Ancient Remedies for Managing Migraine

0:00 thank you everyone for having me back to
0:02 migraine Canada I really enjoyed doing
0:04 these talks for people you know I’ve had
0:05 a lot of patients actually get referred
0:07 to my clinic and talk about how they
0:09 learned about their migraines through
0:10 the webinars and things first and so I
0:12 think it’s a really great tool to raise
0:13 more awareness about migraine and I hope
0:16 you find it helpful this topic is one by
0:19 popular demand I get these questions a
0:21 lot in my clinical practice
0:23 about different types of alternative
0:25 treatments that people will often pursue
0:27 for migraine and what really is the
0:29 evidence behind them and what do I think
0:31 of them as a neurologist so I wanted to
0:34 kind of put together a smattering of
0:35 topics this is kind of a fun pop culture
0:37 history traits and uh so we’re going to
0:40 talk about some interesting factoids out
0:43 of ancient history you know other
0:44 theories that people have had about
0:45 migraine Through the Ages and from
0:47 different cultures and then we’re gonna
0:49 kind of take that into modern day people
0:51 are trying to use things like essential
0:53 oils which have a lot of basis in some
0:55 ancient medicines for using headache
0:57 treatment today and so you know what
0:59 kind of quality of evidence do we have
1:01 for that we’ll also kind of take a quick
1:03 look at things like topical treatments
1:05 so some of you may have already had
1:07 experience with a compounding pharmacist
1:09 who can make different preparations for
1:11 you and what kind of role do these have
1:13 in people with specific types of
1:14 headaches
1:16 so uh this is just a quick bio on me I’m
1:19 a neurologist at the Royal College here
1:21 in Canada uh also a headache medicine
1:23 specialist I’m a member of the Canadian
1:25 Headache Society my clinic is in London
1:27 Ontario and we have quite a busy
1:30 practice focused mostly on migraine but
1:32 also other types of rare headache
1:34 subtypes and unusual headaches and my
1:36 research looks at things like
1:37 cannabinoid and thalocybin used for
1:39 headaches I’m doing a project on
1:41 residency education curricular content
1:43 for headache because you know if we’re
1:45 going to tackle this problem that
1:46 affects so many people we need the
1:47 doctors to do it and just as a caveat I
1:50 think is relevant to this one I did some
1:52 a program through Stanford University
1:54 where we we did an exchange and went to
1:57 China for a summer to learn about
1:59 various alternative types of medicine
2:00 and how it could be integrated with
2:02 family medicine and so I think it’s
2:04 important to keep an open mind you know
2:06 when you’re thinking about other
2:07 cultural traditions and different types
2:09 of medicine you know some of these have
2:11 been going for thousands of years and so
2:12 uh you know to just dismiss it in hand
2:14 and say that you’re going to throw the
2:16 baby out with the bathwater I think is a
2:17 mistake
2:18 um but you know coming from the Western
2:20 Scientific tradition I’m a skeptic
2:22 always and I demand a certain level of
2:24 evidence if I’m going to recommend
2:25 something for my patients so uh we’ll
2:27 give you some hot takes on that
2:29 uh in disclosure uh so I did my
2:33 fellowship with Canadian Headache
2:34 Society so it’s funded through them and
2:36 I’ve had some research grants from some
2:38 Pharma companies to help with our
2:39 residency curricular uh exploration I
2:43 also take part in a lot of advisory
2:44 boards for companies where we look at
2:46 all the data as it comes out on these
2:48 new medicines so doctors will get
2:49 together to talk about where we think
2:51 these new drugs fit into the the
2:53 treatment landscape and and how we can
2:55 best use them or or advocate for our
2:57 patients to use them and I also give
3:00 lots of talks like this whether it’s for
3:02 patient groups doctors nurses
3:05 pharmacists trying to spread some more
3:07 information about migraine
3:09 um and so with that we’ll turn to our
3:11 objectives
3:12 like I mentioned but I want to go over
3:14 briefly with you tonight is an
3:16 introduction to the history of migraine
3:18 and headache treatments and this is by
3:19 no mean exhaustive like you could take
3:21 an entire you know undergraduate course
3:23 in studying history of headache and
3:25 medicine and of course we won’t be able
3:28 to go through every possible folk
3:30 medicine or different culture but I
3:31 wanted to highlight some of the greatest
3:33 anecdotes that that you know headache
3:35 doctor like to exchange
3:37 then we’re going to go into the oils and
3:39 I gave a little short list of some that
3:41 are most commonly used for removing and
3:44 like I mentioned we’re going to talk
3:45 about the topicals with a focus on
3:47 things like amitriptyline lidocaine
3:49 capsaicin and how can you use them so on
3:52 to our trip through history
3:54 we’re going to start with trepanation
3:56 which you know many of you will probably
3:59 have heard about and it’s kind of
4:00 horrific and and fascinating at the same
4:02 time and the word trepanation comes from
4:05 the Greek tripan on which means abor
4:07 like drilling a hole and the earliest
4:10 skulls that we have found we’ve dated to
4:12 about 10 000 BC and they come from North
4:16 Africa but these kind of skulls and even
4:19 in healed states have been found all
4:20 over the world in Asia South America
4:22 Europe across the the board so it seems
4:27 like this is a common procedure
4:29 and just in folklore you know like
4:32 modern common popular culture it’s often
4:34 suggested that this was a treatment for
4:36 headache but there is actually a lot of
4:39 evidence for that like the first
4:40 writings that we have about this come
4:42 from the 17th century and he’s a famous
4:44 uh physician who wrote a very famous
4:47 medical textbook called William Harvey
4:48 and he suggested that it was likely for
4:50 migraine you know the migraines are so
4:52 terrible of course anyone would want to
4:53 cut their head open to try to get the
4:55 demons out but you know we think that at
4:58 least there’s some good writing and
4:59 evidence to suggest that it was used for
5:00 things like epilepsy uh dystonias are
5:03 weird with stiffness and and certain
5:05 types of mental illness
5:07 um and so you know it’s a fascinating uh
5:10 kind of procedure that existed across
5:11 many different cultures
5:13 um and you know it kind of makes sense
5:14 if you think it’s a problem with the
5:15 head and you’ve got this pain that you
5:17 can’t get rid of you’ll do anything to
5:18 take it out luckily we do not do this
5:21 anymore for migraine
5:23 uh then we’re on to Egypt and Samaria so
5:27 this is about 2 500 BCE and we are lucky
5:31 enough to have a few surviving copies of
5:33 incredible papyri that detail different
5:36 surgical procedures a number of
5:39 different potions and incantations and
5:41 things and it’s not all magical thinking
5:43 like some of these are incredible lists
5:45 of different plants and uh things that
5:47 are ground and treated into
5:48 Pharmaceuticals and used for various
5:50 conditions and uh this Everest papyrus
5:54 named after the guy who picked it up uh
5:56 it describes sick headaches uh and so
5:59 the Egyptians would take linen and it’s
6:02 it’s kind of written on with magical
6:04 prayers and names of of some of their
6:06 healing gods and then they would take a
6:08 clay crocodile stuffed with herbs in the
6:11 mouth and then they would tie a
6:12 crocodile to your head and tie it really
6:14 tight
6:15 and you know that may seem kind of crazy
6:17 by today’s standards but if you think
6:19 about it you know they’re on to
6:21 something empirically by discovering
6:24 external compression you know and so it
6:28 we have a lot of patients that massage
6:29 their temples when they have a bad
6:30 headache or they tie a tight cord or
6:33 tourniquet around their head because
6:34 they’re affecting all those nerves the
6:36 super trochlear the supraorbital
6:38 auricular temporal occipital they’re
6:40 going around the head and activating
6:41 these nerves kind of like a little a
6:44 little bit of a lazy nerve block you
6:46 know and so I think there’s probably
6:49 something to it uh the crocodile is
6:51 probably just for sure maybe a boosted
6:53 Placebo or something
6:55 um then we’re on to the Greeks so you
6:58 know Hippocrates is probably one of the
7:00 most famous doctors everybody has heard
7:01 of the Hippocratic Oath you know but you
7:04 know doctors actually they don’t even
7:06 have to swear it and there’s a good
7:07 reason for it because if you actually
7:08 look at what’s written in there it’s
7:10 kind of crazy
7:11 um and it really doesn’t apply to the
7:12 care that we provide today in fact some
7:15 of those things would go against what is
7:16 considered normal
7:18 um so you know he is considered the
7:20 father of modern medicine
7:22 and his textbooks were studied for
7:24 centuries
7:25 um and you know there’s some good stuff
7:26 in there but there’s also a lot of
7:27 Mythology and things that we’ve
7:29 abandoned you know thinking about the
7:31 body in terms of humors and and things
7:33 like that
7:34 um in his writings though he is one of
7:36 the first to record things about
