YC-SCAN2 March 2026 Webinar

Transcript

• 00:03Okay. Why don't we get
• 00:04started?
• 00:06Just a
• 00:09a a brief announcement.
• 00:10I'd like to share some
• 00:11exciting
• 00:13news. Earlier this month,
• 00:15the Yale Center for the
• 00:16Science of Cannabis and Cannabinoids
• 00:18announced a new
• 00:19collaboration
• 00:20with, with the McGill
• 00:23Research Center for Cannabis in
• 00:25Canada.
• 00:27This is a partnership that
• 00:29reflects a shared commitment to,
• 00:32to really advancing
• 00:33science
• 00:34on cannabis and,
• 00:36and is also an international
• 00:38collaboration.
• 00:39As part of this effort,
• 00:41McGill University will cosponsor and
• 00:43help promote
• 00:44these monthly webinars that we
• 00:46have, like today's,
• 00:48further expanding
• 00:50the re our reach and
• 00:51impact.
• 00:52We also plan at some
• 00:53later point in time to
• 00:54launch
• 00:56a new kind of lunch
• 00:57and learn
• 00:59session for trainees and early
• 01:01career investigators
• 01:03to talk about their research,
• 01:05in the cannabis
• 01:07space, space, and that'll offer
• 01:09an opportunity for,
• 01:11for mentorship and collaboration.
• 01:14So with that,
• 01:16I want it's my pleasure
• 01:18to introduce Tangam Venkatesan. Doctor
• 01:20Venkatesan is an internationally
• 01:23recognized physician scientist,
• 01:25and a leader
• 01:27in neurogastroenterology.
• 01:29Her work has been instrumental
• 01:31in advancing our understanding
• 01:33and treatment of
• 01:35cyclical vomiting syndrome, particularly in
• 01:37adults,
• 01:39where she has helped even
• 01:40define some of the diagnostic
• 01:42criteria and,
• 01:43and evidence based care.
• 01:45She has played us,
• 01:47an important role in distinguishing
• 01:49cyclically vomiting
• 01:51syndrome from cannabis
• 01:53hyperemesis syndrome, which we are
• 01:55hoping to hear a lot
• 01:56about today,
• 01:57improving its clinical recognition and
• 01:59management.
• 02:01More broadly, her research
• 02:03explores the brain gut access,
• 02:06including the role of stress,
• 02:07autonomic function,
• 02:10and
• 02:11the cannabinoid related
• 02:13mechanisms in
• 02:14gastrointestinal
• 02:16disorders. So,
• 02:17in addition to that, doctor
• 02:19Venkateshyan is a dedicated educator
• 02:22and collaborator whose work continues
• 02:24to shape,
• 02:25the field and improve patient
• 02:27care. So
• 02:28without further ado,
• 02:30Tanga, it's your stage.
• 02:33Yeah. Thank you so much,
• 02:35for those, kind words,
• 02:37Cyril. And I'm just gonna
• 02:38get my PowerPoint here.
• 02:43Alright. I think everybody can
• 02:44see my slides
• 02:49and hear me okay?
• 02:50Yes. Yes. I believe. Fantastic.
• 02:53So, again, thank you so
• 02:55much. Thank you so much
• 02:56for having me. And, today,
• 02:58I'm gonna talk a little
• 02:59bit about
• 03:00cannabinoid
• 03:00hyperemesis
• 03:01syndrome
• 03:02and,
• 03:03try
• 03:04and maybe, you know, discuss
• 03:06some myths and so on.
• 03:08And, so here we go.
• 03:11These are my disclosures.
• 03:14And, I'm gonna start with
• 03:16a case.
• 03:17So this is something that
• 03:18I see in my clinic,
• 03:19very often. Twenty eight year
• 03:21old female, she comes in
• 03:23with episodes of nausea, vomiting,
• 03:25and abdominal pain every three
• 03:26months for the past five
• 03:28years.
• 03:29Her triggers include stress and
• 03:31travel. She says her symptoms
• 03:32are relieved by sleep
• 03:34and hot showers.
• 03:36Past medical history is significant
• 03:38for anxiety, which she attributes
• 03:39to the illness.
• 03:41She smokes marijuana, she says,
• 03:42about four times a week,
• 03:45for about seven years, and
• 03:47she says it helps with
• 03:48nausea,
• 03:49appetite, and also some stress.
• 03:52She has been hospitalized multiple
• 03:54times in the past, and,
• 03:56typically, she's treated with IV
• 03:58fluids and antiemetics,
• 03:59and then she improves.
• 04:01She's also seen three gastroenterologists.
• 04:03So lo and behold, she's
• 04:04had three EGDs, a colonoscopy,
• 04:07and, multiple CT scans of
• 04:09the abdomen.
• 04:11She also has a four
• 04:12hour
• 04:13gastric emptying study, which is
• 04:14actually mildly delayed.
• 04:16She has been given a
• 04:17trial of metoclopramide
• 04:19because she's told that she
• 04:20has gastroparesis.
• 04:22She's been asked to quit
• 04:23marijuana, which she actually did
• 04:25for six months and reported
• 04:27some improvement but continues to
• 04:29have episodes.
• 04:32And, so I just want
• 04:33you to think about that
• 04:34case a little bit and,
• 04:36sort of keep it at
• 04:37the back of your head,
• 04:38and we'll move on to
• 04:39marijuana now. And as we
• 04:41all know, marijuana has really
• 04:43sort of gone mainstream, particularly
• 04:45in the US. And I
• 04:46think every time I present
• 04:48this,
• 04:49particular talk, I really have
• 04:51to update my slides.
• 04:52If you look at this
• 04:53particular map, the only state
• 04:56right now where it is
• 04:57completely illegal
• 04:59is in Idaho. So you
• 05:01can get potatoes, but you
• 05:02can't get cannabis there, at
• 05:03least legally.
• 05:05Now what about patterns of
• 05:07cannabis use? And if you
• 05:09look here, you can see
• 05:10that between two thousand and
• 05:12two to two thousand and
• 05:13nineteen,
• 05:14the prevalence of cannabis use
• 05:16has gone up.
• 05:18It's gone up in,
• 05:19in those who are aged
• 05:21eighteen to twenty five
• 05:23as well as those who
• 05:24are twenty six years and
• 05:25above.
• 05:26And, this is another study
• 05:28that looked at, cannabis use
• 05:30in the United States
• 05:32and also Canada. And so
• 05:34in the United States, in
• 05:35this particular study, about thirteen
• 05:37percent reported use within the
• 05:39past month. So that's kind
• 05:41of a pretty significant number.
• 05:42It's more than one in
• 05:44ten.
• 05:44And, in twenty twenty one,
• 05:46more than fifty two million
• 05:48people
• 05:49said that they used it
• 05:50at least once during that
• 05:51year.
• 05:52And, most many users, at
• 05:54least forty five percent of
• 05:55new users, were between the
• 05:57ages of twelve to seventeen.
• 05:59So, really,
• 06:00there's considerable use particularly among,
• 06:03adolescents
• 06:04in the US, and that's
• 06:05very concerning.
• 06:07This is another study that
• 06:09looked at cannabis use in
• 06:10about a third. So about
• 06:12twenty seven percent of adults
• 06:14in, the US and Canada
• 06:16reported lifetime use for medical
• 06:18purposes.
• 06:19And I think we hear
• 06:20this quite often from our
• 06:21patients.
• 06:22Many of them say they,
• 06:24use it for pain, so
• 06:25about half.
• 06:27Another half use it for
• 06:28anxiety and insomnia,
• 06:30though I'm not sure the
• 06:31data is that robust to
• 06:33actually,
• 06:34support its use in this
• 06:36particular for these particular indications.
• 06:39About ten percent of the
• 06:40US population also report using
• 06:43CBD for therapeutic purposes.
• 06:46Now this is another sort
• 06:48of scary slide, if you
• 06:49will, and if you look
• 06:50at these,
• 06:51the this graph,
• 06:53you can see, that people
• 06:55really don't perceive cannabis to
• 06:57be very risky at all.
• 07:00And, if you look at
• 07:01multiple sort of populations,
• 07:03adolescents,
• 07:04emerging adults, adults, middle
• 07:06aged adults, and older adults,
• 07:08their perception as it being
• 07:10risky has gone down considerably.
