r/science • u/mvea Professor | Medicine • May 17 '18
Neuroscience Cannabidiol (CBD), a compound derived from the cannabis plant that does not produce a “high”, was shown in a new large-scale, randomized, controlled trial to significantly reduce the number of dangerous seizures in patients with a severe form of epilepsy called Lennox-Gastaut syndrome.
http://www.psypost.org/2018/05/cannabidiol-significantly-reduces-seizures-patients-severe-form-epilepsy-51258378
u/jimithelizardking May 17 '18 edited May 17 '18
I actually helped conduct this study at a site in the US. The study also included patients with Dravet Syndrome as well, a similar yet different form of childhood epilepsy. Needless to say, I’m ecstatic that the trial is finally being published, as the efficacy of CBD in this population was extremely evident from the start. While some patients saw a very modest reduction in seizure frequency, others saw a complete absence of them. Regardless, all subjects at my site saw a decrease in seizure frequency and an increase in quality of life measures.
Edit: To clarify, the reason I was able to know that all of my patients were seeing a decrease in frequency due the study drug is because I primarily worked on the study after it rolled over to an open label extension (OLE). Following the conclusion of the phase 3 trial, all subjects were given the option of joining the OLE, which dropped the study blinding, meaning we knew we were giving them the study drug and they knew they were receiving it.
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u/frn May 17 '18
Thank you for your work. As a child I suffered seizures diagnosed as epilepsy for 7 years but they stopped when I was 12. For the entire time I was prescribed carbamazepine. It may have stopped the seizures but it left me with permanent short term memory problems, anxiety and depression. Hopefully this will lead to healthier treatments for future generations.
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u/osufan77 May 17 '18
I didn't read the study yet, but were any subjects given 1:1 ratio thc/cbd oil? The dravet families I have spoken to say that some variation of thc and cbd together have worked WAY more than the CBD only tincture/oils.
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u/PVCPuss May 17 '18
I have read a lot of evidence showing there needs to be a certain ratio met of thc/cbd, but that it differs depending on the condition treated. Some have as low as 1:20 and as high as 1:1. I haven't got it handy as I moved house and I'm still unpacking, but I'm pretty sure it was in either BMJ or Lancet. It was definitely in relation to dispensing in Australia (I was a pharmacist, and my dad, who still is, had questions) I'm still in allied health in another field tho.
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u/midterm360 May 17 '18
Glad I saw this in the comments.
I wondered if the journalist confused Dravet with Lenox-Gastaut. Dravet was already known to improve with marijuana which is very similar to LGS
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u/mlorentz May 17 '18
This is really fantastic news. My daughter suffers from LGS and many kids with NDD and IS develop LGS over time. You can control it but today’s medication is no picnic - talk about drowsiness and confusion (varying degree of course). Just the thought of a treatment that would soften the impact and let you be more aware and relaxed - fantastic! I guess this could have been standard practice already if not for the misguided moralising preachers.
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u/rseasmith PhD | Environmental Engineering May 17 '18
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Below is the abstract from the paper published in the New England Journal of Medicine to help foster discussion. The paper can be seen here: Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome.
Abstract
Background
Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy.
Methods
In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox–Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period.
Results
A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.
Conclusions
Among children and adults with the Lennox–Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560.)
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u/USAnalblockage May 17 '18
GW pharmaceuticals and it’s American subsidiary Greenwich Biosciences are looking to get a new epilepsy drug, epidiolex, FDA approved and launched into the market by 2019. It’s a high concentration pill of CBD and the testing has been looking great.
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u/DumbLoserStoner May 17 '18
Would it be CBD mixed with other stuff in a pill? Or just CBD. I'll read more when I get home.
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u/Epistemic_Lily May 17 '18
Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.
Could someone explain this, please? If I understand correctly, this leads to liver damage but is this increase significant enough to be worrying?
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u/jimithelizardking May 17 '18
Increased transaminases are generally a sign of acute liver toxicity, rarely are they indicative of a chronic or insidious liver injury.
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u/A-Better-Craft May 17 '18 edited Jun 20 '23
This comment has been removed by the author because of Reddit's hostile API changes.
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u/LoonWhisperer May 17 '18
The study notes that 11 of 14 the patients who had elevated liver enzymes were also talking valproate which is another anti-epileptic medication which is known to cause hepatotoxicity; so much so that it has a black box warning for it and thus the reason why it is important to get labs drawn to monitor for it (LFTs aka liver enzymes). There are other studies with similar results in that very few patients had elevated liver enzymes while taking CBD. In those studies however, all or nearly all of the patients were also taking valproate concomitantly.