7:38 headache and migraine in particular and
7:40 he documented a severe type of headache
7:42 that would commonly occur on only half
7:44 the head or behind one of the eyes
7:46 and he observed that vomiting would
7:49 improve the nausea that was associated
7:50 with this type of headache and I think a
7:52 big chunk of my patients often say you
7:54 know after I actually bring up I feel a
7:56 lot better with the migraine perhaps
7:57 that’s some kind of you know valsalva
7:59 maneuver raising the pressure in the
8:01 abdomen that that activates the vagus
8:03 nerve or something to stop it
8:05 you know uh he was the first one to
8:07 describe visual symptoms with with
8:09 headaches that that typically preceded
8:11 the attack and in his writings he talks
8:13 about a Shining Light usually in the
8:15 right eye which I guess that’s specific
8:16 to one kind of patient followed by
8:18 violent pain beginning in the temples
8:19 and eventually reaching the whole head
8:21 and the neck and you know a lot of
8:23 people come to me talking about
8:25 cervicalgenic headaches you know and
8:28 that’s actually pretty controversial
8:29 because I haven’t found many true
8:30 cervicogenic headaches and we think of
8:33 the trigeminal complex as a highway that
8:35 kind of goes both ways and uh so
8:38 migraine people often have neck pain and
8:41 it’s bleeding down through that
8:42 cervicogenic complex into the upper
8:43 cervical roots and causing that
8:45 stiffness so he was already seeing the
8:48 same thing you know I see every day in
8:49 my clinic uh and documenting it uh a
8:52 little bit later we fast forward to the
8:54 future in ancient Rome and we have two
8:56 very famous Physicians here that
8:59 commented on headaches and and tried to
9:00 make sense of them uh aristes and this
9:03 is kind of a very nice idealized statute
9:05 of him uh and also Galen another very
9:07 famous uh you know father of medicine is
9:09 surgical books and anatomy books were
9:11 studied for a long time and Arista
9:14 described many kinds of migraine and
9:17 parsed them into some of the variants
9:18 that we still talk about today uh and so
9:21 there were shorter lasting attacks there
9:23 were longer duration attacks multiple
9:24 days there was chronic migraine where it
9:26 was happening quite frequently and he
9:29 gave migraine its first name
9:31 which was heterocrania and then we move
9:34 on to Galen a few years later and he
9:36 describes them as attacks specifically
9:39 and use the term hemichrania to say half
9:42 of a head
9:43 so Hemi is half and Cranium is your
9:45 skull
9:46 and so as we you know rewrite the
9:49 textbooks and everyone’s language
9:51 evolves you know through the world
9:52 eventually into the Middle Ages
9:54 hemicrania becomes megrim so if you look
9:56 at Micron to megram and magrum
9:59 eventually becomes migraine and you know
10:01 I think for like French or Spanish
10:03 speakers it’s more apparent the
10:05 etymology of this because you like think
10:06 of mikran or migrana you’re like Hemi
10:10 grania you know so it kind of makes
10:12 sense
10:13 um so that’s the origin of the migraine
10:15 term
10:17 an interesting little pause in the
10:19 Middle Ages and this is one of my
10:21 favorites uh is Hildegard of vom bingen
10:25 and she’s a fascinating fascinating
10:27 woman very ahead of her time she was an
10:29 abacus in Germany so the head of a
10:31 Cloister of nuns but her studies were
10:34 focused on music and art and medicine
10:37 she made incredible illuminated texts of
10:40 various herbs and remedies for medicine
10:42 and was searching the ancient books for
10:45 various Medical Solutions and what’s
10:48 fascinating is that Scholars today
10:50 looking back at her illuminations the
10:52 the kind of beautiful pictures that come
10:54 along with the calligraphy they suspect
10:56 that a lot of the visions that she
10:58 claims she was having from God were in
10:59 fact migraine aura and she credits these
11:03 images with helping her to compose
11:05 beautiful beautiful music and to draw
11:07 art like this and she believed she was
11:09 seeing Windows into you know the the
11:11 Sacred City in heaven uh but in fact
11:14 perhaps she was seeing scintillating
11:16 scotomas and and uh migraine auras so if
11:19 you look at her pictures here uh you
11:22 know the bottom left and the top right
11:23 you can see the fortification Spectra so
11:27 when we think of the classic migraine
11:28 Aura which is the tichopsia
11:31 um it’s it’s named after the kind of
11:34 walls you would see on an old castle
11:35 where there’s kind of little holes for
11:37 people to shoot a bow and arrow through
11:38 and so she is perhaps interpreting some
11:42 of her visual symptoms as the kind of
11:44 walls of the city and many patients will
11:46 describe that kind of crescent-like
11:48 c-shape thing starting in their vision
11:50 and it spreads and evolves zigzag lines
11:52 or blocks or cubes and it varies a lot
11:55 between people
11:56 she also saw lots of stars and sparkles
11:58 and things like this
12:00 um and so it’s just very fascinating to
12:02 think that you know migraine is
12:04 something that has been with us you know
12:06 for as long as we’ve been recording
12:07 history if you want to learn more about
12:09 her I would really recommend it there’s
12:12 a really excellent
12:14 um movie in German
12:16 I think a vision or something in English
12:19 but it’s um it’s an excellent movie uh
12:22 and you know it’s a really great view
12:24 into a very different time
12:26 um so I would I would recommend you
12:27 check into that
12:29 now of course we’re not going to be able
12:30 to stop by through every uh cultural
12:33 tradition of medicine but I do want to
12:34 highlight a few because so far we’ve
12:36 been focused on the Western Medical
12:37 story
12:39 um of course uh there are ancient
12:40 medicines from Persia and China that
12:43 date back uh many thousands of years as
12:45 well and one that I wanted to touch on
12:48 was acupuncture
12:50 because this is something that many many
12:52 of my patients pursue
12:54 um and you know it’s not just one point
12:56 I’m just showing one here for you hugu
12:58 which I think is is you know a commonly
13:00 used acupoint that you don’t even need
13:02 to put needles
13:03 that people often use and practitioners
13:07 of acupuncture will tell you that you
13:08 know there are a lot of different uses
13:10 of this including toothache dizziness
13:13 hemorrhoids headache asthma blood
13:16 pressure and anxiety and I think that’s
13:18 kind of casting the net a little bit
13:19 wide
13:20 um but you know it seems to be commonly
13:23 recommended for headache and I have some
13:24 patients that tell me that they like it
13:26 and I think you know it doesn’t seem to
13:28 hurt and I don’t think it has many side
13:30 effects so that’s fine by my books
13:32 um what’s interesting is that um
13:34 acupuncture I studied it a little bit
13:36 when I was in China I I think it has a
13:39 lot of benefit and the people that
13:40 practice it will say it does but it’s
13:42 not sustained and so perhaps maximum
13:45 you’re going to get two weeks of benefit
13:46 and you need to continue to repeat it
13:48 and there are lots of things that we do
13:50 that are not you know a permanent fix or
13:52 don’t change it forever like botox or
13:53 even the cgrp antibodies they require
13:56 repeat dosing to continue to benefit you
13:59 um so it’s just something to take into
14:00 account when you’re calculating the
14:02 risks and benefits of a treatment
14:04 there were some small studies the
14:06 trouble with a lot of the literature we
14:07 have on acupuncture is that these are
14:09 large uh you know huge cohorts there are
14:12 a few studies that try to meta-analyze
14:14 acupuncture for lots of conditions and
14:15 lump them all together but there’s a lot
14:17 of methodologic issues with those
14:19 studies
14:20 this one was a pretty uh good study uh
14:23 done conducted in Germany across the
14:25 variety of centers I think 18 centers
14:27 and it included 302 patients with
14:29 migraine
14:30 but it didn’t exactly you know make a
14:34 differentiation between episodic and
14:36 chronic the way we might in a more
14:37 rigorous study and things like that
14:39 um they did the typical points which
14:41 aren’t just so good but they do some in
14:42 the head and some in the back and stuff
14:44 and um what they found was that the
14:47 people who did the typical meridians you
14:50 know so if you look at that diagram on
14:52 the left there’s this idea that there
14:54 are lines or channels of energy to our
14:56 body
14:57 and that there are specific points in
15:00 particular muscles and and locations
15:02 that correspond to nodes on these
15:04 meridians and there might be an
15:05 obstruction or you need to adjust the
15:07 flow of energy through them
15:09 um
15:10 interestingly enough
15:12 the comparison of this was sham needling
15:14 and what a sham needle means is that you
15:16 don’t necessarily follow the accurate
15:18 meridians of this kind of ancient idea
15:20 and you just put needles in the local
15:22 area
15:23 when we compare sham needling and the
15:26 traditional meridians the effect is
15:28 comparable so there’s no significant
15:30 difference there but both sham needling
15:32 and the the Meridian style acupuncture
