WORLD DRUG TRAFFIC AND IT'S IMPACT ON U. S. SECURITY HEARINGS BEFORE THE SUBCOMMITTEE TO INVESTIGATE
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Publication Date:
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WORLD DRUG TRAFFIC AND ITS IMPACT
ON U.S. SECURITY
HEARINGS
SUBCOMMITTEE TO INVESTIGATE THE
ADMINISTRATION OF THE INTERNAL SECURITY
ACT AND OTHER INTERNAL SECURITY LAWS
COMMITTEE ON THE JUDICIARY
UNITED STATES SENATE
NINETY-SECOND CONGRESS
PART 5
RESEARCH ON MARIHUANA AND HASHISH
U.S. GOVERNMENT PRINTING OFFICE
82-848 WASHINGTON : 1972
For sale by the Superintendent of Documents, U.S. Government Printing Office
Washington, D.C. 20402 - Price 45 cents
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COMMITTEE ON THE JUDICIARY
JAMES O. EASTLAND, Mississippi, Chairman
JOHN L. MCCLELLAN, Arkansas
SAM J. ERVIN, JR., North Carolina
PHILIP A. HART, Michigan
EDWARD M. KENNEDY, Massachusetts
BIRCH BAYII, Indiana
QUENTIN N. BURDICK, North Dakota
ROBERT C. BYRD, West Virginia
JOHN V. TUNNEY, California
ROMAN L. HRUSKA, Nebraska
IIIRAM L. FONG, Hawaii
HUGH SCOTT, Pennsylvania
STROM TIURMOND, South Carolina
MARLOW W. COOK, Kentucky
CHARLES MCC. MATHIAS, In., Maryland
EDWARD J. GURNEY, Florida
SUBCOMMITTEE To INVESTIGATE TILE ADMINISTRATION OF THE INTERNAL
SECURITY ACT AND OTHER INTERNAL SECURITY LAWS
JAMES O. EASTLAND, Mississippi, Chairman
JOHN L. McCLELLAN, Arkansas HUGH SCOTT, Pennsylvania
SAM J. ERVIN, JR., North Carolina STROM THURMOND, South Carolina
BIRCH BAYII, Indiana MARLOW W. COOK, Kentucky
EDWARD J. GURNEY, Florida
J. G. SouRWINE, Chief Counsel
SA~XUEL J. SCOTT, Associate Counsel
WARREN LITTMAN, Associate Counsel
JOHN R. NORPEL, Director of Research
ALrONSO L. TARABOCHIA, Chief Investigator
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WORLD DRUG TRAFFIC AND ITS IMPACT ON U.S.
SECURITY
MONDAY, SEPTEMBER 18, 1972
U.S. SENATE,
SUBCOMMITTEE TO INVESTIGATE TIIE
ADMINISTRATION OF TIIE INTERNAL SECURITY ACT
AND OTHER INTERNAL SECURITY LAWS
Or THE COMilIrrEE ON THE JUDICIARY,
Washington, D.C.
The subcommittee met, pursuant to recess, at 10:30 a.m. in room
2228, New Senate Office Building, Senator James O. Eastland (chair-
man) presiding.
Present: Senators East] and and Gurney.
Also present : J. G. Sourwine, chief counsel.
The CIIAIRMAN. We are honored to have as our witness today Mr.
Olav J. Braenden, the distinguished Norwegian scientist who is the
head of the United Nations Narcotics Laboratory in Geneva for the
past 14 years. We decided to invite your testimony, Dr. Braenden, on
the recommendation of Gen. Lewis W. Walt who, as you know, has
been directing a study of the world drug traffic for the subcommittee.
There has been a great deal of confusion in our country on the subject
of marihuana and what to do about it, and it was General Wait's con-
viction that your scientific experience, especially in the field of can-
nabis research, would help us to make up our minds. It was also Gen-
eral Walt's conviction that the problem of heroin cannot be considered
in isolation from the problem posed by the spreading use of other
drugs, including marihuana.
Doctor, do you have a prepared statement?
Dr. BRAENDEN. Yes, I have.