• 07:15And, now when you couple
• 07:16this with trends in potency
• 07:18of marijuana products, and this
• 07:20is something looking at,
• 07:22really the content of THC
• 07:24and CBD. As we all
• 07:26know,
• 07:27you know, marijuana, the most,
• 07:29important constituents, if you will,
• 07:31are THC and CBD.
• 07:33And THC sort of gives
• 07:34you the high. It's, psychotropic.
• 07:37And, typically,
• 07:39if you looked at a
• 07:40joint, so maybe in the
• 07:41nineties,
• 07:42you would see that it
• 07:43has a lower percentage
• 07:45of THC, maybe around four
• 07:47percent or so. And if
• 07:49you look at these samples,
• 07:51it's really increased to fifteen
• 07:53percent in a joint, and
• 07:54meanwhile, the CBD concentration has
• 07:57gone down significantly.
• 07:59And if you actually look
• 08:00at what is available,
• 08:02in the market right now,
• 08:04you have cannabis products that
• 08:07have anywhere between even sixty
• 08:09five to eighty five percent
• 08:10THC.
• 08:11So this is enough to
• 08:13knock our hearts down.
• 08:14And and I think what
• 08:15is being sold and what
• 08:17is being marketed is very
• 08:18different from what is, quote,
• 08:20natural.
• 08:22So maybe there's some hope.
• 08:24And, so when we talk
• 08:26about marijuana and cannabis,
• 08:28they actually,
• 08:30exert their effects by working
• 08:31on what we call c
• 08:32b one receptors.
• 08:34There is something called the
• 08:35endocannabinoid
• 08:36system. So we all produce
• 08:38sort of, if you will,
• 08:39marijuana like substances.
• 08:41There are two ligands called
• 08:42anandamide and two AG.
• 08:44They act on their, respective
• 08:47receptors called c b one
• 08:48and c b two.
• 08:50And then there are enzymes
• 08:51that actually can degrade these
• 08:53endocannabinoids.
• 08:54So they're called, fatty acid
• 08:56amide hydrolase
• 08:58and also malic lipase.
• 09:00And you do have things
• 09:01like fatty acid FAB blockers
• 09:03and so on. And so,
• 09:04potentially, you can actually increase
• 09:06anandamide
• 09:07in somebody,
• 09:09and anandamide was actually derived
• 09:11from a Sanskrit term called
• 09:12ananda, which actually means bliss.
• 09:16And, so this system is
• 09:18very important. It's very important
• 09:20for the regulation of stress,
• 09:21nausea, and vomiting.
• 09:23And if you look at
• 09:24the endocannabinoid
• 09:25signaling system, it's actually very
• 09:27unique. There is a basal
• 09:28tone and there's also an
• 09:29on demand tone. And here
• 09:31we are, you know, we
• 09:32have deadlines. This person is
• 09:34very stressed.
• 09:35And then if you look
• 09:36at it, there's actually a
• 09:37production
• 09:38of endocannabinoids
• 09:39from the postsynaptic
• 09:41terminal. So this is a
• 09:42little different, and then this
• 09:44actually adds on c b
• 09:45one receptors that are present
• 09:46on the presynaptic
• 09:48terminal.
• 09:49And then this actually helps,
• 09:51reduce sort of neurotransmission
• 09:53and excitability,
• 09:55and, it brings you back
• 09:57to homeostasis,
• 09:58and that's important.
• 10:00You know, whenever you have
• 10:01stress as an activation of
• 10:03the HPA axis,
• 10:05and you really sort of
• 10:06have maybe a flight or
• 10:07fight response, so you need
• 10:08to adapt to that. But
• 10:10the HPA system actually works
• 10:12in concert,
• 10:13with the endocannabinoid
• 10:15system
• 10:16to make sure that you
• 10:17are healthy and happy.
• 10:19And, we all know that
• 10:21cannabinoids have a role to
• 10:22play in stress regulation,
• 10:25in nausea and vomiting. It's
• 10:27very important for appetite.
• 10:29In fact, they use CB
• 10:30one receptor antagonist,
• 10:32for obesity.
• 10:34And then it also has
• 10:35anti inflammatory effects, and it's
• 10:37very important for cognition,
• 10:39mood, and memory.
• 10:41So in a sense,
• 10:43you know, for maybe the
• 10:44students there, if you wanna
• 10:46just kind of think about
• 10:47it, it makes you happy,
• 10:48fat, and dumb. And if
• 10:49it's not working, it's a
• 10:51problem. So, certainly, there is
• 10:53some hope that we can
• 10:54actually manipulate this. And, what
• 10:57about cannabinoids as antiemetics? I'm
• 10:59talking about a vomiting disorder,
• 11:01but here you have cannabinoids,
• 11:02which are actually used or
• 11:03were used as antiemetics.
• 11:06You have nabilone and marinol,
• 11:08which has synthetic analogs of
• 11:10THC, and they were used
• 11:12in chemotherapy induced nausea and,
• 11:15vomiting.
• 11:16And so, obviously, you have
• 11:17better drugs now for those,
• 11:19and you don't use it
• 11:20as much.
• 11:21But they have been shown
• 11:22in studies to be effective
• 11:24for these conditions.
• 11:27And, what about cannabis based
• 11:29medicine? So they had sort
• 11:30of this half and half,
• 11:31one is to one ratio
• 11:32called Sativex.
• 11:34It's delivered by a oromukacil,
• 11:37spray.
• 11:38And, here, it reduced the
• 11:40incidence of delayed chemotherapy induced
• 11:42nausea and vomiting compared to
• 11:44placebo.
• 11:45So, certainly, you know,
• 11:47cannabinoids
• 11:48seem to have obviously
• 11:50antiemetic effects, and and we
• 11:52sort of know that.
• 11:53But what about weed? So
• 11:55why is weed causing hyperemesis?
• 11:58And, I think this is
• 12:00actually a study that, Cyril
• 12:02did with the holy festival,
• 12:04and
• 12:05he described how he did
• 12:06it. So it's just amazing.
• 12:07It's aside from hyperemesis, it
• 12:09can also, you know, result
• 12:11in psychosis and so on
• 12:12and be associated with psychosis.
• 12:15So, anyways, I'm gonna switch
• 12:17gears a little bit. If
• 12:19anybody wants to kind of,
• 12:21you know, ask questions, feel
• 12:22free to jump in because
• 12:24I, you know, would like
• 12:25for this to be
• 12:27interactive.
• 12:28So,
• 12:29I'm not sure I can
• 12:30see anybody, but I'll let
• 12:31Cyril
• 12:32let me know if anybody
• 12:33has any questions.
• 12:38No no questions so far.
• 12:40Okay. Perfect.
• 12:41So,
• 12:42so we're gonna kinda switch
• 12:44gears and, really talk a
• 12:46little bit about cannabinoid
• 12:48hyperemesis syndrome.
• 12:49So this was a term
• 12:51that was coined in two
• 12:52thousand and four, and it
• 12:54actually started and the first
• 12:55person to actually report it
• 12:57was, was an internist who
• 12:59is in the Adelaide Hills
• 13:00in Australia.
• 13:02That's just my daughter. She
• 13:03wants to go to Australia,
• 13:04and she loves marsupials.
• 13:05But be as it may,
• 13:07the first reports were from,
• 13:09from Australia.
• 13:11And so,
• 13:12this person, Allen et al,
• 13:14and, their group noted that
• 13:15there were about nine adults,
• 13:18and, they actually reported
• 13:20cases of,
• 13:21cyclic vomiting. And, these patients
• 13:24also happen to be in
• 13:25a hot shower all the
• 13:26time,
• 13:27and he actually followed these
• 13:29patients for one or two
• 13:30years. It's kind of a
• 13:31small hospital, and they were
• 13:33able to follow these patients.
• 13:35And he noted that with
• 13:37cannabis abstinence, their symptoms seem
• 13:39to resolve.
• 13:42And so here's the, report
• 13:44that was, first published.
• 13:46And then if you move
• 13:47on, this is actually the
• 13:49second case report, and this
• 13:50comes from England.
• 13:52And it looks like they
• 13:53had a chef who was
• 13:54vomiting and using cannabis. And
• 13:56so these guys called the
• 13:57guys in Australia and said,
• 13:59hey. Do you know what's
• 14:00going on? And so this
• 14:01was the second case
• 14:03of CHS or cannabinoid
• 14:05hyperemesis
• 14:06that was reported.
