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- This is Lab Medicine Rounds,
a curated podcast for physicians,
laboratory professionals, and students.
I'm your host, Justin Kreuter, the Bow Tie Bandit of Blood,
a transfusion medicine pathologist at Mayo Clinic.
So, today we're gonna be talking about CBD.
I think a lot of us have been seeing,
there's a lot of stores selling CBD products
in our communities
and I think a lot of us are getting curious
about the kind of medical implications for this
and certainly in laboratory medicine about testing as well.
So, today we're rounding with Dr. Paul Jannetto,
associate professor of laboratory medicine and pathology
and director of the clinical and forensic toxicology lab,
clinical mass spectrometry lab,
and metals lab at Mayo Clinic.
Thanks for joining us, Dr. Jannetto.
- Thank you, it's a pleasure to be here.
- We're welcoming you back
because you're such a great guest to interview,
and I think this topic, I was just telling you
before we got started here
that I've got colleagues that were wanting to listen
to this interview live because they were curious
to learn stuff about CBD.
So, can you maybe kick us off by,
let's kind of compare and contrast
or what's the difference between these, like,
you know, marijuana, there's hemp, THC, CBD.
- Sure, well, let's start with marijuana.
Marijuana is also commonly known as weed, pot, or dope.
That refers to all parts of the dried flowers,
the stems and leaves of the cannabis sativa plant,
and it has to have more
than 0.3% Delta-9-tetrahydrocannabinol,
or THC by dry weight.
Now, hemp on the other hand,
is any part of the plant
that has less than 0.3% Delta-9-THC.
Now this is important
because Delta-9-THC is
the main psychoactive ingredient in marijuana
that's responsible for the euphoria
and other effects like increased heart rate,
decreased alertness, and motor instability.
Cannabidiol, or CBD, is one of the many cannabinoids
that can be found in marijuana.
It can also be derived from hemp,
but CBD is not psychoactive,
so it's not impairing or mind altering
and it doesn't cause that high associated with marijuana.
- Okay, so, thanks for taking us through
and understanding how this kind of falls out.
That's kind of interesting...
Because certainly, marijuana,
there's been a lot of hemp, you know, sold from,
I think, clothes you can find a lot of times
are made out of hemp,
and then now with the CBD stores kind of popping up.
So, I'm guessing it's legal in the United States.
- So, back in 2018, the US Congress signed into the law
the Agricultural Improvement Act, that actually removed hemp
from the Federal Controlled Substance Act
and that effectively legalized CBD if it comes from hemp.
However, it should be noted
that a few states have not removed hemp
from their state's controlled substance act,
so the legality of CBD products differs across states.
Furthermore, the vast majority
of CBD products sold in the United States,
whether it's online, or in stores, or gas stations
are unregulated as they're currently not considered drugs
or even legal dietary supplements by the FDA.
However, the FDA has utilized its authority
under the Food Drug and Cosmetic Act
to enforce some regulations of hemp derived CBD products
including false marketing claims,
but there's no regulation
or oversight regarding the content of these products.
- I gotcha.
So, I guess we're finding these
in a couple of different products.
Are there some common ones?
- Yeah, so, if you look at the online
or in the various stores, you'll see CBD oils or lotions.
It can be in capsules, cosmetics,
and of course, everybody's favorite gummies.
- And how does this have an impact
on the health for the user that we know of?
And I guess that's with a huge asterisk, right?
Because you just said it's not a regulated thing,
but what do we know about how this affects our health?
- Well, using CBD isn't risk-free.
The FDA actually has very limited safety on data on CBD,
but some possible side effects and risks include things
like drowsiness, diarrhea, changes in appetite,
and changes in mood or in irritability,
and even potential liver damage.
In fact, CBD is actually not even recommended
during pregnancy, because some animal studies have shown
that high doses of CBD
have caused negative effects on the developing fetus.
It's also unknown if it passes through breast milk.
So, people who are breastfeeding should also avoid CDB
due to potential negative effects.
- Wow, okay.
So, this is how it's affecting us,
and then, I guess, for us in the laboratory medicine,
is this kind of impacting,
I know you run our drugs of abuse and forensics lab, I mean,
is this having any effect in the testing that you're doing?
- Yes, and one of the reasons is
because there is also some medical benefits to CBD
and in 2018, the FDA actually approved
the first plant derived pharmaceutical grade purified CBD.
It's Epidiolex that was approved
for the treatment of epilepsy and seizures in patients,
and so, there is some prescription based usage
of this in our patient populations,
and so, from a testing standpoint, I know when that started,
we originally asked
if we could do some TDM tests, sort of to monitor CBD.
