| Epilepsy – Cannabis Reduces Seizures according to research
If you or anyone you love has epilepsy you will have heard about the incredible benefits cannabis has had to reduce the number and severity of seizures. Charlotte Figi made cannabidiol (CBD)-dominant cannabis (Charlotte’s Web) famous and influenced governments everywhere to re-evaluate their laws prohibiting this natural therapy. Cannabis has in fact been used for hundreds, if not thousands of years, to control seizures as evidenced in ancient texts and in Dr. JR Reynolds essay written in 1861, entitled, Epilepsy: its symptoms, treatment, and relation to other chronic convulsive diseases. While we have a lot to learn about how cannabis improves seizure disorders researchers are getting closer to understanding the underlying mechanisms. Epilepsy is thought to affect at least 69 million persons worldwide (cdc.gov/epilepsy) impacting quality-of-life and potentially causing cognitive, psychological, and social impairments. Seizure disorders are commonly described as generalized or focal (affecting a local region in the brain) in nature but can be manifested in a variety of ways. Our modern pharmaceutical therapies are not always effective, leaving many people to live with drug-resistant epilepsy. For some people the drug therapies may work to control seizures but often cause side effects of drowsiness or make concentration difficult enough to be disabling. In other words, our available antiseizure drugs are not as effective or safe as they need to be. As healthcare providers we have no choice but to help our patients find another way to treat these types of difficult-to-treat disorders. The cannabis plant contains diverse phytocannabinoids, such as delta-9-tetrahydrocannabinl (THC) and cannabidiol (CBD), and terpenoids that act on the abundant cannabinoid G protein-coupled receptors (e.g. CB1, CB2, GPR55) and non-cannabinoid receptors, such as transient receptor potential, serotonin and glycine receptors (e.g. TRPV1, TRPV2, TRP1A,5-HT). Like our natural cannabinoids, called endocannabinoids, THC and CBD create homeostasis, or balance, throughout the human body. In the central nervous system (CNS) THC primarily actives CB1 receptors causing the neurons to reduce excitatory neurotransmitter release, such as glutamate. On the other hand, CBD has a low affinity for CB1 and CB2 receptors and exerts its effects at TRP receptors, T-type voltage-gated calcium channels, and G protein-coupled receptors (GPR55) to maintain balanced neurotransmission or to reduce neuronal hyperexcitability, or overstimulation. CBD restricts neuroinflammation, or inflammation of the brain, by reducing nitirc oxide (NO) and interleukin (IL)-beta, and by limiting glia cell activation, which is involved in brain scarring. CBD also works to increase the body’s own natural endocannabinoids (anandamide, 2-arichidonoylglycerol) to calm down an overexcited nervous system. A variety of factors, including the type of seizure disorder and natural endocannabinoid tone, or the natural day-to-day function of your endocannabinoid system (ECS), will determine whether cannabis will work for you. By far, the majority of human and animal studies show that both THC and CBD are effective in reducing the frequency or severity of seizures. In 34 animal studies CB1 receptor agonists (THC or THC-like analogues) produced an anticonvulsant effect in 68.1% of subjects, while 5.6% had no response, and 2.9% had increased seizure activity. It is important to note that none of the studies showed that CBD was a proconvulsant. While case studies in humans gives us some clues it doesn’t provide us with consistent guidelines to recommend any specific cannabis dosing with the many studies recommending CBD 100 mg to 800 mg daily. Phase 1 clinical trials of Epidiolex, a purely isolated CBD molecule, recommends patients start at 2.5 mg to 5 mg/Kg twice daily and increase to a maximum of 20 mg/Kg daily. Subjects of Epidiolex showed convulsive seizures were reduced compared to baseline by 51% recommending doses of 10 mg/Kg daily while Phase 3 studies found that 25 mg/Kg to 50 mg/Kg were safe with about 50% with improved seizure control. Importantly, these studies help us understand the effects of CBD compared to THC or whole plant cannabis therapy. While the benefits seen are encouraging the dose required may make it unpalatable or unaffordable. For example, a person weighing about 110 pounds may need 1,000 mg to 2,500 mg or 10 mLs to 25 mLs divided daily. Besides being difficult to swallow these very high doses of Epidiolex showed some adverse effects such as an increase in liver enzymes. Generally, studies have tended to use large doses of oral cannabis to produce an antiseizure effect. This might be because many antiseizure pharmaceutical drugs induce liver enzymes in the cytochrome P450 system making THC and CBD less bioavailable. For example, topiramate and oxcarbazepine are CYP 3A4 inducers which may make CBD and THC less effective. An increase in the isoenzyme CYP 3A4 upregulation means that a lot more cannabis oil has to be given to improve symptoms. This is significant because seizure disorder typically requires high doses of CBD to be effective. Since CBD is able to regulate the nervous system across several neuronal networks and pathways it makes sense to start with a CBD-dominant, low THC chemovar. I always recommend that my patients use cannabis derived from a whole plant so that it can work synergistically together so that less of each molecule is required to produce a positive effect. Most whole plant cannabis oils contain about 25 mg-50 mg/mL of CBD and less than 2 mg/mL of THC. Start with 0.25 mLs twice daily with a small fatty snack. For example, I recommend that patients eat a small fatty snack, like peanut butter or cheese and a cracker on an otherwise empty stomach. Hold the cannabis oil under the tongue for as long as is comfortable then swallow. For seizure disorders I recommend to increase your dose slowly over time every 1 to 2 weeks until you reach at least 1 mL twice daily providing (25 mg to 50 mg twice daily of CBD). You can safely increase the dose every 24 hours but is better to see what improvements occur overtime. Remember cannabis works by keeping one’s nervous system balanced and it may take time for the body to adjust to this new level of support. At the same time the entourage effect as explained and expanded by, Dr. Ethan Russo, describes how all of the cannabinoid molecules and terpenoids found in the whole plant work in harmony so that both THC and CBD are more effective and safer when taken together. With this body of research growing around the idea of an entourage effect, and with numerous studies showing that THC has antiseizure activity it is reasonable to suggest a 1:1 cannabis oil with a balanced amount of THC to CBD, usually about 10 mg of CBD and 10 mg of THC. If seizure activity has not improved with a CBD dominant cannabis oil consider adding a 1:1 cannabis oil to your protocol. Start with 0.25 mL twice daily with a small fatty snack and increase by 0.1 MLs to 0.2 mLs every 1 to 2 weeks and no more than every 24 hours. Keep a diary of how you took the cannabis (time of day, food eaten), and seizure frequency. Consistency and good journal keeping will help you and your doctor figure out the right THC to CBD ratio, terpene profile, or plant variety (e.g. Sativa versus Indica). Since our bodies are powerfully affected by cannabis affecting our natural endocannabinoid tone, reducing body and brain inflammation, and balancing neuronal over-excitation it is reasonable to expect that each person will need a unique dose and type of cannabis. This is why it is helpful to work with an experienced healthcare professional to receive a regulated cannabis product who can guide you to find the most effective and safe options. Consider speaking with one of our experienced physicians or pharmacists to see if this is right for you. References: |