CANNABIS CULTURE – “What about the children. Oh, why won’t anyone think about the children?”

A common refrain amongst opponents of cannabis legalization. However, opponents of cannabis legalization didn’t bank on the idea that the pro-legalization side would actually start thinking about the children. So now, here we are, talking about cannabis and its potential as pediatric medicine. In fact, cannabis is very much a frontier medicine when it comes to pediatrics, and for very good reason.

We have spoken to many different people, and we still speak to many people, who have used cannabinoid- and terpenoid- based medications to help treat themselves, their child’s, or another child’s condition. Alexis Bortell, Jason David, Amy Berliner, Mara Gordon … Honestly, we could reel off names all day, and these are just some of the more prominent stories. People write in to us with some rather harrowing stories of their children going through some rather nasty conditions, and finding that cannabis (and sometimes one of the only things) that helps treat them. And yes, we here at Doctor Frank have written recommendations for kids’ medical marijuana cards.

Sadly, this realization often only comes after all other avenues have been exhausted and parents were at the end of their tether, looking for any way they can treat their child. However, things are changing, and more and more people are starting to treat cannabis more as a second or even first resort to either a) treat their condition and/or b) use cannabis to treat the side-effects of other treatment modalities.

The reasoning behind this is quite simple, and it is one of the main reasons why cannabis is being treated so seriously as a potential medication for children. In comparison to other medications, cannabis is comparatively safe. The minimum lethal dose is extremely high, almost to the point that overdose on cannabis alone is a theoretical possibility rather than an actual one. Cannabis isn’t anywhere near as addictive or damaging as the benzodiazepines, barbiturates, super-powerful nonsteroidal anti-inflammatory drugs (NSAIDs) and yes, even the opioids that are often prescribed by doctors to kids with serious conditions.

Targeting the endocannabinoid system (ECS) rather than the body’s dopamine, norepinephrine, gamma-Aminobutyric acid (GABA), opioid peptide, epinephrine, glutamate and/or serotonergic receptors. Eagle-eyed readers will notice that the ECS seems to play a role in regulating three particular types of receptor groups/categories, whether directly or indirectly: amino acids, monoamines and peptides. More research needs to be done in order to see how cannabinoids affect other types of receptor (including immune response), but it seems overall that the ECS plays a significant part in homeostasis.

Furthermore, learning how to manipulate the ECS, as well as learning when there might be a deficiency or overabundance of cannabinoids, might be one of the safest ways of keeping a person’s body in homeostasis. Keeping the body’s physiological processes in balance is of utmost importance to any healthcare practitioner, as this means that no particular system within the human body is over- or under-stretched, and any conditions become easier to treat and beat. In turn, this will lead to a better and healthier quality of life overall, even after any illness or disease is beaten or kept under control.

Anyway, there are two particular conditions that seem to bring children to cannabinoid-based medications more than any other: epilepsy and cancer. Let’s take a look at why cannabis could be used to help treat these conditions …

Epilepsy

There are several types of childhood epilepsy, some more rare than others. Generally, their symptoms are similar, but some types of epilepsy may be more severe than others. Symptoms include uncontrollable jerking of the arms and legs, loss of consciousness, difficulty concentrating, confusion, staring spells, difficulty speaking/slurred speech, photosensitivity, migraine, body aches and pains due to seizures, fevers, and depression/anxiety.

Other than the symptoms, epilepsy is usually diagnosed with an electroencephalogram (EEG), which picks up and records patterns of electrical activity in the brain. Learning and/or behavioral difficulties are also common in children with epilepsy. The more severe types of childhood epilepsy may require the use of antiepileptic drugs (AEDs, and also known as anticonvulsant or anti-seizure drugs) such as acetazolamide, clobazam, topiramate, gabapentin, phenytoin, sodium valproate and many others. They are usually used to block sodium channels or enhance GABA function.

