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April 14, 2023 • 115 mins

The vast majority of cannabis enthusiasts and patients are also taking some prescription drug or another, and cannabis patients often ask about the potential for drug-drug interaction without ever getting a satisfying answer. On this episode of Shaping Fire, host Shango Los talks with pharmacologist Jahan Marcu PhD about the complex biology of cannabis interacting with other drugs, how to discern if you may be experiencing an interaction, and some red flag drugs that should be watched closely.

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Episode Transcript

Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:07):
Patients always want exact answers.I know when I go to the doctor,
I too want specific answers to specificquestions and I rarely get them.
Similarly, when cannabis patientsask me detailed questions,
often the answers are also elusive.
The best medicine is individualizedmedicine, and by definition,
individualized medicine is going tobe somewhat unique to every person.

(00:29):
That said, when it comes to cannabis,
if you identify the proper blend ofcannabinoids and start slow and low in the
dosage, a path to resolving theissue usually presents itself.
Cannabis is safe for nearly everyone andhumans have had thousands of years to
get into relationship with the plantand learn it to be reliable and with few
side effects. However,

(00:51):
when you add complex chemicalpharmaceuticals to the mix,
sometimes things don't go as planned.
And most pharmaceuticals have only beenaround for a mere fraction of the time
that cannabis has beenused by humans. And also,
while a layperson can easily understandthe dosing dynamics for cannabis,
that is entirely untrue for mostpharmaceuticals whose contents are

(01:12):
intentionally obscured and instructionsfor use are shrouded in legally
defendable double talk,
it is enough to frustrateanyone just trying to get well.
If you wanna learn aboutcannabis health, business,
and technique efficientlyand with good cheer,
I encourage you tosubscribe to our newsletter.
We'll send you new podcastepisodes as they come out,
delivered right to your inbox,

(01:32):
along with commentary on a couple ofthe most important news items from the
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(01:56):
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you are listening to Shaping Fire.And I am your host, Chango Los.

(02:19):
My guest today is Jhan Markou. Dr.
Markou is a molecular pharmacologistwith over 15 years of experience in
cannabinoid research and a PhD focusingon the pharmacology of cannabinoids.
Not only has Johanna committedscientist, but he goes way back too.
As a cannabis activistand policy influencer, Dr.
Markou is a founding partner at theconsulting firm of Markku and Aurora,

(02:40):
which provides life science consultingto the cannabis and psychedelic fields.
He's also chief scientific officerat Physicians Research Center.
Plus Jahan also co-developed abiotech application to predict
drug drug interactions between cannabisand commonly prescribed pharmaceutical
drugs.
And co-authored one of of the firstproduct safety studies on C B D Dr.

(03:02):
Marco co-authored American HerbalPharmacopia Cannabis Quality Control
and Therapeutic Monographs,
and serves on multiple expert governmentadvisory and trade association
committees.
He is the founding editor-in-chief ofthe American Journal of Endo Cannabinoid
Medicine and is adjunct faculty atthe University of the Sciences in
Philadelphia, teaching thepharmacology of cannabis.

(03:25):
He has many research andmedia publications and has appeared in Rolling Stone
Science, nature Jamma, the WashingtonPost, CNN n and many others.
He is host and producer of the Howto Launch An Industry podcast and is
often called upon as a cannabis andsynthetic drug expert witness. Dr.
Markou has received numerous awards,
including the Mahmud El Soli Awardfor Excellence in Cannabis Chemistry,

(03:49):
and the Billy Martin ResearchAchievement Award from the International
Cannabinoid Research Society. Ontoday's episode of Shaping Fire,
we will talk about how to think throughthe dynamic challenges presented by
cannabis and pharmaceutical interactionand give you a roadmap for doing this
research for yourself or thecannabis patients you care for.
During the second set,
we'll review red flag pharmaceuticalsand drug families that present especially

(04:13):
high risk and how the availability ofnew cannabinoids and concentrates has
exacerbated these issues.And in the third set,
we look at the differences betweenendocannabinoid and phyto cannabinoid drug
interaction, discuss the state ofdrug drug interaction research,
and we encourage everyonewho uses cannabis to visit buds info.com and complete

(04:34):
a short questionnaire to helpin the research into this topic.
Welcome back to Shaping Fire Jahan.
Thank you Shago. It's great to be here.
You know, like what, even though youand I have interacted over the years,
this is episode 104,
and your last visit to appear onshaping fire was all the way back on

(04:54):
episode 29. And that seems likesuch a long time ago. In fact,
it was the week of Christmas in 2017.
. Wow.
Yeah, it was like, like back, backin the before times, you know.
so much as it seemslike that seems like a lifetime ago for
so many things and projects.Um, that's amazing. Yeah, for.

(05:18):
Sure. So, um,
and that was in the early days of shapingfire when we focused a bit more on
business. So, um,
episode 29 is a great one aboutcannabis product manufacturing, uh,
standards. And we don't cover thelicense market as much anymore, but, um,
folks, if you're, if you are inlicensed cannabis or in, in, you know,
in medical cannabis and in production,

(05:38):
that's a really excellent show that hasremained evergreen over the years. So,
so I encourage you to go back and, andcheck out episode 29. If you haven't.
I would say, uh, you know, the bigupdate to that though is I've gone from,
you know,
voluntary certification assessmentsfor regulatory compliance on all

(05:58):
types of cannabis operationsaround the world. And since then,
I actually got to visit hempfacilities in China, uh, Europe.
And I've started to work with, um,state governments on, you know,
determining compliance assessment criteriaand updating regulations, you know,
driven by science from that experience.So, you know, I feel like you're, uh,

(06:19):
you're like the paleontologist chango.You got to walk with a, you know,
a dinosaur like me in the early days.
. That's, that's, I guess that'sone way to put it. Except you're,
you're still so youngthough, so I hope so.
Cause I think you're youngerthan me, so, um, so, so, but,
but today we're here to talk,
to talk and focus on the interplaybetween cannabis and the pharmaceuticals

(06:41):
that cannabis patients may be taking.
And we both wanna be clear right off thebat that we are not giving you medical
advice today. Uh, we have no way ofknowing your actual whole situation.
And our goal today is to flesh outsome of the intricacies of this topic
and, and help you gain some perspectiveso that you can figure out effective
individualized medicine for yourselfor the people that you care for. So,

(07:05):
so, alright, let's getright into it. So, Jahan,
the idea that any one ofso many phyto cannabinoids
interacting with any one ofthousands of prescription drugs,
that they could have an unintended sideeffect seems like a pretty realistic
thing nowadays. But for years inthe medical cannabis community,
no one wanted to admit that itwas possible, including me. And,

(07:28):
and maybe it was simply because therewere so little research into it, or,
and we just hadn't seen it. Um,
but also it could also just be that we'reall really protective of our favorite
plant cannabis.
But now we know that theseinteractions actually do exist as,
as more and more people use cannabisand we're able to collect more data,
are we actually seeing morereports of interactions nowadays?

(07:51):
Yeah. Um,
the potential for drug drug interactions,
regardless of the substance, you know,
cannabis has compounds that interactwith receptors and are metabolized by our
body, um, ELs that wouldn'thave all these, you know,
wonderful therapeutic benefitsthat we hear about. Um, but,

(08:12):
but drug drug interactions or DDIs are,
are increasing generally across the board,
not just for cannabinoids or cannabis,
but it is the primary cause ofadverse drug reactions. And it's,
it's something that creates overhalf a billion dollars of estimated
burden on our healthcare system annually.

(08:33):
And there's a lot of effortsto avoid these drug drug
interactions. Um, you know,
drug regulatory agencies like the FDAusually mandate this sort of thing.
And we know a lot aboutthem for some stuff. Uh,
for like Marinol, whichwas approved, you know,
a decade or so before we even knew theywere cannabinoid receptors as well as as

(08:55):
for Epidiolex or C B D. Sothese have been explored. Um,
but what we're dealingwith now is, you know,
we live in a really lucky time and in areally lucky place if you're listening
to this in the United States,
we have the fda and I know that peoplelike to criticize the fda. Well that's,
that's great. That's, that's, that's oneof the great things about being alive.
You get to criticize things, but it'salso the best drug regulatory agency.

(09:17):
In fact,
it's so good that mostof us simply throw away
the insert on any medicationwe get. It's like,
as a long fold out map of potentialissues. And we're like, oh,
just throw that away.This is FDA approved. Um,
so we do live in a time wherewe buy a loaf for bread,
we buy a bottle of aspirin, weget our prescription medications,

(09:39):
and we just assume that ifit's on a shelf, it's safe and,
and the risks, um, you know,
are known or they wouldn't or wouldn'tbe on a shelf. Um, however, you know,
there's interesting things are happeningwith cannabis compounds, you know,
due to a strong patientand consumer demand.
Cannabis based products don'tfollow the traditional standard drug

(10:02):
development pipeline that we holdpharmaceutical drugs like, you know,
antidepressants or other drugstoo. They just, you know,
you package and labelthem at the state level.
And so there is a lack of understanding or
appreciation of the potentialdrug drug interactions. Um,
and again, a lot of theseoccur from, you know,

(10:26):
oral administration ofmultiple substances,
sort of the more drugs that youuse, the more pharmaceutical drugs,
the more medicines you take,
the higher your chancesof interactions. Um,
and you know, this is not, you know,we have to kind of like, you know,
I've been a passionateadvocate of product safety,

(10:47):
particularly for medical cannabispatients for for almost two decades.
And you know,
I remember a time when the plant productsweren't even tested before giving to
people who had compromised immunesystems. Um, I remember arguing with,
uh,
operators to put voluntarilyput expiration dates and people saying thing like,

(11:08):
well, cookies don't go bad.Um, and, and, but again, we,
we see drug drug interactions all thetime. We talk about them all the time,
but we don't know thatwe're talking about them.
Some of them are for our benefitand some of 'em can increase risk.
Um, let me give you an example ofa conversation I had 15 years ago,

(11:30):
maybe 20 years ago. Uh, I was just a,just a little researcher at the time,
a undergraduate, and Iapproached a cannabis operation,
started talking them up about cbd,you should carry CBD products.
This is like gonna be a great thing.
And people had startedsmall circles to talk about,
and they asked me what itdid and I said, oh, well it,
it actually blocks the intoxicatingeffects of thc mm-hmm. .

(11:53):
And they're like, oh my god, that soundsterrible. Nobody will ever want that.
But CBD and THC is a formof a drug drug interaction.
It's not quite what we'retalking about, but it can be, um,
one that may not be ideal, um,for some people. Uh, you know,
so I think that when we talk about drugdrug interactions, we talk about them,

(12:15):
we talk about, oh, this variety ofcannabis has this mixture of compounds.
It's good for this, ithelps with this, it,
it's has these indications. Um,
there's an array that can be present. Um,
so I think we always have to keep inmind that we are familiar with this.
We talk about it, you know, it's likesaying, I like to talk about, you know,

(12:37):
baseball statistics, butI don't like math. Well,
clearly you do like math cuz you'reanalyzing averages and percentages. So we,
we do have the fundamentals ofthis, I think, in the industry.
So we're not really talking about,I think anything new today that you,
that you've probably haven't,you know, discussed before.
How do drugs interacttogether to produce an effect?

