Psylocibin for Migraine Treatment

0:00 [Music]
0:04 so um welcome everybody and for those
0:06 that continue to join us pop into the
0:08 chat where you’re joining us from but I
0:11 am I’m Wendy Gart I’m the executive
0:13 director of MRA Canada and I’m happy to
0:16 be uh moderating the webinar tonight on
0:20 Silo sein I think I pronounced that
0:22 right probably not um and we have uh Dr
0:26 Alexandra Alexander uh melan joining us
0:30 as our key keynote
0:32 speaker so welcome and let’s see let’s
0:36 try to uh proceed with my slides and
0:41 here we have um I I need to acknowledge
0:43 and and thank all of the sponsors that
0:46 make the webinars um possible so here it
0:49 is um without them um these these
0:52 webinars would not be possible so we we
0:54 are gratefully um thankful for their
0:58 support uh tonight’s agenda is going to
1:01 be an introduction to migraine Canada
1:03 very quickly um I talk very quickly so
1:06 um it won’t be long and then we’re going
1:08 to turn it over to our keynote speaker
1:11 and then we’re going to have our
1:12 presentation on scoin and then we’re
1:16 going to move into a Q&A um and we’ll go
1:19 through a little bit of that in a minute
1:21 um migrant Canada who are we we’re a
1:24 federally registered charity supporting
1:25 all Canadians living with migraine and
1:27 headache disorders our mission is to
1:30 improve the lives of Canadians with
1:32 migraine and other headache disorders
1:34 through advocacy awareness education
1:36 research and support um watch out for
1:39 more of our 2023 webinar webinar series
1:42 including presentations on vestibular
1:45 migraine uh given by our uh chair of
1:48 migraine Canada Dr Elizabeth laru and
1:51 also migraine in children and teens um
1:56 who will be hosted by Dr Marissa lagman
1:59 in December um join um also join us for
2:03 upcoming Instagram Live Events given by
2:07 um heah hany who is a a a pharmacist who
2:10 is specialized in
2:12 migraine and we’re going to do two more
2:14 this year and one is going to be in
2:16 November on holiday stress triggers and
2:19 then also in December on weight and
2:22 management very timely to our festive
2:24 season um also welcome uh invite you to
2:28 join our growing community
2:30 um at at the website there below and
2:33 we’ll include this in the follow-up
2:35 email that will be sent tomorrow um we
2:37 have an advocacy page where if you want
2:40 to write into your elected official your
2:42 minister of Health your MLA or your MPP
2:45 depending on where you live and talk
2:47 about your concerns related to migraine
2:49 care and access to medication we have a
2:51 seamless um really really easy way to do
2:55 that and we really encourage that and
2:58 last but not least um resources for
3:00 migraine management check out our
3:02 library we have added a few more
3:04 resources on gpants and exercise um and
3:08 we will be continuing to add to that
3:10 Library so check into that
3:13 regularly before we begin uh our
3:16 disclaimer this webinar provides
3:17 information and not medical advice we
3:20 note um that all and I have to move my
3:24 thing all information presented and
3:26 discussed might not apply to your own
3:28 medical situation always discuss Medical
3:30 Treatments with your own healthc care
3:32 provider who knows about your medical
3:34 history and I’m going to now introduce
3:37 uh Dr melan um he is a neurologist with
3:41 an additional Subs specialty expertise
3:43 in headache medicine and a member of the
3:45 Canadian headach Society you’ll often
3:47 hear me refer to CHS and many of my
3:50 bulletins and any videos that I produce
3:52 so it’s the Canadian Headache Society Dr
3:55 melan is operates a community- based
3:57 headache medicine and general neurology
4:00 practice in London Ontario his current
4:03 um research interests um sorry I’m
4:07 trying to include
4:08 cannaboid um and I sorry I can’t read
4:14 the next word um and use in headache p
4:16 in patients as well as the assessment of
4:19 residency circular content pertaining to
4:21 headache across Canada um through the
4:24 Canadian Headache
4:25 Society and I’m going to
4:30 um then clo stop my sharing and turn it
4:33 over to Alex who’s going to start
4:36 sharing and carry on with this amazing
4:39 presentation that I’m sure everybody is
4:41 very eager to uh to listen to perfect
4:44 thank you Andy all right we’re just
4:47 gonna swap over
4:49 here okay you got my slides Wendy yeah
4:53 we can see them perfectly perfect
4:54 perfect so we have been talking about
4:57 this subject for a long time and neology
4:59 circles I know it’s a Hot Topic it’s an
5:02 area where we don’t have a lot of data
5:04 people are trying to do new studies um
5:06 and we’re making some promising gains um
5:09 and you know in Canada at least uh we’re
5:12 starting to see shops crop up all around
5:15 where people are able to purchase silos
5:16 ibin and it may not be legal um but
5:20 people are using it anyway some
5:21 therapeutically some
5:22 recreationally um and so it’s becoming
5:24 an increasingly important question in
5:26 the headache clinic and I think probably
5:28 in a given week and I only see headache
5:31 probably three or four times it will
5:32 come up as a question uh and so it’s
5:35 it’s a difficult subject because it’s
5:37 not really Health candada approved and
5:38 so we have to be careful about how we
5:39 talk about it our our goal tonight was
5:42 to try to make sense of the information
5:44 we do have maybe pose some questions
5:47 about where we need to look next and
5:49 kind of put together all in one place
5:51 the information about silos Sabin and
5:53 how it’s relevant for headache treatment
5:55 and give you some resources that you
5:57 might be able to do some more personal
5:58 research
6:00 so here we go disclaimer okay so like
6:05 Wendy mentioned this discussion is not
6:06 really an endorsement for personal use
6:08 but it’s really a digest of my opinions
6:11 and and kind of distilling all the
6:12 latest research trends for you syas cban
6:15 is considered illegal so in many
6:17 Canadian jurisdictions use of possession
6:19 can result in a criminal offense uh
6:22 these molecules like syoc cybin and the
6:24 other hallucinogens are molecules that
6:27 are interesting therapeutically to
6:28 doctors and
6:30 they’re under investigation we do have
6:31 ongoing trials in a lot of different uh
6:33 areas but they still have yet to prove
6:36 kind of concretely that they they are
6:38 very beneficial and we still haven’t
6:40 mapped out really a lot of the side
6:41 effects and problems that might arise
6:43 with
6:44 them again like I said it’s really not
6:47 yet approved by Health Canada although
6:50 you know you may read in the news about
6:51 certain exemptions in really extenuating
6:54 circumstances people who have uh you
6:56 know used pyo cybin to help with the
6:58 anxiety processing end of life uh in
7:01 medical assistance in dying or paliative
7:03 care sometimes with refractory
7:05 post-traumatic stress disorder uh or
7:07 depression that has tried multiple
7:09 different things without success as well
7:11 as cluster
7:12 headache uh psybin is a potent chemical
7:16 you know even though it’s natural you
7:18 know sometimes I get this feedback from
7:19 my patients well it’s natural like how
7:21 bad can it be and natural doesn’t mean
7:23 it’s weak uh you know if it’s strong
7:25 enough to you know shake up your brain
7:27 and reform connections uh you know it’s
7:29 probably potent enough to do some bad
7:31 things if you used improperly too and
7:33 one thing that I think really Bears
7:35 mentioning is you know think of the
7:38 number of Canadians on an
7:39 anti-depressant or or using a serotonin
7:41 like medicine uh including antis
7:43 psychotics maybe even tripton
7:45 potentially but less likely um when you
7:48 combine them you’re really giving
7:50 yourself a boost of Serotonin and this
7:51 can be quite toxic so there is that
7:53 dreaded serotonin syndrome that can
7:55 sometimes even lead to Coma or death so
7:58 you know I would say really you do like
8:00 Wendy mentioned have to consult with
8:02 your
8:03 doctor really talk about the risks and
8:05 benefits of this they’re not going to be
8:06 able to prescribe or recommend it to you
