Good evening and welcome to the Marian Miner Cook Athenaeum. My name is Sophia and I'm one of your Ath Fellows this
yea. I'm sure a great deal of those in this room have known someone who has
suffered from some form of addiction or have seen first-hand the harm it can
cause. Whether it be to alcohol drugs or even food. Addiction is extremely
prevalent in our current society and affects the lives of many. It's easy to
forget that addiction is indeed a diagnosable scientifically recognized
illness and that there are abnormalities in the brain and body that can cause it.
Scientists all around the world are working to uncover and address these
abnormalities so that we can begin to find significant cures and improve the
lives of all those suffering. Dr. Judy Grisel is one of these researchers
uncovering the truth about addiction and working to bring us as much information
as possible with regards to science behind it all. She's an internationally
recognized behavioural neuroscientist and a professor of psychology and
neuroscience at Bucknell University with an expertise in pharmacology and
neuroscience and genetics. Her research motivated by her lived
experiences focuses on determining root causes of drug addiction and has been
instrumental in bringing to light key science behind the issue. She is the
author of the New York Times best-selling book an NB book of the
month "Never Enough the Neuroscience and Experience of Addiction," which
illustrates the neural changes that underlie the development of substance
use disorders and make recovery so challenging. She is recognized as a
distinguished mentor by the Howard Hughes Medical Institute and has been
the recipient of numerous grants from the National Institute of Health. As
always, I now must remind you that audio and visual recording is strictly
prohibited. Please take this time to silence and put away your mobile devices
adjust your seats, serve up a piece of cake if you haven't already, and now
please join me in welcoming Dr. Judy Grisel to the Ath. Thank you,
thank you, I'm really happy to be here to speak with you and to have a lovely
dinner and beautiful setting so and I've enjoyed my conversations and so I thank
you for having me. I'm going to talk about I've been researching addiction I
think for 40 years or over 40 years. The first 10 or so were on the street and
the last 30 mostly in a neuroscience lab when I thought I would solve my problem.
I was, so here I was about seven or eight and a nice young girl and here I was
pretty loaded at 13 or 14. I took my first drink of alcohol when I was 13 it
just seemed like a something fun to try. I drank a half a gallon of wine at least
and it really changed the trajectory of my whole life I spent the next ten years
taking as much of every drug as I could find and as a result of that I was
kicked out of three schools I ended up homeless, I contracted hepatitis C, I lost
the respect of everybody I knew, including myself. So I ended up in
treatment fortunately, which I thought was gonna be like a spa but it wasn't
like a spa it was like a hospital and I was it was there that I learned that I
was going to probably die if I kept using and I wasn't so sure I wanted to
live and seem like a really bitter choice between living sober the rest of
my life I had just turned 23 and or dying you know when some kind of a big
mess pretty soon so I, I figured well maybe there's a backdoor. This is one of
the many attributes I think that addicts have that are useful in some situations
and maybe not in others–but I knew there must be a backdoor somewhere. So I
thought to myself, you know I don't know what this is, I have a disease and I can
see that my life isn't going so well so maybe I'll cure my disease.
I'll find the switch in my brain I how intuited that it was definitely
something wrong with my brain and I'll find that switch, I'll turn it and then
I'll be able to use without self-destructing. So against all odds
also using perseverance that served my addiction it also served my academic
aspirations. I finished my undergrad it took seven
years. I finished graduate school and another seven and then I did a three
year postdoc too and that was in genetics to try to understand what's
different about the brains of people like me from people who don't act like
that. And I'm gonna summarize that here oh so I'm not really that I was gonna
say I'm not really that different.. I wanted to, I forgot what I was doing here,
I am, I grew up in an upper-middle-class family–nice my father
flew air Pan Am airplanes out of the you know Kennedy Airport, my mother was a
nurse, it was a nice neighborhood. So I think, I, in some ways I'm not
typical but I know now that addiction cuts across all demographics so all
ethnicities all economic statuses satisfy any way and all regions of the
world even so it's a huge problem for many people and in some ways I'm really
typical. So here's here's why me this is the bottom line I guess. There's genetic
factors and environmental factors and then developmental factors and some of
those genetic factors I certainly had so people who are really high in novelty
seeking this also serves being a scientist by the way are people who were
prone to try new things and also risk-taking. These are both largely
heritable so these tendencies they're present in third and fourth graders that
have an increased risk reward sensitive, that means that I was–and people like me–are very interested in feeling good sort of more interested than
probably healthy and not so worried about feeling bad. So I used to say I was
grounded about half my teenage years, but when I wasn't grounded I really made up
for it. But my culture, you know, was I guess like much of human culture around
the world we my family had alcohol around. We had people try and get
weddings and funerals and everything in between, so I had lots of access and my
peers were probably typical peers. I grew up in New Jersey so I don't think it's
any worse, but in California, but maybe about the same. Stress is a big
environmental factor too and I'll come back to that later. I had a good
childhood I think so this wasn't a big factor for me, but these these
developmental perturbations, so either an abuse or neglect or some kind of trauma
early on is very predictive. So people are self-medicating things like that but
I think for me probably the single biggest factor was this adolescent
exposure. Turns out that about 80 or 90% of people who develop a drug use
disorder begin before they're 18 and I'll talk a little bit about why that is
and that was certainly my case, but before I do I wanted to say that using
drugs to change the way we feel or think or behave is totally normal.