(12:58):
And let's talk about thathow a little bit, um,
because the different mechanisms, um,
I think it's important for peopleto wrap their heads around the, the,
the first interaction that I was awareof was years ago learning that, uh,
C B D can increase the potencyof some seizure medications,
meaning that the seizure patientstaking C B D could sometimes take less

(13:20):
of that seizure medication and getthe same um, effect in some cases.
Let's dissect that idea because theC B D could be causing the seizure
medication to be morepotent for many reasons.
One being perhaps that the C B D andthe seizure medication are doing the
same thing and working side by sideinstead of actually on each other.

(13:42):
Or secondly, CBD could be acting in away that the seizure medication has get,
gets more resources or something.
There's a lot of different mechanismsfor why that could be happening.
And, um, you know, I,
I know that you have studiedin detail these different
mechanisms of drug drug interaction.

(14:02):
I'd really appreciate if you would teasethem apart and explain a few of them
and like, take your time. Give us,
give us like three or four so that wecan really grok the different mechanisms.
, you know, a absolutely.And when we talk about mechanisms,
um, you know, we can,
I like to think about 'em in three ways.

(14:23):
One is cannabinoids as victim, right?
Where the mechanism is that thelevels of the cannabinoid is changed.
You take a drug and it makes the,you take, you take it with thc,
let's call it drug X, right?
And you take it with a THC product andsuddenly you're feeling way more sedated
or have way higher munchiesside effect or whatever,

(14:46):
pick your side effect for yourconceptual example. And it's just,
it's increased because the cannabinoidlevels are changed by another drug.
So cannabinoid is a victim whereits levels in your body are changed.
Well, cannabinoids canalso be perpetrators.
They can cause changes in thelevels, uh, of another drug.
Um, and so in this case, you know,

(15:07):
they might be increasing or decreasingthe amount of, like you said,
like an anti-epilepticmedication or a pain medication.
And if this information is wellunderstood, you're absolutely right,
it can be leveraged to improve, uh,
healthcare outcomes. Youknow, if you're like, oh,
there's a drug drug interactionbetween cannabinoids and opioids,

(15:28):
you can take less opioidsand get the same effect. Wow.
We thank goodness we knew about thoseinteractions so that we could take steps
to make that a benefit insteadof an increased risk. Now,
there also are, so we've talkedabout cannabinoids as victims,
cannabinoids as perpetrators,
and there are also pharmacodynamiceffects. I think that's the first, uh,

(15:50):
five syllable word we've used so far.But there are pharmacodynamic effects.
And what this means is that both drugshave overlapping effects and our concepts
of victim and perpetrator don'tapply here. But, you know,
one thing is like if we take, uh,
research on THC and baclofenindividually at doses given to

(16:12):
people and studies is alittle bit of sedation,
not too much to write homeabout, but you put them together,
there's like sedationcoming from that drug,
sedation coming from the otherdrug and put it together.
Sedation plus sedationequals a lot of sedation. Um,
and that could be an unwantedside effect and adverse effect.

(16:33):
Um, and so as we continue with thisvictim and perpetrator analogy, you know,
you mentioned cannabidiol. C B D I,
I think this is a greatexample because, you know,
here we have a drug thatis given to pediatric
patients in large amounts who arealso taking other medications.

(16:54):
And in the, you know,
I think even several years ago starting,
I think Divinsky publishedthe paper in 2018,
and those of you listening can emailme, uh, message me on social media.
If anything I mentioned you're like, Iwant that study, send me that link. Uh,
feel free to reach out. But, you know,they should have high doses of cbd,

(17:14):
significantly increasedlevels of nar clobazam, um,
which is an active metabolite of Clobazam.
So basically what you're sayingis you have a baseline amount,
let's call the baseline zero.It's just or normal, right? Um,
and so you, when you takeit with um, C B D, um,
you can start to see that, uh,

(17:36):
the amounts of Clobazam and theratio of Clobazam to nor Clobazam,
the metabolite and the, the, the,
the parent compound justgo a little haywire.
You start to see those levels changeif almost completely different
than without cbd We'retalking, um, you know, the,
the, we're seeing, you know,

(17:58):
a hundred and fifty, two hundred,three hundred 50% above baseline.
Those, uh, you know,
those bars on the graph look likeskyscrapers of New York City,
which is a signal that weneed to pay more attention to.
And that would be an exampleof a cannabinoid as a perpetrator of a drug drugg
interaction. Um, and sohow is this happening?

(18:22):
You might be saying, well,
we have a lot of things in ourbodies that like to handle drugs. Um,
you know, we're, we're hardwiredto, uh, consume things,
have them hit little proteins,
also known as receptors throughout ourbody and send along little messages.

(18:43):
Well, however,
we have to have a system that gets ridof the drugs after they've sort of sent
their message to the brain, tothe body and had their effect.
And we have these drug metabolizingenzymes. What do they do?
Well, they are the garbagetrucks of drugs. They just like,
they like chewing up drugs andhelping us pee them out. Um,

(19:04):
so the enzymes of responsiblefor this, so when I say enzymes,
I say proteins, I say receptors.
These are all things that ourbody makes from our dna, right?
We have, we have dna, it codes,amino acids that form these proteins.
And proteins can do alot of different things.
And these sip p uh, c y p four 50,

(19:27):
we call them sipps, uh, for short,for short, for cytochrome P four 50.
Um, there are many differentforms and um, you know, there are,
um, you know, we inheritdifferent ones from our family.
And I think this next point isimportant because with the advent

(19:48):
of gene testing,
you can find out someinformation about how you might,
uh, metabolize drugs. So, um,
there are people who are slowmetabolizers, like really poor.
That means the drug stick around longer.
There are people that areintermediate metabolizers.
There's people who are extensive,

(20:09):
and then there are peoplewho are ultra rapid.
And that means that if you'rean ultra rapid metabolizer,
you can take a drug andyou may not even feel,
or you may feel just the faintest ofeffects for it before it's metabolized and
excreted from your body.
There are some reallywild examples of this.

(20:34):
Um, uh, you know, for example, um,
there is an associationwith, um, cuz people who,
who suffer from, uh, geneticallyfrom sickle cell disease, uh,
they have some genes, uh, in majorityof the population that are conserved.
And many of them are ultrarapid metabolizers of opioids.

(20:55):
And frequently people with sickle celldisease get prescribed the maximal
allowed amount of opioids,
which has been steadilydecreasing over time,
but they tend to beultra rapid metabolizers.
So whereas most average peoplewould probably fall in the
intermediate, in the mid-rangeof drug metabolizing. Um, and,

(21:18):
and a a little opioid goes a long way.
There are populations that would rapidlyjust and wouldn't feel an effect.
So it would look really weird onsomeone's chart at a doctor like, wow,
you're taking a lot of opioids,
but unless you knew the genetic componentand the other drugs they were taking,
it may not make a lotof sense. So one is, uh,
to know thy self, right?

(21:38):
And so using kind of allavailable tools to understand,
first of all from a baseline, how do I,what, how do I even metabolize drugs?
Am I the type of person who can drinkcoffee all day long and go to sleep
because I'm a rapid metabolizer or willjust smelling a cup of coffee keep me up
for three days? Mm-hmm.

(21:59):
like these might bethings you can playfully tease out.
And so the reason I wanna mentionthat, cuz that is a factor, um,
with this, um, stuff, cuz thereare people who have mutations, uh,
polymorphisms, uh, asingle little change, um,
can cause people to be, youknow, much more, uh, say,

(22:20):
you know, it can change the amountof THC that's even in their body.
So if you are a slow metabolizer of thc,
you'll have more THC floating around. Um,
and much like someone floatingaround with nothing to do,
they might get into trouble.And so that it increases the,
the chances of a drug druginteraction. So you could,
you could have be a slow metabolizerand realize that, you know,

(22:45):
I have to be careful about the timingand method of ingestion because, um,
this is gonna stick around forlonger than the average person.
So you could get, you know, dependingon how well you metabolize things,
you could have threefold higher levelsfloating around. Um, which I have to say,
uh, if you do a rapid orultra rapid metabolizer,

(23:07):
you'll probably have a betterchance of passing, uh, a blood test.
If you were ever pulled overfor a cannabis related dui,
you just better hope and pray you'rea rapid metabolizer if it's based on
thresholds for the amountin your system. Uh,
just to give you an example of somereal world implications for this
information, powerful information isavailable for you to navigate. This,

(23:31):
I think is, is the point I'm making.And so we talked about cbd, uh,
clobazam,
and how that's an interactionwhere CBD is inhibiting a sip that
prevents the metabolism of thisclass of benzodiazepine, not,
not a fun time. Um, and so, uh,

(23:53):
you know, we have these sipps, theseenzymes, and there's a whole bunch of 'em,
and they do different things. Um, Imean, they metabolize different drugs.
And when we think about, youknow, cannabinoids as victims,
um, there's uh,
different sipps and they have funlittle names like sip three A four or
C two C nine. And, and you're probablywondering, those are so beautiful,

(24:16):
I'm so glad scientists named them thatway cuz it's totally easy to understand
what they do. It's not like, you know,. Um, so C P three A four,
um, can be inhibited.They can be activated, uh,
by different drugs. And so chclarithromycin ketoconazole,
there's other proteaseinhibitors that people take.

(24:37):
And when you take those drugs, you're,you're inhibiting some sipps. They,
they like to block thoseproteins for some reason.
And if you take a cannabinoid,
you could have two to four timesthe amount of THC or CBD in your
bloodstream, in your plasma,uh, relative to just, you know,
taking the cannabinoidalone. And that's, again,

(24:57):
these could be drugs that havenothing to do with each other,
like clarithromycin oragain, keto cazal. Um,
and that's a paper I thinkpublished in 2013, you know,
10 years ago theyidentified this reaction.
And so what we see is that youhave these drug metabolizing
enzymes that can be either inhi,

(25:20):
can be largely inhibited by a drugthat then affects another drug.
So t h c needs CYP three A four to be
metabolized and processed by the body.
You inhibit that itstays around longer, um,
which could have unintendedconsequences. But again,
it all comes down to how we usethe information, um, as well.

(25:44):
And so I think that there'sagain, um, you know,
a lot of this information isextrapolated from drug metabolism
studies. Like, there's not,
there's not a lot of clinicalwork where people are like,
we wanna study drug druginteractions. There's,
it's all sort of teased out from studies.