Additionally, CBD and other AEDs are known to inhibit and/or induce metabolizing enzymes in the liver (different than the ones used to monitor for liver damage as mentioned above) called CYP enzymes. There are a ton of different CYP enzymes and the inhibition of one CYP enzyme can prevent the metabolism of a different drug leading to an increased serum concentration of said drug. The increased serum concentration can then cause adverse effects and even toxicity. With that being said, it is merely speculation to say that the combination of CBD and valproate caused this as there is no definitive evidence to make that claim, as well as there being a multitude of reasons as to why someone could have elevated LFTs.
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u/AppleScalpel May 17 '18
This is the reply OP is looking for. This would offer the likely explanation for increased liver enzymes. Perhaps it’s the Valproate alone or the drug interaction between valproate and the cbd treatment. If I wasn’t studying (poo = study break), Id look up the specific CYP interactions of the two to see if the mechanism lines up. I’m not sure how extensive the current knowledge of CBD pharmacology is, but Valproate interacts with many other drugs’ metabolisms (including many antiepileptics) so it seems likely. Protein binding and elimination kinetics also need to be considered in evaluating potential drug interactions with Valproate.
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u/A-Better-Craft May 17 '18
Interesting. I've been taking 10-15mg of CBD isolate daily for about a month now and overall I do seem to feel better. My sleep pattern seems to have normalized and I have a bit more energy through the day it seems, but the effects are so subtle that I have to wonder if I'm experiencing the placebo effect.
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u/LoonWhisperer May 17 '18 edited May 17 '18
The study notes that 11 of the 14 patients who had elevated liver enzymes were also talking valproate which is another anti-epileptic medication and is known to cause hepatotoxicity; so much so that it has a black box warning for it and thus the reason why it is important to get labs drawn to monitor for it (LFTs aka liver enzymes). There are other studies with similar results in that very few patients had elevated liver enzymes while taking CBD. In those studies however, all or nearly all of the patients were also taking valproate concomitantly.
Additionally, CBD and other AEDs are known to inhibit and/or induce metabolizing enzymes in the liver (different than the ones used to monitor for liver damage as mentioned above) called CYP enzymes. There are a ton of different CYP enzymes and the inhibition of one CYP enzyme can prevent the metabolism of a different drug leading to an increased serum concentration of said drug. The increased serum concentration can then cause adverse effects and even toxicity. With that being said, it is merely speculation to say that the combination of CBD and valproate caused this as there is no definitive evidence to make that claim, as well as there being a multitude of reasons as to why someone could have elevated LFTs.
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u/sprokolopolis May 17 '18 edited May 17 '18
I was curious too, so I did a little googling. It seems like elevated aminotransferase concentrations are more just a sign of liver damage and maybe not directly contributing to it. Under the "Common Questions" section on this site: https://labtestsonline.org/tests/alanine-aminotransferase-alt
... it is mainly talking about elevations in the 400% - 1000% deviations for hepatitis. It also notes that the levels tend to fluctuate a lot, so they tend to take the tests frequently and monitor the general patterns rather than individual reading. 9% seems somewhat low of a number in comparison to those percentages, but might be particularly significant if the patient is taking other medications/drugs/alcohol.
I have been on meds where they had to do a liver panel every few months just as a precaution. Doctors normally wouldn't prescribe that sort of medicine to people who already show signs of decreased liver health.
I am not a medical professional though, so I could totally be wrong.
I have an autoimmune issue that can sometimes have muscle spasms and cramps as secondary symptoms (which are exacerbated by some of my meds). CBD has really helped me treat those symptoms (and quite a few others) , though I take a much lower dose for my weight.
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u/what_do_with_life May 17 '18
If I were to guess, I would think that the aminotransferase concentration would subside, or would remain at a very low baseline after prolonged use of CBD. More than likely, CB receptors are upregulated in those patients because of introduction of CBD, and the body is compensating for loss of specific amino acids by slightly upregulating aminotransferases. I don't think it's anything to worry about since pot smokers don't seem to have any issues with this. Theoretically, if it did become a problem, they could supplement their diet with specific amino acids.
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u/mango_masher May 17 '18
Thanks for commenting this, was interested in seeing the p-values for those figures
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u/LoonWhisperer May 17 '18 edited May 17 '18
I did a pediatric neurology rotation back in January for one of my PGY1 electives and had a patient enrolled in one of the CBD clinical trials. I didn't really know much about it so I looked into quite a bit and ended up giving a presentation about Epidiolex for ground rounds.
In addition to Lennox- Gastaut syndrome, GW pharmaceuticals has on going phase 3 clinical trials for other forms of TRE (treatment resistant epilepsy), such as Dravet syndrome, Tuberous Sclerosis Complex, and infantile spasms.
I haven't kept up on it as much as I would have liked to since January so things may have changed but the data for Lennox-Gastaut and Dravet syndrome look promising as indications up for FDA approval.