The CIIAiRtiuAN. You may proceed.
STATEMENT OF DR. OLAV 1. BRAENDEN, DIRECTOR, UNITED
NATIONS NARCOTICS LABORATORY, GENEVA, SWITZERLAND
Dr. BRAENDEN. Mr. Chairman, it is an honor to be called to appear
as a scientific witness before this important and distinguished com-
mittee. My terms of reference are, as I understand them, to report on
certain significant aspects of research on cannabis-of which mari-
huana and hashish are the chief products-and on the findings of the
United Nations Laboratory and of national scientists collaborating
with it in the U.N. research program. After giving you a brief outline
of recent important developments in the field of cannabis research, I
shall, of course, be pleased to answer as far as I can any questions which
the members of this committee may care to put to me.
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Just before leaving Geneva, I made telephone calls to a number of
scientists in different countries who have been collaborating on various
aspects of cannabis research. I had lengthy conversations with Prof.
W. D. M. Paton of Oxford University, with Dr. Ole Rafaelsen of
Denmark, with Prof. C. Micas of the University of Athens, and with
Prof. Cornelius Salamink of the University of Utrecht in the Nether-
lands. The statement I have prepared refers to some of the recent sci-
entific findings on the subject and, I believe, accurately reflects their
views, so far as their own research is concerned.
As you know, careful and profound chemical and pharmacological
studies of cannabis have also been carried out in this country, particu-
larly under the auspices of the National Institute of Mental Health,
The many outstanding scientists who have worked on these studies
include Prof. Ilarry Isbell, Prof. Leo Hollister, Prof. Coy Waller,
Dr. Julius Axelrod, Dr. Glenn Kipplinger, and others. Their research,
in general, corroborates the research of the European scientists work-
ing on cannabis. I regret that there was no time to interview these
outstanding scientists before my appearance.
Among the scientists working in the field, it would seem that there
is a general consensus that cannabis is dangerous-opinions differ,
however, on the degree of the danger to the individual and to society.
In my opinion, it seems that, as progressively more scientific facts
are discovered about cannabis, the more one becomes aware of its
potential dangers.
In spite of the intensive research carried out in many countries,
much remains to be elucidated in connection with the chemistry of
the components of cannabis and their effects on the body. There is no
doubt that this is a highly complex field, much more so than was
previously supposed. For example, it had been believed for some
decades that the main components of cannabis were some few sub-
stances, mainly cannabinoids, of which only tetrahydrocannabinol, or
THC as we call it, was the active principle. However, there. is now
evidence that cannabis contains a very large number of substances-at
least 50. The great majority of these components have not yet been
isolated and characterized, and their pharmacological activity-or
inactivity-remains to be determined.
In our laboratory, a?e have recently found indications of the presence
in cannabis of nitrogen-containing substances. By varying the classical
extraction procedures, certain spots were obtained on thin-layer
chromatograms which led us to suspect that cannabis contained
components of an alkaloidal nature. It was also noted that these
alkaloidal substances were present in greater amounts in the actual
plant material than in the resin.
The CHiAIRMAN. Could you give us a simple definition of an alka-
loidal substance?
Dr. BRAENDEN. Well, that is a common term for an alkali containing
plant, substances. There are a number of such substances found in
nature, and they usually have other specific and strong activities on
the human body. For instance, as an alkaloid I can mention nicotine.
The CHAIRMAN. W.li., morphine or heroin then is an alkaloid?
Dr. BRAENDEN. Can I answer?
The CHAIRMAN. Proceed. Yes.
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Dr. BRAENDEN. The heroin, strictly speaking, is not an alkaloid be-
cause it is not contained in a plant. It is a derivative of an alkaloid.
It is a derivative of morphine. But people call it an alkaloid, so you
are perfectly right, Senator.
The CHAIRMAN. Proceed.
Dr. BRAENDI:N. Application of the usual tests for alkaloids was found
by Dr. II. Samrah, of Egypt, to give positive reactions. Similar results
were obtained by Prof. 0. Aguar, of the University of Madrid.
