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(upbeat music)

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- This is Lab Medicine Rounds,

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a curated podcast for physicians,

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laboratory professionals, and students.

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I'm your host, Justin Kreuter,
the Bow Tie Bandit of Blood,

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a transfusion medicine
pathologist at Mayo Clinic.

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So, today we're gonna
be talking about CBD.

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I think a lot of us have been seeing,

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there's a lot of stores
selling CBD products

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in our communities

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and I think a lot of
us are getting curious

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about the kind of medical
implications for this

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and certainly in laboratory
medicine about testing as well.

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So, today we're rounding
with Dr. Paul Jannetto,

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associate professor of
laboratory medicine and pathology

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and director of the clinical
and forensic toxicology lab,

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clinical mass spectrometry lab,

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and metals lab at Mayo Clinic.

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Thanks for joining us, Dr. Jannetto.

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- Thank you, it's a pleasure to be here.

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- We're welcoming you back

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because you're such a
great guest to interview,

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and I think this topic,
I was just telling you

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before we got started here

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that I've got colleagues
that were wanting to listen

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to this interview live
because they were curious

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to learn stuff about CBD.

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So, can you maybe kick us off by,

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let's kind of compare and contrast

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or what's the difference
between these, like,

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you know, marijuana,
there's hemp, THC, CBD.

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- Sure, well, let's start with marijuana.

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Marijuana is also commonly
known as weed, pot, or dope.

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That refers to all parts
of the dried flowers,

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the stems and leaves of
the cannabis sativa plant,

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and it has to have more

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than 0.3% Delta-9-tetrahydrocannabinol,

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or THC by dry weight.

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Now, hemp on the other hand,

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is any part of the plant

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that has less than 0.3% Delta-9-THC.

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Now this is important

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because Delta-9-THC is

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the main psychoactive
ingredient in marijuana

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that's responsible for the euphoria

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and other effects like
increased heart rate,

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decreased alertness,
and motor instability.

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Cannabidiol, or CBD, is one
of the many cannabinoids

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that can be found in marijuana.

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It can also be derived from hemp,

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but CBD is not psychoactive,

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so it's not impairing or mind altering

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and it doesn't cause that high
associated with marijuana.

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- Okay, so, thanks for taking us through

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and understanding how
this kind of falls out.

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That's kind of interesting...

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Because certainly, marijuana,

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there's been a lot of
hemp, you know, sold from,

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I think, clothes you
can find a lot of times

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are made out of hemp,

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and then now with the CBD
stores kind of popping up.

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So, I'm guessing it's
legal in the United States.

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- So, back in 2018, the US
Congress signed into the law

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the Agricultural Improvement
Act, that actually removed hemp

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from the Federal Controlled Substance Act

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and that effectively legalized
CBD if it comes from hemp.

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However, it should be noted

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that a few states have not removed hemp

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from their state's
controlled substance act,

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so the legality of CBD
products differs across states.

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Furthermore, the vast majority

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of CBD products sold in the United States,

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whether it's online, or
in stores, or gas stations

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are unregulated as they're
currently not considered drugs

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or even legal dietary
supplements by the FDA.

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However, the FDA has
utilized its authority

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under the Food Drug and Cosmetic Act

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to enforce some regulations
of hemp derived CBD products

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including false marketing claims,

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but there's no regulation

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or oversight regarding the
content of these products.

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- I gotcha.

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So, I guess we're finding these

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in a couple of different products.

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Are there some common ones?

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- Yeah, so, if you look at the online

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or in the various stores,
you'll see CBD oils or lotions.

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It can be in capsules, cosmetics,

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and of course, everybody's
favorite gummies.

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- And how does this have an impact

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on the health for the
user that we know of?

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And I guess that's with
a huge asterisk, right?

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Because you just said it's
not a regulated thing,

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but what do we know about
how this affects our health?

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- Well, using CBD isn't risk-free.

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The FDA actually has very
limited safety on data on CBD,

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but some possible side effects
and risks include things

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like drowsiness, diarrhea,
changes in appetite,

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and changes in mood or in irritability,

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and even potential liver damage.

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In fact, CBD is actually
not even recommended

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during pregnancy, because
some animal studies have shown

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that high doses of CBD

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have caused negative effects
on the developing fetus.

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It's also unknown if it
passes through breast milk.

