Group 5 When we first met Alexis Bortell, she was just 11 years-old and had gone 866 days seizure-free thanks to the help of cannabis. Alexis suffers from Lennox-Gastaut syndrome, a rare, treatment-resistant form of epilepsy. She is now 12, and has already gone through with a lawsuit against Jeff Sessions earlier this year, where she and her co-plaintiffs – Sebastian & Jagger Cotte, Jose Bellen, Marvin Washington and the Cannabis Cultural Association – attempted to challenge the constitutionality of the Controlled Substances Act (CSA). Needless to say, the lawsuit was unsuccessful, with Judge Alvin Hellerstein rejecting the suit based on precedent, although it should be stated that he wasn’t unsympathetic to the plaintiffs’ plight. We don’t think Alexis and co. have given up, and they seem keen on challenging Judge Hellerstein’s decision. Whether they’ll ever be successful in actually winning their case and actually get some compensation for their struggles seems unlikely, but doing so certainly acts as a symbol for cannabis advocates everywhere. After all, isn’t the government essentially telling sick people, “We know cannabis is helping you and that the logic behind putting cannabis in the Schedule I category of the CSA is not really based on actual science, we’re going to keep it there anyway”? The science behind it is exactly where the rub comes regarding this issue. The endocannabinoid system (ECS) definitely exists. Learning how to maintain and control it could help us treat a huge number of conditions, and the correspondingly huge number of compounds available in the cannabis plant could help us make medications to deal with these health problems. Moreover, the medications could be far safer and more tolerable than many existing pharmaceutical medications out there. This is certainly the case for many epilepsy sufferers like Alexis, where current treatments would essentially leave them home- and/or hospital- bound. To make matters even more nonsensical, there are already cannabinoid- based medications available in the US that are under Schedule II and III of the CSA, namely marinol and dronabinol – synthetic versions of THC. As we write this, the naturally-derived, cannabidiol- (CBD-) based Epidiolex is undergoing phase III trials for approval by the Food and Drug Administration (FDA). In the meantime, many people across the U.S. and the world who use naturally-derived cannabinoids from the actual cannabis plant are considered to be breaking the law. The question Alexis and so many others are rightfully asking is “How does this make any rational sense?” In such instances, it is probably wise to inject a little rationality into the discussion. So, with this in mind, we shall tell you a little more about two rare, treatment-resistant forms of epilepsy (LGS and Dravet syndrome), and give some reasons as to why cannabis helps people who suffer from epilepsy … Lennox-Gastaut Syndrome (LGS) Slow spike wave of someone with Lennox-Gastaut syndrome (LGS). Lennox-Gastaut syndrome usually starts between the ages of 3-5, although it does develop in adolescence on occasion as well. There are also parallels with another type of epilepsy, West syndrome, with about 20% of West syndrome sufferers going on to develop LGS. This suggests that there is a connection between certain kinds of epilepsy. With LGS, nocturnal tonic seizures – the sudden stiffening and contraction of muscles – are the most common. Brief, shock-like, but sometimes consistent and painful jerks – myoclonic seizures – are also common, and are often bought about by fatigue and tiredness. Approximately 15 in every 100,000 people suffer from LGS. That’s around 5 – 10% of all epileptic patients, and around 1 – 2% of all childhood epilepsies. Extreme fatigue, apathy, dizziness, concentration problems, blackouts, chronic headaches, loss of balance, and slowed/impaired psycho-motor development and behavior are other side-effects of epilepsy, not to mention the pain of constantly-seizing muscles. LGS is also characterized by an electroencephalogram (EEG) pattern of less than 2.5 Hz slow spike wave activity. LGS can be caused by a lack of oxygen during birth, severe brain injuries that occurred during pregnancy or birth, contracting a brain infection such as meningitis or encephalitis, dysplasia (when nerve fibers in the brain don’t line up properly when they are developing in the womb), and the formation of non-cancerous tumors throughout the body and brain (tuberous sclerosis). Cannabis fractal art by 7th Dwarf. https://pixabay.com/en/fractal-chaos-marijuana-cannabis-1224923/ Severe myoclonic epilepsy of infancy (SMEI, aka Dravet Syndrome) Dravet syndrome affects around 1 in every 19,000 people. Dravet syndrome tends to affect children as young as 6 – 10 months old, and is thought to be caused by a mutation in the SCN1A and SCN2A genes. Both genes are responsible for providing the instructions for the transport of positively-charged sodium ions into cells, playing an important role in generating and transmitting electrical signals. This is sometimes referred to as “sodium channelopathy”. Mutations in the SCN2A gene are also implicated in conditions such as autism. However, not every Dravet syndrome patient has an SCN1A gene mutation, which is implicated in about 4 out of 5 cases of Dravet. For the other approximately 20 – 21%, Dravet may be caused by mutations in other genes like FEB1, FEB2, FEB4, PCDH19 and GABAA. Severe brain injuries at birth may also be implicated in the development of Dravet, although having a family history seems to be the most common indicator of the likelihood of developing Dravet. Dravet syndrome affects approximately 