(26:05):
And so a lot of this stuff hasbeen put together from almost like
detective, like work. Um,and, and again, you know,
there are some clinicallysignificant ones and, you know, cbd,
um, you know, with Clobazam, warfarin, uh,
taro, Myas and methadone have all been,

(26:29):
um, implicated in having a potentialsignificant drug drug interaction.
But I'll say that there, the,
the nuance there is that it alsodepends a little bit on your genetic
makeup and, and a couple of otherfactors. But again, on paper,
these things have a clinicallysignificant, uh, interaction potentially.

(26:50):
Um, and THC does share some ofthose similar concerns with, uh,
you know, tb, CBD and TC bothrepresent, um, an issue with warfare.
And potentially as well.
I, I, um,
think that we're seeing now exactlyhow complex this has become,
because I think for most of us,
we're just kind of thinking in thissingular way that the cannabinoids

(27:14):
are interacting with pharmaceuticals.
And generally we think of it's havinga, a, a bad effect. However, you know,
we're getting a better idea now thatwe can have cannabis acting on the
pharmaceutical,
and then we can have the pharmaceuticalperhaps acting on the cannabis and they
could also be going in the, uh, differentdirections. They can be inhibit,

(27:36):
one could be inhibiting the other, orthey could also have additive effects.
So now that's going in twodirections and then, and then,
and then there's another two directionsbecause the additive or inhibited
effects could actually endup being desirous or they could be something that we
don't want. And so suddenly now wesee this like multi-dimensional,

(27:58):
um, uh, you know,
interplay between thesedrug drug interactions and
like our definitions kind ofstart to float away because,
because some of the interactions forone patient are gonna be negative and,
but for a different patient,they're gonna be desirous.
And I think that you've done a reallygood job at illustrating how, how we,

(28:19):
we need to look at, you know,
individual patients and not make big,
grandiose rules that we'regonna try to apply to everybody,
all drugs or all typesof patients. And, uh,
and I like this encouragementfor us to, you know,
dig into our genetics as well. You know,
especially if we're trying to teaseout some kind of drug drug interaction

(28:41):
problem we think we have. Um,uh, and, and we want to get,
uh, specific, um, with that,
I also like this idea of thisperpetrator and victim idea where, where,
you know, you've got,
you've got one compound thatis receiving the action,
and the other one that is,is placing the action. Um,

(29:02):
let's talk a little bit about thecannabinoids that are already in our body,
right? So like up till now we've beentalking about adding phyto cannabinoids,
so cannabinoids fromplants, um, to the mix.
But we know that we already haveendogenous cannabinoids in our body.
They already exist. And,
and usually when we are taking additionalphyto cannabinoids from the cannabis

(29:23):
plant to supplement theendocannabinoids that our body creates,
um, you know, that's, that'sour goal. I'm curious, um,
do we see any, uh,
or or significant interactionsbetween these endocannabinoids that
somebody who doesn't even usecannabis will have in them and these

(29:44):
pharmaceuticals?
Sure. Um, you know,
we certainly can talkabout some of the things
that will make you realize youhave an endo cannabinoid system.
So when we talk about the endocannabinoid system, it's, it's, again,
it's not just anandamide and two,

(30:05):
a g and p a and oea and allthe amino acid conjugated
endo cannabinoids. And, you know, the, we,
we could definitely delveinto the molecular psychiatry of all those compounds,
but we have to remember that alot of these endocannabinoids are
made on demand and theyare metabolized quickly.

(30:27):
And reason that's important isbecause, you know, we ha we,
we want to focus on anandamide two G,
but we also have to focuson them being made. We,
we can't just look at the bullet,
we have to look at the gunthat's firing the bullet.
And in this sense, um, the analogy isn'tperfect, but when we think about fa,

(30:48):
which is the, as in, you know, I like tothink far out research fa out research,
but, uh, fa is an enzyme that, youknow, chews up the endo cannabinoid.
So, uh, it's, it's the, you know,the endo cannabinoid dump truck. It,
they're made quickly byour body on demand. Again,
most signaling molecules aremade and stored and released. Uh,

(31:10):
endocannabinoids are made on demand.
And so one interaction with theendocannabinoid system that I think
most people have experienced,um, I will describe in a moment,
there's actually an over-the-countermedication that anyone can buy that will
interact with your endocannabinoid system. And I'm not,
I'm gonna let you think about itfor a minute, listener and chango,

(31:32):
but I just wanna tell you aboutthis case report real quick.
And so imagine you, uh,
had a history of painlessinjuries in your life,
you accidentally cut yourfinger and everyone's like, oh my gosh, did that hurt?
And you're like, ah, it's all right.Stub your toe, don't feel it. Morphine,
opioids don't really relieve yourpain. You get some minor surgery, uh,

(31:55):
from experiencing life.And, you know, you're like,
I don't need pain medication.And, and you know, you,
people around you and even use like, wow,
I have this high threshold for pain.
So how could the endocannabinoidsystem explain, well,
I'm not really getting an effect fromopioids, I actually don't even need them.

(32:16):
Um, and that's, um,
this is from a story that waslaid out in a case report about
a, a micro deletion in the dna.
And it was in a fa gene,
the gene that tells our bodies howto make this enzyme that breaks
down the endo cannabinoids andthat without the dump truck,

(32:37):
the trash just piles up. And soyou get a lot of anandamide and,
um, you know, decreasesin pain sensitivity.
And so this actually reallyhappened. The mutant walks among us,
it was a 66 year old female,
had history of not requiringany pain medication,
a history of painlessinjuries. Wow. And, and why,

(33:01):
why do I, why does this relate to anover-the-counter endo-cannabinoid drug?
Well, it's a little tongue in cheek,
but peritol or as some ofus call it Tylenol, right,
uh,
requires fo to exert itspain relieving properties.
Um, and so a, uh,

(33:21):
basically Alex Mock Creos,
who's at Northeastern University was anadvisor on my thesis, and, um, was also,
you know, many of my colleagues likeDr. Josh Hartsel and others, um,
worked with him as well.And he discovered, um, a,
a drug. And it turns outthat it's, um,

(33:41):
it's related to this, butbasically, um, without,
when, when you take Tylenol, it ismetabolized into a FO inhibitor,
which temporarily increases the amountof endocannabinoids in your system.
And so if you, uh, created, uh, whatthey did in an experimental model,
a permanent FA inhibitor drug,which irreversibly binds fa,

(34:06):
you know, perol or Tylenol had noeffect. So no endocannabinoid system,
no Tylenol. Um, and this is,again, this is a fun example,
an extreme example for us to playwith these concepts like, wow,
um, I'm taking Tylenol, how does it work?
One of the ways it works is byinhibiting this enzyme that allows my

(34:28):
endocannabinoids to flourish andbe produced in higher than normal
concentrations. It does otherthings as well. And, um,
and so I think like there's oneexample of endocannabinoid interaction.
And, and so the next time you go to agrocery store, you know, look, there's,
there's an endo cannabinoid medicineright there on the shelf. Um,

(34:48):
but obviously, you know,
endo cannabinoids are slightly differentin their activity than THC and cbd.
They share a lot of interactions. Um,
and I think there are other thingswe can think about. You know,
cannabinoids obviously interactwith the endocannabinoid system.
And I think one of theways that we can think

(35:11):
about it, um, is that, um, you know,
cannabinoids can, you know,
inhibit or enhance certainactivities of each other. And so,
you know, if we have, you know, uh,
CBD in there and it's modulatingcannabinoid receptors to
make them more difficult to beactivated, it's actually an, um,

(35:35):
a negative allostericmodulator of CB one. You know,
what does that do to your naturalanandamide signaling, right?
So CBD can definitely influence that. Um,
and I think we can think aboutother aspects, um, there as well.
It's, you know,
I wish I had like a virtual whiteboardto start drawing out circles and charts,

(35:56):
but let me try to sum it upreal quickly. So, you know,
CBD is a great one to talk aboutcause it does a lot of, lot of things.
It's a very promiscuous,uh, molecule, but it,
it increases anandamide levels cuz CBDdoes have a little bit of fa inhibitor
activity. So it increases anandamidelevels that stimulates a bunch of other

(36:18):
channels. Um, and, andreceptors like Trip V one, um,
if you're heard of vlo receptorstrip V one something you,
you stimulate every day. Ifyou eat spicy food, um, it's,
it's a capsaicin from chili peppersstimulates it. And so, you know,
you could take, uh, you know,
CBD increases in anandamidelevels or you're an,

(36:40):
or if you just have naturallyhigh in anite levels,
this will counteract or antagonize, uh,
the effect of potentially of, um,
of CB one receptors on, on gluliturgic neurons. And so you can,
um, you know,
one thing that THC does is itslows brain activity a little bit.

(37:00):
And what I mean by brain activitydoesn't like make your brain dead,
but it's one of the reasonsit has a benefit, right?
Is that people talk about cytotoxicityexcessively active neurons. You,
if you have seizure or traumatic injury,
your neurons might be firing like crazyand firing until they kill themselves.
Just like release, release, release,stimulate, stimulate, stimulate, you know,
red alert, red alert. Um.

(37:21):
And.
Uh, you can decrease that signaling.
That's why one of the reasons itmakes it hard to remember stuff. Um,
but it also makes it, you know, makesit harder to receive a pain signal. So,
so what happens is, uh,
just simply put THC hits a receptordecreases in glutamate release.
Um, however, uh,
you can also enhance glutamaterelease by stimulating trip receptors.

(37:44):
And so you could have this sort of giveand take these forces going in different
directions, um, to impactit. So I know that was a,
a little bit of a heady response.Um, you know, but I mean,
there's lots of examples,um, like this, like, um.
That's probably the one we needfor now though , um, uh, uh,

(38:04):
because you're right, it is,
it is incredibly complex and we'recertainly not going to be able to explain
them all. But, um, in, in one episode.
But you made the point very clearlythat we need to not go into this with
assumptions that a,
we know what's going to happen basedon science that might be outmoded,
and that individuals and the, you know,

(38:26):
really show the importanceof individualized medicine and that cannabis can do
that. And then also in a way,
we're kind of like already swimmingin all of these drug compounds that,
that, you know, we'retaking from over the,
or over the counter drugs plus anypharmaceuticals that were being offered.
Plus, you know, you add to it maybesome cannabinoids and, and you know,

(38:49):
maybe somebody is alsomicrodosing mushrooms. And,
and suddenly now there'sthis like the, this soup of,
of different drug druginteractions going on, and,
and there's no surprise that,that there would be some,
some sometimes unexpected effects.And before you jump on that,
cause I can almost feelyou going for it. ,
we need to take our first shortbreak. We'll be right back.