It's not only normal it's universal. So before humans were humans they were
whatever they were. They were taking compounds to change their feelings and
every human culture that could grow anything so I guess with the exception
of the Inuit you know way of an Arctic Circle has been taking something. It's
not only humans, but all kinds of other animals cats have catnip and
birds go after fermented berries. There's stories of elephants breaking down
distilleries. My favorite story probably comes from a species of ant in South
America in there big ant mound they have a little section that they devote to
raising some beetles and so they can't if they're taking care of these beetles
they have to feed them they have to clean up after them they can't have
quite as many ant babies so it's it there's some cost to this colony this
species of ants but I guess the beetles grow some interesting fungus on the back
of their little hairy beetle legs and that every once in a while the ants
together go and harvest this fungus and then they eat it and they get really
really slow for like two days and then they go back to their own ant stuff so
it's just it's just a normal drive. This is, you know, I just described insects and
birds and mammals and all humans and part of the reason for that has to do
with this dopamine reward pathway you may have heard of. It's really often
called the mesolimbic dopamine pathway it's a small set of neurons not very
many cells actually so here's the spinal cord and the medulla and the pons and
then right at the top–not many cells that contain that make synthesized
dopamine and these cells project up into the limbic systems. That's why it's
called the mesolimbic, because the meso is the midbrain. They project to
the limbic system and when dopamine is squirted out from those cells it feels
really good and it's not good like you're not depressed good or even
content it's good like exciting good. Like kind of titillating good like
sexual foreplay or maybe the red velvet cake. You know something really delicious,
good music, good fun, and that pathway evolved through natural selection and it
promotes eating and reproduction so we all have that. Insects and birds have
their version of it because if we don't have sex and eat then it's
not good for the species so we'd like those things every single drug that's
addictive and behavior by the way that's addictive coops that pathway
the reason it's problematic is because it activates that same pathway and drugs
because we can kind of control the dose and delivery we can stop at the store
and buy as many bottles as we want or you know as many grams as we want and we
can deliver it intravenously if we want these are really more potent than
natural reinforcers so they're out there accessibility and their potency to
stimulate that pathway are you know the cause of this epidemic and addiction
that's all over the place one of the points I want to make now and I'll come
back to that's really kind of important but because they're so potent they also
kind of over stimulate it so in the same way that if you listen to music really
loudly over and over again you have to keep turning up the volume because
you're getting deaf if you keep stepping on this mesolimbic pathway with high
potency drugs over and over again it gets insensitive so then you need more
and this is a big driver of addiction this is a big driver of compulsive use
okay so what is addiction well it's funny I mean I've been studying it for
all these years and I I'll just tell you the truth we don't actually know it's
kind of a word some people don't like the word they think we should say we
have a substance use disorder we before substance use disorder it was substance
dependence kind of argue about it but I think whatever you call it it has
probably five attributes and the first one is craving so you have an obsession
you think about the drug a lot as I said after that first good drink of alcohol I
I really you know completely changed all my priorities so it really became a big
kind of compulsion and then there's tolerance that's a tendency to increase
the dose if you get the same effect or if you keeps
taking the same dose you'll get less and less of an effect dependence which is
withdrawal basically so when you're your dependent when you take the drug away
and you don't feel normal you feel less than normal you feel like something's
lacking it has to have costs so it has to be detrimental to the individual
who's using and also to their context and I think so for me I'm really the
only mind-altering substance I use now is caffeine
I love caffeine and I'm completely kind of obsessed with caffeine so I have a
special grinder and a special pot sometimes I go on vacations with those
things you know I have a whole suitcase for my coffee paraphernalia but I I'm
not really addicted because it's not bad for you caffeine is not bad for you if
unless you're pregnant trying to get pregnant it's probably good for you
don't you think so the last criteria is denial of a drug problem I don't know if
you can see at the very bottom so you can decide if I'm a caffeine addict or
just caffeine dependent but this is what makes it so hard for people who are
trying to work with people who have problems because the those of us who are
addicted are the last ones to see it so we're gonna mostly focus on the top
three of these so craving and tolerance dependence that I'm gonna describe why
that happens it's an inevitable consequence of the way the brain works
so but before I do that I'm gonna kind of get a lot in in my forty or
thirty-six minutes now I guess I want to just summarize a whole semesters worth
of psychopharmacology class in one slide I'm gonna give you the three bottom line
things drugs first of all only increase or decrease what's already happening
they don't do anything new they only speed up or slow down what's already
going on they all have side effects there's no such thing as a drug without
a sigh effect that's because like letters in an
alphabet the neurotransmitters and the substrates for these drugs are used over
and over again so if you want to improve your mood and you take something that
affects serotonin you're also going to affect your sleep your arousal your sex
life your eating because serotonin is not just involved in mood and the most
interesting one my favorite is that drug effects are counteracted by an adaptive
brain so whatever you take a drug to do your brain produces the opposite effect
I said I'm dependent on caffeine and what that means is that when I wake up
in the morning I don't wake up in the morning I open my eyes I make my way to
the coffee pot I have one that goes really fast it's a very quick coffee pot
my dog's the cats my husband my daughter nobody talks to me until I got at least
a cup of coffee in because I can't put a sentence together and I don't want to
talk so my brain is adapted so that when I wake up on lethargic okay
so that's my experience with it but this principle of kind of adaptation which
I'm going to focus it's like sort of the core of the book and which I'm going to
talk to you about today is an old idea and since we're at a wonderful liberal
arts college I thought I would mention it this is something that Socrates said
right before he gave his final lesson so he had been in a Cell with chains on he
got out he knew he was going to be he was sentenced to death for you know
corrupting the youth and not endorsing the state gods so he had to drink the
hemlock soon but as they took the chains off his arms of the shackles of his arms
he said he felt great even though I knew he was gonna die and he pointed out that
Wow I feel so great because I just was in pain and if I have pain I'm bound to
have pleasure and if I have pleasure the implication goes you're bound
Payne so this idea was picked up maybe in a more formal way by French