These alkaloidal substances have still to be isolated and characterized.
Simultaneously and independently, Prof. C. Salemink, of the Uni-
versity of Utrecht, reported on quarternary nitrogen bases in cannabis
seeds, and, very recently, on the presence of indole compounds in can-
nabis itself. (Indole compounds are also nitrogen-containing organic
compounds.)
There is no doubt that the presence of nitrogen-containing com-
pounds in cannabis opens a highly interesting field in connection with
the pharmacological activity of cannabis because as I said, such plant.
substances are frequently active.
Mr. SounWINs. You mean by active that they are poisonous?
Dr. BRAENDEN. Poisonous and active; yes.
Knowledge of the short- and long-term effects of cannabis is far from
comprehensive.
According to Dr. A. M. Campbell and his colleagues, of the Bristol
Royal United Hospital, there is significant evidence of cerebral atro-
phy in young cannabis smokers.
Prof. C. Miras, of the University of Athens, has done consider-
able research on the effects of cannabis on man. As subjects lie uses
chronic hashish smokers only-because he believes that there is a great
risk of damage if the subjects have not previously taken hashish on a
regular basis.
The CHAIRMAN. What does hashish do to a person ?
Dr. BRAENDEN. What hashish does? Excuse me, Senator.
The CHAIRMAN. What does hashish do to the person?
Dr. BRAENDEN. Senator, this is, of course, a question which is some-
what outside my competence. But, I always used to refer myself, when
I get that question, to a report, the report of the Department of
health, Education, and Welfare of the United States to the Congress.
So, you certainly have this document, and outside of that I would not,
could not make any better statement than what is there. This is as com-
prehensive as you can get.
Do you want me to read from it?
The CIIAIR.MAN. No, sir. That is all right. It will be made a part
of the record by reference. Proceed, sir.
Dr. BRAENDEN. Dr. 0. Rafaelsen, of the Central State Hospital of
Copenhagen, Denmark, has found that there is considerable, impair-
ment of driving ability after oral ingestion of cannabis.
Here it should be noted that the effects of cannabis when smoked
are considerably greater than when cannabis is taken orally. This may
be due to the fact that-as reported by Professor Salemink, of the
Netherlands-the components of cannabis may in part be destroyed in
the digestive tract by intestinal bacteria.
A complicating factor in assessing reports on the abuse of cannabis,
particularly by young people, is that those who claim to have smoked
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cannabis may not, in fact, have done so-because cannabis in the illicit
drug traffic is often highly adulterated with tobacco and other sub-
stances, and sometimes it is even completely falsified. In the illicit
traffic, it has been reported that a considerable percentage of the sam-
ples seized did not contain any cannabis.
As I have pointed out, the activity of cannabis has thus far been
attributed entirely to the tetrahydrocannabinol, or THC, which
it contains. While it is trite that ` 11C is active pharmacologically, it is
highly probable that other components of cannabis may also be active.
In the Netherlands, a sample of cannabis was found to be highly ac-
tive despite the fact that no TIIC tivas present.
Although an adequate picture of the fate of cannabis in the body
remains to be determined, it should be noted that cannabis is only
partially excreted by the organism. Professor Paton. of Oxford Uni-
versity has found that some of its components accumulate in the fatty
tissues of the body.
For a number of years now, the United Nations Laboratory has
been engaged in research on cannabis. Acting on a directive of the
UN Commission on Narcotic Drugs, we have, in fact, accorded this
work the highest priority. Governments have indicated their interest
by providing large numbers of cannabis samples for our research, and
also by nominating irational scientists to participate in the program.
'T'hese scientists performing their research on a voluntary basis have
made important contributions to the program.
Mr. SouniWINE:. Mr. Chairman, may I interrupt here, please.
Senator GI RNFY (presiding). Yes.
Mr. Sourw INF. Doctor, I want to go back to your previous pa,ra-
graph. I have been thinking about it since you said it, that some of
the components of. TTIC or cannabis, at least, accumulate in the fatty
tissues of the body. Is that a parallel phenomena with what we find
in DDT, which we are now coming to learn accumulates in the body,
and gradually builds up until it eventually, they say, will reach a
lethal dose.? Is this same thing happening with cannabis smokers?
