Notice: I am not a doctor and this is not at all a medical or other advice, just a summary of my personal understanding of the topic.
Cannabis remains highly controversial in some jurisdictions, but there has been huge advances forward across the globe with legalizations, medical usage and actual prescription drugs being approved. Regardless the number of official pre-clinical work remain scarce and despite the positive outcomes clinical trials are very limited.
Article Content:
Overview and Conclusion (personal recommendation)
THC (and CBG)
CBD
Formulations
Applications
Dosage
Bioavailability
Half-life
There are many types (over 113) of cannabinoids but we will stick with the most common CBD and THC categories from the hemp plant There have been movies/documentaries like "Weed the People" and Cannabis v.s Cancer making strong claims without clinical or peer-reviewed data to separate the hopes of a magical cure from statistically verifiable facts by experts (not governments that might not care or have other agendas)
Cannabinoids are used in medicine, there are indeed a number of pre-clinical studies showing the cannabinoids can kill cancer cells (but many people will say that in the lab almost anything, in high enough contrition, will kill cells: the question is can those concentrations be delivered effectively/safely to a specific part of the brain. Note all cannabinoids have be shown to cross the BBB (Blood Brain Barrier) very effectively.
My take based on what I've seen and heard (most of the details are listed below): one could use CBD+CBG (not THC for kids), use a Nano-emulsion (water soluble) formulation sublingually (I find the sprays being the best (Reliable/reputable Nano formulations are hard to find and the taste might be to strong for kids). Dosage 5mg/kg (as noted in forums by various DIPG researchers and families) and up to 25mg/kg but may experts are shocked as this being too high: see the Dosage section below. There are no clear study/results or guidelines for dosage unfortunately . And treat cannabinoids as an add-on and never a primary therapy.
So the question should not be how many mg of cannabinoids you take, but how are you taking it, what formulation (Nano/water-soulable vs. not (ex. oil)) and do you trust the producer to finally arrive at the amount of bioavailable cannabinoids of your choice.
2. THC & CBG Summary: My understanding is that there is little to no pre-clinical or clinical data that THC could be applicable at required dosage to target cancer cells especially in kids with DIPG / DMG (outside of palliative care). None of the experts that I have chatted to* have had any strong conviction for THC usage for DIPG specifically given the psychoactive (high) effect. (*note there is a clinical trial using THC-CBD combination during radiation). Although CBG has been considered as a good replacement to THC in this 2021 publication: (I know I said we will not add other Cannabinoids, but I promise it is just this one). "CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. ... We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy." A good video with research and dosage at the end: https://www.youtube.com/watch?v=I431p3upEZ8. Anther publication supporting CBG: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409346/
*Another data point listing use of THC as curative in pediatric cases is based on "Sativex Oromucosal Spray": the only official prescription drug with THC + CBD (almost equal concentrations) that is being trialed (NCT05629702 Age 16+ !) for DIPG / DMG, until we get some results we should consider the drug's label for pediatric population: "Sativex is not recommended for use in children or adolescents below 18 years of age. A randomised placebo-controlled trial was performed in children and adolescents with cerebral palsy or traumatic central nervous system injury and its results regarding efficacy were negative."
3. CBD Summary: CBD on the other side had some pre-clinical work showing CBD killing cancerous cells, but in high concentration. see below a list of references and sources highlighting results and mechanism of action.
The Big Question remains: CBD seems that it could help, maybe not as a main therapoy but as an add-on for now. But How and How much should we giving to our little warriers?
4. Formulations: There are many types inhalators, oils, tinctures, paste, gummies, drinks spray ... As well as formulation Nano formulation being one of the newest. I will not discuss the carious tastes as they can vary a lot.
Ref: https://nutraceuticalbusinessreview.com/news/article_page/Nano_CBD_Cannabidiol_made_with_the_human_body_in_mind/187775
Water-soluble formulations are interesting and studies have shown 4.5x higher bioavailability.
5. Applications: here I ma just listing the types as they are self explanatory and there are many other variation of each. Do comment if you need more details here.
Inhalation
Ingestion (eat/swallow): with/after meals (fatty) for higher (allegedly 3-5 times) bioavailability
Sublingually (under the tongue)
Oral Spray
Nasal Spray (few commercial formulations outside of targeting runny-nose)
Topically (rubbed into the skin or patches)
Rectally (saw this somewhere, but have not investigated it further)
6. Dosage: this is where it gets even more complex as we have to do some math to figure out what amount of CBD or THC we are giving, per weight (kilogram/pounds) of the patient, and then go further to calculate the bioavailability (how much will actually reach the tumor). The good thing is that both CBD and THC are molecules known to pass the BBB (Blood Brain Barrier) but we need to know how much end-up there: this is where amount, concentration, formulation and type of delivery matters. Best research: https://pubmed.ncbi.nlm.nih.gov/35605606/
Concentration of what we get: 6%, 10%, 25% ... (the rest could be anything to keep the form, shape of the product). This is usually very different for CBD and THC depending on the product.
From "Sativex Oromucosal Spray": the NCT05629702 trial it is recommended max 12 sprays per day or about 32.5 mg of THC and 30 mg of CBD per day.
Specific research for DIPG/DMG shows dosage of 15 and 25mg/kg https://pubmed.ncbi.nlm.nih.gov/35605606/
Frobes Health had this table on CBD dosage:
See their article here for the reference inks: https://www.forbes.com/health/body/cbd-dosage/
A recommended curative dose for CBD, was reported in one of the Research DIPG groups: "For the CBD we increased by 10 mg every 3 days. The final recommended dose for DIPG is 5mg/kg/day of CBD" the source was reported as "Dr. Koschmann a specialist of DIPG", which have not independently verified.
!!! There is no good data of how much CBD is too much an article with some good references: https://www.openaccessgovernment.org/take-too-much-cbd/71920/
7 Bioavailability
A good summary is: "In some CBD products, most of the CBD you consume will be destroyed before it reaches your bloodstream. How much survives for your body to utilise, is known as bioavailability. Bioavailability can be increased or decreased depending on how you take it.
The source has more detailed explanations if you want to understand that further and this chart they gave is useful although not at all cited but directionally correct and aligned with other sources:
* Few commercial products (targeting therapeutic CBD-to-brain delivery) or human-trials were found. Examples with 2mg CBD/spray marketed as sinus-relief mainly.
In NCT03877991 it is claimed "Although a therapeutic rational for the use of CBD has been demonstrated, an optimal oral dosage form to deliver this compound is not available yet. Oral administration is challenging because of CBD's poor solubility and extensive first pass metabolism, leading to an oral bioavailability of approximately 6%." and thus they try "advanced self-emulsifying drug delivery system" The Nano formulations mentioned above is trying to achieve the same thing.
Another good reference and read is this site (no citations there though!): https://www.canatura.com/en/bioavailability-of-cbd-what-does-it-mean-and-why-is-it-important#:~:text=The%20absorption%20of%20CBD%20is,and%20seeds%20are%20good%20helpers.
6 Half-life
The Half-life, or how long before 1/2 of the bioavailable cannabidiol disappears from your body" in the blood with oral consumption is 1-2 days. Another summary/review of 792 articles highlight the half-life af cannabidiol as:
"between 1.4 and 10.9 h after oromucosal spray"
"2–5 days after chronic oral administration"
"24 h after i.v."
"31 h after smoking"
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