(39:12):
You are listening toShaping Fire and my guest,
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(39:36):
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(39:56):
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(42:01):
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(42:21):
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Welcome back. You are listeningto Shaping Fire. I'm your host,
Chango Lo semi guest, today's molecularpharmacologist, jhan Markku PhD.
So now Jhan, during the first set, youknow, you were very clear that, um,

(45:42):
we are seeing more of thesepharmaceutical and cannabis so cannabinoid
interactions, um, youknow, for two big reasons.
One being there's more peopleusing cannabis and, and then two,
there's more people researching it and,and collecting the data on this stuff,
which is really great. Um, Iwould have to think that like,

(46:02):
not only is there just like morepeople though using cannabis, um,
cannabis itself is expanded. We'resuddenly accessing all these like,
new new cannabinoids thatwe are experiencing in,
in higher amounts than theywould've in land races.
And we're also got like new waysto use cannabis like dabbing,
where you're suddenly getting all theseterpenes and cannabinoids at one time.

(46:27):
And, you know,
it's not uncommon for for people tolike keel over after like a fat dab.
And um, you know, there's just,there's just like so much,
there's so much more than weas humans ever interacted with
when we were, you know, you know,walking the planes and, and,
and mountains and, and pulling cannabisplants out and, and getting, you know,

(46:47):
the kind of land races they had, youknow, 10,000 years ago or whatever. Um,
will you speak to that? Like, towhat effect these new methods, uh,
and new ranges of cannabinoidsare having on, um,
the interaction with pharmaceuticals.
? You know, absolutely. Youknow, I think, you know, our ancestors,
you know, used to just eatcannabis and, you know,

(47:09):
clear some land and there'd be morecannabis growing and fresh cut land.
You know, they, theydidn't have, um, you know,
access to chemicals like butaneand shoved it in a tube and
extracted. I mean, they woulddo manual extractions. And,
and so I think it's always important toremember that concentrating cannabis has
been, been around for a long time.Um, you know, hashish, uh, you know,

(47:33):
Arab merchants, uh, used to tradeit up and down the coast of Africa.
Some of the earliest reports aboutcannabis use are these black Hashish
bars, um,
with guys riding basically naked inhorseback into villages to trade, um,
these products. Um, but thecomposition of the matter has,
has changed greatly. And I, you know,

(47:58):
the, you know, this alwaysreminds me of, uh, a mantra,
a phrase or principle for my colleagueTeresa Simon, who's epidemiologist.
And we've done a lot of databasemining, FDA database, adverse events,
databases, um, collection tools,
unlike the buds info.com thing where wecollect experiential data and adverse

(48:18):
events from campus products. Soit's a part of a student project,
but she says this thing seems likeevery week at every meeting, she says,
um, uh,
efficacy gets it on the market,
safety keeps it on the market. Hmm.
And I think if we've all been in thecannabis industry more than two years,

(48:39):
three years,
we can all probably think of one or twoproducts that hit the market cuz they
were effective. Where are they now?
And we have to really pauseand think about that. Um,
we have to think about a little bit aboutour commitments here when we put these
products out there. And, you know,
I'm trying to get back to yourquestion as I've meandered off the path

(49:03):
a little bit. But it justmade me think about, you know,
a lot of these products areconcentrating things beyond what,
um, our ancestors would've, youknow, encountered in, in the wild.
Um, you know, uh,
CBL and all these othercannabinoids. I mean,

(49:23):
they've never been consumed in largeamounts. It's unprecedented in our,
you know, in our, inour timeframe. I mean,
people even 20 years ago weren'treally consuming huge amounts of
purified cannabinoids. Even the,
the distribution of cannabinoids andproducts in concentrated products from
Morocco over the century saysnot nearly compare to the purity

(49:46):
and refinement of thesedabs waxes, shatters, what,
whatever you want to call it, uh, the stuff that looks like earwax that,
uh, and things like that.And, you know, we're this the,
there's no, there's no question.
Those are very efficientproducts to deliver
cannabinoids into your body.

(50:09):
What is unclear is what is the trade off?
What are the, what's therisk benefits to using that?
And do you need to use as much asyou're using or could you use less? Um,
and I think that those are questions wehave. Um, you know, when we think about,
um, you know, there's this oldquestion, uh, the dose, you know,

(50:30):
makes the poison, you know, nothingis poisonous. Everything is poisonous.
It's all a matter of dose. And,you know, we think about terpenes,
you know, at ambient airlevels, terpenes have,
are wonderful. Um,
you walk into a grocery store andif they've got that produce section,
it smells great to be there, coolbreeze, light, smell of chlorophyll,

(50:53):
and maybe they have some flowers going.
But if you concentrate some ofthose products, um, you know,
you'll find them in as cleaningagents. Uh, laine is a good one.
It's delicious and refreshing anduplifting and lemonade and even
on a cannabis product has been reported.
But if you concentrate it, itmakes a great cleaning agent.

(51:16):
It can strip a stickeroff a metal wall. Um,
not necessarily something you wantto inhale into your lungs is a pure
concentrated terpenes. And,and it, it also depends again,
like there are terpenes thatyou shouldn't even use in a
diffuser if you have a small petlike a cat. Um, and so again,

(51:38):
I think we always have to think about, um,
that some of these compoundsdo carry risks. Uh,
it's not like they're safe at any level. yeah. Mm-hmm. ,
you know, without risk at any level. And,
and what I'm really talkingabout here is, you know, uh,
there are moments where we shouldpause and think. There are,
there are red lights,there are yellow lights,

(51:59):
there's proceed with normal precautions.
There's proceed with extra precautionsand there's considered alternatives.
And I think, you know,
we're really lucky that thc, cbd,
low toxicity, greattherapeutic index, I mean,
they're both FDA approved in oneform. Um, you know, we're the,

(52:20):
the THC appears in threescheduling categories. Um,
if it's below a certainamount, um, you know,
it's been legalized inthe form of hemp. I mean,
hemp chocolates can have more THC inthem than a THC product you buy at a
dispensary. I mean, it's soclearly they've, you know,
through regulation and stuff like that,
and even this public health experimentwe have going on, we found that, hey,

(52:43):
you know, there are certain, you know,
levels that are lower risk than others.
And, and thc, C B D, again,
just because they're relativelysafe doesn't mean that every single
thing on the plant isrelatively safe. Um, you know,
so I think we have to be,it's good to be optimistic,

(53:06):
but also to have skepticism. Skepticismis our friend, like, you know,
okay, thc, cbd, we know about them,
we know about their acidiccomponents a little bit,
but what do we know about the, you know,
other a hundred or so compounds thatcan be found on it in small amounts?
You know, I think of, uh,you know, things in nature,

(53:27):
the most potent things in nature areoften there in the smallest amounts.
Um, you know, if you look atmarine biology like nematodes and,
and other stuff like that fordocumentaries, they have, you know,
really potent compounds for defense inthem. And they're usually, you know,
small amounts. Um, and, youknow, we think about things like,

(53:47):
I think it's T H C P and theseother things that are like, ooh,
a hundred times more potent. And it'slike, what does that really mean?
You know, what does that mean? Does itmean it's just gonna be more pleasurable?
Or does it mean you're gonna be catatonicfor three or four days if you consume
a large amount of it? Andthen, and these stories, um,
are not often popularized for, for anumber of reasons. But there are stories,

(54:11):
you know, back in the, you know,
back in the decades ago, uh,
it was very common for pharmacologists,uh, who developed drugs.
This is something they phased outwhen I was a graduate student,
so no fun for me. But the most,
one of the most common things was thepharmacologist to take it to see if it
actually worked. Um,
and it usually ended with a studentbeing doubled over a sink, vomiting. But,

(54:34):
um, you know, that was what peoplewould do. And I think we have to,
there are lots of stories. If you goto conferences and you ask around, oh,
has anyone ever taken this compoundthat's a hundred to a thousand times more
potent than thc? Someoneway tell you a story. Yeah,
that guy was catatonic for five days andon his floor of his kitchen, you know,

(54:55):
, stuff like that. But, but again,that's not to say there are, I'm not,
and I'm not saying that any compoundslike that exist on the market that we know
of, but again, I'm just wantingto get the idea that, you know,
small changes to a molecule, smalldifferences can have dramatic effects.
You know, ethanol, we like to drink it.
Methanol can make us go blind. Uh, there,

(55:18):
there's a very subtle differencein their chemical structure.
Right on. I want to tie a couple, uh,
things that you said together for thecaregivers who are listening because,
you know, as, as you know, everybody wholistens to the show knows that, like,
I'm, I'm, I'm very patient centric,and while I myself have not a,
a healthcare professional, um, becauseof the role I play in the community,
I talk to a lot of patientsand have, have heard, you know,

(55:41):
anecdotal stories and like, youknow, over a thousand patients.
And so if you're a caregiverbased on what, uh, jhan just said,
these are the couple of the takeawaysthat, that I would offer, which would be,
um, number one, um, justbecause you've had a can, uh,
a just because you're workingwith a patient or you are a patient who has always
used cannabis and, and has used aparticular pharmaceutical for a long time,

(56:06):
don't take out a possibility that thecannabis and the pharmaceutical could be
interacting in a new way now becausethe cannabis that is available to you
as a patient has now changed. Maybeyou're no longer just, you know, you know,
smoking your home grow and,and, and rolling up joints and,
and using that for your pain.
Maybe now you are dabbing andmaybe you are taking edibles with,

(56:31):
you know, 200 milligrams ofthc or maybe you are, um,
you're dabbing and you aresupplementing with straight terpenes,
which I see people do, whichis like, is so dangerous. Um,
because there's, there's noscientific history, uh, of us,
of us dabbing straight terpeneslike that. And so, so, you know,

(56:53):
I'm not saying don't dab.I'm not saying, um, you know,
don't amend with terpenes in youredibles. Other things. What I'm saying is,
is you as a patient or asa caregiver, um, uh, it is,
it is a helpful perspective to realizethat as cannabis changes and in
as it's not the same cannabisthat we had 30 years ago,

(57:14):
that the patient's relationshipwith cannabinoids and the
pharmaceuticals might change as well. Um,
so moving on from, from that to, tothe next area, uh, Jahan, you know,
I wanted to talk just briefly aboutisolate versus whole plant, um, uh,
medicines because, you know, uh, I, I'vewarmed up to isolates a little bit. Uh,

(57:36):
I, I, I, I've, I've never really had allthat much good to say about isolates.
I'm a big fan of, of whole plant,um, cannabis preparations. Um,
but I've had to be moreopen to isolate as,
as the breeding for, uh,specific, uh, you know,
blends of cannabinoidsand plants is, you know,
going slower than we want it to go,

(57:59):
to be able to relieve the suffering of,of so many patients. And so, you know,
before, before CBD was availableeverywhere, um, you know,
we eventually figured out that, okay,if, if you've got a THC type one plant,
but you don't have access to cbd, alright,
spiking it with some CBD isolatein the presence of the rest of the
cannabinoids in the, in the whole plantresin, that's probably a good thing.