15:36 were both Superior to placebo
15:38 so I think the takeaway from this is
15:40 that you know there is some good
15:42 evidence that it works but you know you
15:44 don’t necessarily have to follow the
15:45 ancient idea and the reasoning behind it
15:47 sham needling the effect of actually
15:49 just placing a needle in the local area
15:51 seems to be similarly effective
15:54 so I wanted to take a little moment just
15:57 to pause and kind of give a brief
15:58 overview of this is very rudimentary of
16:01 the theory of Chinese medicine from
16:04 Elemental imbalance so a lot of it works
16:06 on this idea of five Elemental groups so
16:09 you’ve got wood fire earth metal and
16:11 water and each of these you know even
16:13 very similar to our own indigenous
16:15 medicine we all include things like
16:16 Seasons Direction climate stage of
16:18 growth and development internal organs
16:21 body tissue so the categories are you
16:24 know seemingly Limitless
16:26 from a TCM perspective though
16:29 migraine is thought to be due to like an
16:31 invasion of Wind and Fire and then it
16:33 causes Meridian obstructions and then it
16:35 disturbs the flow of blood which you
16:37 know is usually referred to as Chi but
16:39 that has lots of different translations
16:41 she can mean blood but it can mean
16:43 energy and other things like that
16:45 um and so this is thought to to cause
16:48 migrants
16:49 the idea behind the TCM concept of
16:52 treatment is to calm deliver get rid of
16:54 pathogens unblock the meridians uh you
16:57 know and and this idea of disharmony
16:59 between the elements and you have to
17:00 specifically Target it with certain
17:02 foods or poultices or tinctures or
17:04 acupuncture
17:06 um and you know this may seem very
17:08 foreign to people in a western context
17:10 and when I was in China I had some very
17:13 fantastic professors who practice both
17:15 you know and they see the cultural value
17:18 and as a framework for people for
17:20 understanding it and they gave me this
17:23 analogy that I thought would really hit
17:24 it on their nose they said you know
17:26 imagine you have an old cathode ray
17:28 television
17:29 and the image goes fuzzy it got some
17:31 static
17:32 they said well a western doctor what
17:35 would they do they would take apart the
17:36 whole TV
17:37 look at each little piece figure out
17:39 which each little piece does repair it
17:40 and then put it back together and fix
17:42 your TV
17:43 they said you know Chinese doctors over
17:45 many thousands of years we’ve learned
17:46 exactly where to hit the TV and where
17:49 it’s most likely to help you to hit the
17:50 TV and fix the image and so I think the
17:54 basis of that is that our two traditions
17:56 of medicine are very different there’s
17:58 like inductive and deductive reasoning
18:00 there’s kind of empiricism where we just
18:01 kind of collect observations and don’t
18:04 get me wrong like we have that in
18:05 migraine as well well you know like a
18:07 lot of our theories of migraine that we
18:09 relied on to explain our medicines
18:11 before actually were proven to not be
18:13 correct and we had we found a different
18:14 explanation I I think the trick is that
18:17 you have to be willing to change your
18:19 opinion and your theories when new
18:21 evidence arises to the contrary like I I
18:23 don’t believe any idea can rest out on
18:25 Florals
18:27 um but you know so an important point
18:29 for instance is like
18:31 there wasn’t a lot of dissection that
18:33 occurred in in Chinese medicine
18:35 throughout critical periods of these
18:37 ancient texts being written you know it
18:38 was forbidden and so people often relied
18:40 on going to battlefields to look at a
18:42 liver or something and as a result there
18:45 are some kind of
18:47 inferences about certain types of organs
18:50 that unfortunately mean that there are
18:52 organs that don’t actually exist like
18:54 something called the triple burner which
18:56 kind of like a tripartite kind of
18:59 metabolism idea
19:00 but doesn’t actually correspond to any
19:02 organ in the body
19:04 um so so it’s very interesting
19:06 um but that being said it’s been
19:07 practiced for thousands of years and
19:09 fine-tuned by many caring people
19:10 practicing to help people and obviously
19:13 they’ve discovered some incredible uh
19:15 ways to help and treat diseases we just
19:18 need to work on demonstrating the
19:19 efficacy in a rigorous way and and
19:21 finding ways to incorporate it in our
19:23 practices
19:24 uh now flipping over to Persia uh so
19:28 there’s a famous famous uh Dr avicenna
19:32 um who has given us a lot of different
19:34 ideas about migraine in particular this
19:37 kind of hot and cold phenotypes of
19:39 migraine and again this kind of goes to
19:41 a type of humeral theory of of disease
19:45 that there are imbalances of
19:46 temperatures or liquids in your body and
19:49 what he had recommended was rose oil
19:52 from damasina as a tonic for for brain
19:56 issues and disorders even mental
19:57 illnesses but they would prepare it in a
19:59 very particular way
20:01 with sesame oil and so he I guess
20:06 excuse me um so there he had many
20:09 medicinal plants that he purported
20:11 thought could be useful for for Persian
20:13 medicine and so a lot of the evidence
20:15 when I did a review of essential oils
20:18 actually comes from Modern Day Iran
20:20 where they’re studying some of these
20:22 ideas that come from classical medicine
20:24 their tradition to see if they have any
20:27 usefulness for people today
20:29 and so we’re going to go through them
20:30 kind of one by one
20:32 um and you know I think
20:34 in our modern conception of Western
20:36 medicine there’s a lot of ideas about
20:39 these plant extracts that contain
20:41 certain things like terpenes and
20:42 flavonoids molecules that are able to
20:45 exert a strong pharmacologic effect and
20:47 some of them that are recommended are
20:49 shown to have anti-inflammatory
20:50 properties so like reducing nitrous
20:52 oxide
20:53 you know cox2 Inhibitors which are like
20:55 some of the NSAIDs that you may use for
20:56 your migraines and so you know I think
20:59 it’s it’s very interesting to look at
21:01 some of these old plants you may recall
21:03 aspirin for instance
21:05 uh you know and that that originally is
21:08 thought to have or stemmed from some
21:10 observations about uh will it bark and
21:13 various cultures have used this over the
21:16 Millennia uh you know in Egypt and
21:18 Samaria it was documented as being used
21:21 um and then our own indigenous people
21:23 here in North America had been making
21:25 tea from willow bark and but it wasn’t
21:28 until it was observed later uh
21:31 eventually perfected in Germany and
21:33 chemically modified that we were able to
21:35 make the potent version of it which is
21:36 aspirin today and I think aspirin kind
21:39 of fell out of favor for a number of
21:42 reasons
21:42 um but it’s still a very useful
21:44 treatment for migraine for some people
21:47 so what can history teach us about
21:49 migraine and its treatment
21:51 number one obviously migraine is severe
21:54 and disabling illness we all know people
21:55 and loved ones who have carried this
21:58 burden and it has changed the course of
21:59 their life for some of them and it has
22:01 been affecting Humanity even in
22:03 prehistoric times you know and we can
22:05 see that from the trepidation
22:07 people will exhort resort to Extreme
22:10 Measures like drilling holes into their
22:11 head to do anything to relieve
22:13 themselves from migraine and that speaks
22:16 to how severe this kind of problem can
22:18 be I think we’ve made some great
22:20 progress especially in the last century
22:22 but obviously we still do not understand
22:24 everything about migraines Genesis
22:27 and that’s why I think it’s so important
22:29 to keep an open but skeptical mind you
22:32 know everything I still think has to go
22:33 through the grinder to prove is true and
22:35 uh and keep an open mind to new
22:37 potential treatments and avenues
22:39 one thing I want to highlight for you is
22:42 that migraine is a clinical diagnosis
22:44 which means you know we ask you a bunch
22:46 of questions in that consult and we have
22:49 some agreed upon criteria that satisfy
22:52 that for for research purposes
22:55 essentially that allows us to talk about
22:57 a particular set of people with a
22:59 particular set of symptoms as a group
23:00 and what can we do to treat them but you
23:03 know if you are familiar with our ichd3
23:06 criteria that International
23:07 classification of headache disorders
23:09 if you read migraine sure it tells you
23:11 the nausea and vomiting light and sound
23:13 uh you know throbbing severe unilateral
23:16 usually
23:18 um but if you were to come to my clinic
23:20 and watch 100 patients
23:22 with frequency up to like 80 or 90
23:25 percent there are other things like
23:27 visual blurring brain fog neck pain
23:30 vertigo tinnitus
23:32 and mental health conditions like
23:34 anxiety disorders and and depression and
23:36 things that are so comorbid
23:38 and I I do not believe migraine is
23:40 caused by mental health issues but they
23:41 travel along in their comorbid problems
23:43 that feed each other and you know I
