THE CLINICIAN'S
ROUNDTABLE - DOES HEAVY MARIJUANA USE ALTER BRAIN TISSUE
Does heavy marijuana use alter your brain tissue. I am your
host, Dr. Larry Kaskel, joining me today is Dr. Jean Lud Cadet, Chief of the
Molecular Neuropsychiatry Branch of the NIH and NIDA.
DR. LARRY KASKEL:
Dr. Cadet welcome to the show.
DR. JEAN LUD CADET:
Very glad to be here.
DR. LARRY KASKEL:
Can we start just by talking about how common marijuana use
is in the year 2008?
DR. JEAN LUD CADET:
The last papers that were published on the epidemiology
suggest that about 15 million people have used marijuana in the last month. In
2006, about 73% of current illicit drug users used marijuana and about 53% of
those use marijuana alone.
DR. LARRY KASKEL:
So what are the accepted behavioral and physiological
effects of smoking marijuana long term?
DR. JEAN LUD CADET:
Lots of scientists have looked at the acute effects of
marijuana in terms of the cardiovascular system and also in terms of brain
system. For example in controlled studies, marijuana has been shown to cause
tachycardia. It has also been shown to cause orthostatic hypotension with some
people complaining of syncopal changes. Interestingly it increases myocardial
oxygen demand and in some cases in older individuals has been reported to cause
acute myocardial infarction.
DR. LARRY KASKEL:
Those are the negative effects, are their any known positive
effect?
DR. JEAN LUD CADET:
The reason why people use marijuana is because it makes them
feel good, it relaxes people. So those are the positive effects of marijuana,
the psychological well being effects of the drug.
DR. LARRY KASKEL:
Dr. Cadet you did a study that was published in Drug and
Alcohol Dependence on altered brain tissue. Can you tell me a little bit about
that study?
DR. JEAN LUD CADET:
In that study we admitted a number of people to a research
unit that we have in the intramural program of the NIDA Intramural Program. So
in that study we looked at MRI and at the same time we were doing some PET
study. So the MRI, magnetic resonance imaging, we looked at the brain
composition and using computer program and what we found was that the marijuana
users had change in the composition in the brain that were very significant.
DR. LARRY KASKEL:
What part of the brain Dr. Cadet has the most cannabinoid
receptors?
DR. JEAN LUD CADET:
You can finding a lot of cannabinoid receptors in the
frontal cortex in the basal ganglia, that is the stria dome putamen. Lot of
cannabinoid receptors in the hippocampus. There is another very, very
important area that people don’t talk about much, it’s the nucleus accumbens
which is the area that is part of the rewarding system in mammalian brain.
DR. LARRY KASKEL:
What part of the brain stimulates the munchies that people
get when they smoke marijuana?
DR. JEAN LUD CADET:
That’s probably related to the hypothalamus feeding centers
because they have CB1 receptors have been found in the hypothalamic nuclei.
DR. LARRY KASKEL:
If you have just tuned in, you are listening to the
Clinician's Roundtable on ReachMD. I am your host, Dr. Larry Kaskel and my
guest today is Dr. Jean Cadet, Chief of Neuropsychiatry Branch of the NIDA and
NIH and we are talking about how marijuana can actually alter brain tissue.
Dr. Cadet the study you did in neuroimage on PET scanning,
what do you see differently when you look at people that are heavy users versus
normal users or light users or no users.
DR. JEAN LUD CADET:
In this paper that we published in 2005 where we looked at
the neuro substrate or faulty decision making in marijuana users. We looked at
cognitive testing, test called The Iowa Gambling Task and we also looked at
imaging using PET. So in that study what we found was that patients who
chronically use marijuana had abnormalities in learning which were correlated
to abnormalities in the frontal lobe. So….
DR. LARRY KASKEL:
That’s interesting. So you had a physiological effect and
an anatomical effect?
DR. JEAN LUD CADET:
That is correct.
DR. LARRY KASKEL:
And what about in people that were nonusers, was that your
control group?
DR. JEAN LUD CADET:
Our control group was a nonuser group. So if you look at
the nonuser group, they activate their brain one way and when you look at the
marijuana users, they didn’t activate the same brain systems. It is as if the
people who are using marijuana were compensating for abnormalities and some of
those brain systems that are felt to be related to performing this Iowa
Gambling Task.
DR. LARRY KASKEL:
Tell me a little bit more about the Iowa Gambling Task, do
you have them playing blackjack and poker?
DR. JEAN LUD CADET:
It is actually similar to that because what they have to do
is pick from a different deck. If you make decision over a time in 1 what they
call the low-risk deck, you make more money, but if you pick from the high-risk
deck you might make some money on occasions, but you end up losing money in the
long term, yet the marijuana users tend to take cards from the high-risk deck
more often than people who are control group in that study.
DR. LARRY KASKEL:
So it sounds like if you spend time in Las Vegas, you should
not smoke pot or you will even lose more.