8:08 but you know if you need to know more
8:09 about the consequences it’s an important
8:11 discussion to
8:12 have so that aside uh onto the good
8:16 stuff so I wanted to show you some of
8:17 these mushrooms because they’re quite
8:19 diverse and silos cybin is a naturally
8:22 occurring uh compound these mushrooms
8:24 grow all over Canadian Forest there’s
8:26 over 200 species of mushroom that that
8:28 do in produce this chemical um and the
8:32 interesting part is musin uh which you
8:35 might remember that big red mushroom
8:37 with white polka dots that’s always in
8:38 Smurf videos or something that’s amonita
8:40 muscina muscarine is a is the ancestor
8:43 of silos cybin this molecule it’s very
8:45 toxic but can be used medically and over
8:49 two 20 million years probably salocin
8:52 has slowly evolved from muskin into
8:54 these mushrooms that we have today um
8:57 and so you can see pict pictures like
8:59 petroglyphs in caves of early people uh
9:03 depicting in murals the the use of
9:05 mushrooms even in kind of like religious
9:07 type of Ceremonies in mesoamerica it’s
9:09 often used in in religious practices by
9:12 indigenous people and so we have uh
9:14 formal recordings of History by Spanish
9:17 visitors in the 16th century documenting
9:19 the use so use goes well back in history
9:23 uh to Cave people and to various
9:26 indigenous cultures through through
9:28 South and Central America
9:30 so what’s being looked at currently in
9:32 terms of research uh there’s
9:34 neuroplasticity which is that idea that
9:36 your brain can form new connections and
9:38 and change the way it speaks to
9:40 different segments uh intracellular
9:42 signaling which instead of connections
9:44 between neurons we’re looking at within
9:46 the cell how do the different
9:47 departments talk to each other
9:49 functional Imaging which we we’ll get to
9:52 in this talk and it’s a type of Imaging
9:55 that’s not so much concerned with like
9:57 tumors or bleeds or things like that but
9:59 is able to tell us what parts of the
10:01 brain are activating or connecting when
10:03 we’re doing something and then the non-
10:05 Psychedelic congener uh like what is a
10:08 coner a coner is like a little component
10:10 of an organic mix of chemicals and the
10:13 idea is like what if we could find a
10:15 component of of these biologic mixtures
10:19 uh where it has all the therapeutic
10:21 effects but maybe none of the negative
10:22 ones or we don’t want hallucinosis for
10:24 instance um you know and so by either
10:26 tweaking some of these molecules and
10:28 studying them chemically uh or you know
10:31 isolating certain compounds from a
10:32 mixture we might be able to find a
10:35 better tolerable
10:37 medicine specifically for conditions
10:39 we’re looking at headache uh cluster
10:41 headache is probably you know the most
10:43 well-known use for syoc cybin but
10:45 migraine as well other chronic pain
10:48 conditions like fibromyalgia there’s
10:50 anecdotes that it may be important and
10:52 we’re also looking on a biochemical
10:54 level so in terms of the inflammosome
10:57 which we talk about the the whole sum of
10:59 all the different inflammatory molecules
11:00 around our body chemical Messengers that
11:03 often mediate disease uh and how else
11:07 are these implicated in other things
11:08 like mental health disorders you know
11:10 this is like a a gordian knot all these
11:12 problems like chronic pain mental health
11:14 trauma um we’re starting to see even
11:17 through functional Imaging studies that
11:19 there are certain commonalities there’s
11:20 Nexus in the brain in certain areas that
11:23 are bottlenecks and and perhaps this
11:25 molecule might provide some insight into
11:27 how we can unravel that
11:29 um there’s promising anecdotes about
11:31 using these medicines for substance use
11:34 disorders whether it’s alcohol or other
11:37 recreational drugs and then of course
11:40 like I mentioned in paliative care and
11:41 medical assistance in dying uh some
11:44 really excellent uh stories of people
11:46 who have been able to be at peace and
11:48 come to terms with you know these kind
11:50 of very stressful life
11:52 events another kind of thing that’s
11:54 actually just interesting from a basic
11:56 neuroscience perspective is that study
11:59 the hallucinations and the Psychedelic
12:01 phenomena that come from these medicines
12:03 also tells us about how the brain is
12:05 wired and the underlying mechanics in
12:08 terms of our perception so solely from
12:10 that perspective you know there’s
12:12 probably a few people in the audience
12:13 who who have synesthesia where you may
12:15 mix you know colors uh and sounds or
12:18 tastes and things like that um and so
12:21 these things you know when you take a
12:22 psychedelic it tends to loosen those
12:24 boundaries and it’s it’s more common in
12:26 average people uh and so perhaps it can
12:29 tell us something about the workings of
12:31 the brain of the casty uh and in general
12:34 you know there’s an idea not just of
12:36 trying to treat disease reactively but
12:38 being proactive and attending to your
12:40 mental health in a prophylactic manner
12:42 is there a role for this potentially in
12:44 terms of well-being uh before we reach
12:47 the point of disease and I think all of
12:48 these are very interesting lines of
12:50 questioning uh and you know we’re really
12:53 at the beginning of this journey and I
12:54 think there’s a lot of exciting
12:55 developments to be had in the next 10
12:57 years or so
12:59 so why syus ibin you know out of all the
13:01 targets that we could pick all the
13:02 bizarre herbs in the jungle why are we
13:04 picking this mushroom and you know in
13:08 short there’s a lot of conditions that
13:09 people are not happy with the current
13:10 treatments we have um so they are either
13:12 lacking in efficacy or they have a lot
13:14 of side effects uh psychedelics in
13:17 general are thought to have a favorable
13:19 safety profile when you compare it to
13:20 things like opioids for instance which
13:22 are common place and you know the other
13:25 issue is that in the midst of a opioid
13:27 crisis and an addiction and abuse crisis
13:31 psychedelics are thought not to have the
13:32 addictive potential of these and so
13:34 perhaps this is a more viable Avenue to
13:36 explore when we’re looking for
13:38 substitutes for people who are
13:40 suffering in terms of the dosing uh you
13:43 know I would say it’s highly variable
13:45 everybody kind of has their Voodoo if
13:47 people are using magic mushrooms and
13:49 they’ll tell you how they they weigh it
13:51 or dose it um highly variable we really
13:53 need to figure out what is the optimal
13:55 way to dose this in terms of the
13:57 frequency the amount of the substance um
14:00 and then how it should be used on an
14:02 ongoing basis um so you know it can be
14:04 used as a single oral dose in some
14:06 studies or there may be multiple
14:08 intervals uh with different doses some
14:11 studies look at ongoing micro doing and
14:13 this has become very popular you know in
14:15 online forums and and
14:17 colloquially but it may have some
14:19 potential adverse effects which we’ll
14:22 get to in a second sometimes you’ll hear
14:24 people talk about macro doing or the
14:26 hero dose uh which is taking quite large
14:29 amount and that may have a different
14:30 physiologic effect than you know a slow
14:32 gradual exposure um interestingly in
14:36 studies you know syosin can be purified
14:38 and put into Solutions so it can be
14:40 taken intravenously as well as taking it
14:42 orally and that may have a completely
14:43 different effect too because you’re
14:45 bypassing your metabolic organs that
14:48 sometimes would would tweak the amount
14:49 you’re getting so the Psychedelic
14:52 effects probably occur with doses that
14:54 are between four and 10 milligrams and
14:57 recreationally though people are taking
14:58 much High higher doses sometimes 10 to
14:59 50 milligrams uh the typical effects
15:02 usually start to show up about 10 to 40
15:04 minutes after ingestion um and for those
15:06 of you with experience with other
15:07 Edibles like cannabinoids you know it
15:09 does depend on uh what you’ve eaten and