• 14:08And, as you can see,
• 14:10there's been a steady explosion
• 14:11of articles and, you know,
• 14:13it it really took off.
• 14:15But I think what people
• 14:16don't realize is that's
• 14:18cannabinoid hyperemesis syndrome has pretty
• 14:21much the same
• 14:22clinical
• 14:24presentation as cyclic vomiting syndrome,
• 14:26and nobody knew much about
• 14:27CVS either. So it was
• 14:29only in two thousand and
• 14:30six that we actually had
• 14:32the wrong criteria for CVS.
• 14:34And, you know, in two
• 14:35thousand and ten, cannabis was
• 14:36legalized, so people were becoming
• 14:38more aware
• 14:39of,
• 14:40cyclic vomiting, if you will.
• 14:43And, so I think we
• 14:44need to think about this,
• 14:47and it's it's a little
• 14:48more nuanced.
• 14:49And, obviously,
• 14:51marijuana was first or cannabis
• 14:53was first legalized in Colorado
• 14:55and California.
• 14:56And, this is the study
• 14:58where they looked at out
• 14:59of state residents, and as
• 15:01you can see, there's actually
• 15:03a significant
• 15:04increase in the number of
• 15:06ED visits related to cannabis
• 15:08use in out of state
• 15:09residents who essentially came to
• 15:11Colorado,
• 15:13to smoke, to smoke weed.
• 15:16This is another study, that
• 15:18looked, during the COVID nineteen
• 15:20pandemic, and it was, it
• 15:22was it was kind of
• 15:23unfortunate, and it's it's really
• 15:24sad.
• 15:25But there were, children. This
• 15:27is between zero to ten
• 15:28years of age, and, this
• 15:30was because they were being
• 15:32seen in the emergency department
• 15:34because of ingestion
• 15:36of, really, cannabis edibles that
• 15:39adults, I guess, were,
• 15:40just,
• 15:42you know, letting it accidentally
• 15:44lie around. So clearly,
• 15:46you know, there are issues,
• 15:48surrounding this,
• 15:50aside from sick like vomiting.
• 15:51Again, there was a significant
• 15:53increase in ED visits,
• 15:56in the state of Colorado
• 15:57with the legalization.
• 15:59It's little difficult to say
• 16:01if they were these were
• 16:03just,
• 16:04cases of CVS rather than
• 16:06a true increase.
• 16:08Maybe they were previously diagnosed
• 16:09as having gastroparesis
• 16:11or whether there was increased
• 16:13reporting of cannabis used by
• 16:14patients. And so,
• 16:16again, this is a little
• 16:17unclear.
• 16:19And now I think we
• 16:20have, myriad studies showing,
• 16:23associations between cannabis use and
• 16:25health care utilization.
• 16:27So, I wanna present to
• 16:29you this study where they
• 16:30looked at a national survey
• 16:32on drug use and health
• 16:33data between twenty fifteen and
• 16:34twenty nineteen. These were older
• 16:36adults, fifty plus. And so
• 16:38they looked at cannabis use
• 16:39status as to why they
• 16:40use cannabis use, and they
• 16:42also looked at the number
• 16:43of ED visits
• 16:44and hospitalizations
• 16:46in these patients. And importantly,
• 16:48what they found is when
• 16:49they did a regression binomial
• 16:51regression analysis and adjusted for
• 16:53various factors,
• 16:55they actually found that past
• 16:57year users did not differ
• 16:59from never users. And so
• 17:01the number of ED visits
• 17:02and hospitalizations
• 17:03were pretty much the same
• 17:05in those who never used
• 17:06cannabis versus those who were
• 17:08using cannabis.
• 17:10They did find that those
• 17:11who used it for medical
• 17:13purposes had more ED visits
• 17:15than those who used it
• 17:17for other purposes. And, this
• 17:19was likely explained,
• 17:21because
• 17:22those,
• 17:22patients or who were using
• 17:24it for medical only,
• 17:27purposes likely had more comorbidities,
• 17:29and that was why they
• 17:30were really showing up in
• 17:32the ER more.
• 17:33And in this particular study,
• 17:35cannabis use was actually not
• 17:37associated with hospitalizations.
• 17:40Again, this was in older
• 17:41cannabis users. And so I
• 17:43think, you know, clearly, the
• 17:45data is conflicting,
• 17:47and we really need to
• 17:48be careful because,
• 17:50association
• 17:51is not equal to causation.
• 17:55And what about cannabinoids? So
• 17:56we here, we have a
• 17:57syndrome,
• 17:58and, obviously, we don't have
• 18:00any biomarkers.
• 18:01And, so people
• 18:03called CHS or defined CHS
• 18:06any which way they wanted.
• 18:08Initially, they defined CHS as
• 18:11episodic vomiting with hot water
• 18:13bathing. So anybody who had
• 18:15this, quote, hot water bathing
• 18:16pattern, they were they would
• 18:18actually bathe multiple times,
• 18:21in a day along with
• 18:22episodic vomiting,
• 18:24were deemed as having CHS,
• 18:27or any cannabis use as
• 18:28well was deemed as having
• 18:30CHS.
• 18:34And and so as a
• 18:35gastroenterologist
• 18:36I'm a gastroenterologist,
• 18:38and, you know, we have
• 18:39disorders that guide brain interaction
• 18:40and then what we call
• 18:41functional GI disorders.
• 18:43And we don't when we
• 18:44don't have a biomarker,
• 18:46we actually rely on something
• 18:48called Roam criteria.
• 18:50The Roam criteria established by
• 18:52the Roam Foundation, which is
• 18:53an international GI organization.
• 18:56And, the Roam Foundation develops
• 18:58diagnostic
• 19:00symptom based criteria
• 19:02so to make sure that
• 19:03everybody is actually using the
• 19:05same framework
• 19:06for diagnosis.
• 19:08This is typically actually accepted,
• 19:11universally
• 19:12across the globe.
• 19:15And, so in terms of,
• 19:17CHS,
• 19:18we first need to define
• 19:19what CVS is
• 19:21because CHS is thought to
• 19:23be a subset of CVS,
• 19:24and it has the exact
• 19:25same clinical presentation.
• 19:27So as far as CVS
• 19:29is concerned,
• 19:30one needs to have stereotypical
• 19:32episodes of vomiting. They're usually
• 19:34acute and onset, which means
• 19:36they occur suddenly just out
• 19:38of the blue.
• 19:39Typically, the duration is anywhere
• 19:40between few hours to many
• 19:42days.
• 19:43They at least have to
• 19:44be a week apart, and
• 19:45you need to have three
• 19:46or more episodes in the
• 19:48prior year to make a
• 19:50diagnosis.
• 19:51You can have some milder
• 19:52symptoms in between episodes,
• 19:55particularly patients who have severe,
• 19:58CVS. And, obviously, you should
• 19:59not have any metabolic
• 20:01or GI or any other
• 20:03CNS,
• 20:04causes
• 20:05to explain
• 20:06the vomiting.
• 20:08Now what about CHS? So
• 20:09the CHS, this is what
• 20:11we have.
• 20:12It says it's exactly the
• 20:13same. So it resembled CVS
• 20:15in terms of onset, duration,
• 20:17frequency,
• 20:19but then, the wrongful criteria
• 20:21said, well, it needs to
• 20:22you need to have presentation
• 20:24after prolonged excessive cannabis use.
• 20:27Obviously, this should precede the
• 20:28onset of symptoms because, otherwise,
• 20:30it's difficult to say it's
• 20:31causative,
• 20:32and you have to have
• 20:33relief of vomiting episodes by
• 20:35sustained cessation of cannabis use.
• 20:38And they really didn't kinda
• 20:39identify
• 20:40all of this. They also
• 20:42said that a supportive remark
• 20:43or a supportive criteria
• 20:45is the association
• 20:46with the pathological
• 20:48bathing behavior where patients will
• 20:50just go in and out
• 20:51of a shower or a
• 20:52bath multiple times.
• 20:54Now we actually do have
• 20:56the ROAM PHY criteria, and,
• 20:57fortunately, they listened to us
• 20:59a little bit.
• 21:00And so there were a
• 21:01few more things,
• 21:03details that were added,
• 21:05based on some studies that
• 21:07we performed.