(58:22):
And, and you know, you know,uh, Dr. Agarwal and, and Dr.
Russo have all been on the show and,and have said, you know, that's,
that sounds like a really good idea. Um,
and so more of us are usingisolate, um, here and there to,
to spike our differentpreparations. On the other side,
you've got pharmaceuticalcompanies that are using, you know,
isolate and hand chosenterpenes to make, um,

(58:45):
you know, uh, you know, the earlyendocannabinoid drugs like, uh,
like Epidiolex, right? Which, youknow, you know, when I read the,
when I read the descriptions,you know, it, it, it,
it smacks of like kind ofFrankenstein's monster to me a bit. Uh,
I would much rather have a plant thatas a two to one CBD to THC with a proper
terpene profile and,
and have it in the resin from the plantand then just use the plant, right?

(59:09):
Because there's,
there's thousands of yearsof good relationship between us and the plant that I
think is less effective when we,
when we tear it all down and, and putit into a pharmaceutical. But, you know,
um, we have,
we're going into this direction andit's certainly helping people and that's
good. So I've, I've had to soften myopinionated on this, you know, so,

(59:32):
so this is all circlingaround to this question,
is that when we're talking aboutinteractions with other pharmaceuticals,
are there any things that we should, um,as cannabis patients or as caregivers,
be aware of how isolates mightinteract with pharmaceuticals
differently than howwhole plant preparations,
like rosins and stuff mightinteract with pharmaceuticals?

(59:57):
You know, that it's aquestion that, um, you,
the answer is yes and no, you know,to give a truly academic response.
So, you know, spiking adulterating or, or,
you know, can be one in thesame term. Um, so I might,
I might use them interchangeably as Ijust kind of speak off the cuff. Mm-hmm.

(01:00:18):
, but, you know, mixing,let's start with ancient times, right? Uh,
so,
so ch changing the compositionof something you're consuming for the purposes
of, uh, psychoactive effectis, is not a new practice. Um,
I would, uh, I,
I I would give you verypoor odds against the idea

(01:00:39):
that our ancestors mixed lots of plantproducts together and smoke them.
Uh, I'm willing to bet that thingslike lavender or camomile and, um,
callous root, I think even someof these have been documented,
were smoked and probablymixed with cannabis.
Not all too different in conceptfrom spiking with terpenes,

(01:00:59):
adding a foreign compound tothe mix, um, indeed likes ofx.
That's like what you're describing soundslike hows OFX is made. Uh, the, the,
the oral mucosal, the tinturethat's sprayed under the tongue,
that's licensed in over 30 countries,but not in the United States. Um,
that is two cannabis varietiesextracted by CO2 extraction,

(01:01:20):
turned in an oil and mix togetherto get this nice ratio of a
one-to-one THC to C B D.
So it's a proven strategy or tactic, um,
in preparing medicine andmaking consumer products.
Um, anytime you are increasingthe dose or your exposure,

(01:01:43):
you're introducing new complications. Um,
cannabinoids are waxy andsticky compounds. Um, and,
you know, if you're reallyconsuming a lot of the stuff, um,
it can stick to everything.It can stick to your teeth.
It can start to stick to your lungs.There's been some people who, um,

(01:02:03):
have way, and I'm talking extreme,
like a lasagna tray of, you know, uh,
dab sort of thing just to be, you know,um, a little silly there. But they're,
they're, they're consuming alot. And it can coat airways,
it can collect on material andthings like that. And that,
that, that, that may be a bad timefor, for some folks. Um, so again,

(01:02:27):
but that's not gonna happen with moderateor, or low use of these products.
I mean, um, typicallyyou can't, you know, um,
what's sold in a lot ofadult use stores, um,
regulated adult use dispensariesis, is really not enough, um,
to induce some of thesethings. But again, you know,

(01:02:48):
chronic consumption of concentratedproducts can introduce, you know,
new things. And I guess, um, let's,
let's use an analogy. Um,
let's talk like beer, right? Versus, um,
you know, vodka, right?Beer, few percent alcohol,

(01:03:12):
maybe 8%. That's a pretty potentbeer, right? You know, vodka,
they don't even use percents.They use proofs. Uh, you know,
it could be quite, uh, ,
it could be quite a lot more potentby an order of magnitude. Even wine.
Wine can be, you know, upwardsof 20% alcohol. That's, you know,
twice as much that's, uh,than a beer. You know,

(01:03:35):
if you're talking 40 to 60%by weight, alcohol, I mean,
you could be adding a zero onto thepercentage of a beer, or beer is 5%,
and you have a alcoholic beveragethat's above 50% alcohol,
that's an order of magnitude moreethanol. So if you're drinking a beer,
you know, you have all these other thingsin there. Uh, you know, you got some,

(01:03:55):
some flavor compounds, you know,a nice big double hopped ipa.
You know, they just, they smell amazing.If you're into plants, um, you can,
you can smell the terpenesfrom the hops plant. You can,
there are other compounds in therethat give it flavor and body and color.
It's, it's a bit dilute though, thealcohol in that mixture. You're,

(01:04:16):
you're drinking like liquidbread in a sense. You know,
if you look at like aGuinness, for example, um,
or some of those more heavierbeers, unfiltered beers, there,
there's other components. Now, what isthe difference between a beer and vodka?
Well, I just, you know, we can describeit in terms of smell and taste,
but you can also describeit in terms of calories and,

(01:04:37):
and what else is in there.And is it better to drink the,
the ethanol in a liquid bread preparation,
or is it better todrink it in a pure form?
And I wanted to use something thatperhaps people who don't use dabs
or extracts or are consideringit to give them, you know,
an analogy to think about whenit comes to these products. Uh,

(01:05:02):
I think the idea of adding acompound to mitigate the side
effects,
like putting CBD in a productto decrease the potential
adverse effects of someonewho's sensitive to thc,
I think that's a wonderful idea.Um, and, and I'd love to see,
I think more, more ofthat available to people.

(01:05:22):
It's this form of compoundpharmacy, I think . Um,
and so I think, uh, you know, it seems
like, you know, theseextracts have a utility,
I think especially in people withsevere conditions, cancer, chemotherapy,
um, extremely difficult to treatneurodegenerative disorders.

(01:05:45):
You know, when we look at C B D, even,um, you know, the average person,
you know, buys a boutique CBD product,might have five milligrams in it,
maybe 20, and they're like, Ifeel so relaxed. Uh, but, uh,
if you look at what'sbeing used in the clinic,
we're talking hundreds of milligramsof CBD foreign effect. So,

(01:06:05):
um, we can't really say, oh,it's bad and this is good. It's,
it's all a bit of a spectrum interms of the context of use and,
and why you're using it. Um, butagain, the more you take of something,
the more you have in your body. Again,
I use the analogy of the guy walkingaround town with nothing to do might just

(01:06:26):
get into trouble if they walkdown the wrong alley. So, um,
I think about that a littlebit too. Um, you know,
if you're hanging out playing in thestreet, cuz you got nothing to do,
it's all fine till the wrong car comesalong, you know, . So, um,
there are things like thatI, i, I think about too.
So if you're using a lot of cannabinoidsand suddenly you get a new prescription

(01:06:47):
medication, um, you know, that mightpresent some, some complications,
that's why, you know that, that theyhave that advice. You know, go low,
start low and go slow. Take it atnight when you're using new products,
it's to sort of give you like,I'm gonna use it in a safe place.
I'm gonna use a small amount and I'mgonna write down what happened and how I
felt just so I can start to track things.Because no one's really, you know,

(01:07:11):
sh uh, shanga. I don't think eitherone of us are saying, um, you know,
we're not telling people not to use it.
We think we're just giving 'em pauseto think about it, you know, and.
E exactly, exactly know,know what you're doing.
And just because other people are doingit doesn't mean that it's necessarily
right for you. You know, uh, uh,ma make, make informed choices.

(01:07:32):
A absolutely, and I, and Ithink about, you know, I, uh,
I don't golf that often, um, and whenI do, it's, it's pretty terrible.
But, um, you know, I think thesame thing for cannabis is, uh,
same thing. Uh, the things I likein golf are putting the slow putts,
the short distancethings, you know, hitting,

(01:07:54):
whacking the ball as hard as you can withas much force as you can to go as far
as you can, you know, takingheroic doses of things.
You know, it's, uh,
you might spend a lot of time wonderingjust where that ball is, .
.
Versus, you know, putting, you got agreen, there's a lot, there's still a,

(01:08:14):
a lot of fun there and a, anda challenge there as well. Um,
but again, it's, it's different strokesfor different folks. But again, I,
I would really just give people pauseabout that because you wanna take a
holistic approach with this and, and youknow, you, when it comes to patients,
you know, especially avoidingdrug drug interactions,
there might be a real strategyhere. Maybe you prefer edibles,

(01:08:38):
but the edibles stick around so longbecause they're, they're swallowed.
They go through GI tract, then theygo to the liver just like a pill.
However, inhalationavoids that first round,
eventually does get metabolized, but itavoids that first round pass metabolism.
So if you're consuming, uh, let'scall it healthy normal cannabis, not,

(01:08:59):
not special cannabis, not, um, you know,cannabis dipped in hash oil, not dabs,
not cannabis with spiked with othercannabinoids, but just good old fashioned,
uh, plant material, you know? Andyou're inhaling that, you know,
you might be able to decrease yourchances as a strategy just conceptually,

(01:09:20):
you know, the amount ofadministration matters,
swallowing things makeseverything complicated. Um,
there's a reason why savix,
and if you haven't lookedinto nabiximols or tinctures,
I think this is an area worthyof further development. Um,
taking a product that can be applied underthe tongue or in the cheek and absorb
buly, don't swallow it. Don't, don't,

(01:09:40):
don't even visualizeyourself swallowing it. Um,
I don't want any placebo effects onthis podcast, but , you, you, uh,
you absorb it buly, it goes into yourmouth and it goes right into your brain.
Like, why send the,
the cannabinoids on a wild goose chasethrough your digestive track and through
the body? Oh,
they gotta go all travel through thewhole body before they get to the brain.