DR. JEAN LUD CADET:
That's actually very interesting because what this tells you
is that high-risk gamblers might actually have abnormalities in some brain
regions.
DR. LARRY KASKEL:
That’s a new study, to scan people with gambling problems
and see if they have similar or lack of take up on PET scans.
DR. JEAN LUD CADET:
That’s a very important set of study to do. I think there
is a group, I cannot remember them offhand who are actually doing that study
and the interesting thing about it, if you look at the psychiatric diagnosis in
terms of what's listed on the pathological gambling and drug abusers, marijuana
abusers, cocaine abusers, they have a lot of characteristics that are very,
very similar.
DR. LARRY KASKEL:
Has anyone been able to reproduce the results of your study
or has it not been attempted? You know either the physiological one or the PET
image scanning.
DR. JEAN LUD CADET:
Other people have replicated that the marijuana users make
that decision in terms of using the high-risk deck instead of the low-risk
deck. That’s been replicated. In terms of the physiological studies, we are
not aware of anybody who has done the study similar to the way we have done it,
but other people have reported the abnormalities in the frontal lobe of
marijuana users. People like Linda Chang have done studies using PET and
looking at marijuana users and they find abnormalities in marijuana users.
DR. LARRY KASKEL:
Dr. Cadet are these results permanent of if someone is a
heavy user and they quit, will their brain kind of come back to normal?
DR. JEAN LUD CADET:
It is very difficult to tell based on what we have done.
What we have done is bring a patient in and study them over a period of a
month. So we bring them in on the research unit. They stop using drug after
they arrive, they are not exposed to drug for about a month and we test them at
the end of that month. Our reports basically deal mostly with that time period
of being abstinent from drug for about a month. So the only thing we can
really report about is abstinence of 1 month, you still have the abnormalities,
but if somebody were to be abstinent for 6 months or a year, we are presuming
given the state of the art in brain recovery that a lot of these people would
do much better in terms of learning and memory tasks after 6 months to a year.
Because as you know the literature now suggests that we keep on making new
cells in our brain and there is potential for recovery.
DR. LARRY KASKEL:
When you mentioned the parts of the brain that have the most
cannabinoid receptors, you mentioned the basal ganglia and I immediately
thought of, does this make a patient more likely to develop Parkinson disease
later in life if they kind of destroy that part of the brain. Is there any
connection between those 2?
DR. JEAN LUD CADET:
Not with marijuana users, we are not predicting that people
will develop Parkinson's disease. It more likely in terms of movement
disorders, the 2 drugs one could think about that might do that,
methamphetamines and Ecstasy, but in terms of the cannabinoid receptors, the
way they are located and the chronic administration of this drug, you should
look at dopamine level in the stria dome, there isn't any evidence that
dopamine level which is responsible for the symptoms of Parkinson's disease
decrease, so we do not expect that they will develop movement disorders such as
tremors or rigidity kind you seen in Parkinson's disease.
DR. LARRY KASKEL:
Dr. Cadet the drug Acomplia which was not approved in the
United States, but has been approved in Europe and other countries, were you
upset that it wasn’t approved. Do you agree that it shouldn’t have been
approved. Do you have any experience with it?
DR. JEAN LUD CADET:
We haven’t had any experience with it. I have talked to, I
guess I had talked recently to somebody who was interested in that drug and I
don’t think the people in the United States think that those drugs will be
approved in the United States. I have not worked with them, so I don’t have a
view about it, but from what I was told, I don’t think it would be approved in
the United States.
DR. LARRY KASKEL:
My last question is a personal one. I am a practicing
internist and I have many patients who smoke marijuana chronically and they
seem to be doing well, but if they do suffer some consequences and I want to
get them to stop, is there something you know of that I can help them stop
smoking marijuana?
DR. JEAN LUD CADET:
It is very difficult as you know addiction is a recurrent
disease as in diabetes and high blood pressure. Patients do well if they take
the medications that you give them and with addiction it is very, very difficult
because people take these drugs because these drugs make them feel good, so it
is even more of a problem trying to get people to stay abstinent. My best
thing is to look in your lookout to see whether there is a very good addiction
medicine that as know, there is the addiction practitioner in every city and
state nowadays, so I will refer them to a practitioner who has experience
dealing with that patient population. That is the best we can do in terms of
trying to treat a population, it is very difficult. People like using
marijuana, it is very difficult for them to give it up. Could be a potential
problem. The reason I am saying that is because in the case of somebody if you
are following patients who have had a myocardial infarction and given that
study that was published out of Harvard, the chance of them suffering from
another myocardial infarction is increased, the mortality rate is also
increased if they continue to use marijuana. For the young population, the
major side effects of marijuana might not be a major issue at this point in
time, but people who use marijuana get to be in their 40s in their 50s and if
they have other risk factors, I think that’s where your problem as a physician
arises because you need to be able to work with those patients and they might
not want to give up using marijuana.
DR. LARRY KASKEL:
Dr. Jean Cadet thank you very much for coming on the show.
I am Dr. Larry Kaskel and you have been listening to the
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