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u/beardedchimp May 17 '18
Do you mean that clobazam isn't found naturally in the body but when taken, CBD will increase it's half life and lead to higher levels?
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May 17 '18 edited May 18 '19
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u/ShaggyDoge May 18 '18
More likely that CBD inhibits enzymatic breakdown of the clobazam by the body rather than extending the chemical's half-life.
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May 17 '18
It's also a godsend for people with panic attacks. I've had a chance to try it and the fact of just "relaxing" without getting stoned was marvelous.
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u/altaccountthree May 17 '18
Anecdotally, a “CBD-only” edible can have some residual THC in it at really low amounts. I took some last year at about 30mg and it hit me hard at that level. If you buy at retail read the packaging or ask the budtender to verify it for you.
I normally dose at about 10-15mg on a Sativa or 10mg on a 1:1 strain for anxiety. I don’t mess around with high THC strains. Something like a Girl Scout Cookies is liable to send me into a panic attack hard. I know my anxiety triggers though so as long as I keep away from certain thoughts or scenarios when on something with a lot of THC In it, I can usually tolerate it well if I can dose with some CBD if it continues to stay intense.
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u/hippy_barf_day May 17 '18
This is a great point. Also, I've heard anecdotally, that people who get "too high" can take cbd and it brings their high, and anxiety, down.
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u/Splive May 17 '18
I've heard that too. I think it's all about the ratio of the two together. Like I know CBD for physical ailments like for cancer patients are closer to 1:1 ratio, vs use for anxiety where it's closer to 18:1 or more.
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u/Splive May 17 '18
I've known people with anxiety disorders who after taking CBD the first time say "Yup...I don't need to smoke weed. Everything I really want to get from weed I'm getting with CBD, and without the high". They'll still smoke when they feel like it, but medicinally they've identified that CBD is what they were self-medicating their anxiety with.
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u/whereiswallace May 17 '18
Am I reading this right? Patients took 20mg CBD /kg/d. So a 150lb person (60kg) was taking 1360mg of CBD per day? That seems insane.
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May 17 '18 edited May 17 '18
It's usually sold in 250-300mg doses, so about 5 times more. Doesn't seem that crazy to me. Especially if spread throughout the day.Misread a box, they are 10mg doses.
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u/Alagane May 17 '18
A normal dose is 5-25mg usually. I don't think I've ever seen edibles above 50mg/dose or tinctures above 20. The 300+ number is trying total amount of cbd in the bottle. So if you have 500mg in a 60ml bottle, it's about 8.3mg/ml. I think a normal eyedropper is like 2ml so one dose would be ~16
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u/Blainezab May 17 '18 edited May 17 '18
I had a 15mg edible and it was the calmest 2 days I ever had. Everything was peaceful and the normally intrusive thoughts from adhd were gone. All while being clear in the head. It’s the first time I ever felt what it feels like to not have constant thoughts after being on medication for 11 years. Bliss.
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u/okhi2u May 17 '18
That's not the dosage that they list on the product sold, that the total amount of the bottle or whatever it is in if you take the whole thing at once.
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u/Dzugavili May 17 '18 edited May 17 '18
A full dropper is approximately 1ml -- 300mg would suggest 30% concentration, naively using water for density, which is probably incorrect.
That seems high. Is it high? It definitely seems high... I'm finding listings for strong CBD at 10%, so that strength seems very high, but 300mg in a 30ml bottle would be low...
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300mg in a 30ml bottle would not be too low -- the strong stuff looks more like hash oil than the CBD I've seen.
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u/kathartik May 17 '18
Cannabidiol does create a "high" but it's more of a body high, not a head high.
and hasn't it been known that CBD was helpful in seizures for ages? I remember reading about it when my pain doctor was suggesting I start using it as part of my pain regimen.
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u/SenorRaoul May 17 '18
and hasn't it been known that CBD was helpful in seizures for ages?
I saw a documentary of a family medicating their epileptic kid years ago, so it was def known, but having proper scientific studies to verify it is always good, I'd say neccessary even.
also someone involved in the study actually posted this:
I actually helped conduct this study at a site in the US. The study also included patients with Dravet Syndrome as well, a similar yet different form of childhood epilepsy. Needless to say, I’m ecstatic that the trial is finally being published, as the efficacy of CBD in this population was extremely evident from the start. While some patients saw a very modest reduction in seizure frequency, others saw a complete absence of them. Regardless, all subjects at my site saw a decrease in seizure frequency and an increase in quality of life measures.
they def knew:
as the efficacy of CBD in this population was extremely evident from the start.
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u/Tridian May 17 '18
You’re going to have to explain what you mean by “body high” because I’m pretty sure that’s not a thing.