(01:10:02):
It's little, little crazytrip they have to take.
So why not just load the magicschool bus and send it right,
right to the brain and avoiding,um, some complications potentially.
So you have option. Youknow, the point of this is,
is you only option isn't inhalation.Your only option isn't oral.
Um, there are potentially otherstrategies that you could use,

(01:10:24):
and I think these are greatconversations to have with the,
your PCP or your primary care physician.
not talking about anotherdrug there. Um, but, uh, the, or,
or any medical health professional, um,
doctors are trained to talkabout drug drug interactions.
They can look up any of this informationquickly, or you can, you know,
reach out to me or, orcheck out, you know,

(01:10:46):
rewind the show and pull some of the,the, the references we talk about, um,
and bring those to your clinician.
I used to advise medical cannabispatients and I did a lot of advocacy.
I'd give them, you know, papers.
I'm sure there's like a couple cliniciansat like Kaiser or some medical place
in California are being like,
who the hell was giving my patients allthose peer reviewed studies and having

(01:11:06):
them bring 'em to my office, ,you know, so I was sometimes arming, uh,
medical canvas patientswith peer reviewed studies,
studies to share with their clinicianto have these types of discussion.
How should I consume it?
What are the benefits and risks ofconsuming these products, uh, topically,
orally, sub mucosally, um, by inhalation,

(01:11:27):
um, and these are all, and, and,and in what amounts and, and,
and things like that.
So these are all great conversationsto continue to have. And as you said,
it's gonna continue to change cuz productschange, varieties of cannabis change.
Um, and I think it's always goodto just check in about that.
Right on. So, um, when we come backfrom our commercial break in set three,

(01:11:51):
we're gonna talk about some,uh, uh, red flag drugs and, uh,
ca categories of drugs,um, that we wanna be, uh,
especially aware of, um, if you area cannabis patient or you are doing,
um, uh, you know, caregiving for somebodyelse. And, uh, we'll go through those,
um, with, uh, jhan. So, uh, we're gonnatake a short break and be right back.

(01:12:14):
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(01:18:04):
You are listening to Shaping Fire.I am your host Shose, and my guest,
today's Molecular pharmacologist,jhan, Markku, PhD. So Jhan,
you know, we, we, we've talkeda lot about, um, like the,
the mindset and theperspectives and the complexity,
and we've teased these things apart mostlyjust so people can see like all these
different avenues that we couldsay are avenues of, of, of concern,

(01:18:27):
but the really avenues of solutions,right? Because usually by the time, um,
a cannabis patient iseither A, US and sick, or b,
we are a caregiver and we'vebeen called in to help out. Um,
usually there is, um, aproblem to be, you know,
resolved and and healingto be applied. And,

(01:18:47):
and so what I want to ask you is that, uh,
there have gotta be some,
some categories ofpharmaceuticals that are just
red flag because theyare, you know, like up,
up at the top of the list of drugs thatare likely to interact with cannabis.
And, and while, while ourgoal today has been to like,

(01:19:09):
hopefully arm cannabis patients andcaregivers with lots of different ways
to, you know, dive into whatthey're trying to suss, suss out,
um, there's probably a, a few thatwe should just put a big red flag on.
And so, so, uh, why, why don't we gothrough two or three of these? So,
so what's at the top of yourlist of red flag drugs, um,

(01:19:30):
that are going to interact in cannabisin, uh, potentially sketchy ways?
So, um, things to be concerned about.
First I'm gonna start withalphabet soup real quick,
and then we'll go into morespecifics. But if you're taking, um,
potential drug drug interactions have todo with drugs that are looking at sip c
y P two, C nine,

(01:19:52):
healthcare professionals will knowexactly what you're talking about.
So if you are listening,
pulling out a little piece ofpaper and writing these down and,
and then throwing them into an airsearch browser will reveal all. But,
uh, sip two C nine, SIP180, 82 C two B six,
and C two C 19. Um,

(01:20:13):
and even some of the acidiccannabinoids, um, like T hc, T H C V A,
uh, C B D C B D V A, um, C B G A,
these all interact, forexample, a CYP two C nine.
So if you have taking a medication,which is probably, you know, it's very,
these are very commontargets of medications, um,
you could have a victimperpetrator effect going on.

(01:20:37):
So a couple of red flag potentials,you know, , um, you know, I,
I used to think like I want, um,you know, I already, uh, you know,
I have my own podcast as well,
and I thought about starting anotherone just called What the Hell Happened,
where people would call in with,um, drug experiences and be like,
I was doing fine. I washaving fun at this party,
and I just got lightheaded and passedout, and like, what the hell happened?

(01:21:01):
And you know, these stories, um, you know,
j joke a little bit there to cut thetension because this is about hypertension
and hypotension and, and thehypotensive effects of cannabis.
Most people probably don'teven notice, or it's transient.
You've been sitting downfor a while playing a board game or whatever, you know,
FIFA on your Xbox, and you, you stepup, oh, I feel a little lightheaded,

(01:21:26):
and then you like, oh, oh, I'mbetter now. But some people that is,
is really severe. And so if you're takingcardiovascular medication, I think,
and you have a cardiovascular condition,
it's a great idea to really pause andthink about things and maybe have a
discussion because, um, cannabis doescause hypotension. The blood vessels, uh,
you know, will dilate. Um,and, and, and the heart,

(01:21:49):
heart will work a little harder topump blood around because, you know,
things are a little more relaxed. Um,
but that hypotension could resultin being so lightheaded that,
that you have to sit down or,you know, you really feel,
feel the pull of the gravity of the earthand just bam. And that that could be,
that could be bad, especially ifyou hit something on the way down.

(01:22:10):
So I'd say red flag interaction,
cardiovascular medications thattreat hypertension. Um, you know,
I I would say, look, lookinto that if you're on, um,
anything having to do with cardiovascularmedications. All right. What's an,
what's another area?Yeah, um, I'd say, um,
uh, warfare in, um, and I, I pronouncedrugs a little weirdly cuz I had, uh,

(01:22:33):
my mentor was from Lebanon. Um,
one of our collaboratorsthat I listened to a lot, uh,
was born in Scotland andspent 30 years in Australia.
So I'm used to hearing drugs, ,pronounced , really weird ways.
And so, I don't know the quick wayto say apoptosis or apoptosis or ap.
You know, there's all these ways.So, uh, bear with me here. Um, but,

(01:22:54):
uh, warfarin is one, and this is, uh,most people probably clot enjoyed, right?
Right. Blood thinning. Soyeah, so you, if you take,
if that you could potentially, you know,
this is where cannabinoidsare perpetrators, warfarin will stick around longer.
Um, increased risk ofexcessive bleeding there. Um,
so that would be potential red flag.Something to think about. Consider,

(01:23:18):
again, that's where this mantra wehear or start low and go slow comes in.
Uh, we mentioned Clobazam, and thisreally is again, a risk of, um,
benzodiazepine toxicity. So, uh,and, and most notably with C B D.
Um, so again, thinking aboutbenzodiazepines and cannabinoids, uh,

(01:23:38):
you may want to proceed slowly there. Um,
central nervous depressantscould have additive effects.
We already talked about that. Um,um, the, the, a lot of the pens,
the clozapine and olanzapine,um, will have reduced efficacy.
And I think that that, um, you know, andagain, I'll just tie it in the C three,

(01:24:00):
A four and CYP two C nine, um, you know,
you should think about, um, those and,
and drug drug interactions.
If you have drugs that aremetabolized or interact with those,
I I would say discuss alternatives, um,
that might be appropriatein, in that instance,
just based on the literatureand, and what's available.

(01:24:21):
It may not be clinically feasible, soyou might have to consider, you know,
different routes of administrationor something, you know.
So you mentioned the, uh, the CLObaan, which is a, a benzo diazepam. So,
so while that one,
most of us don't comeacross in our regular life,
but I believe another benzo diazepamis Valium, which is like all through,
you know, our sceneand, you know, you know,

(01:24:43):
your aunt gives one toyou or whatever, you know,
these are very common tocome across. Would we,
should we be careful similarlymixing Valium with cannabinoids?
Um, yeah, absolutely.
And I would say probably true for anyanti-anxiety medication. Like, so.
Xxx.
Librium, uh, evenanti-depressant, Zoloft Proac, uh,

(01:25:06):
Prozac, Lexapro, um, just likenaming things off the top of my head,
you know, these things even like carryover to the psychedelic space too,
you know, people, you'renot supposed to, you know,
go on a psilocybin therapeutic sessionwhile on these things either. And so,
um, you know,
mostly what we're concerned aboutwith a cannabis or hemp product

(01:25:27):
is that these increased side effects,dizziness, drowsiness, confusion, um,
and, and other difficulties whenyou're using a diazepam together
with something like cannabis. Nowagain, everyone's gonna be different.
Um, some people are probably listeningto be like, I do that all the time,
and it's fine. And other people are gonnabe like, I'm never doing that again.

(01:25:49):
And, and what we're really talkingabout here, I think is, you know,
cannabis can be a beneficialthing in people's life.
And we don't want it to be a, a badthing. We want it to be a good thing in,
in people's life, or at leasthave no net effect, ,
no net effect and a good thing.That'd be, that'd be great.
And so we're really trying to figureout how do we prevent people from,

(01:26:12):
you know, having to outta the phrase,I'm never doing that again. Mm-hmm.
Or that was terrible. Um, you know,
I think of how hard the cannabis industryhas worked to get where it is. And,
you know, you don't want a,
a first time patient who could benefitfrom cannabis to get the wrong product,
have a drug drug interaction, or a sideeffect and say, you know what, I'm,

(01:26:32):
I'm never touching that stuff again.And it might have just been a,
a simple issue as timing, routeof administration, or again,
dosing.
I wanna focus on onething that you said. It,
it makes a lot of sense thatif you would take a, uh,
a benzo diazepam likeValer xxx and add, um, thc,
uh, blend to it, that you are going, youknow, you're, you are more likely to,

(01:26:57):
you know, have, have decreased ddexterity and increase drowsiness and,
you know, won't be ableto drive your car as well.
And these things that likeslow your human down. Right?
That all makes sense. , butyou caught me off guard when you,
when you mentioned those SSRIs,
because so many people whoare taking, you know, uh,

(01:27:20):
you know, some of these,these, um, you know,
long-term anxiety anddepression medications like Wellbutrin and, and you know,
that whole basket that you mentioned,
many of them also supplement withcannabis either for quality of life
or just, you know,
because they still have residualanxiety even on those drugs.