Unfortunately, there really isn't reference ranges
or therapeutic reference ranges for CBD,
- And what's TDM, you said?
- Therapeutic drug monitoring.
So, looking at the concentrations of, in this case, CBD,
in the blood to see if they're reaching therapeutic levels.
In the case of seizures and epilepsy,
is there a target range
like there are for many other pharmaceutical agents
for epilepsy, where you want to hit this target range
where seizures are well controlled?
Unfortunately, we don't have those ranges for CBD,
but you asked a very specific question regarding drugs
of abuse testing and CBD,
and this is a very interesting story
and this is where I actually get a lot of calls
from patients who end up testing positive for things
like THC, tetrahydrocannabinol, or marijuana,
but they claim, "I only took CBD."
Okay, so let's look at this,
take a step back and look at this.
Most of the testing that we do using urine is
the most common matrix we test.
We use immuno assays
and these antibodies target actually a metabolite
of that psychoactive Delta-9-THC,
specifically the Delta-9 carboxy THC,
and now in general, these antibodies,
they don't cross-react with CBD,
and so, they're pretty specific in the sense
that they bind this unique metabolite of THC,
the Delta-9 psychoactive metabolite, Delta carboxy THC.
Even our confirmation methods
where we use chromatography combined with mass spectrometry,
those methods are very specific
and they only will identify
the cannabinoids that we're looking for,
and again, we typically look
for that Delta-9-carboxy-THC.
So, we won't pick up CBD, however, this is the big if,
and this is what people have to really remember is
that the content of CBD products are not regulated,
so the real risk with CBD products is
that they may be contaminated
with higher concentrations or percentages of that THC,
or even other drugs like synthetic cannabinoids,
or contaminants like residual solvents or heavy metals.
There was a recent paper that just came out in 2022,
where Dr. Johnson looked at over 80 unregulated CBD products
along with Epidiolex, that FDA approved drug for seizures,
and they measured all of these products for Delta-9-THC.
Remember, they're supposed
to have less than 0.3% Delta-9-THC,
and in all of these products,
even if they're labeled "THC-free,"
they found detectable levels
of Delta-9-THC in 52 of those 80 products,
and the concentrations
of the Delta-9-THC went all the way up
to two milligrams per mL,
with an average concentration around 0.6 milligrams per mL,
and you have to take that in context
to the FDA approved pharmaceutical grade "pure CBD"
that had less than 0.008 milligrams per mL
of detectable THC.
So, some of these CBD products
have over a hundredfold higher concentration
of the "Delta-9-THC" or psychoactive component,
A.K.A., the active ingredient in marijuana,
even though they're labeled as THC-free,
and that is actually where we're seeing cases
where patients who "are only using CBD products"
are actually testing positive for THC or marijuana use.
- Wow, okay.
So, this really deals, then,
with the idea this is not a regulated thing
and so, manufacturers are able to kind of do what they want
or do their thing.
Wow, and so, somebody may intentionally
not be using marijuana,
but using something that even specifically says
in the label "THC-free,"
I guess, is that where you kind of mentioned
that the FDA is coming on to false claims?
Is this where the FDA's getting involved with those?
- Yeah, that's really where there's trying to step in now
and regulate the content, and, you know,
so that it's not supposed to contain those things,
but they really need to come in
and do a full regulatory oversight of it,
so that they can have direct control of what goes into it
and not just the claims they make with it.
- Wow, so, maybe if we take a step back then
and just kind of generalize this out for, you know,
our laboratory medicine colleagues
that are listening to this podcast, you know,
what's important for them to understand
about CBD and then marijuana drug testing?
- Sure, based on the trends that we're seeing
with cannabinoid use, in general,
we're seeing many people turning to CBD
or now the the latest craze, if you want to call it,
is they're looking at Delta-8-THC usage
because this is seen by many producers and consumers
as the legal alternative to Delta-9-THC,
that psychoactive component of marijuana,
but we already know that CBD can be converted
to actually Delta-9-THC under acidic conditions,
and many of its isomers like Delta-8-THC.
Delta-8-THC is one of those interesting cannabinoids
that actually exists naturally in the cannabis plant,
but it's in very small quantities.