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So, people who are breastfeeding
should also avoid CDB

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due to potential negative effects.

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- Wow, okay.

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So, this is how it's affecting us,

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and then, I guess, for us
in the laboratory medicine,

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is this kind of impacting,

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I know you run our drugs of
abuse and forensics lab, I mean,

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is this having any effect in
the testing that you're doing?

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- Yes, and one of the reasons is

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because there is also some
medical benefits to CBD

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and in 2018, the FDA actually approved

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the first plant derived
pharmaceutical grade purified CBD.

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It's Epidiolex that was approved

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for the treatment of epilepsy
and seizures in patients,

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and so, there is some
prescription based usage

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of this in our patient populations,

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and so, from a testing standpoint,
I know when that started,

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we originally asked

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if we could do some TDM
tests, sort of to monitor CBD.

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Unfortunately, there really
isn't reference ranges

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or therapeutic reference ranges for CBD,

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- And what's TDM, you said?

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- Therapeutic drug monitoring.

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So, looking at the concentrations
of, in this case, CBD,

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in the blood to see if they're
reaching therapeutic levels.

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In the case of seizures and epilepsy,

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is there a target range

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like there are for many
other pharmaceutical agents

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for epilepsy, where you want
to hit this target range

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where seizures are well controlled?

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Unfortunately, we don't
have those ranges for CBD,

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but you asked a very specific
question regarding drugs

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of abuse testing and CBD,

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and this is a very interesting story

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and this is where I
actually get a lot of calls

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from patients who end up
testing positive for things

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like THC, tetrahydrocannabinol,
or marijuana,

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but they claim, "I only took CBD."

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Okay, so let's look at this,

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take a step back and look at this.

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Most of the testing that
we do using urine is

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the most common matrix we test.

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We use immuno assays

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and these antibodies target
actually a metabolite

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of that psychoactive Delta-9-THC,

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specifically the Delta-9 carboxy THC,

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and now in general, these antibodies,

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they don't cross-react with CBD,

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and so, they're pretty
specific in the sense

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that they bind this
unique metabolite of THC,

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the Delta-9 psychoactive
metabolite, Delta carboxy THC.

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Even our confirmation methods

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where we use chromatography
combined with mass spectrometry,

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those methods are very specific

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and they only will identify

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the cannabinoids that we're looking for,

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and again, we typically look

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for that Delta-9-carboxy-THC.

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So, we won't pick up CBD,
however, this is the big if,

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and this is what people
have to really remember is

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that the content of CBD
products are not regulated,

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so the real risk with CBD products is

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that they may be contaminated

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with higher concentrations
or percentages of that THC,

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or even other drugs like
synthetic cannabinoids,

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or contaminants like residual
solvents or heavy metals.

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There was a recent paper
that just came out in 2022,

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where Dr. Johnson looked at
over 80 unregulated CBD products

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along with Epidiolex, that FDA
approved drug for seizures,

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and they measured all of these
products for Delta-9-THC.

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Remember, they're supposed

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to have less than 0.3% Delta-9-THC,

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and in all of these products,

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even if they're labeled "THC-free,"

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they found detectable levels

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of Delta-9-THC in 52 of those 80 products,

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and the concentrations

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of the Delta-9-THC went all the way up

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to two milligrams per mL,

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with an average concentration
around 0.6 milligrams per mL,

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and you have to take that in context

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to the FDA approved
pharmaceutical grade "pure CBD"

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that had less than 0.008 milligrams per mL

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of detectable THC.

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So, some of these CBD products

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have over a hundredfold
higher concentration

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of the "Delta-9-THC" or
psychoactive component,

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A.K.A., the active
ingredient in marijuana,

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even though they're labeled as THC-free,

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and that is actually
where we're seeing cases

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where patients who "are
only using CBD products"

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are actually testing positive
for THC or marijuana use.

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- Wow, okay.

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So, this really deals, then,

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with the idea this is
not a regulated thing

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and so, manufacturers are able
to kind of do what they want

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or do their thing.

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Wow, and so, somebody may intentionally

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not be using marijuana,

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but using something that
even specifically says

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in the label "THC-free,"

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I guess, is that where
you kind of mentioned

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that the FDA is coming on to false claims?

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Is this where the FDA's
getting involved with those?