15:12 if you have gastric motility problems
15:14 gastroparesis those kind of things um
15:17 and so the effects can persist for up to
15:20 six hours and in some cases uh more uh
15:23 and that’s just in terms of the
15:24 immediate kind of psychedelic effects
15:26 but as we’ll see in this presentation
15:28 there may be other changes in brain
15:30 neuroplasticity and other persistent
15:32 changes that may last even a month or
15:35 Beyond so I wrote here uh there’s a
15:38 slide here of these mushrooms and this
15:39 was taken from Emanuel Schindler who is
15:42 a prolific uh siloc Ian researcher down
15:45 south uh and she presented at one of the
15:48 American headach society meetings about
15:50 her research which we’ll we’ll recap
15:51 here and I just wanted to show the
15:54 different kind of dosing algorithms and
15:55 I wrote here the the low dose you know
15:58 think in the beginning days we’re trying
15:59 to do proof of concept studies we’re
16:01 trying to demonstrate safety so that we
16:03 can have a solid ground to to do more uh
16:06 you know larger doses longer studies um
16:09 we’re using very tiny doses of 0.143
16:12 milligram per kilogram um so you know it
16:15 ends up being quite
16:18 low so micro doing this is probably the
16:21 Hot Topic that you know you’ll hear
16:23 everybody talk about if you have friends
16:24 who are using these things
16:26 recreationally basically it is the self-
16:29 administration of tiny doses of mushroom
16:31 and it’s allegedly not at doses high
16:35 enough to impact regular functioning but
16:38 you know I would argue this is the same
16:39 kind of thing we heard about cannabis oh
16:41 it’s you know it’s not centrally acting
16:42 and yet you’re saying it’s an
16:43 anti-depressant if it’s causing changes
16:46 in pain processing reprocessing trauma
16:48 in your mood I mean it’s impacting your
16:50 functioning so I think it really you
16:52 know it depends what you mean we got to
16:54 be careful about how we Define these
16:56 things early research shows that even
16:59 the low doses that do not provide a
17:01 hallucinogenic effect may still have
17:04 therapeutic value for other conditions
17:06 like panic attacks or headaches or
17:08 things like that um so you know there’s
17:10 a promise that you know perhaps at very
17:13 low control doses uh you may not need to
17:16 have a chaperone or someone to watch you
17:18 uh take these small
17:20 doses there is a concern though um
17:23 because siloc cybin belongs to a class
17:26 of medication called the indolamine
17:28 hallucinogens and this includes other
17:30 things like LSD and things there is some
17:34 activity at a specific serotonin
17:35 receptor 5ht 2B and there have been
17:39 other drugs like methysergide other
17:42 types of Agonist that have been shown to
17:44 link to valvular heart disease and cause
17:46 fibrosis and this can lead to pulmonary
17:49 hypertension cardiac issues potentially
17:51 reduced quality of life and and
17:53 mortality um so you know that to me is
17:55 quite concerning and so then we start
17:58 start to generate interesting questions
17:59 should we be just pulsing this one time
18:01 here and there or should we be doing
18:02 chronic lowgrade exposure does that
18:04 increase the risk the truth is we do not
18:07 know we just don’t know um and that’s
18:09 why formal studies are needed you know
18:11 it’s not that people are trying to
18:12 withhold promising Therapeutics but uh
18:15 there is a reason we proceed very
18:16 carefully with these kind of Trials
18:18 because we do really want to minimize
18:19 the amount of risk we expose people
18:21 to um like I mentioned there are
18:23 congeners these kind of
18:24 nonhallucinogenic versions of molecules
18:27 that may still have the therapeutic
18:28 benefit and there’s some exciting ones
18:30 um this bowl of BL 148 which is a coner
18:33 of LSD um is under development and it’s
18:36 shown some promising therapeutic effects
18:40 so I wanted to show you this interesting
18:42 diagram and you know you don’t have to
18:43 be an organic chemist to to get it um
18:46 psybin this is the molecule here on the
18:48 left when you ingest it is rapidly
18:51 metabolized down to cocin so you take
18:53 off some of those extra groups there up
18:55 at the top the phosphate and then maybe
18:58 you gain an extra hydrogen on your
19:00 nitrogen what that does is it turns
19:03 silos cybin which is really not active
19:05 biologically it turns it into syosin
19:07 which is really the agent that’s giving
19:09 you all the receptor effects and causing
19:11 the Psychedelic and therapeutic effects
19:13 now just for comparison sake I want you
19:15 to look at serotonin melatonin and the
19:18 triptans these are all molecules that
19:20 are implicated in neurotransmission and
19:22 especially important for migraine and
19:24 headache Pathways you know triptans work
19:25 for migraine and cluster they share a
19:28 shape so you can see there’s a Benzene
19:30 ring and a purole ring which is that
19:32 little Pentagon and then a tail with the
19:34 nitrogen so all these molecules have
19:36 some we call it homology they look the
19:38 same they got the same shape and what
19:40 that means if you think back to Fisher
19:42 Price bucket there’s some that are going
19:44 to be able to squeeze through the holes
19:45 and some that are not and they have
19:47 different activity at different
19:48 receptors so you can think of it like
19:50 the most confusing terrible Fisher Price
19:52 bucket because that’s pretty much what
19:53 it is just for the sake of comparison I
19:56 think it’s not worthy that the DHE like
19:59 for those of our migrain who have had
20:01 lots of experience and have been
20:03 suffering for decades they may have been
20:04 exposed to DHE um you know it can be a
20:07 wonderful drug for some people for
20:08 migraine um but DHE also has activity at
20:12 the receptor we think is the primary
20:14 target of siloy this is the serotonin 2A
20:17 receptor 5 ht2a um and in addition to a
20:20 number of other receptors but you know I
20:22 think again we need formal studies to
20:24 see if if this is a shared mechanism of
20:26 action in migraine between cocy in DHE
20:29 or or things like that and that’s going
20:31 to take more
20:32 study so why does it work well like we
20:36 said psilocybin is a prod drug it’s
20:38 rapidly turned into syosin in your body
20:41 once you ingest it and this is the
20:43 active ingredient in the magic mushrooms
20:45 that produces the effects um and the
20:47 most important receptor if you could
20:49 take away one receptor uh and I’ll show
20:51 you some just to give you nightmares
20:53 because that’s what I have to memorize
20:55 uh is the 5 ht2a receptor antagonist
20:58 and you know interestingly we think
21:00 about the antis psychotics you know some
21:03 of our newer antis psychotic drugs they
21:05 are antagonists so they’re blocking that
21:06 receptor so this is you know that’s why
21:09 you can think of like sometimes
21:10 psychotic effects can be hallucinations
21:12 auditory or visual um and we block that
21:15 to turn it off well this is kind of the
21:17 opposite and so it’s creating these kind
21:20 of
21:21 hallucinations and uh it’s preim
21:23 preliminary uh primarily eliminated from
21:26 the body by renal excretion through the
21:27 kidney
21:28 and the halflife is about three hours I
21:30 would say A good rule of thumb uh if you
21:33 want to totally clear a substance from
21:34 your body is five half lives so 15 hours
21:36 or so but I would say for the
21:38 Psychedelic effects it’s somewhere
21:39 around six hours that will
21:41 last so just to show you a very brief
21:44 overview again even this is kind of a
21:47 gentle selection of The receptors I tell
21:49 you this only to show the complexity
21:51 because you know I spend a lot of time
21:54 reading about this and it boggles my
21:56 brain and I’m trying to break it down
21:59 but there’s so much more that we don’t
22:00 know and that’s why I want to balance
22:03 kind of the hope of having a new
22:04 therapeutic agent which I know many
22:06 people are desperate for against like
22:08 jumping head first into the unknown
22:09 because we’re dealing with some pretty
22:11 powerful brain chemistry here so we’re