physiologist Claude Bernard who was also an interesting guy he he married his
wife for her dowry and he was kind of he did a few kind of questionable
experiments lots of good ones too but anyway he he wanted he took her dowry so
he could fund his experiments but he was studying our physiology so things like
body temperature and glucose levels sleep we were just talking about and he
recognized that these things these sort of core aspects of our physiology needed
to be maintained pretty tightly so like 98.6 is necessary for us if we get too
hot we're gonna sweat if we get too cold we're going to shiver just to maintain
that 98.6 and he said this you know you and to you is a condition for free and
independent life which i think is brilliant and again he was mostly
talking about body you know systems eighty years later an american
physiologist this one at harvard Walter cannon took Bernards ideas and use the
term homeostasis to describe that hopefully everybody's heard of
homeostasis it's my favorite word in all of language it's so great anyway
he this guy also coined the term fight-or-flight you probably have heard
of that so he was a brilliant scientist and he was actually describing
homeostasis in terms of the fight-or-flight response which is the
sympathetic activation of the sympathetic nervous system and how that
was counteracted by the parasympathetic nervous system so that these two were
kind of imbalance so getting back to drugs they all of those ideas beginning
with Socrates and Barnard and Cannon are were applied by to I don't know if you
can see it at the bottom two researchers at the University of Pennsylvania in the
1970s so this is a long time ago for most of you these guys took those ideas
and applied them to in the States and so I'm gonna have a
few kind of Harry slides describing that but what they noticed was that if you
took a drug and this red bar is supposed to show where the drug is on board
you're feeling state goes from feeling neutral so you're neutral might be
different than mine but we all have a neutral and it's really stable if if
something wonderful happens to you or something terrible happens to you don't
worry because it doesn't really change your your basic state you think you
would be happy but it's only a little blip so here the wonderful thing is a
drug exposure and you get a little rush that's for sure and then it kind of
evens out but you always have a dip just like the sympathetic and parasympathetic
kind of work in concert so if this is alcohol let's say you would maybe feel a
little euphoric and then you'd be relaxed and have fun and then you maybe
be a little hungover or wake up in the middle of the night if it's whatever
drug it is it's the same sort of pattern so this happens to you all the time
maybe it seems like this is too arcane let's say this probably hopefully
doesn't happen to you but let's say you discover a lump somewhere and you're
worried that it may be cancer while you don't know before you can get the
results of a biopsy you're probably anxious and worried and not sleeping
well and fretting but if you find out it's benign then you feel you don't go
right back to life as usual you feel really grateful and happy life is
wonderful it's like a new lease on life so kind of from one extreme to the other
another example is while you're on vacation things are great and wonderful
what happens when you come home from vacation it's like you know what or the
classic example I'm sure you can relate to falling in love so it's so great at
the beginning right it's it's actually if you look at that
an MRI you can fMRI can't tell the difference between falling in love and
cocaine so effects it's so great you don't need sleep you don't need to eat
you don't need anybody else in the world it's just you in this sweetie pie but
then you get used to it and you kind of balance out right it's
not that great he's okay if she's okay so everything goes along like that for a
while until maybe you get dumped or they die or something
and then you're bereft right so you it was exactly the same pattern as the
drugs wasn't it it doesn't go from one extreme back to normal it goes from one
extreme to the other and why is that oh by the way that should remind you a
little bit of Socrates's shackles does it by taking these off then you feel
euphoric it's kind of the same principle as midterms I guess okay so why does the
brain do this I'm gonna tell you this is a this is a fundamental aspect of how
the brain works why does it counteract change by producing the opposite effect
and in the book I was so proud of this I had about three chapters on this I
really got into it and I loved it and my editor who was not a scientist said are
you kidding no one wants to read this stuff so I got it down to you know maybe
10 pages but I'm gonna get it down to one side for you so let's say this is
the brain your brain having its normal brain activity you're thinking about
what I'm saying and how much desserts left on the table or what you have to do
tonight and there's all this electrical chemical activity kind of having all
this kind of movement as you have these thoughts and then let's say something
really important happens you have a great idea or you sit next to someone
you're interested in it's kind of hard to tell that something important happen
whereas if your brain activity is maintained really tightly and something
then important happens you can tell it's really clear kind of like if you were
gonna look at the effect of dropping a stone in a in a lake and if the lake is
very turbulent you're not going to be able to tell anything happened
so the brain maintains its homeostasis so that we can tell if something is
happening it's constantly tamping down you say oh there's that oh there's that
and then you put it right back down it's just the way it is and this is these
pictures are from Solomon and Corbett's paper in 1974 which I really recommend
you read it's it's long but it's crystal clear
it gives lots of examples but let me just tell you because this is how most
neuroscientists who study addiction think about addiction so this in terms
of homeostasis and in terms of Solomon and Corbett's 50 year old model it's
still driving research today so here's the what you experience this is how you
feel you go off of neutral when you get a drug you have a little rush and then
it mellows out while the drug is still on board and then you have this rebound
you remember that the reason for that is because there are two things that are
happening in the brain the first is called the a process they called it the
a process it's a direct result of what the drug does to the brain so it could
be THC binding to cannabinoid receptors it could be nicotine binding to
acetylcholine receptors it could be cocaine blocking dopamine reuptake or
something it's what the drug does to the brain
that's the a process and the B process to maintain homeostasis is what the
brain does to what the drug does to the brain to counteract it so it does the
opposite and we're going to go through at least we're going to go through one
example because that's what I have time for so when you add what the drug does
to the brain and what the brain does to what the drug does to the brain together
you get that that's why the experience is that way now you know that this is
not so bad this is sort of the idea a little hangover well worth it for
instance but if you use a lot regularly what happens is you get tolerant and you
get dependent and you have big craving and you experience something more like
that if anybody's knows a No addict for instance they don't get high
they just don't feel sick by using so it's really a kind of a sad way to be I
think and the reason for this is obvious the brain is a genius in a way it's it's
probably best feature is its ability to adapt and to learn and to change and so