(01:27:41):
Um,
what is the mechanism ofcannabis interacting with
this, this basket of drugs?
And is there anything that patients whoare blending those themselves at home
should watch out for?
Great. Um, great question there. Um, hm,

(01:28:01):
hm, let me think aboutthat for a second. ,
um, the MEUs of action, I meanthe, the antidepressants are,
is a very broad feel. Um,
so we could think about maybe,um, like flexine or, or Prozac.
Um,

(01:28:24):
and, and you know, some of these havelike that one I like to talk about.
Cuz again, it has no knowndrug interactions according to,
to information available, but it canhave overlapping, um, side effects.
So that would be more in thepharmaco dynamic area, um,
with some of these antidepressants. Um,
I'd have to dig in a little bit deeperon some of the mechanisms of actions,

(01:28:50):
um, with those pharmaceuticals. Um, fair.
Enough. Let, let, let's talk about inuse then. All right. So may, so maybe,
maybe I caught you off guard withthe actual, uh, pharmacodynamics,
but w if you are taking, um,you know, one of these SSRIs,
would these,
would the side effects that you wouldwant to be cautious of when taking
cannabis, the same ones asthe benzo diazepam, are we,

(01:29:13):
are we with the SSRIs? Are westill talking about, um, um,
uh, uh, like loss ofdexterity and, and, you know,
sedation and difficultydriving cars? Yeah. Or,
or are we talking about something, youknow, potentially more serious like, um,
you know, serotonin poisoning orsomething? I don't know, I'm just,

(01:29:36):
I'm just guessing. Right?
So you might, I think you mightexperience, um, like, you know,
so some of the SSRIsspecifically, right? Um,
citalopram I think is a prettypopular one. It's extensively me, uh,
metabolized by, um, CYP two C 19,
one of the alphabet soup things Imentioned in the beginning of this thing,

(01:29:57):
which is one of the major enzymesthat metabolize cannabinoids.
And so you could run the riskof having cannabinoids be a
victim of an interaction, which couldmake them more or less effective,
make them more likely tohave an unwanted effect. Um,
again,
just going back to that analogy of theguy strutting around town with nothing to

(01:30:19):
do might walk down the downstreet or just, you know,
it's okay to sit in the middle of thestreet when it's not busy and do
your work that you need to do,
but it can get more dangerous thelonger you sit there. So, uh, again,
just to try and cobble together ananalogy. Um, so I think with the,
some of those SSRIs, you might be,think it could be go either way,

(01:30:40):
victim or perpetrator. And thisis, you know, kind of at the limit.
I think of a lot of information outthere. Um, if even if you go, you know,
I worked with, uh, uh, with Penn State,
they have a cannabisresearch center there and,
and been advising and participatingwith their center, and they put up, um,
uh, like a,
like a little database where you canput in cannabinoids and look up, uh,

(01:31:03):
potential drug drug interactions.And, you know, it's, it's like,
I think of it like this,
like they've made the beach and alittle bit of shoreline and you can wade
into the water and explore what's there.
But if you want to go any deeperand like see dolphins and, you know,
the shipwrecks and things that we're notthere yet with being able to go to that

(01:31:24):
level of exploration.
But we do know thatSSRIs and cannabinoids do
share common routes ofmetabolism. And that could be,
um, something to thinkabout. Um, you know,
cuz not every SSRI goesthrough the, the same,

(01:31:44):
um, sip, but a lot of them do.
All right. The, the, the last,um, medicine category I want to,
I want to touch on, um, it may be aspecialty that you may or may not like,
you know, overlap with,but, but what about, um, uh,
children children's medicines, right?Because, um, you know, the fact that, uh,

(01:32:05):
children who have got, you know,a range of issues, you know,
very, very easily pointing atlike immunocompromised type kids,
like they have, uh,
literally been the poster children forcannabis medicine and helping to expand
it, you know, over the last 20years because, um, you know,
the way that cannabis medicinehelps kids, uh, it, it, it, it,

(01:32:29):
it pulls at your heartstringsand people are like, yes,
these kids should be able to be usingcannabis oil for their seizures and,
and let's get this lawpassed, right? And so, um, uh,
would you have anything to addabout interaction between, um,
cannabinoids,
which might be be coming from a parentwho is feeling desperate and other
pharmaceuticals that they might alreadybe on? And just to be reiterate,

(01:32:52):
we are not giving medical advice. Allwe're doing is pointing out things for,
um, caregivers to stay aware of.
I am so glad that we're talkingabout this because so often
when we talk about healthy,
normal adult volunteersin a research study,
we extrapolate that tothe entire population.

(01:33:14):
And in the absence of pediatric drug,
drug information,
adult information is used. Um, however,
there are subtle differencesin development and all sorts of things between
children and adults. I mean,
just look at the differences between atwo year old and an eight year old and a
15 year old right there.Mm-hmm. , there's a huge, the, you know,

(01:33:37):
and so the magnitude of adrug drug interaction in a
pediatric patientpopulation may differ from
adults because of age dependent changes.You know, puberty and prepubescent,
for example, can change the drugdisposition or response. Um, you know,
in some of the early studies with, uh,

(01:34:00):
THC C compounds in pediatric populations,
like by the late Raphael Ulum, you know,
they didn't really see what they thought,
what they would see in adults giventhat compound. Um, and, you know,
the brains are still in a high stateof development. And so, you know,
there may not be the same responseto th h c or other cannabinoids,
and there could be other factors, doseformulation, the dis disease state,

(01:34:24):
body mass, things like that. AndI'll say again, that the, the,
it needs to be assessed in childrenseparately from adults. And,
and this is a challenging thing,but careful consideration,
you need to account forage dependent changes. Um,
and you have to build a littlemore confidence, um, about that.

(01:34:45):
But it is absolutely aconcern. Um, and it may,
you know, these, these, again,
these DDIs are re routinely performedin healthy adult volunteers in early
clinical studies. But, you know,it's, there's a lot of ethical,
logistical and methodchallenges to, you know,
doing these types of study in pediatricpatients. I mean, you know, uh,

(01:35:09):
I don't know if you've ever tried toget like a four year old to fill out a,
a form or a survey mightbe a little tricky.
Um, adults can can dothat thing just fine.
So I think there's a wholerange of it, but, you know,
po pediatric patients in thehospital often receive multiple

(01:35:31):
drugs. And so there areefforts to characterize,
um, those things.
Um, I, I like this phrase thatyou've got age dependent changes,
and I know that youwere talking about kids,
but that definitely applies toadults too, because I know that, um,
the effects that, um, you know, uh, my,

(01:35:52):
my plant-based drugs and fungus baseddrugs and my pharmaceutical based drugs,
they have all changed as I've gottenolder. And my reaction to it, you know,
I was kind of impervious inmy twenties and now, you know,
I'm a little more awarecuz it's a, you know,
it's easier to knock me out of balance.
But I like that phrase age dependentchanges. Yeah. Um, so that could.

(01:36:14):
Give one solid example.All right. Can more,
and this is across the boardexample, cannabis is not special.
I'm just gonna say acrossthe board, anytime there's a,
I think morphine andopioids, fentanyl, um,
combined with anything ina clinical setting, um,
can have effects onrespiratory depression.

(01:36:36):
And so that is something I think,
especially when we talk aboutchronic diseases, hospitalization,
outpatient stuff, you know,
just because in adult populationswe're observing this phenomenon of,
um, decreased opioid, um,
overdoses and deaths and adultpopulations. Again, this is a thing,

(01:36:56):
like we talk about age dependence, right?
It may not be quite as clearcut in pediatric population.
So I just want to throw that outthere as like, um, you know, you can,
you can look this up, uh,don't take my word for it,
do some of your own research, but again,
you can find a lot of information aboutwhile these are the potential most
difficult areas.

(01:37:17):
Right on. So I've got two morequestions before we wrap up here. Um,
I know that, uh, you know,
it was our goal today tonot answer every potential
question that could be asked,asked about this, because there's,
it's just too complex. We.
Would need 20 more minutes.. Yeah. .
Oh. But, but our goal was to help give,

(01:37:39):
give patients and caregivers a, um,
a a perspective of how tosuss out their solutions in
their unique situation. And so I, Iwant to, uh, I want to kind of like, uh,
you know, kind of like throw you this,
this kind of of umbrella questionfor you to, to answer here. Um,
in what manner would you recommendpatients and caregivers go about their own

(01:38:04):
research to discover if theymay be having, you know,
interactions between their pharma andtheir cannabis, very specifically,
let's say that either you know,
you're the patient or you're thecaregiver and you're like, you know what,
I thi I think that mightbe what we're seeing.
What would you say is their first andtheir second step to try to suss that out?

(01:38:25):
Keep, uh, meticulousrecords? Um, you know,
and that doesn't have to meanyou're journaling all day.
It just means that you area bit vigilant about that.
You're controlling yourinputs. Um, so, you know,
if you're like, oh, I went tobrunch and, and drank four mimosas,

(01:38:45):
and then I took my medicine, and thenlater that night I smoked cannabis,
and boy did I feel funny. I must have hada drug drug interaction with cannabis.
And those, um, you know,my, my prescription meds well, could be the alcohol,
could be other things. So, and thencould be diet also plays a role.
So I think first thing to do,get a journal, find the criteria,
find some baseline things.Um, there's no shortage.

(01:39:08):
I think of like questionnaires. Youcould even draw a smiley faces like,
do I feel frowny face today? Do I feelflat line smile today? Um, that's a,
you know, people use those types ofcharts, um, and things like that. Um,
different scales. So find your scales,find your measurements. Um, but again,
I think, um, uh, keepingtrack of what you,

(01:39:30):
you know, I have talked to patientsand caregivers in the past,
and sometimes I say, Hey, if you havea label on a product, take a picture.
Keep a digital journal if you want todo it. It looks almost like a scrapbook.
You have a journal. You, youcan peel off the product label,
put it in your journal,
or write down the information from itand keep track of what you're taking when
you're taking it. Um, and, andwhen you're taking other things,

(01:39:53):
and this is even a strategy that'sused for pharmaceutical drugs.
So doctors will be like, okay,well you're taking drug x,
I'm gonna prescribe you drug y.
If you take 'em both in themorning and you feel X or Y,
then then then take this drug twohours later, take it four hours later,
take it six hours later. And so startby taking, if you're new to this,

(01:40:13):
everything, you know, this is based onliterature that's out there, Russo and,
and MacCallum have a great paperon, on dosing strategies and,
you know, taking things at nightand low amounts, if that's okay,
feels all right. You don't feelthe DDIs, you can, you know,
start to play with the timing and thedosing and finding that range where you're

(01:40:35):
not getting adverse effects. Butagain, if you don't feel good, um,
you know, it's, it's not great if you get,
if you get like all the side effects ofcannabis, like, oh man, I feel sedated,
I feel hungry, my mouth is dry. Uh,
I feel dizzy and I can'tremember anything. You know,
that's like a lot of boxesto check. And, and you,
and that may not be what you're lookingfor from a product. And so again,

(01:40:59):
I think it has to do with, um,
keeping track of the inputs, controlas many variables as you can.
Um, and I think you, you'll start to,
you'll find that there's a lotof things you'd be like, wow,
I've been drinking caffeineall day, and, uh, or I,
or I haven't been drinking it all day.And so I think finding those baselines,

(01:41:21):
um, will help you. Is, is.
There a database that yourecommend more than Google?
Because after the patient journalsand they've got some suspicions,
they're probably gonna search thesedrugs and cannabis and see what they
get. And Google may be our best option.
And I'm always a big fan of theproject cbd.org at conditions

(01:41:41):
section , because that,that's always great too. But, um, is,
is Google still our best bet?Um, I mean, until AI takes over.
Um, you know, you know,
the internet can be helpfuland I would look for
multiple resources thatcorroborate your evidence.