23:46 think we need to also expand the way
23:47 that we think about this problem because
23:49 many of those other symptoms get ignored
23:51 or minimized so
23:53 as it’s a clinical diagnosis the problem
23:55 is that we don’t have good Imaging like
23:58 an MRI is not going to find much except
24:00 for a non-specific white matter lesions
24:01 which you should not be too worried
24:02 about
24:03 um as well as you know we don’t have a
24:06 great blood test sometimes in clinical
24:08 trials we’ll read about the measuring
24:09 cgrp levels but this is not a prime time
24:12 kind of thing you know you have to be
24:14 carried on ice and tested immediately
24:15 and it’s just really a really unstable
24:17 kind of test so I think that’s the holy
24:20 grail for us is to find a way to
24:21 quantify migraine and measure it over
24:23 time and see that you’re improving so
24:25 that we can better track it
24:27 the path forward for developing new
24:29 treatments it has to require careful
24:32 observation you know so really thinking
24:34 about the definitions we use being very
24:36 careful about how we record outcomes for
24:38 patients uh thinking of new ideas
24:40 different Pathways that are involved and
24:42 of course rigorous testing and proof
24:45 uh you know there’s a famous quote from
24:47 Harvard philosopher uh Dr santayana you
24:50 know those who cannot remember the past
24:51 are condemned to repeat it so with that
24:53 I want to turn our ideas to looking at
24:56 how can we perhaps incorporate some of
24:58 these ancient things into to modern
25:00 medicine so essential oils do they
25:02 really work for migraine I have many
25:04 patients that use them some patients
25:06 that sell them
25:07 you know and some people are making
25:09 their own uh and I think it’s an
25:11 interesting an interesting Way Forward
25:13 not all of them I think are as good as
25:16 some people purport but there are a few
25:18 that are very interesting to me that I
25:19 think may may be useful so the ones that
25:22 are commonly used would be things like
25:24 lavender oil rose oil
25:28 peppermint and Eucalyptus
25:30 so how to use them uh people use them in
25:33 different ways you can apply them to
25:35 your temples uh you can dilute them
25:37 often with another carrier oil like
25:39 coconut or something they massage them
25:40 into their temples there’s head their
25:42 scalp the back of the head the neck and
25:44 you know I remember we often had uh
25:47 nurses on my stroke Ward who would use
25:50 oregano oils and mint and everything and
25:53 we come in and it’s not so fresh and
25:54 nice and anyway it was a it was a
25:57 running joke about the the stroke word
25:59 causing all the migraines but uh you can
26:02 also inhale it so some people put it on
26:04 a tissue and hold it under the nose to
26:06 breathe deeply
26:07 um you know I remember when we were
26:09 working on gastroenterology we used to
26:10 put a little bit of mint oil under our
26:11 mouth on the filter on there and it
26:13 would keep it nice and fresh and uh you
26:17 can also use a compress you can soak a
26:19 towel in cold water out a few drops you
26:20 can apply to your poor head or neck some
26:22 people use diffusers like you see in the
26:23 picture here you can pick them up
26:25 they’re pretty common now and they’re
26:27 not too expensive
26:28 um and you know the good kind of
26:30 spa-like atmosphere in your bathroom
26:32 other people will add them directly to
26:34 the bath and you get a nice aromatherapy
26:37 so lavender this is the first one and uh
26:41 again like I mentioned a lot of these
26:42 studies are coming out of uh Iran Modern
26:44 Day Iran and looking at the specific
26:47 components of it there’s uh linole so
26:50 linole and linal acetate
26:53 and people have purported a lot of
26:55 things about this that you know it can
26:56 be anxiolytic uh you know reducing your
26:59 stress or anxiety it can have local
27:01 anesthetic properties which I’m not too
27:03 convictable uh and that some have
27:05 recommended an ancient medicine as an
27:07 anti-epileptic uh which I would not
27:09 recommend because we have very good
27:10 drugs that work wonderfully
27:13 um and you know I would not say that it
27:15 has particular antineoplastic properties
27:17 although it has been studied for this
27:19 and there isn’t a lot of good evidence
27:20 but but you’ll see that
27:23 um
27:23 in terms of lavender this study looked
27:26 at it as an oral prophylactic therapy
27:27 and so they wanted to mix it into a cup
27:30 of water and see see how it works for a
27:33 migraine and so I recorded here kind of
27:36 how they’re they’re parsing it and
27:38 diluting it and they want to follow up
27:40 in three months and the primary outcome
27:42 was looking at their Midas course so if
27:43 you’ve been to a migraine clinic you’ve
27:45 probably done the Mardis which you know
27:47 is probably very difficult to interpret
27:49 and varies between patients
27:51 and uh they’re comparing at three months
27:53 of after taking this uh compared to
27:56 Baseline and they looked at other things
27:58 like uh headache days and the severity
28:00 of the headaches so the one thing that I
28:03 thought was kind of a confounding factor
28:05 of this is that every participant who
28:07 took this therapy was also previously
28:09 started on Propranolol uh and it doesn’t
28:11 say exactly when they started the
28:12 Propranolol and then they received the
28:15 lavender extract as an adjunct
28:17 um which you know ideally you’re not
28:19 adding two variables at once and
28:21 propranol also has very good
28:22 demonstrated evidence for migraines so
28:25 unfortunately we saw that I confounder
28:27 when you’re when you’re mixing two
28:28 variables
28:29 uh which was one thing that was nice
28:31 though is that it doesn’t seem to have
28:32 side effects
28:35 um this is just a quick overview of how
28:36 they parse the study so you know 30
28:38 patients were essentially cleared to
28:40 participate and they divided them in
28:41 half for placebo
28:43 it didn’t exactly mention how they
28:45 created the placebo because Lavender is
28:47 very potent as you may know
28:50 and so
28:52 it would be pretty hard to mask that
28:53 unless perhaps it’s just around the cup
28:56 or something and they’re smelling it but
28:57 it’s not in the actual solution that
28:58 they’re drinking but it does tend to
29:00 have a characteristic taste as well the
29:03 demographics that were involved uh
29:05 pretty well balanced between the case
29:06 and control groups and there weren’t
29:08 really any problems seen there
29:10 and let’s get to the results here
29:12 um so we’re comparing the number of
29:14 headaches at Baseline uh the first month
29:17 and the third month and as you can see
29:19 uh both in the control group and the
29:21 case group uh so the control group is
29:23 the placebo both see some reductions
29:26 over time and you know this is common
29:28 that we see across all migraine trials
29:30 there’s a very strong Placebo response
29:32 for a lot of our treatment
29:34 um but you know we want to be able to
29:35 demonstrate that our intervention is
29:37 better than that significantly so it
29:40 does seem to fall off in the the case
29:42 group
29:43 and the other you know perhaps getting
29:46 rid of the confounding effect is that uh
29:49 you know the the control group is also
29:52 taking Propranolol so perhaps this is an
29:53 additive an additive effect with some
29:56 Synergy there so it seems very promising
29:59 that they’re falling off over time but
30:01 we have to take into account this is a
30:03 very small sample size of only 60
30:04 patients and the propranol that still
30:07 can sound the results so I I’m not quite
30:09 ready to recommend this but it
30:11 definitely deserves some additional
30:12 study I think
30:15 um old is new again okay so building on
30:17 what avicenna was talking about the rose
30:19 oil so this is kind of the one that they
30:22 were most excited to investigate
30:24 um based on how to send this Theory and
30:26 so this was a double-blind
30:27 placebo-controlled crossover trial of
30:30 rose oil and they’re using it not as a
30:31 preventive but as an acute abortive so
30:33 for when you have the migraine you want
30:34 to get rid of it they took 40 patients
30:37 again the small sample size but you know
30:39 a pilot buddy and they were randomly
30:41 assigned to treatment versus placebo
30:44 one wrinkle here is that they
30:45 differentiated not on the basis of the
30:47 frequency of the migraine as we might
30:49 have preferred uh chronic versus
30:51 episodic
30:52 but instead they used this kind of idea
30:54 of a hot and cold migraine which borrows
30:57 from that kind of ancient classification
30:59 of the headache and I’ll show you on the
31:00 next slide what that means so the first
31:03 two consecutive migraine attacks were
31:04 treated with
31:06 um either the topical rose oil or a
31:08 placebo which kind of smelled the same
31:10 and they used the ancient technique of
31:12 macerating the rose petals in sesame oil
31:15 the active ingredients that you would
31:16 find in rose oil would be like
31:18 citronella so Citron like lemon and
31:20 geraniol which is geranium and you know
31:23 once you get into the Fantastic world of
31:25 all these molecules that give you
31:27 flavors and smells you’ll see that a lot