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- Yeah, that's really where
there's trying to step in now

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and regulate the content, and, you know,

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so that it's not supposed
to contain those things,

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but they really need to come in

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and do a full regulatory oversight of it,

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so that they can have direct
control of what goes into it

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and not just the claims they make with it.

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- Wow, so, maybe if we
take a step back then

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and just kind of generalize
this out for, you know,

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our laboratory medicine colleagues

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that are listening to
this podcast, you know,

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what's important for them to understand

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about CBD and then marijuana drug testing?

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- Sure, based on the
trends that we're seeing

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with cannabinoid use, in general,

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we're seeing many people turning to CBD

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or now the the latest craze,
if you want to call it,

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is they're looking at Delta-8-THC usage

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because this is seen by
many producers and consumers

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as the legal alternative to Delta-9-THC,

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that psychoactive component of marijuana,

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but we already know that
CBD can be converted

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to actually Delta-9-THC
under acidic conditions,

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and many of its isomers like Delta-8-THC.

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Delta-8-THC is one of those
interesting cannabinoids

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that actually exists naturally
in the cannabis plant,

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but it's in very small quantities.

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However, Delta-8-THC is
psychoactive, much like Delta-9-THC,

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but at a lesser extent,

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only about 50% of the
psychoactivity of Delta-9-THC,

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and what we're seeing now is

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that a lot of these Delta-9-THC products

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are showing up in both
marijuana and hemp marketplaces,

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and most states actually permit full

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or even restrict marketplaces

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to actually sell these
hemp derived CBD products,

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and some of these products

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that have these concentrated Delta-8-THCs,

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you can buy online if
you do a Google search,

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and they're marketed actually

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as this "weed light" or "diet weed,"

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but what you have to recognize is

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that the health effects of Delta-8

253
00:12:34,766 --> 00:12:37,140
aren't also fully understood

254
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and haven't been researched yet,

255
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and you also have to recognize

256
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that Delta-8-THC is psychoactive

257
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and therefore has similar risks

258
00:12:45,240 --> 00:12:47,950
of impairment to Delta-9-THC,

259
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and so, products that
contain both Delta-8-THC,

260
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but are labeled only
with Delta-9-THC content

261
00:12:54,990 --> 00:12:58,890
can actually have a combined
greater THC content,

262
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and so, we can see people have
more psychoactive potential

263
00:13:01,650 --> 00:13:04,023
and potential toxicity
from these products,

264
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and so, it's one of those things
that we're starting to see

265
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from a laboratory standpoint,

266
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that we're actually having to
adapt our testing and assays

267
00:13:11,682 --> 00:13:13,950
to actually, now, in addition to looking

268
00:13:13,950 --> 00:13:17,151
for that Delta-9-THC and carboxy
THC, the main metabolite,

269
00:13:17,151 --> 00:13:19,040
to actually being able to
measure and detect things

270
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like Delta-8-THC, and CBD,

271
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and some of these many other cannabinoids,

272
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so that we can sort of
tease out and sort out

273
00:13:26,910 --> 00:13:28,295
all of these different cannabinoids

274
00:13:28,295 --> 00:13:31,764
that are now being marketed
and used, essentially,

275
00:13:31,764 --> 00:13:35,970
as people try to skirt around
the laws and the regulations.

276
00:13:35,970 --> 00:13:38,585
- I see, so that we can
actually separate out

277
00:13:38,585 --> 00:13:42,117
what is an issue versus what may not be,

278
00:13:42,117 --> 00:13:45,175
or seeing how that law evolves.

279
00:13:45,175 --> 00:13:48,010
So, you know, that's kind of...

280
00:13:48,010 --> 00:13:51,440
We've been talking about the
general public here so far.

281
00:13:51,440 --> 00:13:54,510
What about, you know, certain industries?

282
00:13:54,510 --> 00:13:57,840
You know, I'm thinking, you know,

283
00:13:57,840 --> 00:14:01,280
certainly, like, airline
pilots, you know, I don't know.

284
00:14:01,280 --> 00:14:04,800
I think a lot of times, I see CBD oils

285
00:14:04,800 --> 00:14:08,880
like, advertised for athletes in recovery.

286
00:14:08,880 --> 00:14:12,960
What do you see in some
of those industries?