it and it is goal is to maintain homeostasis it comes on earlier it's
bigger and it lasts longer to counteract it so now you're really pretty
homeostatic and also it learns to anticipate the drug just like when I
wake up in the morning I don't wake up because my brain knows this is the first
thing she's gonna do go drink some strong coffee and a lot of it so
therefore I'm gonna decrease you know any any hope of arousal naturally really
so let me give you an example of how it learns to anticipate the paraphernalia
that's associated with the drug it predicts this is classical conditioning
for the psychologists in the room these things predict using they predict that
somebody's going to experience the effects of the drug so the brain knows
that so the be process is elicited it could be the people you use with you
know if you party with these particular people seeing them will induce a be
process it could be the time of day or the time of week or a particular end of
campus I had a nice campus tour today so certain yeah anyway okay maybe just
walking in that area it makes your mouth dry I don't know it could be sports
events or hanging out at the beach for me it was concerts I love live music and
I couldn't go to concerts when I stopped using for a while because all I could
think about was getting high in fact that the first concert I went to taught
me a big lesson was Prince who probably know at a small bar it was great music
and I walked in I don't know why I must have been like a magnet and somebody
walked up to me probably three minutes later and said
hey do you want to get high and all I could do I broke out in a sweat I said
now I don't I don't I don't smoke anymore I don't do that anymore no
thanks thanks but no no the guy was like this okay it's okay
it's alright no problem but I couldn't enjoy the music because I I was craving
it could be feeling states it might be that you know if you're sad or
disappointed or even happy and that's associated with having a drink or having
something else then those feeling states elicit the craving
so whenever could be money this is a big problem for a lot of people especially
stimulant addicts you know they'll they'll swear it off it's terrible you
know they wasted their money and they miss their kids birthday or whatever
they're not going to use and then they get their first paycheck and it isn't
twenty minutes later I mean I don't mean to be light about it but it's pretty
much the rule rather than the exception that they're spending because all these
things predict getting high the brain elicits the beat process and what does
that feel like that feels like with craving right because here's your
neutral state at the top now you're not neutral you're less than neutral you
feel tense and anxious or you're suffering because the brain expects that
the drug is coming so this has all been pretty theoretical and there's their
papers pretty theoretical oh I guess I just wanted to say in fact for those of
you keeping track or thinking about this in real terms
there are really three main causes of relapse in people trying to get clean
one of them is cues that I just showed you which elicits a be process another
is a taste of drug and it doesn't matter what drug it is because all the drugs
activate that same as a limbic dopamine pathway
anytime it's activated it reminds the brain oh this is gonna be fun and then
it makes the B process I I can remember this is ridiculous but I can remember
one or two times thinking I'm not going to smoke anyway till noon
you know what shouldn't be too hard because I would get up at 11:00 or
something but I would then decide oh I'll have a beer for breakfast and then
a suicide you know that was half down I would think well I'd have one bong hit
maybe it's okay so this is really common if you try to quit smoking cigarettes
and you go to a bar and have a drink and you smoked and drank before forget it
you know start again so the third thing is stress and and I don't know about the
B process or not my research is actually a lot focused on stress this is
especially probably relevant for women maybe more than men but anyway so I just
told you that the brain adapts by creating this B process to maintain
homeostasis and recovery means that you have to readapt you have to not use so
that the B process will go away and that happens so it's also takes some time and
some support but I think the longer the person's been using and the more dose
they've been giving themselves the more regular that dosing is so if it's
everyday as opposed to just once a week then the longer it's gonna take to go
back so that's sort of the general picture but I thought we could talk
about weed since it's California and it was probably my favorite drug it wasn't
the one that brought me to the bottom so fast this is in the 1980s and I lived in
South Florida and I it was stimulants cocaine mostly but but I you know and I
always wonder what do people mean when they say your drug of choice because
it's for most people like me it depends what's there but I think I think I did
really like smoking so what what is it with marijuana is it like reefer madness
would say you know does it make you crazy
or is it does it cause an amotivational syndrome I don't know if those terms are
still around but when I was using this would be one of the big things that
people who smoke a lot of pot are not likely to do much with their lives or is
it medicinal that's maybe some promise so what is the deal I think so I'm
trained in psychology and I I sat on the plane on the way here and I thought I
should probably take this slide out but I just love this psychology stuff so
this is a study from 1984 1974 also old old and these guys had no idea what THC
was doing so this is before we knew anything about cannabinoid receptors or
how it worked in the brain which I'll get to in a second and they were doing
studies and pigeons and what they did was they had a pigeon pecking a key to
get food the pigeon was a little hungry so it would peck the key to get food and
on average it was be pecking about between 80 I don't know if you can see
that up there and 120 so around a hundred pecks
to get a little pellet of food so they just peck away they kind of like that
and then the first day so that was their baseline that session zero they were
learning to do that the first day of the experiment they give that pigeon one
point eight milligrams per kilogram so it's a low dose of THC a regular dose is
about five let's say so they give it one point eight and look at totally stops
pecking so it's just sitting in the cage doesn't pick it all not hungry
just I guess thinking about it but on the second day on the second day they
give it the same dose and it pecks half as much as normal you see forty five
times by the sixth day it's back to normal and when it gets back to normal
they double the dose so they go to three point six and you can see it gets to
normal there there's a lot of days skipped here but they just kept doubling
the dose every time the pigeon would act normal again not wiped out they would
double the dose and you can see that by the
and they're taking a hundred and eighty milligrams per kilogram so hundred times
what they were taking before huge and having no effect
so that's tolerance right that's called tolerance so that's what they said that
the pigeons get tolerant so how do they get tolerant what's going on
well so this that was in 1974 this is in 1988 and I remember where it was am I
out of time thank you oh no that's fine I don't mind I'm used to students but I
just don't want to talk too long good I'm nowhere near out of time right
what am I supposed to stop no if somebody stopped me okay I'm not going
to go that long so I remember where I was in the world when this paper came
out people maybe remember where you were when the Twin Towers went down I guess