Current AEDs have many problems. Enhancing GABA function can increase the amount of glutamate, thereby increasing the chances of negative neurological problems and brain damage. Children who have been taking AEDs for too long also show reductions in IQ over time. Many AEDs are also barbiturate- or benzodiazepine- based, meaning they have several undesirable side-effects such as “brain fog”, constants sleepiness/tiredness, problems with mood regulation, addiction and, in some cases, they can increase convulsions – the right AED needs to be used for different types of epilepsy. In fact, the risk:benefit ratio of these drugs is quite the problem, and could include devastating neurological sequelae secondary to seizure or even death.

The types of childhood epilepsy are:

Benign rolandic epilepsy (BRE) – Makes up around 15% of cases of children with epilepsy. Starts at any age between 3 and 10 years old. Most children with BRE have very few seizures, and most become seizure-free by the age of 16. Children with BRE often suffer from “simple focal/partial seizures”, meaning they get localized seizures, usually starting at night and beginning with a tingling feeling in the mouth, followed by gurgling, dribbling and grunting. Speech can be temporarily affected, and may develop into a tonic-clonic seizure (a seizure that affects the entire brain). AEDs are not always used for BRE, but may be on occasion.

Childhood absence epilepsy (CAE) – Usually starts at between ages 4 and 10, and affects 12% of those with epilepsy. CAE usually goes unnoticed due to seizures lasting only a few seconds. However, seizures may be frequent, and during a seizure a child may go unconscious and “blank out” or stare. Their eyelids will also often flutter, and they may not respond to what’s going on around them, or they may not be aware of what they are doing. Up to 90% of those with CAE will grow out of it by the age of 12, and AEDs are generally quite successful in treating CAE.

Juvenile myoclonic epilepsy (JME) – Usually starts between ages 12 and 18. Three different types of seizure are implicated with JME:

• Tonic-clonic seizures – loss of consciousness followed by stiffening muscles and jerky movements.
• Myoclonic seizures – brief muscle jerks in the upper body.
• Absence seizures – brief loss of consciousness and staring.

Seizures usually occur after waking up. Fatigue, stress and alcohol can trigger seizures. Around 40% of those with JME also suffer from photosensitive epilepsy (seizures that arise after seeing regular patterns in time or space, in particular flashing lights and bright and bold patterns).

Severe myoclonic epilepsy of infancy (SMEI, aka Dravet Syndrome) – Affects about 1 in every 19,000 people. Dravet syndrome is similar to JME in many respects (such as symptomatology), except that the seizures can begin very early in childhood – around 6 – 10 months old. A genetic abnormality is thought to be the main cause of Dravet Syndrome, specifically the mutation of the SCN1A gene. The SCN1A gene is responsible for providing the instructions for the transport of positively-charged sodium ions into cells and plays an important role in generating and transmitting electrical signals. Dravet syndrome is very resistant to AED treatment.

Infantile spasms (West Syndrome) – Often affects children who have had a previous brain injury or who suffered from pre-natal conditions such as hydrocephalus. Often begins in the first year of life, and spasms tend to occur in “clusters” made up of 10-100 individual spasms. AEDs and steroids are used to treat West Syndrome, but are ineffective in about 25% of cases. Many who have West Syndrome develop Lennox-Gastaut Syndrome (LGS).

Lennox-Gastaut Syndrome (LGS) – Usually starts between the ages of 3 and 5, with West syndrome often preceding LGS. Sometimes, LGS starts in adolescence. Several different types of seizure are possible with LGS, including tonic (sudden stiffening of muscles), atonic (sudden relaxation of muscles), myoclonic, tonic-clonic and atypical absences. Learning difficulties and behavioral problems are common with LGS, and it does not respond well to AEDs.

Non-drug treatment methods include vagus nerve stimulation (VNS – a pulse generator placed inside the body and connected to the vagus nerve) and the ketogenic diet (a high fat, adequate protein and low carbohydrate diet). Those with LGS often suffer from epilepsy well into adult life.

So why does cannabis help with childhood epilepsy? Well, as you can see, AEDs are not effective for all types of epilepsy, and many of them carry substantial risks. Using the wrong one could also increase the likelihood of seizures, and brain damage/death is taken off the table. Addiction is also another huge problem, and weaning a child off of these drugs can prove not only painful, but may also result in “rebound seizures” due to the stress of withdrawal.