• 21:08So in order to make
• 21:09a diagnosis of CHS,
• 21:11you you do need chronic
• 21:13cannabis use. And so these
• 21:15were some of the criteria
• 21:16that,
• 21:17we came up with. So
• 21:18presentation
• 21:19should be after prolonged at
• 21:21least a year of cannabis
• 21:22use. It should be more
• 21:24than four days, four or
• 21:26more days per week, or
• 21:27more than fifteen doses a
• 21:28week of cannabis use.
• 21:31Again, you need to show
• 21:32that somebody has relief of
• 21:34vomiting episodes by sustained cessation.
• 21:36So,
• 21:37they really need to abstain
• 21:39for at least six months
• 21:40or three typical emetic cycles
• 21:43because if you remember, this
• 21:44is an episodic
• 21:45disorder. So one person might
• 21:47have three episodes in a
• 21:49year, and another person might
• 21:51have three episodes in two
• 21:52months.
• 21:53And,
• 21:54it can be associated, obviously,
• 21:56with the pathological
• 21:57bathing behavior.
• 22:00Now what about the prevalence
• 22:01of CVS and CHS? It's
• 22:03it's really been difficult to
• 22:07really study or understand this.
• 22:09But, b, as it may,
• 22:10I think some of the
• 22:11best studies which were done
• 22:12using the room criteria with
• 22:14CVS showed that in the
• 22:16US, the prevalence is about
• 22:17two percent.
• 22:18In that same study, they
• 22:20said that there were only
• 22:21about seven cases of CHS
• 22:23in the US,
• 22:25and, there were none in
• 22:26the UK and Canada.
• 22:28However, there are other studies
• 22:30suggesting that CHS is an
• 22:32epidemic.
• 22:33And I'm gonna tell you
• 22:35that, unfortunately, many of these
• 22:36studies
• 22:37really just define CHS
• 22:40as any cannabis use,
• 22:43along with vomiting. And so
• 22:45I think there are certainly,
• 22:47you know, major limitations
• 22:48with some of those studies.
• 22:51In terms of the phases,
• 22:53it's almost like having a
• 22:54migraine headache, whether it's CVS
• 22:56or CHS. Most people are
• 22:57kind of okay,
• 22:59and, they go about their
• 23:00usual routine.
• 23:01And then you get into
• 23:02what is called a prodromal
• 23:04phase where patients can have
• 23:05nausea,
• 23:07abdominal pains. Many of them
• 23:09have an,
• 23:10really an impending sense of
• 23:11doom that something bad is
• 23:12going to happen.
• 23:14And then they, if you
• 23:15are not able to abort
• 23:17that phase, they will go
• 23:18into a emetic
• 23:19phase.
• 23:20And, the people have very,
• 23:22very, very severe vomiting here.
• 23:25They have vomiting and are
• 23:26retching, and, unfortunately,
• 23:28the only thing you can
• 23:29do then is support a
• 23:30therapy.
• 23:31And then finally, they go
• 23:32back to the bowel phase.
• 23:34Doctor doctor Venkatesh, I can
• 23:36interrupt you for just a
• 23:37second Yes. Exactly. To your
• 23:39previous slide. Yes. I saw
• 23:41that,
• 23:42you you mentioned that
• 23:45sumatriptan
• 23:47Yes.
• 23:47Is an abortive medication. And
• 23:50I'm that's I'm really curious
• 23:52about that because
• 23:53we know quite a bit
• 23:54about the mechanism of action
• 23:56of sumatriptan.
• 23:57And I'm curious why,
• 24:00a serotonergic
• 24:01drug would
• 24:02would work
• 24:03for,
• 24:04for kind cannabis hyperemesis syndrome.
• 24:07And maybe you can get
• 24:08to answer this later on.
• 24:10Yeah.
• 24:12So,
• 24:12so that's a that's a
• 24:13good question. And so, you
• 24:15know, so what we when
• 24:16we think about cannabinoid hyperemesis
• 24:18syndrome, because there's so much
• 24:20of,
• 24:21you know, like I said,
• 24:22the literature is so limited,
• 24:23and we tend to, at
• 24:25least think of it as
• 24:26a subset of CVS.
• 24:28And when you look at
• 24:29sixty sickly vomiting syndrome, there's
• 24:31actually a huge
• 24:33overlap with migraine.
• 24:35A lot of children, yeah,
• 24:36a lot of children who
• 24:38actually develop,
• 24:39who have CVS as children,
• 24:41about seventy percent of them
• 24:43outgrow
• 24:44the condition and they develop
• 24:45migraine headaches,
• 24:47and so they can sort
• 24:48of flip flop.
• 24:50In fact, when you're treating
• 24:51a patient with CVS and
• 24:52they're getting better,
• 24:54they might actually start developing
• 24:55migraines, and then you have
• 24:56to increase the medication
• 24:58even more.
• 24:59So in terms of, like,
• 25:01sumatriptan,
• 25:02I mean, there aren't I
• 25:03I
• 25:04there really
• 25:06aren't too many there aren't
• 25:07no randomized
• 25:07controlled trials in adults,
• 25:09but, certainly, we have,
• 25:11you know, retrospective
• 25:13open label studies,
• 25:15to show that they're effective
• 25:17in these, patients. So, typically,
• 25:19when somebody comes with CVS
• 25:21and we really don't know
• 25:22if they have CHS or
• 25:24not,
• 25:24we tend to get, treat
• 25:26them actually like,
• 25:28you would say a migraine
• 25:30and tell them to use
• 25:31sumatriptan and antiemetics,
• 25:33and even some mild sedation
• 25:35to make the, you know,
• 25:36episode better. And so one
• 25:38one other related question is
• 25:40what what does CGRP inhibitors
• 25:42do in for for cyclical,
• 25:44for hype hyperemesis?
• 25:46Because Yeah.
• 25:47It revolutionized the treatment of
• 25:49migraine, and so I'm curious
• 25:50about whether they have some
• 25:52effects.
• 25:53You know, that's a great
• 25:54question. Absolutely. And we were
• 25:56trying to get funding to
• 25:57actually study, like, CGRP
• 25:59and see whether it's CVS
• 26:01or CHS.
• 26:02And, unfortunately,
• 26:03there's no data.
• 26:05I will say that,
• 26:07you know, sometimes when people
• 26:09don't respond and we do
• 26:10have patients with CVS and
• 26:13hyperemesis
• 26:14who also have migraine headaches,
• 26:15and we sent them to
• 26:16the neurologist.
• 26:18Again, this is completely, like,
• 26:20anecdotal,
• 26:21you know, evidence.
• 26:23I haven't seen CGRP,
• 26:25you know, antagonist to be
• 26:27as effective
• 26:29in, you know, either hyperemesis
• 26:31or vomiting,
• 26:33you know, as in migraine.
• 26:34So the migraine headache seems
• 26:35to be, you know, better.
• 26:37So I'm a little unclear
• 26:39as to whether CGRP
• 26:41and you're absolutely right because
• 26:42it's completely,
• 26:44changed the way migraine headaches
• 26:45are managed.
• 26:47There there was, there was
• 26:48also as I was asking,
• 26:49there was another comment in
• 26:51the chat also about
• 26:52CGRP or Amylin,
• 26:55but maybe we can get
• 26:56to that later. I I
• 26:57don't want to,
• 26:58interrupt you anymore. There there's
• 27:00there are more questions, which
• 27:01I'll bring up later on
• 27:03in in your Absolutely.
• 27:04Yeah.
• 27:06And so, the other thing
• 27:08is when you think of
• 27:09somebody with either CVS or
• 27:10CHS,
• 27:12many people kind of, think
• 27:14that they only have nausea
• 27:15and vomiting.
• 27:16But this is almost like,
• 27:18you know, an autonomic
• 27:19attack, if you will. And
• 27:21so,
• 27:22you know, we actually did
• 27:24a study where we,
• 27:26looked at their symptoms with
• 27:27a daily diary,
• 27:28and we found that people
• 27:29have a lot of symptoms.
• 27:31They have nausea, vomiting,
• 27:34profuse sweating in about ninety
• 27:35three percent of patients. They'll
• 27:37actually have abdominal pain.
• 27:39They feel hot or cold.
• 27:40There's something off with their
• 27:42thermoregulation.
• 27:44They have photosensitivity
• 27:46and headaches.
• 27:48And so, again, the hot
• 27:49water bathing was initially thought
• 27:51to be pathognomonic
• 27:53of CHS.