not the students or when something else momentous happens but this was such a
momentous thing because I loved marijuana and I was in graduate school I
wasn't smoking anymore but I was really curious how does it produce those
effects and this paper came out and another one right after showing how
marijuana produced its effects and they labeled the sites in the brain that
marijuana was working and this is a sagittal section so kind of a slice like
this of a rat brain who was humanely sacrificed after being given radioactive
THC and all the black spots which is basically most of what you see are where
THC was acting and this was a huge surprise I can't tell you how surprised
everybody was because there we've never seen this many spots as many binding
sites for any single compound for instance if you look at the places where
dopamine acts in the brain you don't get one one thousandth of this money this
was just crazy it's everywhere people said it is everywhere and in fact they
named these receptors cannot annoyed receptors and now we know this
is the cannabinoid one receptor there's two of them but this is the important
one cannabinoid receptors are the most prevalent receptor in the brain of this
kind of type they're all over the cortex which is the whole outside of the brain
they're in the hippocampus which is important for learning and memory
they're in the hypothalamus which is important for motivation eating sacks
sleeping they're in the nucleus accumbens where pleasure is found so
basically where they're not is where there's no connections between cells it
seems like cannabinoid receptors are in every single synapse and the synapse is
a gap between two nerve cells enough in the entire brain which was shocking and
so of course it said to a lot of people Wow what the heck is this doing we don't
obviously have these receptors in case you smoke some marijuana plant these
receptors are produced at pretty big cost they must be doing something and
what they were doing was responding to their own signals THC is mimicking an
and amide and to arachidonic lisrel or to AG and these are the endocannabinoids
that the cannabinoid transmitters that we make an and amide is the Sanskrit
word for bliss we need a better name probably for this but these are really
interesting neurotransmitters that I don't want to go into for too long and
the reason that THC works is because it mimics those compounds which are acting
possibly in every single synapse so the marijuana plant has over a hundred
cannabinoids THC is entirely responsible for the recreational benefits of
marijuana so it produces the high that I liked a recent paper came out about
three weeks ago showing no medicinal benefits of THC
it was a huge study it was let's see began I took notes on and then I forgot
it was just so I don't have my notes but it's a
meta-analysis beginning I think in the 1980s of many many studies thousands and
thousands of patients but get all kinds of promising things and the conclusion
in The Lancet psychiatry is that there is no evidence for medical benefit from
THC in fact there are significant risks the two big ones that we know of right
now are psychosis we think that another good paper recently luck came out last
June where we their researchers suggested that about 40% of new cases of
psychosis which is the sort of hallmark symptom of schizophrenia are
attributable to smoking high potency weed on a regular basis and also reduce
cognitive function that means you don't think as well so not at all probably
beneficial cannabidiol is another one though of
that cannabinoids and that is beneficial cannabidiol definitely helps with people
who are children usually who have a kind of untreatable epilepsy and maybe with
other things and III think it should be over-the-counter because well
everything's over-the-counter here I guess but this is is if anything it's a
be process for THC so the more cannabidiol you have the less THC works
so it's not at all recreational it doesn't produce any kind of high it
might be helpful for some things it's definitely helpful for these childhood
seizures so to describe why this works I thought you've been really patient with
all my grass I'll talk about my dog for a second this is Bowden when he was a
puppy he was like probably 12 weeks old here was so cute now he's a hundred and
fifteen pounds or something but he was out walking in the yard one day and my
daughter dropped a piece of bacon in the grass and this is actually DNA that's my
bacon but I couldn't you know this is good to put up there so he's walking
around he the bacon drops and you could almost see his brain he went crazy
because probably this was such a meaningful
stimulus think about it for a puppy he didn't even know bacon existed and he
suddenly gets a whole piece his olfactory bulb you know where it smells
as taste receptors so what likely happened is that in the places of his
brain that are processing bacon they're sending out these signals he's
endocannabinoids signals to kind of strengthen the connections between those
cells Wow something really big happened bacon so cannabinoids modulate all the
brain activity because they act like a highlighter to enhance the connections
to sharpen the connections between cells when something is worth noting and that
plays a big role in neuroplasticity which is how we learn and remember we
sort out what's important from what's not important and these and you never
know what you have to learn what the bacon is gonna be and so that's probably
how they work and so an and amide and to arachidonic us are all in us these
endocannabinoids i don't know what your bacon is but maybe a great poem or a
wonderful class or job interview or something but you're likely to have
these compounds squirt out sort of selectively when something important
happens that you're processing and the reason they're all over the brain is
because you never know what's gonna be important does that make sense but teach
these different isn't it because we don't have little squirts of it here and
there we take it and inhale it and it goes all over the brain and so
everything is bacon right isn't it I mean the the texture of the carpet and
I remember one of the first couple times I got stoned I I came back to a friend's
house and we had we were hungry we made rice a roni and I could not believe how
good that's I couldn't believe it stayed on the shelves it's like why is this
I've never had this it's so delicious like I wouldn't eat that now for
anything but you know if if the music is amazing the skin is amazing that
whatever it is it's all great so this is fun right because it causes pleasure and
relaxation those receptors are in that nucleus accumbens
it makes stimuli more rich and meaningful that I really loved so any
drab day could be interesting couldn't it to me it was an antidote for
boredom acedia but because of that it impairs your memory it slows your
response time so the response time because you're so busy looking at the
texture of the carpet that you you know forget the other stuff and so you have
critical your errors and critical tracking but what's the big deal that's
not so bad considering how fun it is right well
there is a big process and for this drug every drug has a be process for this
drug it's really a simple one the cannabinoid receptors down regulate so
here is an animal and it's I know you can probably see it from the back just
fine so on this column somebody this mouse or rat got it was a rat actually
got it's not my study but got a placebo saline injection here the rat got one
dose a high dose of an analog of THC and you can already see with one dose
there's many less receptors here they got eight days of a low medium or high
dose and you can see especially in the last column
how much fewer receptors there were so this is true in animals and it's true