31:28 of plants and even Canada all these
31:30 things have overlapping uh kind of
31:33 properties that give all the plants
31:34 their incredible smells and uh you know
31:37 one thing that I think is so fascinating
31:38 and I recommend all my patients is
31:40 Forest bathing they go out into the
31:41 forest it’s wet and raining and you’re
31:43 smelling all these incredible green
31:45 things and stuff and you know it has
31:47 also been shown to have anxiolytic
31:49 properties and I also think it’s just
31:51 good to go for a hike and get your
31:52 migrant under control so if you’re able
31:55 to and you’re able to get out to the
31:57 forest you know this is one cheap way
31:59 you don’t have to buy expensive
32:00 essential oils
32:02 um so after one week washout period Then
32:04 they cross over so those who are taking
32:06 Placebo go to the Rose Hall and those
32:08 who are taking the rose oil go to
32:09 Placebo
32:10 um and so they watch them again and
32:12 watch to see if there’s different uh
32:14 statistical probability of improvement
32:16 so the primary outcome is looking at
32:18 intensity of the migraine at onset and
32:21 then they looked at 10 intervals all the
32:22 way up to 24 hours and then the
32:25 secondary outcome was looking at you
32:26 know what we now call the most
32:27 bothersome symptom lighter Sound
32:29 Sensitivity or nausea or vomiting
32:32 and again like I mentioned the data was
32:34 then uh analyzed after post talk in
32:37 terms of uh looking at hot and cold type
32:39 syndromes
32:40 so Baseline characteristics you know
32:42 this is pretty characteristic of what
32:44 you would see in a migraine clinic from
32:45 young people all the way to 65
32:49 um you know they have headaches that are
32:51 as brief as an hour or lasting over up
32:53 to a day and and having them quite
32:55 frequent
32:57 um
32:57 the other stuff is like this hot
32:59 temperament of headache you know perhaps
33:01 16 of them uh had this hot temperament
33:05 um
33:06 what we’ll look through here is the mean
33:07 pain intensity of patients migraine
33:09 headache at different time points and so
33:11 we start at zero minutes and we’re
33:13 looking at Rose versus placebo
33:15 and it’s pretty high it’s up there it’s
33:17 moderate it’s six-ish and over time as
33:20 you go you can see it’s dropping slowly
33:22 and by the end at 24 hours uh we’re 2.18
33:25 with the rose oil and 2.20 with the
33:27 placebo
33:28 uh so I mean just off the bat you think
33:31 well that’s not a huge difference I mean
33:33 they’re both seeming to naturally
33:34 resolve so maybe this is just the
33:35 natural course of migraine
33:38 uh so looking now at the nausea and
33:41 vomiting uh we also see similarly that
33:44 you know there’s not really
33:45 statistically significant differences in
33:48 the rates of nausea and vomiting or
33:49 lighter sensitivity between the two
33:51 groups so at first pass you’re like well
33:54 okay maybe it’s not so great but then
33:56 they decide to do this post-hoc analysis
33:58 and they say okay well if we go back
34:00 through the text and look through the
34:03 ancient definitions and stick to this
34:04 hot migraine
34:06 and hot migraine is the defined by
34:08 having eye redness content fatal
34:10 injection perhaps like uh they have some
34:13 autonomic features light sensitivity
34:15 positivity made worse by heat
34:18 and odors sensitivity to things like
34:20 pepper and cardamom
34:22 uh and having a heart sensation like
34:24 flushing in in during the attack in the
34:26 face and if we look at those patients
34:28 who satisfy you know at least three or
34:30 more of those criteria and then just
34:32 look at that subgroup uh there does seem
34:34 to be a significant difference between
34:36 the hot and cold people in terms of who
34:39 responds
34:40 um but you know the issue is
34:43 um and we’re taught to do this in
34:45 statistics is you have to be very
34:46 careful about subgroup analyzes uh you
34:49 know being careful to design your study
34:51 from the get-go to be large enough to
34:53 prove that a small subgroup already has
34:56 uh you know a difficult difference
34:58 because otherwise you would see drug
35:00 companies doing hundreds of tiny little
35:02 subgroup analyzes on everything and if
35:04 you throw a thousand darts eventually
35:06 like one of them is going to be a
35:08 bullseye so I think it’s important uh
35:10 you know to make sure that your trials
35:12 are designed in a robust way so you know
35:15 mean intensity of migraine not
35:16 significantly different from Placebo
35:19 Associated symptoms not significant
35:21 between groups but it does seem to be
35:24 like you know perhaps in this hot
35:26 subtype of thinking about migraine that
35:29 uh it has more of an effect and so I
35:32 think that’s the Pearl for me taking it
35:34 from this was that it’s important to
35:36 always revisit our definitions of
35:38 migraine clinically you know they’re in
35:40 flux even right now you may hear that uh
35:43 we’re revisiting the idea of chronic
35:45 versus episodic and do we really need to
35:46 think of it on that arbitrary 15-day cut
35:49 off so I I think for me it’s the spirit
35:51 of inquiry and and thinking that we need
35:53 to constantly revisit our ideas and
35:55 entertain perhaps some of these older
35:57 ideas they may have observed something
35:59 useful that we’re ignoring now
36:01 so bear issues of the study small sample
36:04 size is ancient definitions confounded
36:06 by additives like Sesame that perhaps
36:07 have some other additives so I can’t say
36:09 it’s only roast so unfortunately I think
36:12 uh you know no roses for Amazon up
36:15 um next up and I want to give you some
36:16 good success stories too is chamomile
36:19 um so they they next turn their
36:21 attentions to chamomile
36:23 and again this stems back to traditional
36:25 Persian medicine they would often boil
36:27 aqueous chamomile extract and sesame oil
36:29 and you know there are some plausible
36:31 ideas about the mechanism of how this
36:33 might work
36:34 um so there’s certain chemicals in it
36:36 that inhibit
36:37 um inducible nitrous oxide synthase
36:39 which you know makes a chemical that
36:41 dilates blood vessels and and improves
36:43 pain transmission and nerve endings it
36:45 activates them
36:46 um so it may have some sort of
36:48 neuroprotective effect as well the
36:51 flavonoids that are included in it have
36:52 like strong inhibition of prostaglandins
36:55 and a selective Cox II inhibitor so some
36:57 similar properties to
36:58 anti-inflammatories and the polyphenols
37:02 in it also have anti-inflammatory
37:03 effects
37:04 um so you know it’s very interesting to
37:07 think of as another kind of alternative
37:09 treatment
37:10 so in this one they took 100 patients
37:12 again a double-blind crossover trial
37:14 Placebo control
37:16 um and then each patient took two troops
37:18 of drug and two tubes of placebo during
37:19 the study but like the last one they
37:21 would cross over halfway
37:23 um and so the primary outcome again
37:24 looking at pain intensity of the
37:26 migraine over those intervals in the 24
37:27 hours and the secondary outcome was
37:29 those other symptoms
37:31 so uh demographic information of the
37:34 crossover arms uh we’re looking uh again
37:37 uh pretty comparable between the groups
37:39 like not a lot of significant
37:40 differences so I’m not concerned about
37:41 that I don’t normally uh include
37:44 marriage status in my clinical trials
37:47 um and just to kind of give you an idea
37:49 this is more just for reference if you
37:51 want to go back but just showing you how
37:53 the trial was divided in terms of the
37:55 placebo arm and the allocated uh do
37:58 treatment
37:59 and then that wash over with the
38:01 crossover
38:02 so this was an intention to treat
38:04 population which means
38:06 um you know you’re supposed to keep
38:08 everybody that even if they fail to use
38:11 the medicine properly because perhaps
38:13 it’s capturing something that’s
38:14 difficult about it like if you had a
38:16 really difficult applicator or something
38:17 and then people just give up because
38:18 they don’t like using it you couldn’t
38:20 only really include the patients that
38:23 took the medicine properly unless you
38:25 already announced that you’re doing a
38:27 subgroup analysis
38:28 so you know they initially described it
38:31 as an intention to treat population
38:33 um but then eventually did kind of per
38:35 protocol which means they were just
38:37 studying the people who applied it
38:39 properly
38:41 um so when we look at that in a per
38:43 protocol population it was much improved
38:47 um so if you’re able to adhere to the
38:49 proper application to the forehead and
38:51 temples and everything you have a lot
38:53 better chance of being pain-free at uh
38:55 two hours
38:56 uh 30 roughly
38:59 um and recurrence have had a rebound you
39:01 know at 24 hours seems to be much lower
39:03 versus plus people
39:05 um as well as sustained pain relief up
39:07 to 24 hours
39:09 um so you know this one actually it
39:12 seemed very promising and interesting
39:13 but again uh limited by kind of small
39:16 sample sizes and uh you know this per
39:19 protocol analysis
39:23 um I won’t spend too much time here but
39:25 basically the gist of it was just