• 27:54While it is statistically
• 27:56associated with cannabis use, we
• 27:58didn't do a study, and
• 28:00about half the patients who
• 28:01don't have any cannabis use
• 28:04also have this hot water
• 28:05bathing pattern. It's actually very
• 28:07peculiar
• 28:08to this condition. It has
• 28:09not been described in any
• 28:10other medical condition,
• 28:12you know, that I'm aware
• 28:13of. And so patients go
• 28:15in and, they will feel
• 28:17better
• 28:18after ten minutes or so.
• 28:19And we actually looked at
• 28:21this and, again, this was
• 28:22a study we did where
• 28:23we asked patients about their
• 28:25hot water bathing patterns.
• 28:27And then we divided these
• 28:29patients and we looked at
• 28:30the cannabis users.
• 28:32So we looked at occasional
• 28:33and nonusers versus cannabis users.
• 28:36And as you can see,
• 28:38there were, you know, greater
• 28:39number of males,
• 28:41in the, in the regular
• 28:43cannabis users group.
• 28:45The other thing we noticed
• 28:47is that if you looked
• 28:48at the CU group or
• 28:49the regular cannabis users group,
• 28:52we looked at the number
• 28:53of symptoms they had during
• 28:54the prodromal phase as well
• 28:56as the vomiting phase.
• 28:58And, you know, curiously, they
• 28:59actually had more symptoms. So
• 29:01they had a greater
• 29:03symptom burden,
• 29:05and they also tended to
• 29:06use very hot water.
• 29:09So, I mean, these are
• 29:10some clues as to what
• 29:12is going on,
• 29:13you know, with cannabis, and
• 29:15it's,
• 29:15it's really very intriguing.
• 29:18Now when we talk about
• 29:19CHS, I know that people
• 29:22have co coined this disorder,
• 29:24but we tend to think
• 29:25of it as a subset
• 29:27of CVS,
• 29:28you know, and analogous
• 29:30maybe to
• 29:31Crohn's disease where NSAIDs can
• 29:33make Crohn's disease worse. Perhaps
• 29:35cannabis is making making things
• 29:36worse.
• 29:38We do have some data
• 29:39looking at c n r
• 29:40one,
• 29:41you know, polymorphisms,
• 29:43and we found that there
• 29:44has been a that has
• 29:45been associated with an increased
• 29:47risk of, cyclic vomiting.
• 29:50Now, obviously, cannabis use is
• 29:52a huge trigger, we think,
• 29:55for episodes.
• 29:56Certainly, stress is a big
• 29:58factor,
• 29:59and and and endocannabinoid
• 30:02functioning and so on and
• 30:03so forth.
• 30:05So is CHS a valid
• 30:07diagnosis?
• 30:08You know, people keep saying
• 30:09that
• 30:10it's you it's it's thought
• 30:12to be related to cannabis.
• 30:14Now we actually this was
• 30:15a study that I did
• 30:16in my patient cohort. There
• 30:17were more than hundred patients,
• 30:19And, this was the first
• 30:21study which actually used a
• 30:22validated questionnaire called the QDIP,
• 30:24the cannabis use disorder identification
• 30:27test. And so we found
• 30:28that in this particular cohort,
• 30:31about sixty percent really never
• 30:33used any cannabis,
• 30:35and there were, one in
• 30:37five patients. So about twenty
• 30:38five twenty one percent used
• 30:41cannabis four or more times
• 30:42a week.
• 30:43Obviously, this is by patient
• 30:45report,
• 30:46and they essentially said they've
• 30:47improved all their symptoms. So
• 30:49it improved vomiting. It improved
• 30:51abdominal pain, appetite.
• 30:53They even said it helped
• 30:55them,
• 30:55avoid going to the emergency
• 30:57department and so on.
• 30:59And and and many of
• 31:01these patients,
• 31:02almost eighty six percent, did
• 31:03try to abstain from cannabis
• 31:05for at least a month.
• 31:07And in this entire cohort,
• 31:09there was only one patient
• 31:10who reported resolution of symptoms.
• 31:13This particular patient actually started
• 31:15using cannabis with higher CBD.
• 31:19And, on long term follow-up,
• 31:21he was actually symptom free.
• 31:23So I think cannabis abstinence,
• 31:25obviously, is a very, very
• 31:26difficult bar because most people
• 31:28don't think it's harmful,
• 31:30and it's very difficult to
• 31:31convince your patient.
• 31:34And then we also looked
• 31:35at we also did a
• 31:36systematic review of CHS CHS
• 31:38when we did the twenty
• 31:39nineteen guidelines and the management
• 31:41of CVS,
• 31:42because there were multiple case
• 31:44series and case reports.
• 31:46And, many of these case
• 31:48series and case reports were
• 31:49before the Rome criteria were
• 31:51actually established.
• 31:52And so, certainly, the diagnosis
• 31:55was made,
• 31:56using really different criteria in
• 31:58these various, case series and
• 32:00case reports.
• 32:02B as it may, in
• 32:03CHS or purported CHS, the
• 32:05duration of cannabis use was
• 32:07between six and eight years.
• 32:09But what was really striking
• 32:10in the systematic review is
• 32:12that most of these patients
• 32:13did not have any follow-up.
• 32:16And I think in an
• 32:17episodic disorder, it is very
• 32:19important to have a longer
• 32:21term follow-up.
• 32:22And then we retro,
• 32:24retrospectively
• 32:25applied the room for criteria,
• 32:27and we found that only
• 32:29fourteen to twenty percent actually
• 32:31met the criteria,
• 32:33for CHS,
• 32:34in this entire cohort of
• 32:36patients.
• 32:37So it's really difficult to
• 32:39understand why all of this
• 32:40is happening.
• 32:42Could there be a genetic
• 32:43predisposition,
• 32:44like in, say, alcoholic liver
• 32:46disease? Perhaps there are only
• 32:47certain
• 32:48small subset of patients who
• 32:50develop hyperemesis.
• 32:52Could there be an endocannabinoid
• 32:54deficiency? We have some studies
• 32:56in CVS patients,
• 32:58you know, pointing to that.
• 32:59And the other thing is,
• 33:00you know, really the potency
• 33:02of the cannabis products. Like
• 33:03I said in the previous
• 33:04slide,
• 33:05you know, the amount of
• 33:07THC in a joint was
• 33:08four percent in the nineties,
• 33:09and now people are using
• 33:10sixty five and eighty five
• 33:12percent.
• 33:13And, it appears that THC
• 33:15has a biphasic effect. So,
• 33:18you know, where low doses
• 33:19are antiemetic, but higher doses
• 33:21and frequent dosing actually leads
• 33:23to hyperemesis
• 33:25and, c b one downregulation.
• 33:29Now I'm gonna come back
• 33:30to that case,
• 33:32and, you know, so, essentially,
• 33:34like I said,
• 33:35this patient came to me
• 33:37and she, tried to quit
• 33:38marijuana. She reported some improvement,
• 33:42but she was having episodes.
• 33:44And,
• 33:45we actually treated her with
• 33:47amitriptyline. She reached a target
• 33:48dose of hundred milligrams
• 33:50at night, and, she improved
• 33:52significantly with market reduction in
• 33:54symptoms.
• 33:55She does continue to smoke
• 33:56cannabis, though I do tell
• 33:58my patients to reduce cannabis
• 33:59usage. So she did reduce
• 34:01it,
• 34:02to two times a week.
• 34:03She's happy with her progress.
• 34:06And, so here's the case.
• 34:08And then, this was actually
• 34:10by the Canadian society, and
• 34:11this is actually a real
• 34:12book.
• 34:13They said this has to
• 34:14be shared with adolescents,
• 34:16because use is so high
• 34:18nowadays, particularly in adolescents.
• 34:21Obviously,
• 34:22there are so many adverse
• 34:24effects with cannabis,
• 34:26and so the most effective,
• 34:28the most effective advice would
• 34:30be abstinence, but that can
• 34:31be quite difficult.
• 34:33So, typically, for my patients,
• 34:35I I tell them to
• 34:36choose maybe lower potency
• 34:38t THC,
• 34:40nonsmoking
• 34:41methods, and I do encourage
• 34:42them to reduce the frequency
• 34:44considerably.
• 34:46Obviously, early age initiation is
• 34:48also a problem,
• 34:51and it really remains to
• 34:52be seen.
• 34:53So there are actually a
• 34:55lot more questions
• 34:57and, you know, and
• 34:59for research. So so what
• 35:00is the relationship
• 35:01between cannabis use and hyperemesis?