in humans and it was definitely true in me I by the time I so I changed smoked
marijuana it wasn't so potent as it is now but I I got to the point where I
only really enjoyed anything if I was high I didn't want to do family events I
didn't want to think about school or work or any kind of interests because
nothing was that interesting actually unless I was high so the same thing
happens in humans I don't you might like this picture better I don't like it
because I don't these big yellow blobs are sort of vague to me but take my word
for it the receptors down regulate in humans the longer people smoke the fewer
receptors they have and like me they do come back if you're abstinent I was
clean about four months and I was walking down the street one day in
Minneapolis and I could not believe the color it was October of the lease so
there were red and purple and orange and green and pink I mean it was
unbelievable to me and I hadn't seen I don't remember seeing color for years
before that now I'm gonna just skip I have just one more like few sets of
things to say and then we'll have plenty of time for questions but one of the
points I'm going to just try to make right now and maybe as obvious to you is
that the brain is always plastic plastic means it can change as a result of
experience but sometimes it's more plastic than others it's really plastic
when you're a kid before you're born but then early in development and then it's
really gets this big burst of plasticity in adolescents between puberty and about
age 25 after that it's it's still a little bit plastic but
not so much so what happens in teens who are smoking marijuana is that the
effects I just showed you are much stronger because the structures are
being laid down the the plasticity is you know sort of organizational and
maybe is more likely to have permanent effects so these are areas that's
probably really foggy where all of these areas is where the structure of the
cortex is altered in people teens who smoke pretty regularly and pretty
heavily and the receptors are down regulated so it's probably that this
happens first you down regulate those receptors changing the way the brain
processes information and that then alters the structure of the cortex
it also here's an example so in rats eight injections during adolescence or
in humans about ten years of use beginning around age 15 these are well
documented studies down regulate the pleasure pathway probably forever I
think this probably is the case for me I mean I I feel like I get plenty of
pleasure now because I try to do lots of exciting things but that drives my
husband crazy because he'll say things like okay you've just be satisfied
hanging around the house or you know do you always have to turn everything
upside down and buy a plane ticket to some foreign place and I think partly
I'm less content in a way so and this results in more in both the humans and
the rats when given a chance more likelihood of taking other drugs and
taking them more often and I gave some papers here I'd be glad to send anybody
this slide set but there's lots and lots of studies so well-documented effects
and there are fewer of these receptors and mezu limbic structures and in other
places they're also more impulsive 60 percent less likely to graduate high
school this is heavy smoking teens and more likely to attempt suicide I
think when one of the most common things after I wrote the book and like maybe
anyway somehow something got on Instagram I
don't do Instagram so I can't really say what it was but I got a flood of notes
maybe hundreds from young kids over about a three or four day period saying
you know what you described exactly my experience just like I had I've been
smoking for years and years and now all I do is kind of sit on the couch and
feel lost the to make it even worse very quickly these this b-process
seems to maybe be going across generations so the offspring of
adolescent rats who had eight injections of THC and they had those injections
when they were adolescence and weren't even thinking of having baby rats or
maybe they were thinking but they didn't have any opportunity those rats grow up
without any THC mate have offspring and those offspring are more anxious more
likely to take more alcohol and opiates and more depressed and these offspring
of those rats so the grand babies of the first rats show similar things and this
is epigenetics which I'm sure most of you have heard of I really recommend
this paper which summarizes a lot of the research but it's pretty clear I mean
sometimes I wonder maybe it was the 70s that caused the epidemic of addiction
we're experiencing today because there seems to be long term effects so the
brain compensates for any drug that alters its activity especially when used
during adolescence and what it really does there is it decreases sensitivity
to reward and pleasure I try to say to my students and my kids and I'm sure
they just think I'm old but you know is there is there something I could I tried
to bribe my own child with plane tickets that works for me to
say if you could just put it off until you're 25 or so you could enjoy it more
later and you'd also enjoy other things more later probably and you can have a
plane ticket I don't think it worked though marijuana is a gateway drug
because every drug is a gateway drug because when you stimulate that
mesolimbic pathway over and over again it gets less sensitive then you have to
take more of other drugs and so I think that it's really important to look at
the data and before we just decide you know oh it's probably legal means
innocuous and if you need any convincing that legal does not mean innocuous you
just have to look at alcohol and tobacco okay so I think that widespread use is
likely to have lasting impacts for at least one generation maybe more so
because I'm a teacher I'm gonna end with a quiz opiates that what's the why do
people use those they want to feel euphoric they want to feel relaxed
they're they're dreamy producing so you feel pain and discontent when you're
withdrawing so opiate addicts mostly experience this if they're not high they
don't really get high alcohol I'm sure we have maybe more answers here helps us
relax helps us sleep helps us feel euphoric so you have decreased pleasure
anxiety chronic people who drink a lot are anxious for sure and they can't
sleep it's funny a sedative produces those effects nicotine is is kind of a
complicated drug it makes us focus and relax so then you can't concentrate and
you're anxious when you're trying to quit it's miserable to quit I quit
ecstasy you don't even have to know what it does causes depression for sure and
benzodiazepines like xanax cause insomnia and anxiety
because the brain is trying to maintain homeostasis so the brain adapts every
drug that alters its activity to produce by producing the opposite state and
that's what causes tolerance dependence and craving and that is what
characterizes addiction so that's it I think if you have questions and you
don't get to ask them you can write to me at Bucknell or at this e-mail but I
hope to have some questions so we'll now have some time for
questions so if you have a question please raise your hand and law layer I
will bring the mic to you please do try to keep your questions brief please
stand up when you ask them and as always priority will go to students hi thank you very much for your talk my
question is what the role of like obsessive-compulsive disorder is an
addiction like if they're connected or if you can say that like anyone with
addiction has obsessive-compulsive disorder yeah that's a great question we
don't know exactly some people think that OCD or obsessive compulsive
disorder is the big umbrella disorder and addictions are something under that
umbrella what they share in common is the compulsive part so the obsession has