Dr. I3RAFNDEN. Yes; Senator. I would be inclined to think so. It
accumulates according to the way that you use it.
Mr. SOURwINr. Doctor, I ani not a Senator. The chairman is a
Senator, and I am the committee counsel. Thank you for your reply.
Dr. I3RAFNnEN. Shall I go on?
Senator GrRNFV. Go ahead and proceed.
Dr. BR,AENnEN. The United Nations Laboratory concentrates its at-
tentionon those aspects of the research which. cannot easily be carried
out by national laboratories and, in this connection, its most important
function is to coordinate, as required and as far as possible, the research
being carried out in various countries within the framework of the
program. In particular, we seek to avoid unnecessary duplication of
effort. The Laboratory cooperates with researchers in the ITnit.ed
States of America, tlrough the National Institute of Mental Health,
and it also is in close contact with the Laboratory Division of the
Bureau of Narcotics and Dangerous Drugs. In the research program,
the laboratory provides its national collaborating scientists with the
basic research rnater; als-samples of cannabis, cannabis resin, and
cannabis seeds, and it also distributes TI-IC which has been made avail-
able through the National Tntitute of Mental Health.
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Senator GURNEY. Doctor, can you explain in a little more detail
how your research differs from that done by the national laboratories
of various countries?
Dr. BRAENDEN. Senator, our research is more of a coordi:natiug
nature. We do not have the stuff to go deep into the investigations
ourselves. We do not have, for instance, animals for pharmacological
testing, so this is done by national laboratories. We provide material
to these national laboratories which we receive from governments
and from institutions.
Does that answer your question?
Senator GURNEY. Yes. Go ahead.
Dr. BRAENDEN. It is well known that the chemical composition of
cannabis varies according to the ecological conditions of the region
where it is grown, and that, after harvesting, changes occur with time
and according to the conditions of storage. The Laboratory has, there-
fore, organized an ecological study of the variations in the amount
and potency of cannabis resin according to ecological conditions. For
this purpose, cannabis seeds from the sarne batches are being cultivated
under carefully controlled conditions in various climatic regions. The
preliminary studies have yielded some highly interesting results. It has,
for instance, been found that the cannabis cultivated experimentally
in Iceland and Norway, north of the Polar Circle, from seeds of South
African origin, contains appreciable amounts of TIIC. These findings
contradict the previously held belief that cannabis grown in temperate
or cold regions is not pharmocologically active. It is our hope that this
ecological study will be completed toward the end of next year.
The systematic analysis at regular intervals of the samples of
cannabis in the United Nations collection is now being undertaken in
order to determine the nature and the extent of changes occurring in
composition with time.
The variations in the chemical results obtained in early research on
cannabis were probably due, at least in part, to the variations in the
cannabis samples used by different scientists. To overcome this diffi-
culty, the United Nations Laboratory has, from time to time, prepared
reference samples of cannabis to be used for comparative purposes.
It may perhaps be of interest to mention that, in the illicit traffic,
cannabis is now being encountered in a new form-known as "liquid
hashish" or "marihuana oil." This is many times as potent as good
grade hashish and is potentially very dangerous. The exact technique
for producing liquid hashish is not known, but, according to the
Bureau of Narcotics and Dangerous Drugs, the hashish is apparently
extracted with an organic solvent which is subsequently evaporated,
and a vegetable oil is added to the residue. Earlier this year, our Labor-
atory received interesting samples of some "liquid hashish" or "mari-
huana oil" seized in Norway. It was said to be of Middle Asian origin,
and it had an extraordinarily high concentration or TIC-66.3 per-
cent, as against about 10 percent in ordinary hashish and 2 percent in
marihuana.
Senator GiTuNrv. What is the sbrnificance of this? Is the high con-
centration of TTTC fatal to somebody using it?