39:27 showing people that you know you also
39:28 had reduction of things like nausea
39:31 light and Sound Sensitivity
39:33 so small sample sizes they mix kind of
39:36 an intention to treat in a protocol
39:37 approach which I think could be cleaned
39:39 up in a repeat study and again there’s
39:41 additives like Sesame but you know this
39:43 could just be part of the magic of how
39:45 this medicine works and it needs to be
39:47 multiple components
39:49 um but it would be very difficult to
39:51 kind of make these traditional Persian
39:53 preparations yourself you know so I
39:55 think uh access would be an issue but
39:57 but this may be a cost-effective
39:59 alternative if we can find a way to to
40:01 use it properly and study it
40:03 on to eucalyptus and peppermint these
40:06 are probably way more commonly used here
40:08 in North America
40:10 and uh this is a great uh paper looking
40:13 at it from Keel in Germany
40:15 um published in the pathology and uh it
40:18 was uh looking at the topical
40:20 application of eucalyptus and peppermint
40:22 and this seems to be very promising
40:25 um some of you may have heard of stop
40:26 pain
40:27 probably more common in the States but
40:30 there’s other things you can get here
40:31 like the sage roller or things like that
40:33 that include some of these chemicals in
40:35 it and this was another small study a
40:38 very tiny one 32 patients enrolled only
40:40 25 completed the study but they would
40:43 apply stop pain during an attack and see
40:46 if it had any good effect
40:48 and you know it does seem to be useful
40:51 there was a significant Improvement in
40:52 headache intensity by two hours after
40:53 the application
40:55 um but you know for me 25 patients is
40:57 very small and if you really believe in
41:00 it I want to see some zeros after that
41:03 so uh Menthol and trpma so what is trpma
41:07 it’s a mouthful it’s a transient
41:09 receptor potential action Channel
41:11 subfamily M which stands for milastatin
41:14 member number number eight
41:16 um but basically we study all these
41:18 different protein channels that are in
41:20 your nerve endings and some of them
41:22 respond to different stimuli some are
41:24 for mechanical activation by pushing on
41:26 your nerves some of them are activated
41:28 by temperature some of them are
41:30 activated by chemical things and most
41:33 receptors can be activated by everything
41:34 if you reach a strong enough threshold
41:37 so this one in particular
41:39 um is is thought to be the only
41:41 temperature receptor that mediates a
41:43 response to kind of moderate cold
41:45 temperatures
41:46 and evolutionarily like anthropologists
41:49 and geneticists kind of think that this
41:50 allowed for an adaptation or like a
41:53 homeostatic response to cold
41:54 temperatures so you know humans have
41:57 adapted to a variety of climate
41:59 um and so what’s very fascinating about
42:01 this when they do large-scale genetic
42:03 studies across the globe they’re able to
42:05 see that the the variants in this Gene
42:08 vary by latitude
42:10 and so they think that the very original
42:12 phenotype or phenocopy allele of this
42:15 Gene is probably most prominent
42:18 equatorially especially in African
42:21 countries and then as you move out
42:23 further north and further south you
42:26 start to see uh people that are more
42:28 cold resistant and actually have this
42:31 other type of Gene and what’s
42:33 fascinating is that the original copy
42:35 the one that’s prominent equatorial is
42:36 protective against migraine
42:38 and so perhaps uh you know even
42:41 developing a susceptibility to migraine
42:44 was the trade-off that we suffered for
42:47 for adapting to colder climbs as
42:49 populations drifted so it’s very
42:52 fascinating kind of paper I invite you
42:53 to look at this paper because if you can
42:56 get your hands on it it’s very
42:57 interesting read
42:59 um so this receptor is expressed in pain
43:02 and temperature sensitive neurons in the
43:04 dorsal root ganglion and so this is one
43:06 of the little uh nerve centers um beside
43:09 the spine that help to process sensory
43:10 input and we think it has the role in
43:13 pain perception of cold stimuli and also
43:15 like the inflammatory conditions so at
43:19 uh 15 to 30 degrees Celsius
43:21 it kind of let these positively charged
43:23 ions in through the hole into the door
43:26 and the strength is inversely
43:28 proportional to temperature so as the
43:30 temperature goes up less goes through as
43:32 the temperature goes down more of these
43:34 ions are going in and if you know
43:35 anything about nerve uh pretty much the
43:38 way they have that electrical impulse
43:40 travel down is a constant change of flux
43:43 Inward and outward of different uh
43:45 concentrations of ions negative and
43:47 positive charge thing
43:49 um we won’t get into that today because
43:50 you’ll fall asleep and uh so very very
43:54 interesting and so this uh what’s
43:56 fascinating to me is that a receptor
43:58 that’s meant for temperature can also be
44:00 activated chemically
44:03 and so when you apply Menthol or
44:05 eucalyptus you get this cooling
44:07 sensation but it’s not actually cold
44:09 you’re just activating the same receptor
44:11 and your brain is interpreting it as
44:12 cold you know and cold is probably like
44:15 like wet you know it’s like pressure and
44:17 temperature and all these things that
44:18 come together and and your brain
44:20 interprets it as a certain type of
44:21 sensation
44:22 and you know we’ll get into it in a
44:24 second but you see a similar thing with
44:25 capsaicin the chili pepper extract it
44:27 gives you hot sensation
44:29 um so very interesting that this is
44:31 potentially protective against migraine
44:35 um so that’s something to think about
44:38 um moving forward from this because I
44:39 think that’s probably the most promising
44:41 of the topical oils would be things like
44:42 Menthol and Eucalyptus
44:44 um is into like what other kinds of
44:46 topical preparations are available for
44:48 use and headache
44:50 um and so why on Earth would you
44:52 compound a medicine yourself you know it
44:54 seems like a lot of effort and cost
44:55 where do you get it why would you use it
44:58 um you know it can be used for
44:59 everything from migraine cluster
45:01 headache trigenal neuralgia surgical
45:03 sight pain
45:04 um the other types of things people
45:06 sometimes use is like intranasal
45:07 lidocaine I throw this in here as kind
45:09 of an odd one but you know there’s uh
45:11 the Dr maisel protocol and viscous
45:15 lidocaine and a syringe in your nose it
45:16 gets into that fpg the Espino Palatine
45:20 ganglion and it helps to treat migraines
45:23 um you know it’s quite safe and
45:24 effective
45:26 um and then hot and cold we’re going to
45:28 talk about kind of the difference
45:29 between capsaicin and menthols effects
45:30 on pain processing
45:32 um so very interesting
45:33 when I see the pros and cons you’re
45:35 going to get fewer systemic side effects
45:37 because you’re not absorbing as much
45:38 into the bloodstream as acting mostly
45:40 locally rapid termination more
45:43 medication is applied at the area that
45:45 is needed you know conceivably which I
45:47 think this is debatable because we think
45:48 a lot of the migraine actually comes
45:50 from the brainstem but you know you’re
45:51 modulating peripherally which I think is
45:53 important
45:54 you avoid the first path metabolism what
45:56 this means is when you eat a medicine
45:58 and it gets absorbed from your stomach
46:00 all that blood from the stomach first
46:01 goes through the liver of the filter
46:03 before it enters the general circulation
46:05 so the liver is going to remove some of
46:07 it if it’s hepatically metabolized
46:09 before you even get in so you’re losing
46:11 a chunk of what you ate this approach
46:14 avoids that it’s also useful for people
46:16 who don’t want to take pills like I
46:18 still have a lot of adult patients who
46:20 are like I could never swallow pills of
46:21 the kid and I hate it like I just don’t
46:23 want to follow anything
46:24 um and so this is a good option
46:26 some people have purported using this as
46:29 an option in pregnancy personally I
46:31 would not probably recommend that but
46:34 some some doctors have used it in that
46:36 context
46:38 the other issue though is that there can
46:39 be time you know time drain to to apply
46:43 them multiple times per day and then you
46:45 got this goopy oily mixture like in your
46:47 scalp or something so it may not be a
46:49 day that you’re going out to work or
46:51 something because this might you know
46:53 conceivably be better for a day where
46:55 your bed bath
46:56 so the applications can be messy or
46:58 uncomfortable
46:59 so topical terminology you got all these
47:02 different types of things like it’s
47:04 almost dizzying I think a lot of doctors
47:06 even feel intimidated by compounding
47:08 because there’s too many options you
47:11 know so you can have a solution which is
47:12 kind of a water-based or alcoholic
47:14 lotion uh which isn’t very oily at all
47:17 lotion is thought to be thicker and it
47:19 contains a little bit of oil in it but
47:22 you know it’s an Emulsion so you gotta
47:23 shake it up to keep it like that cream