probably got a different substrate for the OCD obsession it's probably a
different part of the brain and this accumbens
but the compulsive part is always these striatal circuits I don't know if you've
talked to this but these habit habitual circuits and in OCD or relieving anxiety
and in drug addiction it's more like you know a habit that you can't kind of
break so I think they're related but we don't know exactly how we do know that
depression and anxiety which is an you know a broad umbrella under which a CD
goes are genetically correlated with addiction thanks so much for your talk I wanted to
ask you about your thoughts on research looking at like using psilocybin for
treating addiction to other substances and whether you think that's promising
approach yeah I actually do so psychedelics and I would call those LSD
psilocybin mescaline DMT which is an ayahuasca but not MDMA which is ecstasy
so those four psychedelics are not addictive they don't release dopamine
the nucleus accumbens you can't use them habitually the fact that they've been
scheduled one just reflects the fact that our scheduling the FDA is
scheduling and DEA scheduling is completely irrational I do think there
might be some medicinal benefit so there's I read I have a whole chapter on
those in the book and I review some studies but they're pretty compelling so
experiences with psychedelics are therapeutic possibly helping people cope
with things like anxiety trauma aggression I don't think they're you
know something to be taken really lightly but I think that they're a
different category altogether not addictive don't have a be process and
they don't have a be process because they're so incredibly potent they do
have a be processed but it's very short acting and you can't really use them
every day and get any effect at all so three days in a row there's nothing to
it so anyway I talk about it a lot but I think it's really interesting hi thank you so much for your talk I was
wondering your opinions on naloxone mm-hmm
naloxone is great drug it should be very cheap because it's an old drug it's not
I'm some naloxone is for treating overdoses so the way people die from too
much opiates is that they can't get high anymore
and I and I have a whole other set of my talk about describing the be process for
opiates it's just really interesting and I'll just tell you the bottom line your
brain our brains produce anti opiates we produce chemicals that block the opiates
so we don't down regulate the receptors so much but we counteract them directly
and some so people are trying to beat that which they can't really do because
your brain is producing these things really well and then they suffocate
because it decreases respiratory respiration and the lock zone will
reverse that so I think it's great to have around I don't think it's a cure I
don't think it should be I think they charge a thousand dollars something for
a pen which is unbelievable because it was really cheap before they had this
epidemic it's an old drug um now naloxone is also
combined with buprenorphine in suboxone which you may have heard of and this is
a drug that I have strong feelings about so suboxone is drug used in treatment
and what it does is it's kind of a not a very great opioid so it Dupin orphan
isn't opioid and it will produce a high but not quite as potent as something
like heroin and so people you know it staves off withdrawal but it doesn't
give you the same high and then they put in the lock zone in it so that if you
take more and more of it to get more high then the lock sound kicks in in a
counter accent so it's a great crutch short-term crutch I think it's being
used for months and years in people and I think that's horrific because they
don't want it nobody to go through withdrawal it's miserable
to quit this thing you know it's your it's what your life has been about but
staying on a drug like that means that in Pennsylvania where I live most of the
funding for fighting the opioid epidemic is going straight to the drug companies
sorry and not to counseling or you know rehab for vocational staff or any kind
of you know your dentist or anything it's going to suboxone and also I saw
some really recent data suggesting that bonding so one of the things that are
natural opioids do are endorphins is help us bond with our parents and
parents who are on suboxone and children don't bond normally so it's not a free
lunch in a way it should be used I think briefly while people get the
support they need to kind of titrate down but nobody wants to do it that way
yeah that's a good question anything else yeah I was just wondering if you like
investigated like if your if your parents had any mental health issues or
maybe like the affection or just generally how important that is in like
their early years so if you did I hear you right if your
parents have mental health issues how likely are you to have them like nurturing I think there's probably
nothing more important than the first two years actually so but that's a
different so I I did talk about some of the environmental factors that can have
an influence and nurturing plays a big role I think I personally got pretty
decent attention when I was a kid so that wasn't it but you asked a lot of
questions so one of the things is that depression and anxiety disorders in your
parents or a drug addiction predicts any of the other three so it doesn't almost
matter the sort of interchangeable like you know poker chips or something if you
have a parent who's anxious or depressed or alcoholic you're more likely to be
any of those things certainly the not being resilient to stress makes people
want to use more to cope with stress and that's a big factor so stress resilience
is largely set in the first few years of life and then trauma is something that
the field the clinical field is really interested in we recognize now that one
of the best predictors sort of aside of from everything else is any kind of
trauma so sexual abuse or neglect or physical abuse can really increase the
odds so all those things make it uphill but it's it's really good to know like
in the u.s. right now a recent study in JAMA said that one out of eight adults
has is alcoholic and more people are dying of opioids overdoses than anything
else right now so we have an epidemic not only
not only in the US but all over the place it's really you know you can
almost think of the world as a place for a big group of people are trying to
self-medicate as fast as they can and take as much as they can to escape their
suffering and the other people are just suffering and probably those two things
are not unrelated but I think I'm going off too long but I think it's a good
question it's a big hairy problem I think that could be your dissertation
maybe okay I'll go back up here so everybody can see hi
congratulations on your very long term abstinence that's really remarkable I
was wondering what kind of personal strategies you have for I mean you
undoubtedly encounter cues in your environment that trigger intense
cravings what do you do in those moments that you've found to be effective I have
a funny story about one of those moments I was I was trying to figure out was my
last year of undergraduate and I was volunteering in a research lab I suggest
everybody do some scholarship but anyway and we were injecting rats and when you
inject them a rat it's very unlikely but you could get in a blood vessel which is
about as big as your hair so when if the protocol is usually to pick up the rat
who's used to it put the needle in and then pull back and then make sure you
don't have any blood which I never had for many many many injections except
this one day I pulled back and I forgot to say this but so I I guess I did imply
it but I I injected cocaine and methamphetamine for a while so I pull