22:14 going to start with the 5ht receptor
22:15 antagonist um so uh this one this slide
22:18 for you is presented as a reference um
22:21 it works at the 5H t2a receptor like we
22:23 talked about it works at the 5H t2b
22:26 receptor which you know potentially has
22:27 that risk for fibrosis in the heart
22:29 valves it works at the 2C receptor which
22:33 can affect mood Behavior appetite and
22:35 other hormones and it also works at the
22:38 1A receptor which can help to kind of
22:40 regulate your blood pressure and heart
22:41 rate through a number of different
22:43 mechanisms and so you know I I think as
22:47 we learn more about that we’ll be able
22:48 to tweak different versions of it to
22:50 have fewer side effects or to Target
22:52 specifically different activities of
22:53 this
22:54 medicine now I show you these kind of
22:56 ancient diagrams of the brain
22:58 you know a lot of people are familiar
23:00 with the loes and I think even thinking
23:03 about a classical neurology training we
23:05 all learned the loes and everything the
23:06 loes do and different lobules and and
23:08 gyri and everything but we don’t really
23:11 get the whole picture of modern
23:13 Neuroscience which talks about
23:14 functional connectivity and so the lobes
23:17 talking about like one area of the brain
23:18 does this this does this you knock it
23:20 out with a stroke you lose this ability
23:22 that’s extremely reductionist like that
23:25 I I feel really fails to grasp the
23:27 complex of your brain and it’s not doing
23:30 you any favors to think of it that way
23:32 um the other myth that I really
23:33 absolutely hate is and this actually
23:35 comes up a lot even from doctors the
23:37 myth that you use only 20% of your brain
23:40 that is not true you use all of it your
23:42 brain is a highly conserved like
23:44 evolutionary miracle and you need every
23:46 little piece of it um and you know you
23:48 may not use it all at once but you
23:50 definitely use all of it um so if
23:52 someone tells you that you tell them I I
23:54 correct you otherwise um I want to show
23:56 you this picture which I thought was
23:58 fantastic it’s it’s an exerpt a spread
24:01 from Scientific American in 2019 and
24:03 it’s freely available on the internet
24:05 you can find it at the link below and if
24:08 you want to start delving into the real
24:10 complexity of the brain the 100 trillion
24:12 connections and how that actually helps
24:14 us form Consciousness and perceive the
24:15 world around us like it is a
24:17 mindboggling adventure so I would
24:18 encourage you uh to look up this article
24:21 and start to read about it so the way
24:24 these scientists started to try to pick
24:26 away at these systems was look at areas
24:29 of the brain how they connect to
24:31 different areas of the brain noes what
24:33 are the hubs which are the areas that
24:35 have a lot of connectivity to other
24:37 groups of nodes and then we look at the
24:39 edges which are the actual connections
24:41 and they ended up uh putting it together
24:43 in terms of seven main modules that help
24:45 us process everything in terms of uh
24:47 visual processing attention uh you know
24:50 speech and and all these kind of things
24:52 uh and so like this is going to go well
24:55 beyond the scope of our talk tonight but
24:56 I think you know if if you really want
24:59 to start picking away the brain
25:00 understanding itself which is a really
25:02 fascinating idea to me uh this is a
25:04 really great place to start and they
25:05 will give you good references to read
25:07 more and this this leads us to the next
25:10 topic which is the idea of the
25:11 functional connectivity of the brain and
25:14 so the brain is composed of these
25:16 anatomically distinct regions like the
25:18 lobes or the gy but they’re functionally
25:21 connected to a series of networks and
25:23 what that means is that uh you
25:26 know brains will activate in different
25:28 patterns depending on the task you’re
25:29 doing U fmri which is the functional
25:32 magnetic resonance imaging um and other
25:35 types of scans can help us shed light on
25:37 the Dynamics of these Network so if
25:39 you’re doing a particular task you’re
25:40 going to use more sugar and oxygen in
25:42 one area and you know you’re going to
25:44 see that the metabolism changes and we
25:46 can measure these things to see which
25:48 parts of the brain are active during
25:49 which tasks so it can also show us
25:52 interestingly in a healthy brain you
25:54 know you can compare uh during different
25:56 states and tasks you you can also make
25:58 comparisons between brains in disease
26:00 State and healthy brains so in that way
26:03 you know sometimes diseases can shed
26:04 light on how things are
26:06 working now there’s this really
26:08 important concept of the default mode
26:11 Network um and I would say this is a
26:13 critical concept when it comes to
26:15 understanding functional connectivity
26:17 and it refers to connections between
26:18 brain regions that are responsible for
26:20 everyday Consciousness and you’re going
26:22 to see it most when you’re kind of in
26:24 the resting state just idling you know
26:26 kind of like your computer goes on the
26:28 screen saver or something and your
26:30 overall neural activity shows a global
26:33 decrease and you reach this kind of
26:34 Baseline default activity now the key
26:38 areas for the the default mode Network
26:41 are in areas of the cortex which is the
26:43 outer part of the brain the bark that
26:45 are specifically related to emotion and
26:48 memory and you know I think in the early
26:50 days we thought maybe it was going to be
26:51 more important to be looking at sensory
26:53 motor cortex the sensation and and motor
26:55 action but it seems that it’s actually
26:57 the emotion and memory areas that are
26:59 most
27:00 critical as we come to understand it we
27:02 think that basically the pattern of the
27:05 default mode network is responsible for
27:07 your ego or basically your sense of self
27:09 and awareness your internal and external
27:11 representations and we’ve shown that in
27:13 various mental health conditions and
27:15 chronic pain conditions there are
27:16 aberration in the organization of the
27:19 default mode Network and so this has
27:21 become a very interesting way to look at
27:23 the brain instead of just measuring
27:24 things in the fluids or the spinal fluid
27:26 or blood or just looking at lesions of
27:28 areas uh as we come to understand the
27:30 Dynamics how things move through time uh
27:33 you know we see there’s a reason why we
27:34 haven’t been able to crack certain
27:35 diseases like those like chronic pain
27:37 and and mental
27:39 health so um I’m gonna again blow
27:42 through some really high level crazy
27:44 science language I put these in with
27:46 references so that you can look up these
27:48 things if you want to read more and then
27:49 we’re going to crack it down and make it
27:51 understandable for everybody um so we
27:55 talked about 5H t2a being the main
27:57 recept
27:58 that this works on to cause therapeutic
28:00 effects when you activate it the neurons
28:02 get very excited specifically these
28:04 paramal cells and that means that the
28:06 outer part of your brain the cortex um
28:09 it really changes the way it signals
28:11 between different regions and so it
28:13 becomes completely excited very
28:15 irregular uh very disordered and they
28:17 refer to that as high entropy um and
28:20 then that state can be referred to
28:22 sometimes in research as the primary
28:24 State the typical connections that you
28:26 would see in your default mode Network
28:28 are broken down and then all of a sudden
28:30 it’s like no holes barred they’re
28:32 connecting with everything really
28:34 unusual unexpected connections between
28:36 tons of different parts of your brain
28:38 and that may even be the basis of
28:39 synesthesia where you interpret multiple
28:42 senses overlapping and things like that
28:44 um and then what’s interesting is that
28:47 you know both immediately and in the
28:48 long run there’s been studies that show
28:50 that this changes the plasticity of the
28:52 brain so the dendrites are like the
28:53 little fingers or branches on these