47:26 is even thicker yet
47:28 um so 50 50 Emulsion and you probably
47:30 need to add some preservatives to extend
47:32 it
47:33 ointments now are getting like pretty
47:35 greasy they’re usually or 80 oil
47:38 and uh you know you often don’t actually
47:41 need preservatives for this because the
47:42 oil is keeping it prepared and they’ll
47:44 often include other things like
47:45 different waxes
47:47 um or Oils uh depending on your
47:49 pharmacist
47:50 gels are more of an aqueous or alcoholic
47:53 type it’s a different thing based in
47:54 cellulose which is like a plant type of
47:56 carbohydrate
47:58 and usually like you would think of like
48:00 hand sanitizer but kind of like a gel
48:01 and it turns into liquid as you touch it
48:04 um paste is more concentrated and
48:07 thicker uh as you think of like a clay
48:09 or something like that
48:10 so in terms of the thickness uh you know
48:13 thick skin absorbs more than uh or thin
48:15 skin rather absorbs more than thick you
48:17 know so if you’re applying to the face
48:19 you need less than if you’re applying to
48:20 your heels you know and the thickness
48:23 varies with the body side your age as
48:24 well as other skin conditions like
48:26 psoriasis eczema
48:27 and so we think of the skin its primary
48:30 purpose is a barrier to protect your
48:32 body from the outside world it also
48:34 regulates temperature and a million
48:36 other things but in this context it can
48:38 be disrupted by things so if you have
48:40 scaly skin ichthyosis
48:42 um if you have carotolytic agents so if
48:44 you’re using things like salicylic acid
48:46 for warts or something you know you got
48:48 to be careful about these medicines
48:49 because they’re going to get right in
48:50 there and other things like inflammatory
48:53 conditions and rashes can make it worse
48:55 uh lotion is probably greater absorption
48:57 where there’s occlusion you know which
48:59 means you’re going to hold more of that
49:00 liquid in there so a crease where you’re
49:02 going to hold the liquid for longer time
49:04 or under dressings
49:06 uh the location and in formulation
49:09 um you know it’s probably greater when a
49:12 greasy ointment formulation is used for
49:13 penetration through the first layer of
49:15 the skin smaller molecules of medicine
49:18 are easily absorbed through the skin
49:20 compared to larger stuff which just
49:21 bounces back and then lipophilic what
49:24 does this mean so there’s hydrophilic
49:26 and lipophilic hydros water lipo is fat
49:29 and philia means to like something so
49:31 they like fat that means they can get
49:33 through the kind of thick area of the
49:35 skin easily if it’s hydrophilic it means
49:38 it can kind of travel through a water or
49:40 aqueous layers a bit more efficiently
49:43 um and so ideally you want kind of a
49:45 mixture of these things so that you can
49:46 get to different layers and it depends
49:47 what you’re targeting and obviously the
49:50 concentration of the medicine you know
49:52 higher concentrations are more likely to
49:53 get through the skin
49:55 um so you know even seemingly tiny
49:58 differences in the formulation can
49:59 actually make a big difference in how
50:02 effective patients perceive them to be
50:04 just quickly to show you the skin
50:05 anatomy because we’re going over a lot
50:07 of the stuff very briefly but there’s
50:09 lots of layers to your skin as you know
50:11 but the outer one is the stratum corneum
50:13 and it’s got a lot of stuff called
50:14 keratin in it and keratin makes your
50:17 skin waterproof and durable
50:20 um you know and so you really want to
50:22 try to get past that first layer and to
50:24 do that it’s got to be a little bit
50:25 lipophilic but once you get into the
50:27 kind of deeper layers there’s aqueous
50:30 layers of the skin that are more
50:32 water-based and so the fat really hyper
50:34 fast soluble stuff isn’t going to make
50:36 it past that layer very well so you kind
50:38 of want to balance your properties
50:41 um so when to consider topical
50:43 preparations we already talked about the
50:44 stop pane other things are like
50:46 ketoprofen gel uh or other topical
50:48 things you may have tried like 8535 or
50:51 other things like that uh Voltaren
50:54 um we also think about it in some
50:55 patients who are really refractory and
50:57 have tried everything like cluster
50:58 headache a really excellent example is
51:01 post herpetic neuralgia so if any of you
51:03 have had uh shingles or zoster
51:07 and it’s affecting part of your skin an
51:10 excellent excellent remedy is is to try
51:12 one of these compounded creams with
51:14 amitriptyline capsaicin uh and and maybe
51:17 some other agents but you should be seen
51:20 at the pain clinic because it’s one
51:21 excellent way to treat this and it has a
51:23 lot of good evidence behind it
51:25 um trigeminal neuralgia you know like I
51:27 see patients who are desperate enough to
51:29 try you know botoxing their face you
51:32 know until they’re paralyzed like
51:33 they’ve had a stroke or a Bell’s Palsy
51:35 in
51:36 I think it’s it’s probably better to try
51:38 some of these topicals first or maybe in
51:40 the mouth even
51:42 um and and other types of atypical
51:44 Facial Pain this might be one potential
51:46 option uh but it still is not very
51:48 commonly used because most doctors don’t
51:50 don’t feel comfortable using these
51:52 topical preparations so again I think
51:55 it’s useful for side effect prone
51:56 patients you know like a lot of people
51:58 tell me they’re like oh you probably
52:00 never met anyone like me you know I’m
52:01 sensitive to every single medicine and
52:03 and I have side effects to everything
52:05 but that’s actually pretty common that
52:07 people feel a lot of side effects so
52:09 this might be one way you know to pick a
52:11 medicine that’s not really systemically
52:13 absorbed and interacting with your
52:15 system and to the same extent
52:17 um you know Botox is a great option for
52:19 that the monoclonal antibodies for
52:21 migraine are generally very well
52:23 tolerated but are still systemic and
52:25 again the pilophobic people so let’s get
52:28 started just very quickly uh if you want
52:30 to get started with this find a
52:32 compounding pharmacist first okay before
52:34 you go to your family doctor or
52:36 something and you know just a historical
52:38 vignette since we’re on the topic
52:39 compounding was the routine okay before
52:42 Pharma standardized all of these pills
52:44 which is a good quality control measure
52:47 um you used to go to all your different
52:48 farmers and they would make up whatever
52:50 your doctor wrote on this prescription
52:52 um so a lot of the things that you were
52:54 making even in one pill were many things
52:55 combined
52:57 um and so search your internet find a
52:59 good compounding pharmacist make sure
53:00 they’re reputable and they’ve got all
53:02 their qualifications and then uh call
53:04 them or make an appointment to discuss
53:06 what you’d like and what they can do
53:08 and then they’ll often even give you a
53:10 copy of their prescription patch for
53:11 compounding that you can take to the
53:13 family doctor
53:14 um so you know when you’re thinking
53:15 about this not that you’ll necessarily
53:17 be prescribing but just that you’re
53:19 aware of the process you got to pick a
53:21 base like we talked about is it a gel uh
53:23 or or some other type of uh cream or
53:26 lotion
53:27 and then you’re gonna pick the
53:29 ingredients
53:30 um so you know the basic ones would be
53:32 things like anesthetic sodium channel
53:33 blockers is it lidocaine or benzocaine
53:36 you know you’ve all had probably dental
53:37 procedure that numbs you uh capsaicin
53:40 which is the chili pepper extract
53:42 um and an interesting point about that
53:44 is that it burns okay like they even
53:46 sell lip balm to make your lips
53:48 beautiful and full that it just like
53:49 swells up your lips from capsaicin so
53:52 not great for areas of mucous membranes
53:54 like you’re not going to put it in eyes
53:56 or mouth really in mucosa or in genital
53:59 area or anything you have to be very
54:00 careful
54:02 um and so I have used it very
54:05 judiciously on people on scarves like
54:07 from post incisional neuropathic pain
54:10 from neurosurgery and stuff but I worn
54:12 them I’m like you have to be so careful
54:13 and wash your hands so thoroughly
54:15 because if you let it even drip sweat
54:16 into your eye it’s gonna swell shut and
54:18 you’re gonna really feel it um so not
54:21 the greatest choice for that but you
54:23 know an active desperation other things
54:25 you can put in are the anti-convulsive
54:27 Gabapentin phenytoin
54:29 ketoprofen which is anti-inflammatory
54:31 and sometimes we use Alpha II adrenergic
54:34 Agonist clonidine for pain and of course
54:37 ketamine and amitriptyline
54:39 so this here is like not for
54:41 memorization obviously but just to show
54:43 you the broad breadth of what can
54:46 possibly be included in uh compounding
54:49 but you know not every pharmacist has
54:51 access to all of this but they’ll often
54:53 be able to order things in for you if
54:54 you if you
54:57 um I put a little few pearls on the side
54:59 for reference that you know like for
