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12/08/2004

Receptive Topics

Last week I received a summons to report for jury duty and was
reminded of the three cases I’ve served on as a juror. The last
was such a minor open and shut case that the judge actually
apologized to us that we had to be called but described it as a
legal necessity. I also served on a hung jury when a lone
member of our panel refused to convict two perpetrators caught
red-handed in a department store in the wee hours of the
morning. As we were leaving the courtroom after being
dismissed by the judge, he remanded one defendant back to the
“penitentiary”!

While that case was quite disturbing, my first jury experience
was even more so. There was no disagreement in the jury room
and we quickly convicted a young man of possessing marijuana.
The next day, we were back with the jury pool waiting to see if
we would be called for another case when someone spotted an
article in the morning paper. The article quoted a very well
known singer as saying that she only gave the “best stuff” to
members of her band. It was clear that the “stuff” was pot.
Needless to say, we all felt troubled that we had convicted this
young man while celebrities were openly using marijuana. Then,
in the sports section of the paper, we found an item about a
hockey game in some kind of local league that I didn’t know
existed. One of the players was our young man. Now we were
doubly upset. This was back in the 1970s.

Today, marijuana is still very much in the news, with the
Supreme Court taking up the case of whether its medical use is
or is not legal. We have impassioned pleas from cancer sufferers
and others saying that life would be unbearable without the
marijuana. Outside the medical arena, we’ve had politicians at
the highest levels admitting to taking at least one puff of pot,
sometimes inhaling, sometimes not. According to an article
titled “The Brain’s Own Marijuana” in the December issue of
Scientific American, an estimated 30 percent of Americans over
the age of 12 have tried marijuana. I’m not among that 30
percent and suspect that the percentage would be higher if my
generation were removed from the statistics.

The Scientific American article is by Roger Nicoll, professor of
pharmacology and a member of the National Academy of
Sciences, and Bradley Alger, professor of physiology and
psychiatry at the University of Maryland School of Medicine.
They lay out some of the history of marijuana and show how
studies of the effects of marijuana in the brain have led to better
understanding of the brain’s responses, not only to marijuana but
also to compounds resembling marijuana’s active ingredient that
we manufacture in our own bodies.

The effects of marijuana are many and vary from one person to
another. Some find it intoxicating and experience the well
known “high” generally attributed to pot; some may hallucinate
while others just fall asleep. In some cancer patients, marijuana
suppresses the nausea induced by chemotherapy; it may help to
relieve chronic pain or it may enhance the appetite, important to
those patients who tend to waste away for lack of a desire for
food. On the negative side, marijuana impairs coordination and
short term memory as well as motor coordination. Also,
smoking pot subjects the smoker to similar health risks as those
associated with tobacco usage.

Why does marijuana have so many different effects on its users?
A key to the answer lies in “receptors”. Receptors are found in
the membranes of all our cells and are small proteins that have
distinctive shapes and chemical structures. These receptors are
like one piece of a jigsaw puzzle waiting to match up with
another molecule that “fits” like the complementary piece of a
puzzle. When the molecule attaches to the receptor, it triggers a
response of some kind depending on the particular type of cell.
In the brain, for example, there are lots and lots of neurons. A
response might be that some channels in the membrane open up
to allow various ions to pass through. This movement of ions
could initiate passing of signals to other neurons.

Back in 1964, Raphael Mechouam at the Hebrew University in
Jerusalem identified delta-9-tetrahydrocannabinol (THC for
short) as the active compound in marijuana. Identification of this
“cannabinoid” THC was the culmination of about a century of
work on marijuana by many researchers. It took another 24
years to find a receptor for THC. A group at St. Louis University
incorporated a radioactive tracer in THC and followed its path in
a rat’s brain. It ended up settling down on a receptor they called
the CB1 (for cannabinoid receptor). The connection between
CB1 and THC was nailed down when independent workers in
Germany and in Belgium bred mice that didn’t have CB1. Sure
enough, unlike normal mice, the mice without CB1 receptors had
little or no reaction to THC.