28:55 neurons and it changes the way they
28:57 connect the way they talk to each other
28:59 the way they express different proteins
29:01 and grow um and so the thinking the
29:04 theory behind this is that the new
29:06 healthy functional connections will
29:08 remain and the dendritic plasticity will
29:10 will kind of sustain these even long
29:12 after the syosin has actually left your
29:14 system so it’s creating changes that
29:17 persist beyond the duration of the drug
29:18 in your
29:19 body now the other observations they
29:22 made were that taking psychedelics can
29:24 reduce your neuron activity in certain
29:26 areas and also Al reduce blood flow in
29:28 certain areas and uh so again this may
29:31 change different functional connectivity
29:34 and uh other parts like the insula so
29:37 insula is an area deep inside the
29:39 temporal lob it goes in and it regulates
29:41 your autonomic system heart rate blood
29:43 pressure uh but it does much more than
29:45 that in terms of sensory processing um
29:48 and so we see that in chronic pain
29:51 conditions over time you’re going to
29:53 have shifts in the areas of the insula
29:55 that activate um and we’re thinking that
29:58 perhaps the psychedelics or salab may
30:00 able to reverse that or perhaps create
30:02 different patterns that may not uh you
30:04 know perpetuate that kind of chronic
30:06 pain picture so in English
30:09 please if I had to give an analogy I
30:11 would say think of the brain like an
30:13 orchestra all these different parts of
30:15 your brain are doing things individually
30:18 but when you power up to do a specific
30:20 task you know different patterns of the
30:21 brain turn on or off in concert to get
30:23 things done and so in some disease
30:25 States it’s like you have like the wind
30:27 section is Out Of Tune or something and
30:29 it’s creating some Discord um silos cbin
30:32 changes the way that the neurons talk to
30:34 each other and can change the patterns
30:35 in the way that parts of your brain
30:37 connect to each other it can change the
30:39 amount of blood flow and brain
30:41 selectivity in certain brain regions and
30:43 it can also calm down parts of the brain
30:45 that seem to be important for chronic
30:47 pain perception and emotional processing
30:49 and so I think that’s probably the basis
30:51 of why it’s so exciting now this graphic
30:54 for those who are more visual Learners
30:56 um I always like a a good heat map and
30:58 you can see the red areas of this brain
31:00 you’re seeing it from the inside so if
31:02 we split your brain down the middle uh
31:04 and we open it up uh this is kind of the
31:06 inside of your brain and the red areas
31:09 have a lot more of concentration of
31:11 those 5 ht2a receptors so these are
31:14 where they’re they’re strongly expressed
31:16 and if you look on the right uh you can
31:18 see that uh on the bottom of there that
31:21 little red tree like thing that’s a
31:23 neuron and those little fibers are all
31:25 the
31:25 dendrites and when you look at that
31:28 graph to the right of it it’s kind of
31:30 just chugging along at its normal
31:31 activity and then you give psychedelics
31:33 and then suddenly you see that jumps up
31:35 and it’s just going up and down up and
31:36 down it almost looks like a toothbrush
31:38 there that is the new excited activity
31:41 State and uh so again when you look at
31:44 the very top of it now that kind of
31:46 interesting ball of yarn thing when you
31:48 administer the psychedelic drug you’re
31:50 seeing the formation of tons of new
31:52 connections um and eventually that does
31:55 reduce to some extent but some of those
31:56 connection persist long after the drug
31:58 is
31:59 used so in this study this is another
32:02 one that was trying to answer the
32:03 question well how long do these changes
32:05 actually persist um they found that
32:07 emotions and brain function are altered
32:10 up to one month after a single dose of
32:12 high high Doocy um and I think they got
32:15 maybe like 25 milligrams per 70 kilogram
32:19 uh and uh so you know this is very
32:21 promising but again only studied up to
32:22 one month like perhaps the changes
32:24 actually go even longer and so this ball
32:27 of yarn type picture is actually an
32:29 interesting connecto it’s a way to
32:31 depict all the connections of these
32:32 different brain regions in a visual way
32:35 that that is a little bit easier to
32:36 understand and the four main sustained
32:39 effects that they found in the study was
32:41 improved mood for up to a month and I’m
32:43 simplifying this language a little bit
32:45 um less activation in brain centers that
32:47 respond to strong emotions for up to a
32:49 month changes in brain circuitry some of
32:52 them lasting up to a week others were
32:53 persisting at one month depending on the
32:55 region and then they found many many
32:57 many new connections between brain
32:59 regions some which did not exist
33:00 previously up to a month and possibly
33:02 longer so the effects were observed well
33:04 after the Pyon had been eliminated from
33:07 the body and Beyond what you would
33:08 expect just from activating The
33:10 receptors
33:11 alone so how does this all translate
33:15 into headache medicine like why am I
33:17 even talking about this as a headache
33:18 neurologist well here please enter
33:21 Emanuel Schindler you know she is a star
33:23 researcher in the field of psychedelics
33:26 for for both migraine and cluster
33:27 headache and she wanted to answer this
33:30 question for
33:31 migrer and uh you know so we start off
33:34 like I mentioned with very lowd dose
33:36 proof of concept studies to demonstrate
33:38 safety and tolerability and then we move
33:39 from there so in terms of this initial
33:42 study we took patients between the ages
33:44 of 21 and 65 21 being you know age of
33:47 majority for for substances and things
33:49 in the states and they had to have a
33:51 confirmed diagnosis of migraine episodic
33:53 or chronic but at least two attacks per
33:56 week
33:57 and we did not include people who had a
33:59 lot of significant medical diseases
34:01 which kind of made it difficult to give
34:03 the salocin safely any psychotic or
34:05 manic diseases with because of their
34:07 altered neurochemistry uh with the 5ht
34:09 2A receptor as well as people who had
34:12 active substance misuse or bad reactions
34:15 to uh psychedelics previously they also
34:17 couldn’t be like I mentioned the
34:19 important thing is you cannot Mi silos
34:20 ibin with serotonergic medications uh so
34:23 they these people were also excluded
34:25 they’re given a very low dose of silos
34:27 cbin and this was a double blinded study
34:30 so the patients the subjects and the
34:33 Physicians both did not know what they
34:35 were going to receive at the
34:37 time we were had a baseline collection
34:39 of two weeks where we saw how many
34:41 headaches they’re having on average and
34:43 then if they did not qualify for the two
34:45 per week they were you know dismissed
34:47 and then they were given a placebo first
34:50 so everybody who enrolled in the study
34:51 was given the placebo followed them for
34:54 two weeks with Diaries then at that
34:55 point everyone is is given silos cybin
34:58 and so this is a kind of a unique trial
35:00 design and it’s because each subject
35:02 acted as their own control Placebo was
35:05 given first just because we don’t want
35:07 the potential long-term effects of Salos
35:09 cybin I just told you it last a month or
35:11 more um so we don’t want that to
35:13 confound the placebo period because then
35:15 it wouldn’t really be a fair comparison
35:17 if we had two groups crossing
35:19 over um so then they were followed up
35:22 even longitudinally up to four months to
35:24 see how they were
35:25 doing the subjects completed the two
35:28 experimental sessions separated by at
35:30 least 14 days and and we’ve already kind
35:32 of covered how they they crossed over so
35:35 the main thing that we were looking for
35:37 here in terms of outcome measure was the
35:38 migraine day frequency and uh luckily we
35:42 did see both clinically and
35:44 statistically significant reductions in
35:46 headache days but again these are people