287
00:14:12,960 --> 00:14:16,860
- Well, due to the
unregulated status of CBD

288
00:14:16,860 --> 00:14:20,580
and the fact that you can
actually find Delta-9-THC

289
00:14:20,580 --> 00:14:23,155
in these products at higher than the 0.3%

290
00:14:23,155 --> 00:14:25,140
that's supposed to be there,

291
00:14:25,140 --> 00:14:26,230
employment testing,

292
00:14:26,230 --> 00:14:28,310
the Department of Transportation testing

293
00:14:28,310 --> 00:14:31,400
in the case of truck drivers,
airline pilots, et cetera,

294
00:14:31,400 --> 00:14:33,930
people who use those
products could potentially

295
00:14:33,930 --> 00:14:38,930
test positive for marijuana
use, and for athletes,

296
00:14:39,180 --> 00:14:44,180
the World Anti-Doping Agency,
or WAA, has excluded CBD

297
00:14:44,890 --> 00:14:47,220
from its list of prohibited cannabinoids.

298
00:14:47,220 --> 00:14:49,260
However, if you look at

299
00:14:49,260 --> 00:14:51,810
the latest list of their prohibited list,

300
00:14:51,810 --> 00:14:54,150
cannabinoids in general are still listed

301
00:14:54,150 --> 00:14:58,020
as forbidden to be used in competitions.

302
00:14:58,020 --> 00:15:01,650
Now remember, CBD products
are sold as sort of, kind of,

303
00:15:01,650 --> 00:15:03,937
these full spectrum products,
but they still contain

304
00:15:03,937 --> 00:15:06,650
these other cannabinoids like Delta-9-THC.

305
00:15:06,650 --> 00:15:10,440
So, an athlete that uses CBD
could potentially test positive

306
00:15:10,440 --> 00:15:14,340
for one of the prohibited
cannabinoids on that water list

307
00:15:14,340 --> 00:15:19,340
and therefore essentially be
de-qualified from their event

308
00:15:20,310 --> 00:15:23,310
or have a medal or element
taken away from them,

309
00:15:23,310 --> 00:15:25,230
and so, it is a real concern

310
00:15:25,230 --> 00:15:26,656
for people using these products,

311
00:15:26,656 --> 00:15:29,190
again, because they're unregulated

312
00:15:29,190 --> 00:15:33,540
and they can contain some of
these prohibited cannabinoids.

313
00:15:33,540 --> 00:15:34,373
- I see.

314
00:15:34,373 --> 00:15:36,720
This actually clarifies a lot for me.

315
00:15:36,720 --> 00:15:38,670
So, I'm taking away from this conversation

316
00:15:38,670 --> 00:15:42,971
that, you know, yes, I'm
seeing a lot of CBD out there

317
00:15:42,971 --> 00:15:46,317
and CBD by itself, you know,

318
00:15:49,230 --> 00:15:52,020
is not necessarily causing
issues for, you know,

319
00:15:52,020 --> 00:15:54,240
my employment drug screen,
and things like that,

320
00:15:54,240 --> 00:15:57,483
but the fact that it's unregulated,

321
00:15:58,400 --> 00:16:01,035
it probably sounds like I
guess we could safely say

322
00:16:01,035 --> 00:16:06,035
it's likely not a
purified compound solely,

323
00:16:07,180 --> 00:16:10,530
and that may have implications.

324
00:16:10,530 --> 00:16:13,620
So, I guess for all of us
listening, to understand that,

325
00:16:13,620 --> 00:16:16,710
you know, we may be running positive

326
00:16:16,710 --> 00:16:21,710
or finding THC and the person
may not be smoking marijuana,

327
00:16:23,120 --> 00:16:27,690
but using CBD oil may be a source for it.

328
00:16:27,690 --> 00:16:29,553
That's really helpful to understand.

329
00:16:30,510 --> 00:16:35,510
Do I use my wife's CBD oil soap or not?

330
00:16:37,380 --> 00:16:40,647
And then, you know, for
some of these industries,

331
00:16:40,647 --> 00:16:42,840
you're kind of talking about, yeah,

332
00:16:42,840 --> 00:16:47,580
there are potentially huge
ramifications for people,

333
00:16:47,580 --> 00:16:50,820
us in healthcare, athletes, we mentioned,

334
00:16:50,820 --> 00:16:52,890
are there any other kind of takeaways

335
00:16:52,890 --> 00:16:55,710
you want the audience to
appreciate out of this?