When you look at most cannabinoid-based medications for childhood epilepsy, you’ll find that they’re usually high in cannabidiol (CBD), with low amounts of THC. The profile will be something like a CBD:THC ratio of 20:1. Now, this is not only because of the psychoactive effects of THC, but also because CBD works on the transient receptor potential cation channel subfamily V member 1 (TRPV1), aka capsaicin receptor or the vanilloid receptor. TRPV1 is a protein that is encoded by the TRPV1 gene, and is responsible for the detection and regulation of body temperature. TRPV1 is a calcium-permeable channel. It is thought that at least some types of epilepsy is caused by an overstimulation of the TRPV1 protein.

The TRPV1 receptor is responsible for mediating the effects of CBD, and using CBD can “desensitize” the protein via “flooding” the receptor. THC also has antiseizure properties, but in approximately 10% of people may actually induce seizures if taken in too high an amount. For this reason, the amount of THC is kept comparatively low in cannabinoid-based tinctures and sprays usually made with epilepsy in mind. However, in comparison to AEDs, CBD is a far safer alternative, and many would argue far more effective, too.

The precise mechanism of how CBD works to treat epilepsy still needs research, but the real-life results are there to see. CBD can also act as an anti-inflammatory, and small amounts of THC helps the CBD enter cells more effectively. This gives cannabinoid-based treatment for epilepsy a multi-pronged use.Cannabinoid-based medications could therefore be used to potentially replace numerous AEDs, and be far safer, more effective and less addictive to boot. CBD could very well be the epilepsy medication of the future, so it’s no wonder companies like GW Pharmaceuticals are developing medications like Epidiolex.

Cancer

Cancer is one of those things that strikes fear into the heart of many people, perhaps due to the fact that there is no known “cure”, per sé. So far, our best efforts are a mixture of chemotherapy, radiation therapy and surgery. Though some cancers react better to treatment than others, the likelihood of getting cancer increases once a person has had it. Cancers have a tendency to spread and affect other organs once it’s developed in one part of the body.

Almost everyone the world over has likely known someone affected by cancer and, like every life-threatening condition, it feels particularly heart-wrenching when a child is diagnosed with it. Seeing anyone go through the bone and joint pain, fever, fatigue, headache, nausea, drastic weight loss, vomiting & nausea, bleeding and bruising that comes with pretty much any kind of cancer is tough enough, let alone a child. Add to this the constant surgeries and the side-effects of chemo- and radiation- therapy (often as bad as the cancer itself), and you have a very bad and painful situation on your hands.

One of the main difficulties in finding a “cure” for cancer is the fact that there are so many different types of it. In children, the most common types of cancer are leukemia (approx 30% of all cancers in children), brain and spinal tumors (26%), neuroblastomas (6%), Wilms tumor (5%), Hodgkin lymphoma (3%), Non-Hodgkin lymphoma (5%), Rhabdomyosarcoma (3%), Retinoblastoma (2%) and bone cancers (3%). Just as with other treatment methods, cannabis reacts to specific cancers in markedly different ways. Though a lot more research needs to be done, it does seem that different cannabinoid-terpenoid profiles have different effects on different types of cancer. Cannabinoids and terpenoids seem to work by inhibiting the growth of tumors or causing them to “explode”.Another advantage of using cannabinoid-based treatments is that they can help prevent or reduce the need for opioids in managing pain. On top of this, the appetite-stimulating effects of cannabis can help prevent drastic weight loss caused by both the cancer and the chemotherapy. Cannabinoid-based treatments therefore act as a potential “multi-pronged” medication for cancer treatment, to be utilized alongside the traditional radiation and chemotherapy. This is because cannabinoids have not only anticancer properties of their own, but can be used to treat the side-effects of other treatment modalities. On top of this, CBD may help protect against some of the damage caused by radiation therapy.

There is some hope that cannabis may well be a cure, if not the cure. There are various cannabinoids that been have shown to have antiproliferative effects on many types of tumor cell lines, including breast, prostate, skin, bone, thyroid and neural. The main issue here is that most research is done in vivo or in vitro in the lab, or in animal studies. Most other data out there is anecdotal, and it will remain this way due to cannabis’s class I scheduling. This is not to say that there are absolutely no studies in other parts of the world coming out, though, as is the case with GW Pharmaceuticals’ study on cancer (specifically, gliomas).