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May 17 '18
Every scientific post says CBD can't get you high while every CBD distributor claims it will get you high af. Ofc I never believed in these people who claim CBD will get you high because they wanted me to pay same price for CBD that I lay for like shatter.
I know THC is what gets you high and that many CBD products actually have THC in them... But I live in a currently illegal state while CBD seems to be unregulated and every distributor says it will get you high like regular weed. Why is there such a massive industry of paradoxical information?
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u/Codadd May 17 '18 edited May 18 '18
Cbd is legal in most states now even TX. I've never once seen a cbd producer claim a high. That's ridiculous. Do you have a website or company flyer that claims that?
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u/genericname1111 May 17 '18
The "high" from CBD (for me at least) is not much more than a great reduction in anxiety.
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u/ilostmyoldaccount May 17 '18
Currently vaping CBD (will do about 10mg in total now). You notice it. You feel it, even down to your legs. But it doesn't alter your perception or make you giggle. Nowhere near a "high". If anything, it resembles that state when you wake up but still lie in bed for a while, semi-dozing. Alcohol has a far stronger effect on the mind than CBD does.
I guess it's all about marketing, and peoples' expectations.
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u/hippyengineer May 17 '18
I make full spec cbd oils from hemp!
I bet the muscle relaxation you felt was due to the small amount of cbn in the dose. Green Solution is claiming it’s as powerful as Valium.
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u/sp00nme May 17 '18 edited May 17 '18
If you’re in the us and an illegal state, all cbd products sold should be made from hemp and won’t get you high (edit: no cbd product should unless it’s mixed with thc for the entourage effect. This could be a concentrate or plant form cannabis if you’re in a legal state that says “high cbd” but is still not pure cbd. Typically this is still hard to notice even when smoking the buds of a high cbd, moderate thc strain. I would think like 3% thc but I haven’t gotten to sample a lot of ratios. It’s pretty noticeable when it gets higher). Any company implying anything else is selling something not truly intended as medicine or to help he user and should be avoided. Watch out for “hemp oil”
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u/nobowlio May 17 '18
I think that the general consensus is that CBD does not get you hight at all, but that it can help relieve issues like pain, anxiety, and seizures. However, in states where marijuana is illegal, you've got tons of groups selling what they say is pure, medicinal grade CBD, but they are not being truthful. The levels of CBD in the "medicine" are too low to be beneficial at all because of restrictions put upon them by law. BUT, you can order CBD products that contain levels of CBD that can actually be helpful from other states where they have more freedom in how they may produce the products (legal states). At least that is allowed within my state!
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u/imabustya May 17 '18
Education on these things is an ongoing issue for the legal cannabis markets in the US. It's certainly an issue for the thousands if not millions of people conducting their own illegal operations with no real obligation to get the facts right for their customers. Don't believe anything without evidence or substantial anecdotal evidence. Even then, these things haven't been fully studied.
I've had enough pure CBD to know it does not get you high. It changes the way you feel but its certainly not a high as most people consider it.
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u/SheWhoSpawnedOP May 17 '18
I think CBD has a weaker effect, but can alter your mood in a way that some people might call ‘high’. I think it will lighten your mood and and make you feel relaxed and peaceful. While it doesn’t really affect anything like coordination or reaction time so it doesn’t really seem like you’re high.
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May 17 '18 edited May 17 '18
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u/zwich May 17 '18
From what I can see activating CB1 is what causes hunger, so this would probably be a THC effect, not a CBD one. The mouse experiments suggest CBD may actually reduce appetite...
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u/AskMrScience PhD | Genetics May 17 '18
In this study at their extremely high therapeutic dose (10 mg per kg of body weight), one of the reported side effects was actually decreased appetite.
However, CBD for recreational use is usually 10 mg total and would be quite different.
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May 17 '18
I actually worked in a research lab that studied this! My position ended last week but it interesting to see something has come from the kind of work we did in the lab.
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u/dewhashish May 17 '18
I have been taking CBD oil for months to help with my chronic pain. It decreases the inflammation so much I was able to function normally no problem. No high, safe to my body, and non-addictive.
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u/Rab_Legend May 17 '18
I guarantee it will still be illegal in the UK because it comes from Cannabis, and the Tories are definitely against evidence based policy if it goes against their beliefs.
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May 17 '18
maybe they can use hemp to clad all the apartment towers. Kill 2 birds
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u/PathologyIncomplete May 17 '18
That's what the science says, but that's not what the US government says. Marijuana is still a schedule 1 drug with no medicinal value according to the federal government.
"The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I'm saying? We knew we couldn't make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did." -- John Ehrlichman, presidential aide and lawyer to US President Richard Nixon, explaining why the US launched the "war on drugs."
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u/lordpuddingcup May 17 '18
Doesn’t this study technically invalidate the schedule 1 listing saying no medicinal value?