How safe is CBD? (2018 Study)
What did the study look at?
*I receive no financial perks from Urbal Activ.
The goal was to look at how safe and tolerable highly-purified CBD extract is, and how the body metabolizes ingested CBD products.
How did they do this?
First of all, for all of you research sticklers, the trial was randomized, double-blind, and placebo-controlled for dosing groups. (For you non-sticklers, a double-blind RCT is the gold-standard in the research world, so this is considered a reliable study to evaluate).
These researchers took 56 healthy men and women between 18 and 45 years old with a BMI between 18-28. The women were either unable to bear children or were non-pregnancy and non-lactating.
So primarily, they looked at your average, non-pregnant, Jane and Joe looking to take CBD products. The safety, tolerability, and pharmacokinetics (how CBD is metabolized and handled) were studied in these individuals.
The individuals were split into three groups.
Group 1: Single Ascending Dose
There were 4 "sub-groups" here to look at the effect of one single dose of CBD
6 people took 1,500mg compared to 2 placebo control people
6 people took 3,000mg compared to 2 placebo control people
6 people took 4,500mg compared to 2 placebo control people
6 people took 6,000mg compared to 2 placebo control people
Group 2: Multiple Dose
There were 2 "sub-groups" here to look at the effect of multiple doses of CBD for a week.
9 people took 750mg two times per day compared to 3 placebo control people
9 people took 1,500mg two times per day compared to 3 placebo control people
Group 3: Integrating Food
This was the only open-label arm of the study (meaning the people knew they were taking CBD and not a placebo). There were 12 people selected from the single dose arm (except the 6,000mg people) of the study for this feeding part of the study. The groups were "fed then fasted" and "fasted then fed."
In the fasted state, people had to fast 10 or more hours before receiving 1,500mg of CBD.
In the fed state, people had to eat a high-fat breakfast before receiving 1,500mg of CDB. (The breakfast was 2 fried eggs, bacon, fried potatoes, 2 slices of toasted bread with butter, and a glass of high-fat milk… poor things…). The meal had to be eaten within 20min, and the CBD was taken within 30min of starting breakfast (or roughly 10min after finishing eating).
So, what did they find?
Good news first…
Not a single, clinically significant finding was demonstrated in lab work, physical exam, vital signs, ECG, body weight, sleep/sleepiness scales, and no suicide-related behaviors in any of the people in any of the trial arms.
Additionally, there was zero evidence of any drug withdrawal syndrome during the study.
Now for the real talk…
Overall, single and multiple doses of CBD were well-tolerated. Any of the adverse events were categorized as mild to moderate in severity.
Diarrhea, nausea, headache, and daytime sleepiness were the most reported adverse events across all of the treatment groups.
In the single-dose group 24 people (75%) reported adverse events, and in the multiple-dose group, 23 people (96%) reported adverse events. This was irrespective of being fed or fasted.
An "adverse event of interest": In the 1,500mg multiple-dose group, there were 3 people (33%) who experienced a skin rash that started after their last dose of CBD. Everyone recovered within 6-12 days. And don't worry too much, it was also noted that these rashes were deemed unrelated to CBD treatment.
Quick reality check. At 1,500 to 6,000mg of CBD 75-96% of study participants experienced one or more of the following: soft or runny poop, mild-moderate nauseous feeling, mild-moderate headache, and mild-moderate daytime sleepiness. I don't know about you, but that sounds better than even half of the side-effects from most prescription drugs advertised on TV (which, drug ads on television, is a whole other topic). Be sure to read my two-cents at the end of this article to put some context and perspective to these side-effects.
So how do we metabolize CBD?
3D chemical representation of CBD compliments of Wikipedia.
Well, we metabolize it A LOT, and we do it FAST.
7-COOH-CBD was the primary circulating CBD product in the blood, accounting for approximately 97% of circulating CBD metabolites. After that, we saw, in decreasing order, CBD, 7-OH-CBD, and 6-OH-CBD.
Given this conversion, CBD itself has a relatively low bio-availability.
The CBD metabolism quick stats:
CBD Time to Peak: CBD itself reaches peak levels in the blood in 4-5hrs (other CBD metabolites 3.5-5hrs) regardless of the dose.
CBD Half-life: CBD half-life is 14-17hrs. The half-life is the time it takes for half of the CBD to leave the body (e.g., the time it takes for CBD to go from 10 units to 5 units in the blood).
CBD's "effective half-life" (i.e., the amount of time it is likely exerting an effect in the body) is likely 10-17hrs.
CBD Steady State: In multiple doses, CBD reaches a steady-state level in the blood in 2 days. The bigger the dose, the higher the steady-state in the blood. When looking at "CBD and friends" (aka CBD metabolites), there is a steady state that occurs within 2-4 days.
CBD and food: When CBD is taken with a high-fat meal, the bioavailability (the amount that gets absorbed and makes it into the blood) increases 4 to 5-fold.
Alright, so what did the researcher make of all this data? (Plus my two cents)
The researchers concluded that CBD doses of up to 6,000mg (6g) per day are well tolerated in humans and that all adverse events were mild or moderate in severity.
The results of their trial concluded that twice-daily administration of CBD is (medically) preferred and that taking CBD with a high-fat meal could increase bioavailability and decrease therapeutic fluctuations throughout the day.
My only two cents, are to put in the perspective of the dosing used in this trial.
This was a safety study, so doses need to be pushed quite hard. Most CBD-only products are prescribed in the range of 25mg to 2,000mg per day. (25mg is only 0.4% and 2,000mg is only 33% of the 6,000mg dose used in the trial to deem safety.) The doses in the study were much larger than real-life doses.
However, that said, in individuals who are not accustomed to CBD, doses of 50-200mg can potentially lead to the experience of CNS effects (e.g., that daytime sleepiness mentioned above).
So in "regular life" dosing (25-2,000mg), I would expect far fewer adverse events reported. If unsure of how you tolerate CBD and/or hemp products, a tincture is a good option. "Drop dosing" by increasing your dose 1 drop at a time over a period of time can help you to understand how you tolerate whichever product you are using.
References:
Anderson, P. S., ND. (2017, July 18). Clinical uses of Cannabinoids: Indications, Dosing and Management.Lecture. Retrieved January 11, 2019, from www.ConsultDrAnderson.com
Taylor, L., Gidal, B., Blakey, G., Tayo, B., & Morrison, G. (2018). A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects. CNS drugs, 32(11), 1053-1067.
DISCLAIMER: These statements have not been evaluated by the Food and Drug Administration. There are no financial ties to any supplement companies, pharmaceutical companies, or to any of the products mentioned in this post. This post is not meant to treat, cure, prevent, or diagnose conditions or diseases and is meant for educational purposes. As always, please consult your doctor before trying any new treatments or supplements.