55:00 those worried about cough baclofen is
55:02 cheaper than you know other muscle
55:04 relaxants like cyclobenzaprine
55:06 um like some of them like the pharmacist
55:08 gets really irritated when you ask them
55:10 to make it like diclofenac if it’s too
55:12 uh not concentrated enough it’s actually
55:15 very viscous which means it’s thick and
55:16 gooey and it’s very hard for them to
55:18 make it properly
55:19 um and some of them like ketoprofen you
55:21 know maybe it’s going to irritate the
55:23 skin less than if you use diclofenac so
55:25 these are just all the little nuances
55:26 that you pick up after you know making
55:28 these a couple times and uh some of them
55:31 work better together like if you combine
55:33 amitriptyline and ketamine
55:35 um so very very interesting and uh I
55:38 think a neat way to help patients
55:41 um so this is a series of different
55:43 sample combinations
55:45 um but you know I would say always
55:47 consult with your provider and see what
55:49 they recommend
55:50 um for peripheral or non-susceptive
55:52 symptoms like we’re trying to
55:53 hyperologies yeah things hurt more than
55:55 they should allodynia which means things
55:57 that shouldn’t hurt hurt like touching
55:58 your hair or combing it
56:00 um peripheral neuropathy or or you know
56:02 other types of pain including headache
56:04 uh you can start with something like
56:06 this for some people
56:08 um and we tend to like increase it very
56:09 gradually you know it’s a trial and
56:12 error process always start low go slow
56:14 you can adjust it and Time After Time
56:16 and sometimes we sub out ingredients if
56:18 we don’t think they’re working
56:20 um but you know a good place to go if
56:22 your family doctor doesn’t feel
56:23 comfortable with this is ask for a
56:25 referral to your local pain service
56:26 probably not your neurologist
56:28 but uh like a there’s usually an
56:31 academic pain center nearby and they’ll
56:33 have some experience preparing these so
56:35 what’s the evidence for this the truth
56:37 is there isn’t a lot you know with a few
56:39 Exceptions there was a really bad review
56:42 that came out about triple cream uh
56:44 amitriptyline gabapentin and ketoprofen
56:46 or something and um
56:49 you know the triple cream was commonly
56:50 used in pain centers and then they
56:52 actually said well I actually don’t
56:53 think it’s doing a lot and so that
56:55 didn’t seem to be particularly good but
56:57 we still have those few handful of
56:59 patients that had such excellent success
57:01 that it still lives on in a lot of pain
57:03 people’s memory
57:05 um a few agents have reached probably
57:07 you know a sufficient level of evidence
57:09 to support uh systematic use and
57:12 capsaicin is one of them ketoprofen is
57:14 another
57:15 so this was a good study looking at well
57:17 again small actually 42 patients with a
57:20 history of episodic migraine again
57:22 double-blind crossover Placebo control
57:25 study and they applied ketoprofen uh
57:28 bilaterally to the faith and this is in
57:31 V1 V2 and V3 the distributions of
57:33 trigeminal nerve for severe headaches
57:36 um and so you know at the end of the 24
57:39 hour mark probably 50 percent of the
57:42 headaches treated with it had pain
57:43 relief
57:45 um or were pain-free versus 25 compared
57:48 to Placebo and this is thought to be
57:49 statistically significant
57:52 um the problem with this one is that it
57:53 does cause some irritation at the
57:55 application site it’s usually mild to
57:57 moderate and would go away quickly after
57:59 applying it but you know sometimes the
58:01 treatment is worse than like here like
58:03 you don’t want to come out of a migraine
58:04 with a giant flaky red face so
58:07 um you know still I I’m not quite
58:09 convinced that this is you know my
58:11 preferred method of treatment
58:14 um but again you know I often see people
58:16 who have tried uh you know 20 different
58:18 drugs or something and they need to try
58:19 something else and so this might be
58:22 something to try
58:23 um capsaicin so we briefly touched on it
58:26 before but if you see this picture in
58:27 the top right that’s the receptor and it
58:30 can be activated by all sorts of things
58:32 the chili pepper extract nerve growth
58:35 factor acidic uh stuff heat and ethanol
58:39 but that makes sense like acid and heat
58:41 and alcohol like you’ve all felt it burn
58:43 you know and and that’s kind of it
58:45 activating that same receptor
58:48 um so very interesting active component
58:50 in Chili Peppers
58:51 um and you know normally it’s activated
58:53 by physical heat but capsaicin also can
58:56 do this and uh so what’s fascinating is
58:59 that this receptor is really important
59:00 for pain processing
59:02 and so it depolarizes the neuron which
59:05 means it sends a little electrical
59:06 signal and it’s important for pain
59:09 pressing sending pain signals back uh to
59:12 the the brain for processing and it
59:14 releases something called substance P
59:16 which is an important chemical messenger
59:17 in pain but what’s really interesting is
59:20 that if you continue to stimulate it you
59:22 know you get something called
59:22 tachyphilaxis you run out of the
59:24 messenger so you run out of that
59:26 substance p and so by depleting
59:28 substance B and also cgrp which you know
59:31 from migraine studies
59:33 um you know eventually it’s like you’ve
59:35 used up all your pain for that time and
59:36 you’ve got a refractory period so you’re
59:38 left with kind of like a pleasant
59:39 tingling numbness you know and so for
59:42 some people it’s worth it to kind of
59:44 concentrate all their pain at once and
59:45 and try try this approach
59:48 so there was a systematic review of
59:50 topical capsaicin for different chronic
59:51 pain conditions
59:53 um and the ones I want to highlight in
59:54 particular post herpetic neuralgia
59:56 diabetic neuropathy you’ll see all the
59:58 abbreviations in the bottom right here
01:00:00 osteoarthritis and rheumatoid arthritis
01:00:02 but it’s used for a lot of different
01:00:04 things people use it for itchiness like
01:00:06 just like I don’t know why I’m itchy you
01:00:08 know you’ve tried everything you saw the
01:00:09 dermatologist they try this psoriasis
01:00:12 sometimes they will try uh I’ve seen a
01:00:14 lot of post incisional site for
01:00:15 mastectomy that they’ve had success with
01:00:17 capsaicin and different blood disorders
01:00:20 so I mean people have tried it for a lot
01:00:22 of different conditions it seems to have
01:00:24 minimal adverse drug events so local
01:00:26 burning stinging redness systemic events
01:00:29 are pretty rare like having an
01:00:30 anaphylaxis or something is pretty
01:00:32 uncommon but if you inhale it you know
01:00:35 into your lungs you can cause bad lung
01:00:37 irritation which is not great you want
01:00:39 to keep it clear of mucous membranes
01:00:41 because it can be quite painful
01:00:44 so looking specifically uh at this one
01:00:46 in neuropathic pain conditions the
01:00:48 number needed to treat it eight weeks so
01:00:50 you’re following them for a course of
01:00:51 eight weeks with capsaicin was about
01:00:53 0.075 it was 5.7 so for every six
01:00:57 patients what that means is that one
01:00:59 would achieve at least 50 reduction in
01:01:02 their pain who would not have done so
01:01:04 otherwise like if they were just taking
01:01:05 a normal cream
01:01:07 um like one and six will have the
01:01:08 benefit of 50 pain reduction
01:01:10 um and you know maybe that sounds
01:01:12 impressive or not but for people that
01:01:14 have been struggling with horrible
01:01:15 debilitating chronic pain and they’ve
01:01:17 tried everything else you know I still
01:01:18 think those are pretty good numbers
01:01:21 so the one that really kind of made me
01:01:24 blink and do a double take with
01:01:26 intranasal capsaicin like you have to be
01:01:29 pretty desperate to snort capsaicin to
01:01:31 be honest
01:01:32 um that is excruciatingly painful and
01:01:35 will actually cause a lot of the
01:01:36 autonomic symptoms that that you’re
01:01:38 getting with a cluster headache
01:01:40 um but for the most ultimate refractory
01:01:42 cases perhaps it could be tried for
01:01:44 migraine or cluster headache I
01:01:46 personally I do not recommend this at
01:01:48 all like it is the worst kind of pain
01:01:50 the studies are small the effects are
01:01:52 small I mean it makes sense to me based
01:01:55 on the physiology of how we understand
01:01:56 how this molecule works but I think the
01:01:59 trick is we need to develop a version of
01:02:01 it that doesn’t result in more pain than
01:02:03 it’s treating
01:02:04 so summary of the topicals we really
01:02:07 need better trials before routine
01:02:09 recommendations can be made Menthol has
01:02:12 some decent evidence to support its uses
01:02:14 in a board up so you could try things
01:02:15 like stop pain or the stage roller
01:02:17 chamomile I think holds some promises on
01:02:19 topical but we need better studies to to
01:02:21 look at it further lavender I think
01:02:23 maybe more on some more study but uh you
01:02:26 know maybe rose oil not so much
01:02:28 and with that I want to abruptly thank
01:02:31 you for your wrap detention and I want
01:02:34 to turn the time to some questions