However, Delta-8-THC is psychoactive, much like Delta-9-THC,
but at a lesser extent,
only about 50% of the psychoactivity of Delta-9-THC,
and what we're seeing now is
that a lot of these Delta-9-THC products
are showing up in both marijuana and hemp marketplaces,
and most states actually permit full
or even restrict marketplaces
to actually sell these hemp derived CBD products,
and some of these products
that have these concentrated Delta-8-THCs,
you can buy online if you do a Google search,
and they're marketed actually
as this "weed light" or "diet weed,"
but what you have to recognize is
that the health effects of Delta-8
aren't also fully understood
and haven't been researched yet,
and you also have to recognize
that Delta-8-THC is psychoactive
and therefore has similar risks
of impairment to Delta-9-THC,
and so, products that contain both Delta-8-THC,
but are labeled only with Delta-9-THC content
can actually have a combined greater THC content,
and so, we can see people have more psychoactive potential
and potential toxicity from these products,
and so, it's one of those things that we're starting to see
from a laboratory standpoint,
that we're actually having to adapt our testing and assays
to actually, now, in addition to looking
for that Delta-9-THC and carboxy THC, the main metabolite,
to actually being able to measure and detect things
like Delta-8-THC, and CBD,
and some of these many other cannabinoids,
so that we can sort of tease out and sort out
all of these different cannabinoids
that are now being marketed and used, essentially,
as people try to skirt around the laws and the regulations.
- I see, so that we can actually separate out
what is an issue versus what may not be,
or seeing how that law evolves.
So, you know, that's kind of...
We've been talking about the general public here so far.
What about, you know, certain industries?
You know, I'm thinking, you know,
certainly, like, airline pilots, you know, I don't know.
I think a lot of times, I see CBD oils
like, advertised for athletes in recovery.
What do you see in some of those industries?
- Well, due to the unregulated status of CBD
and the fact that you can actually find Delta-9-THC
in these products at higher than the 0.3%
that's supposed to be there,
employment testing,
the Department of Transportation testing
in the case of truck drivers, airline pilots, et cetera,
people who use those products could potentially
test positive for marijuana use, and for athletes,
the World Anti-Doping Agency, or WAA, has excluded CBD
from its list of prohibited cannabinoids.
However, if you look at
the latest list of their prohibited list,
cannabinoids in general are still listed
as forbidden to be used in competitions.
Now remember, CBD products are sold as sort of, kind of,
these full spectrum products, but they still contain
these other cannabinoids like Delta-9-THC.
So, an athlete that uses CBD could potentially test positive
for one of the prohibited cannabinoids on that water list
and therefore essentially be de-qualified from their event
or have a medal or element taken away from them,
and so, it is a real concern
for people using these products,
again, because they're unregulated
and they can contain some of these prohibited cannabinoids.
- I see.
This actually clarifies a lot for me.
So, I'm taking away from this conversation
that, you know, yes, I'm seeing a lot of CBD out there
and CBD by itself, you know,
is not necessarily causing issues for, you know,
my employment drug screen, and things like that,
but the fact that it's unregulated,
it probably sounds like I guess we could safely say
it's likely not a purified compound solely,
and that may have implications.
So, I guess for all of us listening, to understand that,
you know, we may be running positive
or finding THC and the person may not be smoking marijuana,
but using CBD oil may be a source for it.
That's really helpful to understand.
Do I use my wife's CBD oil soap or not?
And then, you know, for some of these industries,
you're kind of talking about, yeah,
there are potentially huge ramifications for people,
us in healthcare, athletes, we mentioned,
are there any other kind of takeaways
you want the audience to appreciate out of this?
- Yeah, I think one of the takeaways is
that a lot of these cannabinoid products
do have some potential medical use and benefits.
So, we don't wanna necessarily downplay or ignore that.
You know, I think if you talk to our neurologist
in the case of seizures,
in some of these pediatric patients,
CBD has been very beneficial,
but I think the ultimate message or takeaway is
for some of these products
where people are using the CBD oils,
gummies, and other things,
it's sort of like the old buyer beware, right?
It's unregulated.
So, if you are concerned about potential implications
with your job or other employment issues, you know,
maybe you may not want to use it
and stick to other forms of medicine
that would have less risk
just because we are seeing it at higher levels
and in detectable concentrations in some of these products
that could lead a clinician, or your employer,
or WATA, or some agency to think
that you are actually using marijuana
when in reality you're not.
- I'm glad you're the voice of reason,
of let's not throw the baby out with the bath water.
There is a medical place for this,
and it sounds like that is, you know,
prescription grade is a different story.
It's the stuff that we see marketed direct
to consumer on the street.
- Exactly. - Excellent.
Well, hey, thank you so much Dr. Jannetto
for shedding some light on CBD.
I know a lot of my colleagues are really interested
to learn from you on this topic.
- Well, thank you.
Pleasure to be here.
- We've been rounding with Dr. Jannetto talking about CBD,
and to all of our listeners, thank you for joining us today.
We invite you to share your thoughts
and suggestions via email at mcleducation@mayo.edu.
If you've enjoyed Lab Medicine Rounds podcast,
please subscribe, and until our next rounds together,
we encourage you to continue to connect lab medicine
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