1 in every 20,000 – 40,000 people, representing about 7% of all childhood epilepsies developed before the age of 3. Dravet syndrome is one of the most severe types of epilepsy, and it’s not uncommon to get hundreds of seizures a day. Common symptoms of Dravet syndrome are quite similar to LGS, although seizures may be induced when the child has a high body temperature (fever). Tonic-clonic seizures (loss of consciousness followed by stiffening muscles and jerky movements), myoclonic seizures (brief jerks in the upper body) and absence seizures (sudden loss of consciousness and staring) are all common types of seizure with Dravet syndrome. Dravet sufferers may also have photosensitive epilepsy, where seizures are triggered by viewing bright, bold, repetitive patterns. Why Does Cannabis Potentially Help Epilepsy Sufferers? Most kinds of epilepsy seem to be caused by a mutation in the SCN1A gene. Cannabinoids, in particular CBD, have shown particular promise in helping prevent the occurrence of seizures. Cannabidavirin (CBDV) has also shown some efficacy in animal models. There could be a several key reasons as to why cannabinoids such as CBD and CBDV work for epilepsy, including: CBD and CBDV exert an influence on sodium channels, with CBD blocking sodium channels when in high concentrations, and and can antagonize both CB1 and CB2 receptors, suggesting it has anticonvulsant properties. Although CBD seems to have a weak affinity to CB1 and CB2 receptors, but acts on them indirectly and exerts influence on serotonergic, vanilloid and norepinephrine receptors. CBD also acts as an anti-inflammatory, as “cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses.” CBD affects the vanilloid receptors. The vanilloid receptor is also sometimes called the TRPV1 receptor, and is responsible for the detection of pain and heat, and regulates body temperature. CBD may desensitize the TRPV1 receptor, thereby reducing neuronal excitability. Many people who suffer from epilepsy may have mutations in the liver enzyme cytochrome P450 (CYP450), CYP2C9, CYP3A, CYP2C19, and CYP2D6, which are all enzymes that are responsible for the metabolism of many anti-epileptic drugs (AEDs) like Clobazam. Due to these malformations, many children with certain types of epilepsy may be being prescribed benzodiazepine- and barbiturate- based AEDs that might not even work for them. Many AEDs are also inhibitors of these kinds of enzymes. CBD also inhibits these enzymes. Using CBD may experience a doubling of the concentration of another anticonvulsant due to inhibition of these enzymes. CBD can therefore be said to interact negatively with AEDs. Epilepsy sufferers can get a cannabinoid that’s much safer and more well-tolerated in CBD. Many AEDs have nasty side-effects such as addiction, constant drowziness, nausea, headache, vomiting, fatigue, blurred vision, tremors and death-via-overdose. There are many other cannabinoids that act as an anticonvulsant as well. Cannabidivarin (CBDV) is one such example of this, and alongside CBD can work to regulate excitatory neurotransmitter release via modulation of calcium, as well as adenosine, glycine and serotonin receptors. Cannabidiolic acid (CBDa) – the non-decarboxylated, acidic form of CBD – is another potentially important cannabinoid for the treatment of epilepsy. Do not think that tetrahydrocannabinol (THC) doesn’t have its uses for epilepsy. Small amounts of THC can help the CBD do a better job via the entourage effect. THC may also act as a painkiller and, as it does with many other neurological conditions, help overcome muscle stiffness. Moreover, some THC may also help wean a patient off other, more damaging drugs. Jason David talks about this in this interview here. So, the science behind cannabis’ efficacy for epilepsy is pretty much laid out. Can the lawmakers continually choose to avoid it, at the expense of so many people? CBD has been singled out as one of the key compounds of cannabis with medical benefits. Are There Any Potential Negatives? As with all medications, cannabinoid-and-terpenoid-based formulas may not be suitable for everyone, or certain ones may prove positive whilst other prove negative. Due to the general lack of placebo-controlled and double-blind trials, many treat the idea of CBD as a potential AED with some degree of skepticism. Now, although some amount of THC may help CBD work better, some people with epilepsy may not tolerate higher doses of THC so well. For this reason, many products made with epileptics in mind tend to have high concentrations of CBD, in CBD:THC ratios of 20:1 or more. Those thinking of using hemp-based CBD to treat epilepsy should be wary – they do not often contain the amount of CBD needed for a serious condition such as epilepsy, and these products are often badly made. Also, it is worth remembering that hemp is an industrial plant, made to grow fiber. They will not likely be safe enough or have the right cannabinoids to treat you. Using cannabinoids derived from well-grown, tested non-industrial Cannabis sativa plants where the focus is on flower rather than stalk is likely to be several orders of magnitude better. On this matter, there are dispensaries like Jayden’s Journey and companies like Aunt Zelda’s doing some excellent work, and who seem to take the term “medical marijuana” or “medical cannabis” seriously. Anything Else?There is lots of information on the Leafwellwebsite regarding the potential therapeutic uses of the cannabinoids and terpenoids found in cannabis. We try to keep as up-to-date as we can regarding the science and research, and we highly recommend looking through it in order to grasp what we’re all about.