• 35:03Does it really cause it?
• 35:05What is the underlying mechanism?
• 35:07Is it c b one
• 35:08receptor down regulation, and how
• 35:10long does it take? And
• 35:11if even if your c
• 35:12b one receptors,
• 35:15really sort of come back,
• 35:16how long does it take
• 35:17to reverse all of these
• 35:19effects in CHS,
• 35:22high potency
• 35:23products? And, you know, obviously,
• 35:24there are other countries where
• 35:25cannabis is legal such as
• 35:27in Amsterdam,
• 35:28and, there is no epidemic
• 35:30or there are no major
• 35:32reports of CHS coming out
• 35:33of Amsterdam.
• 35:35And, you know, the genetic
• 35:36predisposition,
• 35:38is there a correlation between
• 35:39THC concentration
• 35:41and the symptoms?
• 35:42Do symptoms improve with cessation,
• 35:44or is just reduction enough,
• 35:47and and and so on.
• 35:48So I think there are
• 35:49really
• 35:50a lot of questions. I
• 35:51think,
• 35:53you know, the area is
• 35:54ripe.
• 35:55And,
• 35:55I I really would like
• 35:57to thank,
• 35:57Suril so much. I was
• 35:59very excited to be here.
• 36:00And,
• 36:02you know, I was I
• 36:03was just wishing, oh my
• 36:04god, I would just, like,
• 36:06salivate at being at the
• 36:07center of cannabis and talking
• 36:09to you guys more often.
• 36:11And, of course, thank you
• 36:12so much,
• 36:13to Wendy who's been very
• 36:14patient in in getting this
• 36:16all organized.
• 36:18And I think I'll pause
• 36:19here and,
• 36:21take questions.
• 36:23Great. Thank you. That was,
• 36:26that was really informative.
• 36:27There's a question in the
• 36:29chat chat from, Beatrice Carlini.
• 36:32What if the patient cannot
• 36:33achieve sustained cessation?
• 36:36Most of them are unable
• 36:38to or unwilling to quit.
• 36:41Correct. So,
• 36:42so, yes, that's a great
• 36:44question. And like I said,
• 36:45it's very important to have
• 36:47this conversation with your patient.
• 36:48I I see hundreds of
• 36:50patients like this. And one
• 36:51is to be nonjudgmental.
• 36:53And two, like everything else,
• 36:54there's a little bit of
• 36:55negotiation, you know, like you
• 36:57do it with your children
• 36:58or anything else, when your
• 37:00patient is there.
• 37:01One is, we do recommend
• 37:03treating them like they have
• 37:04CVS because we don't know
• 37:06if the cannabis is actually
• 37:07causing it. So in general,
• 37:09I give them aborted medications.
• 37:11Cyril was talking about sumatriptan
• 37:14and antiemetics.
• 37:15If they have severe CVS,
• 37:17I'll probably start them on
• 37:18neuromodulators.
• 37:20And I also have them
• 37:21reduced at the same time,
• 37:23and you you'll be surprised
• 37:24a lot of them will
• 37:25actually,
• 37:27respond to that conversation a
• 37:28little bit more.
• 37:30Many,
• 37:32physicians or most people tend
• 37:33to just say, hey. You've
• 37:35gotta stop, and I'm not
• 37:37gonna see you till you
• 37:38stop. And if you do
• 37:39that, you've just lost your
• 37:41patient.
• 37:42A, they're not gonna do
• 37:43it, and b, they won't
• 37:44come back to you.
• 37:45So I think,
• 37:46you know, certainly messaging,
• 37:48unfortunately, it's marketed so widely.
• 37:51And, you know, you see
• 37:52cannabis dispensaries
• 37:54and and cropping up everywhere.
• 37:56So I think, you know,
• 37:58really, we as a society
• 37:59and the medical community and
• 38:01and and and really the
• 38:02government,
• 38:03it's very important that it's
• 38:05regulated and there's messaging and
• 38:07there's more research,
• 38:08you know, so that we
• 38:09can actually educate the public
• 38:10about this.
• 38:13Beatrice, did you,
• 38:14want to ask any more
• 38:16details?
• 38:17Was that
• 38:19okay. Yes.
• 38:21I was wondering. Thank you
• 38:22so much for your response,
• 38:23and thanks so much for
• 38:24your presentation.
• 38:26I was actually wondering in
• 38:28terms of the ROM,
• 38:30diagnostic.
• 38:31Yeah. I'm afraid that very
• 38:33little very few people are
• 38:34gonna get this diagnostic. They
• 38:36have to be,
• 38:37you know, quit cannabis to
• 38:39have their diagnosis. So I
• 38:40was curious about that in
• 38:41terms of getting treatment and
• 38:43support.
• 38:44Yeah. Absolutely.
• 38:45So, you know, again, you
• 38:46just hit the nail on
• 38:47the head because,
• 38:49now be as it may,
• 38:50we do we those are
• 38:52the criteria. And as you
• 38:53can see, it's such a
• 38:54high bar because there are
• 38:55only so many people who
• 38:57are going to completely
• 38:58abstain,
• 38:59for a period of six
• 39:01months,
• 39:01you know, six months or
• 39:03so.
• 39:04And so in some instances
• 39:05and and, again, when I'm
• 39:08so one is for research
• 39:09purposes and two for clinical
• 39:11purposes. Right? So, I think
• 39:13in clinic, more than getting
• 39:15hung up too much on
• 39:16whether it's CHS or CVS,
• 39:17you have that conversation with
• 39:19them and say, well, it
• 39:20could be due to cannabis,
• 39:22and you really need to
• 39:23cut it down.
• 39:24And then I'm gonna give
• 39:25you x, y, and z.
• 39:27It's not potentially
• 39:29wrong to make a presumptive
• 39:31diagnosis of CHS,
• 39:33but I worry that it
• 39:35stigmatizes
• 39:36patients a lot because not
• 39:38all cannabis users equal. I
• 39:40would really look at patients
• 39:42who are maybe heavy users.
• 39:44You do have some people
• 39:45who are heavy users. And
• 39:46when we looked at our
• 39:47cohort,
• 39:49you know, among the cannabis
• 39:50users, the incidence of cannabis
• 39:52use disorder was not much
• 39:54higher.
• 39:55And,
• 39:56so I think we,
• 39:58you know, they really put
• 39:59the cart before the horse
• 40:00with us. And I think,
• 40:02there was this huge hurry
• 40:03to to make up this
• 40:05diagnosis,
• 40:06and I'm not sure there's
• 40:07not enough evidence to show
• 40:09causation.
• 40:10So possibly with high,
• 40:13you know, really high risk
• 40:14cannabis users,
• 40:15there could be that. But
• 40:17you're right. The wrong criteria
• 40:18is not,
• 40:20perfect, and, it does have
• 40:21several limitations.
• 40:23And we have said, okay.
• 40:24You could say make a
• 40:26presumptive
• 40:27diagnosis of CHS
• 40:29if they're not willing to,
• 40:30you know, stop and they
• 40:32truly have either cannabis dependence
• 40:34or cannabis use disorder.
• 40:37Okay. Thank you very much.
• 40:39Yes.
• 40:40Vic, a couple of,
• 40:42questions and comments in the
• 40:44chat by Eric. Eric, do
• 40:45you wanna,
• 40:47do you wanna just
• 40:50unmute yourself and ask? Yeah.
• 40:51Go ahead. Hi.
• 40:53Great talk.
• 40:54I had a few questions.
• 40:55So,
• 40:57regarding the route of administration,
• 40:58there was a recently published
• 41:00study by, Peterson et al
• 41:01this month, actually.
• 41:03And the authors found that
• 41:05consumption of vape cartridges led
• 41:07to a shorter time to
• 41:08develop CHS,
• 41:10compared to other routes of
• 41:11consumption. So I was wondering
• 41:12if you're seeing something similar
• 41:15in the clinic,
• 41:16or overall what your thoughts
• 41:18are on, on this finding.
• 41:21Yeah. So I you know,
• 41:23again, I'm sorry. I haven't
• 41:24actually specifically looked at that
• 41:25study. I'd be interested in
• 41:27knowing a little bit more
• 41:28about the the methodology
• 41:30because when they say it
• 41:32led to a shorter time
• 41:34to develop CHS,
• 41:37you know, do they compare
• 41:38it to people who are,
• 41:39like, you know, smoking was
• 41:41a survey finding.