Dr. BRAENDEN. Yes. The danger increases with the concentration,
of course. The reason for this being clone is that they can make the
volume so much smaller and hide it so much easier. This is the object
of it.
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Senator GURNEY. What are the effects of THC on a person?
Dr. BRAENDEN. Would you repeat that, sir ?
Senator GURNEY. What are the effects of THC on a user's body?
Dr. BRAENDEN. The effects of THC are very similar to that of can-
nabis. It was thought before to be the active principle of cannabis, so
that really you would get the same effects for THC as you get from
cannabis.
Senator GURNEY. All right. Proceed.
Dr. BRAENDEN. In spite of the progress made in recent years, in
cannabis research, much still remains to be done before we have an
adequate understanding of the nature and effects of this complex plant.
Very considerable research is necessary-particularly in order to iso-
late and characterize all the relevant constituents of cannabis; to
definitely establish the active principles; to study the pharmacological
effects of cannabis and its fate in the body; and also to determine the
chemical transformations which occur in cannabis when it is smoked.
I feel; there fore, Mr. Chairman, that every effort should be made
to accelerate relevant, research so that it may be possible, within the
near future, to draw: sound scientifically based conclusions on can-
nabis-conclusions which would be of value to national and inter-
national bodies in their considerations of the control of cannabis.
Thank you, Mr. Chairman.
Senator GURNEY. Well, thank you for your statement, Doctor.
The Shafer Commission, in its report, listed a number of different
countries for gathering of material. Did they visit the United Nations
Narcotics Laboratory in Geneva?,
Dr. BRAENDEN. I must say that we have quite a number of committees
visiting us. When you mention the Shafer Commission, I do not recol-
lect that name, and as I can see, it is not mentioned in the Shafer
Report, so I suppose that they have not been there. But, it could also
happen that I have been on leave at the time when they visited us.
Senator GURNEY. At any rate, no one from that Commission talked
to you?
Senator GURNEY. Had they sought your views, would your views
be the same as you have presented to the committee here today?
Dr. BRAENDEN. Well, Mr. Chairman, I am not quite sure when
this study was made. ;I suppose that was a year ago, was it not?
Senator GURNEY. Do you recall when that study was made?
Mr. SOURWINE. Yes, sir, about a year ago, Mr. Chairman.
Senator GURNEY. Yes, about a year ago.
Dr. BRAENDEN. You know, at that time, it was not possible to give
the information that j have given to you from Copenhagen, from
the tests at Athens, and London, as I have given them to you now,
because they are very recent, the results.
Senator GURNEY. Is it a fair thing to say from your statement that
you consider cannabis to be a dangerous substance ?
Dr. BRAENDEN. Yes; it is. I do not thin] there is anybody who ques-
tions that canr,ab'q is dangerous. The question is the degree of dan-
gerousness, and this is what the research is needed for, in order to
find out.
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r. BRAENDEN. No No. That is what I said, I do not remember
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Senator GURNEY. Would you be in favor of legalizing the use of
marihuana?
Dr. BRAENDEN. This is a legal question which I am not authorized
to answer. For this you would have to ask a legal expert, and you
certainly are in a better position to judge the situation yourself. The
only thing which I can do is to bring to your attention the scientific
facts as they are today, and what we hope, and what research we
hope to do in order to clarify the situation.
Senator GURNEY. Well, let me put the question the other way. For-
getting or putting aside your official capacity as head of the United
Nations Narcotics Laboratory, would you personally, as an individ-
ual, not in your position, but as an individual, favor the legalization
of marihuana?,
Dr. BRAENDEN. I would say well, generally, I would say that it is
better to be careful when it comes to medicine and drug policy than
it is to be careless. I think that you people here in the United States
have an excellent example of this in the thalidimide case, which
you did not authorize for use before you wanted more research done,
and that saved you from some 10,000 malformed children as they have
in Europe from this case.
Senator GURNEY. And then I think it would be, as I understand
your testimony. and your answers to the questions, it would be your
view that not enough is known about marihuana to make a judgment
as to whether its use should be legalized now or not, is that right'?
