxia, ecstasy-induced neurotoxicity; and monitored the potential for neuroprotection by THC.
A single dose of THC administered either 1-7 days before, or 1-7 days after the insult, was found to be neuroprotective for at least 7 weeks. This was confirmed by biochemical analysis of the hippocampus, where relevant proteins were found to be elevated or modified (brain derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase), and these changes have been characterized as hallmark of neuroprotection .
THC Also Has Brain Benefits in Old Mice
Most recently, these researchers tested whether similar neuroplastic changes are observed in the hippocampus in brains of old mice. Indeed, they found that the same single application of THC at 0.002 mg/kg increased the level of a protein called Sirtuin1 in the hippocampus, which has been shown to be involved in memory formation, learning capability, neuronal development and neuronal protection.
Furthermore, they found that the volume of several brain regions, including the posterior hippocampus was increased by 13-24% after treatment with THC.
THC in higher doses has already been approved for medical treatments in humans (dronabinol 1-10mg), but it remains to be determined whether humans have a similar response to THC treatment.
It is nevertheless promising that THC-mediated activation of CB1 has been shown in pre-clinical setting to reverse neuronal hyperexcitability, and that interrogation of this cellular pathway with TRPV1 and NO will likely move the therapeutics field forward. It is likely that future seizure treatment will recommend THC.