• 41:43Yeah.
• 41:44You know, so it's an
• 41:45episodic
• 41:46disorder,
• 41:47and and so, you know,
• 41:48sometimes patients have episodes if
• 41:50you actually go and talk
• 41:51to them. This
• 41:52is one of the disorders
• 41:53where the history is very
• 41:55important, and they might have,
• 41:56say, one or two episodes
• 41:58or in a year. And
• 41:59then if you look at
• 42:00it, they're having three episodes
• 42:01in a year, and then
• 42:02say, well, they're told they
• 42:03have gastroenteritis.
• 42:05And then they have five
• 42:06and they have ten. And
• 42:07so, you know, the fourth
• 42:09year, they'll come to you
• 42:10and say, oh my god.
• 42:11This is really bad because
• 42:12it's happening every month, and
• 42:13I cannot have gastroenteritis
• 42:15every month. So I really,
• 42:18you know, I am, very
• 42:19skeptical.
• 42:21Certainly, I think smoking, most
• 42:22of the cold CHS cases
• 42:24have been associated with smoking
• 42:26or inhalation.
• 42:26It it obviously,
• 42:28you know, is absorbed much
• 42:30faster,
• 42:31and, there is not much
• 42:33data that edibles
• 42:35per se have been associated
• 42:37with hyperemesis, at least looking
• 42:38at all the evidence and
• 42:39everything that's been published.
• 42:42Yeah. Sorry.
• 42:43Good point.
• 42:45And the other question was
• 42:46kind of going back to
• 42:47triptans.
• 42:48You mentioned that it could
• 42:49be used
• 42:51to kinda treat,
• 42:53CHS. And I'm wondering
• 42:55if maybe
• 42:56you think that amylin could
• 42:57be implicated given that,
• 43:00you know, it also plays
• 43:01a role in migraine
• 43:02and,
• 43:03you know, there's a lot
• 43:04more amylin receptors in the
• 43:05gut.
• 43:07I don't think there's any,
• 43:09there's any evidence
• 43:11about amylin specifically.
• 43:13I do think,
• 43:14at least based on what
• 43:15we know about all this
• 43:17and the stress response, I
• 43:18think things that have been
• 43:20looked at very extensively are
• 43:22or looked at is, like,
• 43:23vagal activity,
• 43:25autonomic dysfunction.
• 43:28You know, there's reduced vagal
• 43:29efficiency in in CPS
• 43:32patients,
• 43:33maybe an endocannabinoid
• 43:35deficiency, and all of these
• 43:36are sort of, like, interconnected.
• 43:38They've used, they've looked at
• 43:39fMRI studies,
• 43:41in patients with,
• 43:43with CVS
• 43:44and migraine and controls. And
• 43:46there are some,
• 43:47there are differences between CVS
• 43:49migraine and controls, but there
• 43:51are also some similarities
• 43:52between,
• 43:54CVS patients and migraineurs.
• 43:56I don't think anybody's looked
• 43:57at amylin in this, in
• 43:59this context.
• 44:02It could be interesting to
• 44:03look at. Thank you. Yeah.
• 44:05Thank you.
• 44:08I had a a, a
• 44:10couple of follow-up questions. You
• 44:11you made the point about
• 44:13the route of
• 44:14of consumption.
• 44:16And
• 44:17would you say there's you
• 44:18made a distinction between,
• 44:20inhaled
• 44:21versus edible oral.
• 44:25Do you make a distinction
• 44:26also between vaping and smoking?
• 44:28I'm just wondering
• 44:30to what extent
• 44:31some of the other,
• 44:33you know Yeah.
• 44:35I think we haven't looked
• 44:37at it,
• 44:38and we hope to look
• 44:39at it in the future.
• 44:40But one of the things
• 44:41we're thinking about is really
• 44:43potency of the product
• 44:45and concentration
• 44:47and what is ultimately happening
• 44:49in the blood.
• 44:50You know, if somebody is
• 44:51using a lower potency product,
• 44:54it doesn't seem to be,
• 44:56you know, as harmful as
• 44:57somebody who's using maybe cannabis
• 44:59concentrate or just getting very
• 45:01high,
• 45:02you know, highly potent,
• 45:04products. And and so,
• 45:07you know, we hope to
• 45:08study this where we want
• 45:09to actually look at the
• 45:10concentration
• 45:11itself,
• 45:12of THC in the blood
• 45:14and then see if there's
• 45:15any correlation
• 45:16with, you know, symptom severity,
• 45:19as to
• 45:21necessarily between sort of vaping
• 45:23and using other methods.
• 45:25Great.
• 45:27Couple of questions about management.
• 45:29I know in the emergency
• 45:30room,
• 45:31people have used, haloperidol,
• 45:34capsaicin.
• 45:36Yes. What's your what's the
• 45:38go to treatment,
• 45:39in the emergency room?
• 45:41Yeah. Besides, of course, you
• 45:43know, the people who And
• 45:45and I'm sorry. In the
• 45:45interest of time, I didn't
• 45:46wanna go too much. I
• 45:47didn't wanna go into management.
• 45:49But,
• 45:50unfortunately,
• 45:53you know, the the data
• 45:54on capsaicin is is kind
• 45:56of
• 45:56not good and poor.
• 45:59Many patients,
• 46:00you know, many of these
• 46:01are sort of observational studies,
• 46:03and and and there are
• 46:04a lot of limitations to
• 46:05these studies,
• 46:07and there's really no convincing
• 46:08data necessarily to support its
• 46:10use, and many patients actually
• 46:14so I don't recommend it.
• 46:16I mean, we have, guidelines
• 46:18for our ED, and we
• 46:19don't recommend capsaicin,
• 46:22based on that.
• 46:23Certainly, hallo
• 46:25haloperidol
• 46:26has been used.
• 46:27And, one of the things
• 46:29that people don't,
• 46:31know or realize is that
• 46:33whether it's CVS or CHS,
• 46:36we've looked at this. There
• 46:37are very high rates of
• 46:38anxiety,
• 46:40and in fact, a large
• 46:41number of them meet DSM
• 46:43criteria for panic
• 46:45when they're in the prodrome.
• 46:47And I think what,
• 46:48haloperidol
• 46:49does is that it actually
• 46:50calms them down.
• 46:52So whether it's haloperidol
• 46:53or whether it's, lorazepam
• 46:55or Ativan,
• 46:57it's just kinda calming the
• 46:58patient down.
• 47:00Great.
• 47:01Any,
• 47:03other than, of course, getting
• 47:04people to abstain or cut
• 47:05down on their cannabis use,
• 47:08are there any other prophylactic
• 47:10treatments the way that,
• 47:12you know, you have prophylactic
• 47:14treatments for migraine?
• 47:16Yeah. Absolutely. So,
• 47:18so even though,
• 47:19there's no specific,
• 47:21co treatment,
• 47:22you know, for CHS,
• 47:25we do specify in our
• 47:26guidelines that if you have
• 47:28somebody with CVS who is
• 47:30also using cannabis and they
• 47:31have
• 47:32moderate to severe disease,
• 47:34we use,
• 47:36neuromodulators.
• 47:37And,
• 47:38the first line really is,
• 47:40tricyclics
• 47:41or neuro, amitriptyline.
• 47:43And I can tell you
• 47:44that this is unpublished. There
• 47:46is course of patients I
• 47:47have
• 47:48who've improved significantly with amitriptyline.
• 47:50They were told they had
• 47:51CHS
• 47:52by other people,
• 47:54and so on and so
• 47:55forth, and they actually
• 47:57improved
• 47:58markedly.
• 47:58And there are many people
• 48:00who actually have multiple periods
• 48:02of abstinence,
• 48:04and, they don't see a
• 48:06resolution of their symptoms. And
• 48:08so they said, well, I
• 48:08tried it for one year,
• 48:10or I went without cannabis
• 48:12for one year. So, again,
• 48:14hopefully, we'll be able to
• 48:15put all that data together,
• 48:17which is why I'm I'm
• 48:19concerned
• 48:20that,
• 48:21you know, not all cannabis
• 48:22use in the context of
• 48:24cyclic vomiting is called CHS,
• 48:26and I,
• 48:28I really do believe that
• 48:29there's probably a very, very
• 48:30small subset who really fall
• 48:32into that category.