35:48 who had kind of lowf frequency uh
35:51 episodic headaches you know perhaps like
35:53 8 to 10 or 12 and um you know but still
35:57 think it’s extremely promising even in a
35:59 shortterm study like this one so you
36:01 know I’m really curious to see how the
36:02 data are going to look in studies that
36:04 have higher doses or are following
36:05 patients for longer we also saw
36:08 reductions in the time to the next
36:10 migraine attack it didn’t reach
36:13 statistical significance for the first
36:14 migraine but perhaps for the second one
36:16 and even extended later we’re hopefully
36:19 seeing greater periods of latency in
36:21 between attacks um so these are all very
36:24 promising uh outcomes but again top
36:26 right corner look only 10 people are
36:28 enrolled in this trial so I mean you
36:31 kind of have to take it with a grain of
36:32 salt and even when things don’t reach
36:34 statistical significance sometimes
36:36 that’s a function of having a tiny study
36:38 not that you’re not observing a real
36:43 effect oh here we
36:46 go so side effect wise what did we see
36:50 um you know nothing that reached
36:52 statistical significance but you know
36:53 like I said take that with a grain of
36:54 salt uh main things to look for
36:56 lightheadedness nausea anxiety maybe a
36:59 little bit of paresthesia or dry mouth
37:02 um but in general like it’s extremely
37:04 well tolerated and even some of these
37:06 things we see in the placebo group as
37:08 well so it’s really hard to
37:10 say so let’s summarize this up in the H
37:13 High coup format I would say the single
37:16 dose lowd do silos cybin was studied in
37:18 people with migraine episodic or chronic
37:21 over a short period And We compare that
37:22 to Placebo there was clinically and
37:25 statistically significant reduction and
37:27 headache days in the silos cybin group
37:28 compared to Placebo and promising
37:30 effects in terms of delaying the time to
37:32 your next attack the administration was
37:35 safe and well tolerated and the most
37:37 common side effects we saw were
37:38 lightheadedness nausea and
37:40 anxiety limitations like I mention it’s
37:43 a low dose perhaps more is better
37:44 perhaps not uh small sample size n of 10
37:49 difficulty blinding silos cybin due to
37:50 potential psychotropic effects you know
37:52 many people say well hey this is the sub
37:54 hallucinogenic dose but there have been
37:57 other studies that show even at those
37:58 tiny doses like people feel altered they
38:01 can’t quite put it to words um but
38:03 they’re aware something is different um
38:06 you know maybe that’s kind of similar
38:07 like it’s a positive version of brain
38:09 fog or something you know something is
38:10 off but I don’t know what it is and it
38:11 doesn’t show up on test um so I think
38:14 there’s some difficulty blinding syusy
38:16 and
38:17 truly um the included subjects we kind
38:19 of lump together episodic and chronic
38:21 migraine and we go into a whole other
38:23 debate about the arbitrary division of
38:24 that um and also the brief duration of
38:27 the study so I think the results of the
38:29 study are very promising it’s a good
38:30 proof of concept it’s a good first step
38:32 but it looked at a very small number of
38:34 people over the short term so it’s kind
38:35 of hard for me to draw from conclusions
38:37 from this but I think like I mentioned
38:39 it’s an important pilot study we need
38:42 larger longer trials we need to look at
38:44 different dosing regimens in order to
38:46 best determine how can we recommend this
38:47 to patients in a safe way uh in order to
38:50 treat
38:50 migraine okay on to cluster headache so
38:54 uh hopefully there’s one or two of you
38:56 in the crowd who who have cluster you
38:59 know what it’s like but for the others
39:01 uh you know I would say this is one of
39:03 the most debilitating headaches and of
39:05 course migraine is debilitating but they
39:07 call this a suicide headache for a
39:08 reason um it is one of the worst pains
39:11 uh known possibly and our treatments to
39:14 date some of them are very effective uh
39:16 some patients are very happy but there
39:18 are many that unfortunately despite all
39:20 our charms you know we don’t have enough
39:22 magic to help them um so enter
39:25 clusterbusters dorg
39:27 this website I think is an excellent
39:28 resource for anybody living with cluster
39:30 headache and I direct all my patients
39:31 there and it was founded by he calls
39:34 himself a cluster head uh who he really
39:36 wanted to spread the word that you know
39:38 hey I started LSD and it fixed my
39:40 cluster headaches and you know so he
39:42 started trying to connect people with
39:44 cluster to hear about their experiences
39:46 and things like that and um you know I
39:48 think it’s a great place to discuss
39:50 alternative therapies and and hear other
39:52 people’s experiences but again I cannot
39:54 stress enough you need to always review
39:57 any of these decisions with your your
39:59 Physicians because you know like Wendy
40:01 mentioned your medical situation may not
40:04 be compatible with what they’re
40:06 recommending so they decided after a
40:09 while when they had enough people hey
40:11 let’s do a survey and really try to get
40:12 to the bottom of this if we have you
40:14 know we’re starting to build some basic
40:16 levels of evidence and then maybe we can
40:17 use this as a rationale to get some
40:19 doctors to do some trials and they were
40:21 able to get almost 500 people um
40:24 subjects were recruited from cluster
40:25 headache webs different headache clinics
40:27 put up some posters and it had 41
40:29 questions that looked at things like
40:31 basic patient demographics
40:33 characteristics about their headache uh
40:35 you know recreational smoking and
40:36 drinking medications are taking and
40:39 patients were able to subjectively
40:41 attribute like a for grade scale of how
40:43 effective they thought their treatments
40:44 for cluster were so about 650 people
40:48 responded only 560 really completed the
40:52 survey and of that almost 500 actually
40:54 had a verified diagnosis by neurologist
40:56 or headache specialist and this is
40:58 important because we don’t want to lump
40:59 other people you know many people say I
41:01 have cluster headache or cluster
41:02 migraine what they mean is that they’re
41:04 having migraines that occurring clumps
41:06 um but you know a true cluster headache
41:08 is something very
41:09 different so these are the aborative
41:12 medications that we commonly use to stop
41:14 a cluster attack and it shows their
41:16 relative efficacies here so patients
41:18 were asked to rate them whether they
41:20 were completely effective moderately
41:22 effective partially effective or not
41:23 effective and I would say the
41:25 subcutaneous trip
41:26 you know Summa tripon by far is you know
41:29 the number one winner here um but we
41:31 also commonly recommend high flow oxygen
41:33 which people often even get in the
41:34 emergency department or have tanks at
41:36 home and if you look at silos ibin uh
41:38 you know it was pretty comparable even
41:40 to high flow oxygen which is the main
41:41 State um DHE which is also commonly
41:44 recommended uh also ranked high in here
41:47 um when we look at preventive
41:50 medications we often will’ll start
41:51 people on a prenome taper or give a
41:53 steroid nerve block um and then other
41:56 things we use uh you know like Verapamil
42:00 uh a calcium channel blocker comes with
42:01 you know not insignificant side effects
42:03 sometimes you need cardiac monitoring
42:04 there can be swelling or arhythmia um
42:07 and so when we look at syoc cybin it
42:10 seems quite promising as a preventive um
42:13 but so too do some of the other
42:15 hallucinogens uh in particular I
42:17 highlighted in red here that bo uh you
42:20 know that coner that is
42:21 nonhallucinogenic people are using it
42:23 and it uh it does seem to be quite
42:26 effective for this um but again it
42:28 really has to be stressed that this is a
42:30 molecule under investigation really uh
42:32 you know we do not know the long-term
42:33 effects of this so it cannot be