(01:42:03):
Don't just take thecomputer's word for it.
Find a couple references onlinefrom different types of sources.
Maybe the Mayo Clinic, maybe pubmed.gov,
uh, maybe from, uh,
a webinar where there's a doctortalking about stuff like, use,

(01:42:23):
use a, you know,
you have to take on this challengeusing all available resources
to do that. Cuz things often,
just because the same study iscited over and over and over again,
doesn't mean the study itself isreproducible and the results are
translatable to you.Mm-hmm. . And so finding, um, you know,

(01:42:46):
the information from diversesources, finding the same thing,
the same results from differentpeople running the studies and,
and different reputable organizationscome to the same conclusions,
you know, that will help.Um, you know, as they say,
try and find something written,
something you can watch something,someone you can talk to,

(01:43:09):
to corroborate the evidence. Um,and so I think, you know, that,
that is, um,
just kind of where we're at becauseAI and the internet love to lie
to you, , you know, there's,that's the ongoing thing. Like, wow,
AI will just make stuffup to make you happy.
It knows what you want to hearor want to read or want to see.

(01:43:33):
Um, and we have to always besuspicious if we're getting, you know,
exactly hearing exactly whatwe want to hear. Um, you know,
you're probably about to buy a used car,
so just be becareful out there. Um, and,
and I think that what I would sayis try and test things, you know,
if we feel okay, if I believe X,

(01:43:54):
let me try and stretchout X as far as it can go,
this line of thinking untilit breaks. Where is it,
where is the weakness inthis, this, uh, rationale,
whatever it is you're looking at. Drugdrug interactions or significance,
they're, they're not significance.
So the last question, um,I want to hit on with the,
our last two minutes hereis, uh, I, I want to, uh,

(01:44:16):
go back to and plug thebuds info.com project.
You and I have talked about that, um,you know, uh, be before we started and,
and, uh, you know, the, the listenersof Shaping Fire knows that we support,
um, cannabis research and we arealways trying to plug, um, uh,
research that we know is going on. Weparticipated in, you know, Ethan Russo's,

(01:44:40):
you know, CBD and CBG projectsbefore sending people their way. And,
um, you know, you've told me aboutthe the good folks behind, uh,
buds info.com and, andI looked it up and it,
and it looks like something legitimate.So, so my question for you is, is,
is what does the research look like tounearth these interactions that you and I
have been discussingtoday? And, you know, um,

(01:45:04):
what kind of research is happening,what does that look like?
And then give me a,
a brief plug for buds info.comand then we'll wrap up.
Sure. So, you know,
my exploration and researchhas been, you know,
a lot of frustration with gettingfunding Yeah. And grants. And, you know,
in some ways, you know, you'realways waiting on grants and,

(01:45:27):
and maybe private funding fromthe industry or stuff. And,
and as time's gone on, I found more andmore ways, Robert said, you know what,
this summer I'm just gonnado the dang research,
and I'm not gonna wait for funding.I'm gonna bootstrap this, you know,
I believe in it. I'm gonna invest in it.
And there's so many databases out there,
there's so much you can findat the tips of your fingers if

(01:45:50):
you're just willing to spendtime doing it. And, and,
and so unearthing theresearch for me, you know,
um, doing case reports,contacting clinicians,
and starting to unearth these thingswhere they have these patient files.
No one, they're busy clinicians, theydon't have time to go through 'em.
Some of, most of it's like, you know,not, it's like, I can't read this.

(01:46:12):
This is not like the best of it.You find nuggets, you find signals,
you know, it's like,
it's like searching for extraterrestriallife and suddenly you hear an alien TV
show and you're like, what isgoing on here? And you're like,
I picked up a signal. Youknow? Um, and I have to say,
digging through,
we had a paper come out recently aboutDelta eight THC derived from hemp.

(01:46:35):
And we combed through, um, youknow, the lead epidemiologist, um,
on the paper, you know, broughtthis to our attention. Hey,
there's this database. We canaccess it. We can run these queries.
We got a whole team togetherto go through the data.
And it's really excitingbecause, you know,
this is data that's,

(01:46:55):
people are reporting to theFDA to poison control centers,
and it's just floating around.Nobody wants to comb through it. And,
and I, I, we requestedmore and more information.
They sent us case reports, hospitalfiles, you know, the products,
uh,
scanned and pictures of the productsalong with the reports from the patients

(01:47:18):
and why they showed up to theer, what they were feeling.
And we came to realize that one,
the classification system for how thesethings are entering the databases not
useful. I'll give you anexample. Uh, psilocybin has a,
an e at the end of it in the FDA database.
So if you search psilocybin, you willfind nothing. But if you search psilocybe,

(01:47:39):
you will. Oh, geez. So if you,if you look up, uh, cannabinoid,
you may not find anything. If youlook up, you know, you, if you know,
so think about Delta nine thc.
Is it plus minus version or theminus minus version? Like what,
what version is it? Um, so there,there are some issues around there.
So it takes a bit of knowingwhat you're looking for,
but that led us to create Budsinfo. We're like, you know,

(01:48:01):
there's an explosion of productdiversity here. And, you know,
as a colleague told me, whereare the guardrails? And, um,
and so we, we decided tobootstrap this. So buds info.com,
please check it out, please scan it.
We are trying to use this tocentralize the collection of data,

(01:48:22):
standardize the data. Right Now,
if there is an issue with a Canacannabis product, hemp product,
and a vulnerable population,it goes to local, state,
or city centers and eventually makes it
or not at all to a central database.
So we may not, we maynever, some of this stuff,

(01:48:45):
we may be quite late to the game touncover. So it's been very, I have to say,
it's been very exciting to be sortof on this forefront of public health
where we're finding signalsand very specific ones. Um,
you know, you know, as,as you would expect,
there are not a lot of adverse events forwhole plant cannabis compared to other

(01:49:07):
products. Oddly enough,
there's not a lot of adverse eventsbeing reported yet for psychedelics.
But it might be, again, cuz people can't,
finds Sabin in the database to reportit mm-hmm. . Um, so there,
there are a lot of interestingissues where we've been comparing and
trying to figure out are we using theright metrics to detect these signals?

(01:49:28):
And again, it's not aboutsaying cannabis is good or bad,
it's about we want everyone'sship to reach a safe harbor,
and we wanna know where that big rockis in the harbor so you don't run a
ground. And, and right on. Yeah.
Let, let's bring this on home there.Uh, Jahan. So, so what you wanna do,
dear listener, is go to buds info.com.
There is a short form there for you. Um,

(01:49:50):
it is very easy to fill out.And the questions are about, um,
if you've ever had adverseexperiences with cannabis and for
you to describe that, um, I went aheadand filled one out. It took me like,
like four minutes tops. And, uh, and Jayhun, they're, they're, they're all, uh,
anonymous, right?
So they're not going into like sometagged database or anything, right?

(01:50:12):
A absolutely not, it iscompletely anonymous.
We're doing this in full complianceso that we don't need an I R B board.
So now the great thing about researchis learning how to be like when you need
certain things and when you don't.So it's totally a anonymized,
this was started by students.It's largely run by students.
Um, and we are trying to perfect this.

(01:50:33):
And we think that versus tryingto find the Med Formm watch,
um, or, uh, a poison control center form.
I think we have figured out the as you, as you just said, it,
it takes four minutes to fillout and it's easy. And again,
what will help federally regulate andfederally legalized cannabis is knowing
the risks. And, and I,I strongly believe that,

(01:50:56):
that if we can clearly communicatethat we know what the risks are,
and we're continuing to a commitmentto track what those might be,
that I don't think anything willstand in the way of complete
legalization and regulation of cannabis.
Fantastic. Well, uh, Jan,
thank you so much for joiningus today on Shaping Fire. Again,

(01:51:17):
after all of this time, uh, you know, um,
this is an incrediblycomplex area of work,
and I am grateful that you are, you know,
dedicating your expertiseto it amongst some of your,
your other areas you love because, uh,
we really do need to get to thebottom of this not only for, you know,

(01:51:37):
patient care, uh, but alsoso that we can get, you know,
normalization to have, be more groundedand have its feet under itself better.
Because, you know, we, we are, weare still a long way from that. And,
um, and, and so thank youfor coming and sharing your,
your expertise and your stories and, uh,and you know, your, your goodly nature,

(01:51:59):
uh, with us today, uh, sothat we could enjoy it.
Uh, thank you. And, uh,thank you very much.
I guess I'll see you in 80episodes, . Yeah.
There you go. Well, hopefullysooner than that. Right on. So if,
if you want to, um, uh, hear morefrom Han Markku and you know, you do,
um, uh, uh, he's got a couple of greatplaces for you to go. Well, first of all,

(01:52:20):
let's go ahead and plug, uh,
episode 29 of Shaping Fire about thecannabis product manufacturing standards.
Um, but, uh, Han's, uh,uh, Instagram is great. Uh,
you'll be able to hear about what he isinto from week to week and also where
he'll be speaking. And, uh, that'sjust simply at his name, uh,
jhan Markou at J A H A n M A

(01:52:43):
R C U. So that's his Instagram.And also he's also, uh,
pretty active on, uh, Twitter. And, uh,that is also his name at Jhan Markku.
Um, also, if you're interestedin any of the aspects that I, uh,
talked about either at the top of theshow or came up along the way about, uh,
about his consulting, uh,for, for companies or, uh,

(01:53:04):
legal folks, or if you'vegotten busted for dui, um,
uh, you wanna go to, uh,their, his consulting website,
which is markku aurora.com.And so that's Markku,
M a r C u dash aurora a r o r
a.com. And then, um,if, if you want to, uh,

(01:53:26):
hear him wax brilliant, um,about the, uh, cannabis industry,
um, uh, he has launched a, uh,
a relatively new podcast calledHow to Launch an Industry.
And it's all about the, the, the,the birthing and stabilization of,
of the cannabis industry and, and, andwhat our best practice is going forward.
And that is at How tolaunch an industry.com.

(01:53:49):
You can listen to the episodesthere, um, as well as, uh,
anywhere that you download your podcasts.
You can find more episodes of TheShaping Fire Podcast and subscribe to the
show@shapingfire.com and wherever youget your podcasts. If you enjoy the show,
we'd really appreciate it if you wouldleave a positive review of the podcast.
Wherever you download your review willhelp others find the show so they can

(01:54:12):
enjoy it too. On the Shaping Fire website,
you can also subscribe to the newsletterfor insights into the latest cannabis
news exclusive videos and giveawayson the Shaping Fire website.
You also find transcriptsof today's podcast as well.
Be sure to follow on Instagram.
For all original content not found onthe podcast that's at Shaping Fire and
at chango los on Instagram,

(01:54:33):
be sure to check out Shaping FireYouTube channel for exclusive interviews,
farm tours, and cannabis lectures.
Does your company wanna reach ournational audience of cannabis enthusiasts?
Email hotspot@shapingfire.comto find out how.
Thanks for listening to Shaping Fire.I've been your host, Chango Los.
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