Why so many different effects of marijuana? As in real estate,
the answer is location, location, location. It turns out that CB1
receptors are scattered throughout various locations in the brain.
They’re in parts of the brain involved in appetite, in emotion, in
pain and in memory, in suppression of vomiting, etc. With CB1
receptors scattered all over the brain, the THC in marijuana can
attach to some or many of these receptors in different areas of the
brain and cause different responses in different people.

But wait a minute. How come the brain has a receptor that forms
a match with a compound (THC) from a plant, marijuana? In
1992, Ralph Mechoulam, the same guy that identified THC in
marijuana back in 1964, found the answer. He discovered a
compound produced in the brain that attaches to CB1 and has the
same effects as THC. Later, another compound in the brain was
found that binds to CB1. These endogenous (dictionary:
“growing on the inside”) compounds were given the name
endocannabinoids. THC resembles the naturally occurring
endocannabinoids closely enough to trick CB1 into accepting it
as a match.

Discovery of these and other endocannabinoids that Nicoll and
Alger term the “brain’s own marijuana” has led to work on what
influences the body’s production of endocannabinoids and their
roles in various diseases. Drugs that mimic endocannabinoids or
THC have appeared or are in the pipeline for treatment of
medical problems ranging from obesity to post-traumatic stress
disorder to Parkinson’s disease.

I mentioned that some cancer patients enhance their appetites by
smoking marijuana. There’s now a cannabinoid-based drug that
seems to accomplish the same thing. If such a drug works by
attaching to CB1, what would happen if some other drug worked
to block CB1 from accepting a cannabinoid? Such a drug,
termed an antagonist, might then be thought to work to suppress
one’s appetite. This is one approach being pursued to address
the obesity problem.

In conclusion, I hasten to add that I am mixed up in my own
mind about the medical use of marijuana and am definitely not
recommending any medical or other use of the drug. I’m also
relieved to find that, being over 75, I’m excused from jury duty
and will not have to face the possibility of another drug case.

Allen F. Bortrum



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-12/08/2004-      
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Dr. Bortrum

12/08/2004

Receptive Topics

Last week I received a summons to report for jury duty and was
reminded of the three cases I’ve served on as a juror. The last
was such a minor open and shut case that the judge actually
apologized to us that we had to be called but described it as a
legal necessity. I also served on a hung jury when a lone
member of our panel refused to convict two perpetrators caught
red-handed in a department store in the wee hours of the
morning. As we were leaving the courtroom after being
dismissed by the judge, he remanded one defendant back to the
“penitentiary”!

While that case was quite disturbing, my first jury experience
was even more so. There was no disagreement in the jury room
and we quickly convicted a young man of possessing marijuana.
The next day, we were back with the jury pool waiting to see if
we would be called for another case when someone spotted an
article in the morning paper. The article quoted a very well
known singer as saying that she only gave the “best stuff” to
members of her band. It was clear that the “stuff” was pot.
Needless to say, we all felt troubled that we had convicted this
young man while celebrities were openly using marijuana. Then,
in the sports section of the paper, we found an item about a
hockey game in some kind of local league that I didn’t know
existed. One of the players was our young man. Now we were
doubly upset. This was back in the 1970s.

Today, marijuana is still very much in the news, with the
Supreme Court taking up the case of whether its medical use is
or is not legal. We have impassioned pleas from cancer sufferers
and others saying that life would be unbearable without the
marijuana. Outside the medical arena, we’ve had politicians at
the highest levels admitting to taking at least one puff of pot,
sometimes inhaling, sometimes not. According to an article
titled “The Brain’s Own Marijuana” in the December issue of
Scientific American, an estimated 30 percent of Americans over
the age of 12 have tried marijuana. I’m not among that 30
percent and suspect that the percentage would be higher if my
generation were removed from the statistics.

The Scientific American article is by Roger Nicoll, professor of
pharmacology and a member of the National Academy of
Sciences, and Bradley Alger, professor of physiology and
psychiatry at the University of Maryland School of Medicine.
They lay out some of the history of marijuana and show how
studies of the effects of marijuana in the brain have led to better
understanding of the brain’s responses, not only to marijuana but
also to compounds resembling marijuana’s active ingredient that
we manufacture in our own bodies.