42:35 recommended so nonhallucinogenic LSD con
42:39 bow on par with syoy and LSD and LSA in
42:41 preventive efficacy maybe um and again I
42:45 I think this is under study for now so
42:48 side effects what did people report
42:50 unfortunately there’s a response bias
42:52 you know like a lot of people who are
42:53 here to participate want to share good
42:56 results um because they’re trying to
42:58 advocate for this medicine and so there
43:00 wasn’t a lot of mention of negative
43:02 effects for these but that could also be
43:03 because they’re generally well tolerated
43:06 um you know and again that’s why we need
43:07 formal study so there were some
43:09 headaches caused in one individual some
43:11 people feel kind of sick or woozy and
43:13 other people got like irritable uh
43:16 abdominal discomfort but you know they
43:17 also had a history of IBS so it’s really
43:19 kind of hard to say um in general syy
43:22 has low toxicity relatively low harm
43:24 potential and true reports of lethal
43:27 drug use are rare but again it’s that
43:29 combination with other medicines that
43:31 can prove fatal
43:32 sometimes so what did we learn from this
43:35 survey in terms of those medications for
43:37 cluster they’re probably comparable or
43:39 more efficacious to most conventional
43:41 medications may be useful in aborting
43:44 attacks inducing remission and
43:45 prolonging remission so one medicine can
43:48 be acute and preventive um you know so
43:51 like we we talk about how magical that
43:53 is for the gpants for migraine uh but
43:55 this was already kind of a concept
43:56 emerging here and uh no other single
43:59 drug class has been reported to have all
44:01 these clinical benefits like this um
44:03 especially for cluster and uh I would
44:05 say what was interesting was that even
44:07 infrequent doses people are just pulsing
44:09 it with a large dose once in a while um
44:12 and nonhallucinogenic doses at tiny
44:14 amounts were reported to be
44:16 efficacious so you know the people said
44:19 well hey I don’t have to take it very
44:20 often every few weeks or sometimes even
44:22 twice yearly in some individuals um they
44:25 felt that it had fewer side effects
44:26 compared to what we usually recommend
44:28 and um several participants said that
44:31 even a single dose was enough uh to
44:33 shorten a period or induc remission um
44:36 and so I think you know when you take
44:39 all that together and then it also has
44:41 potential benefit for treating
44:42 alcoholism anxiety or OCD things that
44:44 are often comorbid with these pain
44:45 conditions um you know I think you know
44:47 it’s a very interesting therapeutic
44:50 potential limitations to this one of
44:52 course it’s an online survey so you know
44:54 people are going to self- select there a
44:56 survey bi us um and certain populations
44:58 are more likely to use mushrooms than
45:00 others uh or perhaps they are the ones
45:02 who are medication refractory um recall
45:05 bias you know sometimes people are more
45:07 likely to recall positive events and
45:09 Report those than the negative ones and
45:11 you know lack of diagnostic validity
45:14 they kind of clumped all the different
45:15 types of cluster headache into one thing
45:18 um even though they were said to be
45:19 verified by a neurologist but really
45:22 there’s often confusion in the whole
45:24 family the spectrum of the cluster
45:25 headaches the trigeminal autonomic
45:27 calist like cluster uh sunna or sun uh
45:31 or hemicrania continua you know all
45:34 these kind of things may sometimes be a
45:35 little bit confusing even though they
45:37 shouldn’t there’s overlap um and so you
45:39 know we really want to be precise when
45:41 we do these trials so we can give you
45:42 the best
45:43 evidence the other problem is it’s quite
45:45 subjective like I mean four tiers of
45:48 efficacy is is quite subjective what is
45:50 efficacious to someone may not be to
45:52 another I have patients that tell me
45:53 that medicine didn’t work at all I said
45:55 said okay well how many days do you have
45:57 of headache and they went down from 30
45:58 to 15 days of headache and they say that
46:01 that medicine is horrible um so you know
46:03 I think people have different
46:04 expectations and goals and that can be
46:06 challenging in a survey you can’t you
46:09 know really guarantee Purity in a survey
46:11 like this so you know people are getting
46:12 their mushrooms from all different
46:13 places some are contaminated some are
46:15 already cut with other things um so it’s
46:17 hard to say and many of the survey
46:20 responders were taking multiple things
46:21 at once so you know all of this was a
46:23 very promising survey and I think it
46:25 helped lay the pathwork to get into uh
46:27 you know Dr Schindler’s next trials uh
46:30 but also you know it had its own
46:32 limitations so building on that now it’s
46:35 time to do the hard work and and really
46:37 get into doing some control trials so
46:40 she wanted to do an exploratory study uh
46:43 you know to demonstrate again proof of
46:45 concept and safety of this medication in
46:47 in cluster headache patients and how did
46:50 she do it well again like the migraine
46:52 study she’s taken 21 to 65 year olds
46:54 they had to have a confirmed diagnosis
46:55 nois of cluster headache and uh you know
46:59 we included both episodic and chronic
47:01 cluster headache with Cycles uh more
47:03 than a six week duration for the
47:04 episodic folks and again we excluded the
47:07 similar people to the migraine study now
47:10 cluster headache is notoriously
47:12 difficult uh to perform clinical trials
47:14 for because number one it’s super rare
47:17 so it’s hard to actually find patients
47:18 then when you find them it’s hard to
47:19 find patients that actually want to take
47:21 part in an experiment and then number
47:24 two uh like the nature of episodic
47:26 cluster is that bam it’s gone as quick
47:29 as it came and so you’re like well did
47:31 that medication suppress it or uh did it
47:34 really actually do the trick and turn it
47:36 off and the only way you can answer that
47:38 is with large trial groups so that you
47:41 can truly prove statistically that
47:42 there’s a signal so that’s going to be a
47:44 bit of a challenge so what did they do
47:47 again they did that lowd dose cluster
47:50 syoy regimen 0.143 milligram per
47:52 kilogram but they dosed it three times
47:55 pulse and uh separated by five days or
47:58 so between and again this was double
48:01 blind Placebo controlled but different
48:03 from the other arm it’s not that they’re
48:04 receiving Placebo at some parts uh some
48:06 people were just in the placebo arm and
48:08 some people were in uh syoc cybin
48:10 arm
48:12 so what they were looking for was the
48:15 frequency of the attacks the duration of
48:17 the attacks and the pain intensity there
48:20 were only 14 patients included in the
48:22 study six Placebo eight Sal oyon and so
48:25 unfortunately it’s a little bit small
48:26 that we can’t always draw statistical
48:28 conclusions there did seem to be
48:30 reductions in the silos cying group
48:32 across these these things um however um
48:36 we didn’t reach statistical significance
48:38 but I think it’s still a worthy signal
48:40 that you know we should be looking a
48:42 little bit
48:43 deeper she broke down the two groups
48:45 into episodic participants and chronic
48:47 participants again is not powered to
48:49 really look at the subgroup analysis but
48:51 what she found was that some people
48:53 respond and some people don’t even
48:55 Within These categories um so you know
48:57 again that goes back to the idea of like
48:59 when we make a clinical diagnosis there
49:01 may be multiple underlying causes and
49:03 some respond to one medicine and some
49:05 respond to other so the holy grail for
49:07 this is to find some kind of blood test
49:09 some kind of Imaging where I can tell
49:11 you if you’re going to be the person who
49:12 responds to this um so again another
49:15 area for research what side effects did
49:17 we have from this um again it’s very
49:20 similar to the other study
49:21 lightheadedness dizzy nausea anxiety um
49:24 you know a little bit of fa and things
49:26 like that here but in general very well
