Study after study shows that CBD is effective, but just how effective is THC when trying to stop a seizure? More than you might think.
As cannabis-based medicines make their way from “alternative” fringe medicine, into the realm of Food and Drug Administration (FDA)-approved therapies, the idea that you can stop a seizure with the CBD in cannabis is no longer controversial. However, lately scientists have been applying themselves to the question of how to stop a seizure with THC as well.
Patients who suffer from seizures aren’t only benefiting from CBD-based drugs. Full-spectrum products and specialized cannabinoid formulas containing THC are also showing unique promise for the treatment of epilepsy in the scientific research below. Yes, CBD is highly effective for the treatment of seizures, but how to stop a seizure might almost mean looking at THC as well.
Patients and physicians alike have long reported the anti-seizure activity of CBD’s intoxicating sister: THC. To date, there is only a trickle of studies examining THC, but these show promise. CBD has received more attention because it comes from hemp and is less controversial, but THC’s medicinal powers are worth a closer look.
The Biological Mechanisms of a Seizure
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. One theory about seizure activity examines the activity of the TRPV1 receptor. These receptors are found throughout the central nervous system and play a key role in the modulation of pain. 1)Nazıroglu, M. (2015). TRPV1 Channel: A Potential Drug Target for Treating Epilepsy. Current Neuropharmacology, 13(2), 239–247. doi: 10.2174/1570159×13666150216222543
Cannabinoids, and in particular THC, activate the CB1 receptor. The human brain contains concentrations of the CB1 receptor. Current studies indicate that when the CB1 receptor is activated, it turns off the TRPV1 ion channel. Once slowed down, the TRPV1 receptors trigger an associated reduction in neuron hyperexcitability and therefore, seizure activity.
If there was a way to activate the CB1 receptor, it might lead to a series of events, which eventually might reduce the frequency and severity of seizures. If THC binds to (and activates) the CB1 receptor, maybe the answer to the question “How to stop a seizure” is a little dose of THC?
How Does TRPV1 Activation Lead to a Seizure?
Researchers have recently published data showing the interplay between three things which produce seizure activity: TRPV1 activation, CB1 activation, and nitric oxide. They performed the studies in vivo on anesthetized rats with a synthetic THC compound. 2)Carletti, F., Gambino, G., Rizzo, V., Ferraro, G., & Sardo, P. (2017). Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on control of hippocampal hyperexcitability. Epilepsy Research, 138, 18–25. doi: 10.1016/j.eplepsyres.2017.09.018
When scientists activate the TRPV1 receptor, its ion channels open, allowing calcium ions into the neuron. The excess calcium produces nitric oxide, which leads to the hyperexcitability of neurons – and eventually seizures.
Moreover, activation of CB1 receptors with a THC-like compound (WIN 55,212) prevented the opening of the TRPV1 channel and stopped the whole process in its tracks. There has yet to be any research completed on how THC would impact this series of neurological events.
Current Studies on THC for Epilepsy
Yet, there are several hints in other studies about the value of THC in cannabis-based medicines for epilepsy. Tilray, a Canadian pharmaceutical and cannabis company, published “A prospective open‐label trial of a CBD/THC cannabis oil in dravet syndrome” in 2018. Their cannabis preparation contained 2 mg of THC for every 100 mg of CBD. In the study, pediatric participants received a maximum of 0.32 mg/kg a day of THC. 3)Mccoy, B., Wang, L., Zak, M., Al‐Mehmadi, S., Kabir, N., Alhadid, K., … Snead, O. C. (2018). A prospective open‐label trial of a CBD / THC cannabis oil in dravet syndrome. Annals of Clinical and Translational Neurology, 5(9), 1077–1088. doi: 10.1002/acn3.621
The results of the Tilray trial proved the ratio was safe and well-tolerated among pediatric patients. The study reported, “treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures.” A little bit of THC then, in combination with CBD, may improve the anti-seizure like effects of cannabis-based treatments.
How Much THC Would You Need to Stop a Seizure?
How much THC would be beneficial, and how much detrimental for the treatment of epilepsy and seizure disorders? THC, like all cannabinoids, demonstrates a strong dose-dependent response curve. That means the differences between a small dose and a large dose can be dramatic. For example, a small to medium amount for pain may help alleviate the symptoms, yet a large dose will exasperate them.
Further, as the Tilray study indicates, a little THC can go a long way. According to the Tilary, a maximum dose of 0.32 mg/kg/day (the mean dose was only 0.27 mg/kg/day of THC) was effective. Earlier work, using an animal model, supports the low dose of THC theory.
According to the authors of “Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation‐induced cognitive damage,” perhaps as little as 0.002mg/kg of THC could provide neuroprotection from neuroinflammatory conditions, like epilepsy. 4)Fishbein-Kaminietsky, M., Gafni, M., & Sarne, Y. (2014). Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation-induced cognitive damage. Journal of Neuroscience Research, 92(12), 1669–1677. doi: 10.1002/jnr.23452
Based on this study, a single dose of THC administered up to seven days before (or up to seven days after the insult), provided neuroprotection for up to seven weeks. Moreover, biochemical analysis of the hippocampus confirms this. In the analysis, relevant proteins were found to be elevated or modified (brain derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase). The researchers characterized these changes as hallmarks of neuroprotection.
The question of how to treat seizures with THC might be best determined at the individual patient level. But as a patient, you’ll want to work with a knowledgeable physician to experiment with dose size and cannabinoid profiles to achieve the most therapeutic benefit without adverse effects.
Going Beyond CBD for Treating Epilepsy
CBD remains the most popular option for patients treating seizure conditions, especially among parents treating their children’s illnesses. Scientists agree that it is safe, and people tolerate it well. Further, it seems to be effective for intractable forms of epilepsy. However, as THC expands into more “conventional” forms of medicine, it’s also getting attention for its anti-seizure characteristics.
We might just know more about CBD because it has been easier to study. In the past, federal drug scheduling and restrictive federal funding has prevented many THC-based studies. Now, social and political will is shifting. Research on how to stop a seizure is branching out into the world of THC, as the study from Tilray has demonstrated. Formulas containing minimal levels of THC could continue to earn more scientific attention, and more respect.
References [ + ]
|1.||↑||Nazıroglu, M. (2015). TRPV1 Channel: A Potential Drug Target for Treating Epilepsy. Current Neuropharmacology, 13(2), 239–247. doi: 10.2174/1570159×13666150216222543|
|2.||↑||Carletti, F., Gambino, G., Rizzo, V., Ferraro, G., & Sardo, P. (2017). Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on control of hippocampal hyperexcitability. Epilepsy Research, 138, 18–25. doi: 10.1016/j.eplepsyres.2017.09.018|
|3.||↑||Mccoy, B., Wang, L., Zak, M., Al‐Mehmadi, S., Kabir, N., Alhadid, K., … Snead, O. C. (2018). A prospective open‐label trial of a CBD / THC cannabis oil in dravet syndrome. Annals of Clinical and Translational Neurology, 5(9), 1077–1088. doi: 10.1002/acn3.621|
|4.||↑||Fishbein-Kaminietsky, M., Gafni, M., & Sarne, Y. (2014). Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation-induced cognitive damage. Journal of Neuroscience Research, 92(12), 1669–1677. doi: 10.1002/jnr.23452|