back this is about three or four years later from any drug I see the blood and
the needle the rats blood which it didn't register as rats blood I heard
the sound of the bells in my ear that I would hear with coke it hit the back of
my tongue I dropped the rat I got all sweaty and I said to my lab partner you
know I think I'm done for the day and I went back and thought about that
but this was years later it's like if you bring Pavlov's dog back to the lab
and you ring the bell even if they haven't seen that bell in a long time no
salivate so that was kind of me but I think what I did is I another big
trigger and it much less dramatic was his disappointment so when I was using I
didn't deal with disappointment or sadness I just got high and so every
time I get disappointed I was like it's almost like a knee-jerk thing you know I
just reached for something and so I had to find ways of dealing with
disappointment that involved mostly getting support from other people so
getting support getting time and then if you in psychology 101 you know about
extinction so the the next the second the third the fifth eighth time each
time the B process gets less and less strong because now I'm disappointed and
it's been I've had a lot of disappointments and I haven't picked up
as you said so now my brain doesn't any longer think that disappointment
predicts she's gonna run to the whatever so I think time and support and that's
one thing that our treatment programs right now are short on you know it seems
like we put them in detox for three days give them a prescription and send them
on their way and I don't I think that's kind of not what they probably need
thank you thanks very much I'm curious looking at
any kind of psychiatric drug so thinking about antidepressants anti-anxiety
things like that do those go through similar a and B processes have developed
tolerance that kind of thing and what then are the consuming yes then what are
the consequences of long-term use yeah great question
so for anxiety drugs drugs to treat anxiety they're mostly benzodiazepines
and they cause anxiety we have to just take them forever and if you take the
drug away you can't sleep and you're anxious and people we have you know that
has been such a moneymaker for so long since benzos were developed you know we
give them we're like candy I think we sell more benzos than M&Ms probably in
the u.s. really popular I'm not sure about that but it's a lot now for
antidepressants actually the beet process is the point so if you take an
antidepressant you don't they don't tell you you'll feel better in 20 minutes
when it hits your synapse you'll feel better in about three weeks that's about
how long it takes the V process to come on and it's they're not all that
effective but for them that is the therapeutic part but III think that any
drug that acts to produce a change by affecting the brain is going to be
counteracted now if you take a drug to block pain but it's it's like aspirin or
Tylenol it's doing it in the periphery you don't counteract it but if you take
a drug like opiates to block pain it's doing it in the brain the brain adapts
so yes for every for every drug hi hi sorry for my phone that was really
embarrassing but um I was wondering for what people call like a natural high
from like long-distance running or other types of this long-term cardio and you
experience like post race euphoria and also like in race euphoria as well I was
wondering if there was a be process to that or also if you completely stop and
you have been doing it for a long time if there's withdrawal symptoms yeah yeah
great question so there was a kind of a lot of questions in there so I take it
you're a runner yeah okay so running releases endorphins and other chemicals
that make you feel good and that's absolutely true and if we if your
roommate wanted to see if you had a B process what he could do is right when
you get ready you know you're putting on your sneakers you're plenty of what a
early Sunday morning long run you've been looking forward to it all week
Sunday morning just stop you right there and just maybe interrupt you with some
chores around the room or you need some help changing a tire or something else
you know then you just get really tense and anxious right yeah it's it does go
that way and also I mean hopefully this won't happen but if you get an injury
they'll have to cope with that too so yeah we we release endorphins during
exercise now one of the things about exercise or other natural forms of
releasing it so taking risks or giving talks to new friends or those kind of
things those release opioids and they're here to help us cope and survive so
that's not you know we're not taking we're not getting the kind of doses that
you would be getting with heroin so the adaptation isn't going to be quite as
strong but you know you adapt I am I can just you know somebody should do the
experiment on you where they just interrupt you on your way out
to begin you know you get a little bit anxious you look like you're withdrawing
yeah you're agreeing with me he is looking like that's gonna happen I think thank you for your talk I wanted
to ask what your interpretation of the role of like social support is
especially in the experience such as experiments such as like rat Park where
they put it high like emphasis on the role of social social support and like
lessening the impacts of addiction and the cravings for addiction and I just
wanted to see if your research and your experience lines up with that view or is
it more complicated than that yeah so you're asking about the rat Park
studies where they found that rats who were raised in really enriched social
environments were not likely to take drugs and would stop taking them and in
fact lots and mice and monkeys don't normally take drugs to make themselves
dependent anyway but if you have them in a single house cage totally isolated
from everybody else you know and there's nothing else to do they will I think in
that way it's a great example but we don't have that kind of a life so it's
not I I think going from the enriched environment of rat compared to a really
poor environment of rat and then trying to put that onto us is maybe not helpful
but the general principles are certainly the same and that is that I I think it's
maybe not only important for treatment to have social support and options one
reason I think I was able to get well is because I had I went to a good treatment
center and I had the ability to sort of go to school not have a ton of debt you
know I was I was helped and I that I could enrich my own life in a way with
other things so I think that's a big part of recovery having something to
look forward to and a lot of that involved people and some of it didn't
but I also think more importantly maybe in the prevention realm recognizing what
you know we've used drugs since the beginning of time but we haven't used
them alone until pretty recently so that's sort of a new phenomenon where we
sit in our apartment with the blind down and use that's all new and I think
that having connections basically are the antidote connections especially to
other people but to ourselves also and to things outside of ourselves that are
bigger than ourselves so yeah I think there's there's no time probably where
enriching our lives with things like adventure or art or beauty or
relationships is not good so and and probably going back to the question
about malach zone it might be that that's a much cheaper and more effective
way to intervene than to come up with some you know CRISPR modification where
we can fix the bad switch as I once wanted to do so unfortunately that's all
the time we have for questions tonight I'm just a heads up that her book will
be for sale right there in the back if you're interested definitely check it
out and now please join me in thanking dr. Judy