49:28 tolerated so summarizing this study in a
49:31 couple sentences we have a pulse dose
49:34 here in this study three times separated
49:36 by five days low dose studied in people
49:38 with cluster over a short period and
49:40 compared to Placebo we saw reductions in
49:43 the frequency of attacks the severity of
49:45 attacks and duration but it didn’t quite
49:47 reach statistical significance still a
49:49 promising signal and the treatment
49:52 effect between episodic and chronic was
49:54 thought to be different but even Within
49:56 These categories some people responded
49:58 While others did not um the drug was
50:00 safe and well tolerated and again like I
50:03 said larger longer trials examining
50:06 different regimens uh for a longer time
50:08 are going to be needed to really best
50:11 outline the best treatment algorithm and
50:13 how to minimize the side effects
50:15 limitations low dose small sample size
50:19 in any pain trial you’re going to see
50:20 very large Placebo responses so we have
50:22 to make sure they’re properly powered
50:24 and like I mentioned it’s difficult to
50:26 Blind
50:27 psybin um and we kind of lumped again
50:29 that diagnostic validity lumping
50:31 episodic and chronic cluster together
50:33 um when we’re looking to the Future now
50:36 and thinking about well how do we design
50:38 the next steps I mean they’re already
50:39 underway I I think uh Dr Schindler has a
50:43 number of irons in the fire and and
50:45 other people are starting to get
50:46 interested in this and there’s other
50:48 studies in other
50:49 areas one major Pitfall especially in
50:52 the migraine space is our patient
50:53 populations in these trials you know our
50:56 current studies really aren’t very
50:58 diverse like we don’t need more studies
51:00 only looking at you know 35 to 55 year
51:03 old white ladies from Wisconsin um it’s
51:05 great to include them but we need people
51:07 from different races we need men and
51:09 women represented we need different ages
51:11 um and if it’s going to be able to
51:14 generalize this advice to people in my
51:15 clinic I need to see my patients
51:17 included in it um the stigma of silos
51:20 cybin you know I think society’s getting
51:23 better with this you know after you know
51:25 when
51:26 kind of approval with cannabis people
51:28 are much more open to re exploring what
51:30 it means to use these medicines um and
51:33 rediscovering ways that it can be done
51:34 safely uh but it’s still considered a
51:36 drug of abuse among many patients and
51:39 professionals um and so it carries that
51:42 stigma there may be a risk to patients
51:44 who are using larger doses so especially
51:46 in psychiatric settings or people who
51:48 are taking large doses to do different
51:50 types of therapy um you know and I think
51:52 in those settings it’s reasonable to
51:54 have chaperons multiple providers and
51:56 psychologists who are present but in
51:58 tiny doses in headache I think this
52:00 would represent like making that
52:01 mandatory would be an unfortunate
52:03 barrier to trials in an area where we
52:05 already lack a lot of funding to do this
52:07 important work um the other thing is
52:10 that as we start to study this and we
52:12 start sharing our initial preliminary
52:14 and positive results you know as word
52:17 spreads in the community more people
52:18 will begin to self- Medicaid and you
52:21 know that that worries me in a sense
52:23 because although it may be generally
52:25 cons Ed well tolerated there’s potential
52:27 for serious side effects we don’t know
52:29 the long-term effects of chronic micro
52:31 doing for instance or uh you know
52:33 combinations with serotonin agents the
52:35 combination is not well known among the
52:36 public so there needs to be more public
52:38 service announcements uh you know and
52:40 and patient education and that’s what
52:42 our our goal partially here tonight was
52:44 to share some of the pitfalls with you
52:46 the other problem is that there’s a
52:48 shortage of trained therapists so
52:50 specifically in the area of uh
52:52 Psychiatry and psychology uh you know we
52:54 don’t have a lot of train therapist
52:55 there and even in neurology and and the
52:57 other Specialties who are examining
52:59 silos cybin there aren’t many
53:00 professionals who are aware of this or
53:03 who are interested in kind of using this
53:05 as a potential agent and so I think that
53:07 will present a barrier to care for some
53:09 people and of course this will be more
53:11 prominent in academic centers where
53:13 you’ll have access and people of lower
53:15 sces or who live in Geographic areas
53:17 without uh they’re going to be the last
53:19 to to enjoy the fruits of This
53:22 research like I mentioned can silos and
53:24 trial properly blinded I think we’ll
53:26 have to look at other ways of of making
53:28 sure that our placebos are truly
53:30 blinding and the last point I want to
53:33 make here is that you know while these
53:34 small sample siiz pilot studies they are
53:36 very promising but the caution has to be
53:39 exercised uh because of the large
53:41 placeable response that we see in in
53:43 pain and mental health research you know
53:45 and so even some of the studies that
53:47 compared uh siloc cybin to
53:48 anti-depressants and things like this um
53:51 you know the effect size uh you know
53:53 it’s hard to say like it may be very
53:55 comparable to placeo in some instances
53:57 and this is why we need properly defined
54:00 trials so summing it up for you all
54:04 syosin is the Psychedelic compound most
54:06 commonly found in magic mushrooms we
54:08 have anecdotal evidence and early proof
54:10 of concept studies and they’re showing a
54:12 potential role for this in headache
54:13 disorders like cluster and migraine as
54:15 well as other
54:17 conditions the current treatments that
54:19 we have you know they help some people
54:21 very well but they don’t help everybody
54:23 and they may result in side effects or
54:25 or may not be helping others uh
54:28 psychedelics in general are thought to
54:29 have a favorable safety profile is not
54:31 completely benign um but when you
54:33 compare to things like opioids there’s a
54:35 certain uh benefit to to going down this
54:38 path we also think that they are not
54:40 likely to have the same addictive
54:42 potential of opioids now that’s not to
54:44 say they may not be habit forming or
54:46 cause other behavioral changes but you
54:48 know we don’t think you have the classic
54:50 kind of withdrawal that you might see
54:51 with
54:52 opioids like I said I’m going to harp it
54:54 again and again we need large
54:56 well-designed randomized control trials
54:57 we got to prove the efficacy find the
54:59 optimal dosing and we need longitudinal
55:02 observations so that we can really
55:03 identify the risks and try to get ahead
55:05 of
55:06 it so one last time over the disclaimer
55:09 I think it’s good just to remind you not
55:11 an endorsement for personal use this
55:13 talk is merely my opinions on the
55:15 research that is coming up to date and I
55:17 I want to kind of put it all together in
55:18 one place so that uh you know headache
55:20 sufferers would have a platform to try
55:22 to do some more personal research Sil
55:25 ibin is illegal in many places in Canada
55:27 and you know use or possession can
55:29 result in a criminal
55:30 offense these are interesting mules with
55:33 a lot of promising therapeutic potential
55:36 but they’re still under investigation
55:37 and we haven’t quite proven their
55:39 efficacy it’s not yet approved by Health
55:41 Canada and it’s a potent chemical like I
55:44 said just because something is natural
55:46 doesn’t mean it’s safe you know snake
55:48 venom is natural you know it can do
55:50 terrible things everything in the right
55:51 amount it needs to be properly studied
55:53 and if you mix it with theurgic
55:55 medications anti-depressants antis
55:57 psychotics antiemetics just to name a
55:59 few you can result in very serious side
56:01 effects so it’s important to talk to
56:03 your
56:04 doctor and with that I want to thank you
56:06 for your time and we’ve got a healthy
56:08 chunk of time for
56:12 [Music]