The effects of marijuana are many and vary from one person to
another. Some find it intoxicating and experience the well
known “high” generally attributed to pot; some may hallucinate
while others just fall asleep. In some cancer patients, marijuana
suppresses the nausea induced by chemotherapy; it may help to
relieve chronic pain or it may enhance the appetite, important to
those patients who tend to waste away for lack of a desire for
food. On the negative side, marijuana impairs coordination and
short term memory as well as motor coordination. Also,
smoking pot subjects the smoker to similar health risks as those
associated with tobacco usage.

Why does marijuana have so many different effects on its users?
A key to the answer lies in “receptors”. Receptors are found in
the membranes of all our cells and are small proteins that have
distinctive shapes and chemical structures. These receptors are
like one piece of a jigsaw puzzle waiting to match up with
another molecule that “fits” like the complementary piece of a
puzzle. When the molecule attaches to the receptor, it triggers a
response of some kind depending on the particular type of cell.
In the brain, for example, there are lots and lots of neurons. A
response might be that some channels in the membrane open up
to allow various ions to pass through. This movement of ions
could initiate passing of signals to other neurons.

Back in 1964, Raphael Mechouam at the Hebrew University in
Jerusalem identified delta-9-tetrahydrocannabinol (THC for
short) as the active compound in marijuana. Identification of this
“cannabinoid” THC was the culmination of about a century of
work on marijuana by many researchers. It took another 24
years to find a receptor for THC. A group at St. Louis University
incorporated a radioactive tracer in THC and followed its path in
a rat’s brain. It ended up settling down on a receptor they called
the CB1 (for cannabinoid receptor). The connection between
CB1 and THC was nailed down when independent workers in
Germany and in Belgium bred mice that didn’t have CB1. Sure
enough, unlike normal mice, the mice without CB1 receptors had
little or no reaction to THC.

Why so many different effects of marijuana? As in real estate,
the answer is location, location, location. It turns out that CB1
receptors are scattered throughout various locations in the brain.
They’re in parts of the brain involved in appetite, in emotion, in
pain and in memory, in suppression of vomiting, etc. With CB1
receptors scattered all over the brain, the THC in marijuana can
attach to some or many of these receptors in different areas of the
brain and cause different responses in different people.

But wait a minute. How come the brain has a receptor that forms
a match with a compound (THC) from a plant, marijuana? In
1992, Ralph Mechoulam, the same guy that identified THC in
marijuana back in 1964, found the answer. He discovered a
compound produced in the brain that attaches to CB1 and has the
same effects as THC. Later, another compound in the brain was
found that binds to CB1. These endogenous (dictionary:
“growing on the inside”) compounds were given the name
endocannabinoids. THC resembles the naturally occurring
endocannabinoids closely enough to trick CB1 into accepting it
as a match.

Discovery of these and other endocannabinoids that Nicoll and
Alger term the “brain’s own marijuana” has led to work on what
influences the body’s production of endocannabinoids and their
roles in various diseases. Drugs that mimic endocannabinoids or
THC have appeared or are in the pipeline for treatment of
medical problems ranging from obesity to post-traumatic stress
disorder to Parkinson’s disease.

I mentioned that some cancer patients enhance their appetites by
smoking marijuana. There’s now a cannabinoid-based drug that
seems to accomplish the same thing. If such a drug works by
attaching to CB1, what would happen if some other drug worked
to block CB1 from accepting a cannabinoid? Such a drug,
termed an antagonist, might then be thought to work to suppress
one’s appetite. This is one approach being pursued to address
the obesity problem.

In conclusion, I hasten to add that I am mixed up in my own
mind about the medical use of marijuana and am definitely not
recommending any medical or other use of the drug. I’m also
relieved to find that, being over 75, I’m excused from jury duty
and will not have to face the possibility of another drug case.

Allen F. Bortrum