• 48:35Great.
• 48:38A question about,
• 48:39about,
• 48:41the pathophysiology.
• 48:43I mean, this peculiar
• 48:45constellation of symptoms
• 48:47Yeah. You know, vomiting,
• 48:50it seems like thermal
• 48:52dysregulation
• 48:53Yes. Relieved by warm,
• 48:55or hot showers.
• 48:57It's it's to point
• 48:59to maybe
• 49:00the hypothalamus
• 49:01or Exactly. Has has anyone
• 49:03done work on that in
• 49:04that space to try and
• 49:06investigate,
• 49:07other
• 49:08abnormalities that could be linked
• 49:09to Yeah. I mean, I
• 49:11we we would love to
• 49:12obviously do that because you're
• 49:14absolutely right.
• 49:15And so, I mean, there
• 49:16is data to show that,
• 49:18you know, maybe, like, chronic
• 49:19cannabis use causes core,
• 49:22body temperature
• 49:23dysregulation
• 49:24and can reduce the core
• 49:25body temperature.
• 49:27And so if you look
• 49:28at these hot showers, it's
• 49:29very intriguing.
• 49:31You know, perhaps they they
• 49:33are somehow,
• 49:35working
• 49:36on,
• 49:37c v one receptors
• 49:39in the hypothalamus
• 49:41and,
• 49:42you know, possibly
• 49:43kind of
• 49:44reversing those effects of excessive
• 49:47cannabis use.
• 49:49That hasn't been sort of,
• 49:51looked at really.
• 49:53And,
• 49:54you know, it is very
• 49:55intriguing because clearly there's,
• 49:57they have problems with thermoregulation.
• 50:00And,
• 50:01you know, if if you
• 50:02if talk to many of
• 50:03my patients,
• 50:05they they they feel very
• 50:07cold,
• 50:08and some of them,
• 50:09you know, record their temperature,
• 50:11and they say, oh, it's
• 50:12very low. And, we actually
• 50:14did a study, and we
• 50:15didn't fully publish the data,
• 50:18because,
• 50:19you know, we had them
• 50:20use wearable devices
• 50:22and try to look at
• 50:23temperature, but we just felt
• 50:25like,
• 50:26we were not getting
• 50:27necessarily a good signal because
• 50:29of the contact between the
• 50:30variable devices.
• 50:32But b as it may,
• 50:33you know, the statistician and
• 50:35I were going back and
• 50:35forth because there were outliers
• 50:37where their core body where
• 50:39not core body, but their
• 50:40body temperature,
• 50:42was much lower.
• 50:44And, you know, he said,
• 50:45well, it's artifact, and we
• 50:47have to throw it out
• 50:48maybe. And I said, no.
• 50:49I don't think it's artifact,
• 50:50and I think it's real.
• 50:53So that's something we really
• 50:54need to look at, and
• 50:55that's, you know, that's an
• 50:57excellent, kind of question.
• 51:00Two two more questions if
• 51:01you don't mind. I I
• 51:02No. Of course. No. I
• 51:03don't wanna have this, but
• 51:05if anyone else has questions,
• 51:06please,
• 51:07put them in the chat
• 51:08or unmute yourself.
• 51:10One one question,
• 51:12I have is
• 51:14there are cannabinoid antagonists that
• 51:16are available for use for
• 51:18administration
• 51:19to humans. Are you aware
• 51:21of any
• 51:22work that's being done
• 51:24using cannabinoid
• 51:25antagonists
• 51:26to either
• 51:27reverse
• 51:28the acute syndrome
• 51:30or to treat prophylactically?
• 51:33No.
• 51:34None.
• 51:36We,
• 51:37you know, at one point,
• 51:38I tried calling this company
• 51:40and said, can we have
• 51:41CBD and, you know, something,
• 51:43but that it would just
• 51:44never went anywhere. So
• 51:47k.
• 51:50I I'm curious about whether
• 51:52there are any other syndromes
• 51:53any other symptoms
• 51:55related to this such as,
• 51:57you know,
• 51:58are they hyperalgesic?
• 52:00Are they more sensitive to
• 52:01pain or less sensitive to
• 52:02pain?
• 52:05Yeah.
• 52:06So these patients,
• 52:09do have a lot of
• 52:10abdominal pain
• 52:12during an episode.
• 52:15You know, so abdominal pain
• 52:17is a significant
• 52:18component,
• 52:20really, of the symptoms.
• 52:21And I,
• 52:23you know, we've looked at
• 52:24it. They have very high
• 52:25rates of anxiety.
• 52:27I think the patients who
• 52:28use more cannabis are more
• 52:30anxious, and I think it's
• 52:31this thing, oh, I'm using
• 52:33it for anxiety and you're
• 52:34stoned. But then it's like
• 52:35a vicious cycle, I think,
• 52:37and it's just going round
• 52:38and round.
• 52:41Yeah. I I don't think,
• 52:43like, in the, quote, interepisodic
• 52:45phase, we don't have any
• 52:47indication,
• 52:49you know, that they have
• 52:50this,
• 52:51visceral hyperalgesia,
• 52:52if you will.
• 52:54But they definitely have
• 52:56a significant abdominal pain during
• 52:58the, during the episode.
• 53:01Any sleep disturbances?
• 53:04Most of them have sleep
• 53:05disturbances.
• 53:06Most of them do. And
• 53:07that's not part of that's
• 53:09not an official
• 53:10that's not part of the
• 53:11syndrome.
• 53:12That's not included.
• 53:14I'm curious because, you know,
• 53:15we have cannabis on sleep
• 53:17and Correct. Wondering whether, you
• 53:20know Yeah. That appetite
• 53:22yeah. Yeah. So it's always
• 53:23been a little hard to
• 53:25sort of define this particular
• 53:27population because, you know, how
• 53:28do you diagnose them? And,
• 53:29obviously,
• 53:30like, one of your, you
• 53:32know, one of the other
• 53:33people in the audience said,
• 53:35it's a very high bar
• 53:36to prove that somebody, you
• 53:38know, has CHS. But when
• 53:39you look at it overall
• 53:40and we've looked at it
• 53:41and, you know, we've done
• 53:43questionnaires,
• 53:45not necessarily sleep studies, but,
• 53:47and and they all have,
• 53:49you know, dysfunctional sleep.
• 53:51They have problems with sleeping.
• 53:54Suddenly, you know, we ourselves
• 53:55know many patients, not just
• 53:57serious patients. They use it
• 53:58for,
• 54:00insomnia
• 54:01and sleep.
• 54:03So, yes, a significant,
• 54:05proportion of patients do have
• 54:07sleep disturbance.
• 54:09I think those tend to
• 54:10be more, maybe comorbidities,
• 54:12and it's a particular
• 54:13phenotype.
• 54:15I think, we're looking at,
• 54:17where it's sort of, you
• 54:18know, people who have this
• 54:19also have that and also
• 54:21have that. You never see
• 54:22a patient coming.
• 54:24It's very rare where they
• 54:25say, oh, they have just
• 54:26pure CVS and they don't
• 54:27have anything else. So they
• 54:28have only pure CHS, and
• 54:29they don't have anything else.
• 54:33Great. That's,
• 54:36I I mean, I can
• 54:36continue to ask questions, but
• 54:38I'm not No. No. I
• 54:39mean, it's very intriguing. I
• 54:41yeah.
• 54:43Any other any other questions,
• 54:45for doctor Venkatesh?
• 54:50Great. Well, thank you so
• 54:52much
• 54:53for this talk. It was
• 54:54great. Next month, we have
• 54:56Ziva Cooper,
• 54:58who's,
• 54:59who's gonna be talking about
• 55:00cannabis and likely about addiction.
• 55:03So I hope you all
• 55:04can join us for next
• 55:05month's,
• 55:06webinar, which is on the
• 55:07twenty eighth of April.
• 55:09Yeah. I see.
• 55:11Thank you very much. This
• 55:12was really,
• 55:13this was really great.
• 55:15Yeah. No. Thank you so
• 55:16much, and it's very nice
• 55:17that it's actually available for,
• 55:20for everybody, if you will.
• 55:21So I think some of
• 55:22my mentees also managed to
• 55:24join, and I hope to
• 55:25continue
• 55:26participating. Thank you so much.
• 55:28Sounds good. Thanks. Yeah. Bye
• 55:30soon. Everyone. Bye bye.