So what does this all mean, taken together? Essentially, it means that, in order to use cannabinoid-based treatment methods for any type of cancer effectively, they must be tailored to both the individual’s ECS as well as the type of cancer they are suffering from. Getting the correct ratio of THC:CBD is of utmost importance, and it’s similarly important to remember that terpenoids like pinene and limonene have their antitumor properties as well. The method of ingestion is also important – high quality tinctures, transdermal patches, topicals and suppositories are probably best, as it’s ideal to make cannabinoids as bioavailable as possible, in as safe a manner is possible.

The reason all this is critically important? Using cannabinoid-based treatments may increase tumor growth and allow cancer cells to proliferate, as well as inhibit them (or indeed, have no effect overall whatsoever). In some instances, cannabinoid treatment may lead to an increase in cancer cell count, followed by a decrease. In other words, treatment needs to match the classification.

Dr. Bonni Goldstein, who specializes in pediatric medicine, has written about using cannabinoid-based treatments for children. To quote:

“Cannabis treatment for children with cancer remains controversial, however, in cases of treatment-resistant cancers and severe side effects from treatment, cannabis must be a readily available option, especially since it is significantly less toxic than most cancer treatments.  In addition to the antitumor effects, cannabis can enhance the effects of some chemotherapy while making the adverse effects tolerable. In my experience, I have seen patient survival extended.  We must be careful with claims of “cancer cure” but if cannabis can be rescheduled from Schedule I to Schedule II, researchers can finally find the desperately needed answers and save many lives.”

Are There Any Negatives?

Just as with any medication, there are potential negatives with using cannabis. We’ve already mentioned some of them above in (i.e. the wrong cannabinoid profile might help cancer cells proliferate, or using too much THC may induce seizures in some people with epilepsy). However, just because there are some side-effects, it doesn’t mean that we should throw away cannabis as a potential medicine. We wouldn’t do that with any other medication that has the therapeutic range that cannabis has, so we certainly shouldn’t do it to cannabis itself!

After all, most if not all the drugs being used to treat cancer and epilepsy at the moment have many side-effects and cause far more long-term issues than cannabis. Frankly, when it comes to that all-important safety profile and Lethal Dose 50 (LD 50), cannabis comes out on top in comparison to many pharmaceutical-grade drugs. Yes, cannabinoids may cause some problems on a developing brain, but not necessarily more so than any other drug (and in some instances, perhaps substantially less so). Remember, giving a child strong opioids to overcome the pain caused by cancer is probably going to have far more severe and long-term effects than cannabis, on both the body and the mind!

The route and method of ingestion is obviously also very important, especially when it comes to children. Of course, smoking cannabis is not going to be the ideal way to ingest any medication, but there are some rather amazing tinctures and the like coming out, which are far more accessible – and likely safer – than the traditional methods of ingesting cannabis (even though tinctures are technically just as traditional as smoking).

Also, some scientists posit that the reason many conditions arise is because of a clinical endocannabinoid deficiency (CECD). Now, whilst cannabinoids may have different effects on people at different stages of their lives, this doesn’t mean that a child may also be suffering from a CECD, which in turn either causes other health problems to arise, or at least acts as a factor contributing to the likelihood of an illness developing. Therefore, overcoming a deficiency is just putting the body back into homeostasis, and is unlikely to cause any long-lasting damage if the dosage and profile is properly measured in the first instance. However, this is all theory at the moment, so take all this with a pinch of salt!

Overall?

The safety profile and therapeutic range of cannabinoid-based medications makes it potentially one of the ideal medications for pediatric conditions. The idea that cannabis for kids seems controversial is almost laughable, when you compare it to other medications that are used. Yet, it is still somewhat controversial. Healthy skepticism should definitely be applied, and we should certainly treat cannabis as objectively as possible regarding the science; but we definitely shouldn’t throw the baby out with the bathwater.