336
00:16:55,710 --> 00:16:58,170
- Yeah, I think one of the takeaways is

337
00:16:58,170 --> 00:17:00,570
that a lot of these cannabinoid products

338
00:17:00,570 --> 00:17:03,030
do have some potential
medical use and benefits.

339
00:17:03,030 --> 00:17:05,550
So, we don't wanna necessarily
downplay or ignore that.

340
00:17:05,550 --> 00:17:07,905
You know, I think if you
talk to our neurologist

341
00:17:07,905 --> 00:17:10,590
in the case of seizures,

342
00:17:10,590 --> 00:17:12,484
in some of these pediatric patients,

343
00:17:12,484 --> 00:17:15,150
CBD has been very beneficial,

344
00:17:15,150 --> 00:17:17,550
but I think the ultimate
message or takeaway is

345
00:17:17,550 --> 00:17:18,720
for some of these products

346
00:17:18,720 --> 00:17:20,572
where people are using the CBD oils,

347
00:17:20,572 --> 00:17:22,190
gummies, and other things,

348
00:17:22,190 --> 00:17:25,350
it's sort of like the
old buyer beware, right?

349
00:17:25,350 --> 00:17:27,210
It's unregulated.

350
00:17:27,210 --> 00:17:31,170
So, if you are concerned
about potential implications

351
00:17:31,170 --> 00:17:33,990
with your job or other
employment issues, you know,

352
00:17:33,990 --> 00:17:36,718
maybe you may not want to use it

353
00:17:36,718 --> 00:17:39,933
and stick to other forms of medicine

354
00:17:39,933 --> 00:17:41,856
that would have less risk

355
00:17:41,856 --> 00:17:45,480
just because we are
seeing it at higher levels

356
00:17:45,480 --> 00:17:49,200
and in detectable concentrations
in some of these products

357
00:17:49,200 --> 00:17:53,640
that could lead a
clinician, or your employer,

358
00:17:53,640 --> 00:17:57,603
or WATA, or some agency to think

359
00:17:57,603 --> 00:17:58,993
that you are actually using marijuana

360
00:17:58,993 --> 00:18:01,140
when in reality you're not.

361
00:18:01,140 --> 00:18:02,600
- I'm glad you're the voice of reason,

362
00:18:02,600 --> 00:18:05,159
of let's not throw the baby
out with the bath water.

363
00:18:05,159 --> 00:18:08,550
There is a medical place for this,

364
00:18:08,550 --> 00:18:10,320
and it sounds like that is, you know,

365
00:18:10,320 --> 00:18:13,980
prescription grade is a different story.

366
00:18:13,980 --> 00:18:16,710
It's the stuff that we see marketed direct

367
00:18:16,710 --> 00:18:18,243
to consumer on the street.

368
00:18:19,280 --> 00:18:20,620
- Exactly.
- Excellent.

369
00:18:20,620 --> 00:18:22,778
Well, hey, thank you so much Dr. Jannetto

370
00:18:22,778 --> 00:18:24,870
for shedding some light on CBD.

371
00:18:24,870 --> 00:18:27,600
I know a lot of my colleagues
are really interested

372
00:18:27,600 --> 00:18:29,560
to learn from you on this topic.

373
00:18:29,560 --> 00:18:30,660
- Well, thank you.

374
00:18:30,660 --> 00:18:31,523
Pleasure to be here.

375
00:18:31,523 --> 00:18:35,550
- We've been rounding with Dr.
Jannetto talking about CBD,

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00:18:35,550 --> 00:18:39,150
and to all of our listeners,
thank you for joining us today.

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00:18:39,150 --> 00:18:41,010
We invite you to share your thoughts

378
00:18:41,010 --> 00:18:45,340
and suggestions via email
at mcleducation@mayo.edu.

379
00:18:45,340 --> 00:18:48,270
If you've enjoyed Lab
Medicine Rounds podcast,

380
00:18:48,270 --> 00:18:51,090
please subscribe, and until
our next rounds together,

381
00:18:51,090 --> 00:18:53,900
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to connect lab medicine

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00:18:53,900 --> 00:18:57,991
in a clinical practice through
insightful conversations.

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00:18:57,991 --> 00:19:00,658
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