Dr. BRAENDEN. Well, this would be my feeling, yes, that much
more research should be done so as to be able to take the right position
in establishing controls over marihuana.
Senator GURNEY. A great many statements are made these days
on marihuana in which they say that this really is very little different
than the use of alcohol or tobacco or marihuana, that all of these sub-
stances are harmful if you indulge too much in any one of them, and
there really is little choice between them. One is not any more dan-
gerous than the other. Of course, this is the argument which is made
by the marihuana users-that marihuana ought to be legalized because
it really is not any more harmful than heavy use of tobacco or alcohol.
What is your view on that?
Dr. BRAENDEN. I think there is a substantial difference between
cannabis and alcohol in that alcohol is readily excreted from the body.
It is not accumulated, as I mentioned, is the case with the cannabis. I
think this is one of the rather substantial differences which has to be
taken into consideration.
Mr. SouRwzTrE. Is nicotine also secreted, or does it accumulate in
the tissue?
Dr. BRAENDEN. That does not accumulate either, as far as I know.
Senator GURNEY. I see. We have a vote on the floor now, so the sub-
committee. will recess temporarily subject to the call of the Chair.
(Short break.)
Senator GURNEY. The subcommittee will come to order.
Doctor, it is our understanding that the United Nations Laboratory,
of which you are the head, has developed procedures for identifying
opium by geographic origin. Could you explain how this was done?
Dr. BRAENDEN. Yes. I could have explained it better if we had a
projector, but I will try to explain it otherwise. It is in a way the same
principle as identifying a fingerprint in that, you see, the opium is a
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plant material, and this differs according to the growing condition.
You know, like coffee from Java is different than coffee from Brazil.
And there are a lot of examples like this.
Now, in the case of opium, it is, it develops a difference in the quan-
tity of the various substances there, mainly the alkaloids of opium, and
it is then ineasured on a spectrophotometric. It is kind of a pattern of
curves, and really this is what you have in fingerprints, too, you have a
pattern of curves.
Mr. SOURWINr. Is this a spectrographic process?
Dr. BRAENDEN. Spectrophotometric, not spectrographic. Spectro-
graphic would be more concerned with the metal components of opium.
Mr. SourwlNF. Not spectrographics, but spectro what?
Dr. BRAENDEN. Spectrophotometric or colormetric, we call it also.
Mr. SoiRwiNi,. Coloranetric ?
Dr. BR AENDEN. Colormetric, the intensity of the color.
Mr. SouRwiN],,. Would it be true then, I will try to ask a layman's
question so that whoever reads this will understand, in a sense you are
taking a picture of the differences, the peculiarities and the individ-
ualities of a specimen?
Dr. BRAFNDEN. That is right.
Mr. SourwIN1:. Which shows up interaction or variation in color or
in position, and which is unique to the particular specimen?
Dr. BRAENDEN. This is about right, yes.
Mr. SOL'RWINE. So that once you have this picture, you do not need
another specimen in order to compare ? The picture identifies that speci-
men for all time?
Dr. BRAENDEN. That is probably not so.
Mr. SourwINF. Not so'?
Dr Br 1ENDEN. One has to check from time to time and get new
samples from the region. We do not have enough information on this
to answer this question. As a matter of fact, that work was rather im-
portant about 10 years ago. Now it is less important because the opium
travels much shorter distances. It is transferred into heroin or trans-
ferred into morphine or into heroin very near to the production of the
opium because this is Much easier to transport. But, it could, it could
have very interesting application in some regions. For instance, in
Southeast, Asia, where there is still quite a lot of opium seized from
Thailand,; Burma area, the Laos area and so on, it may be that in that
part, one could, by your: method, trace back to the origin, and this could
be very useful.
Mr. SouRwINa. DoctQr, I will ask you to identify for the record three
documents which you ? samples of illicit production)
5
Nepal --------------------------------
---------- ------------ ----- ----------------------------------
Pakistan---------------------------------------------------------------
1
13
Republic of Korea (including authenticated samples of illicit production)-_
4
Thailand---------------------------------------------------------------
3
Turkey (mostly from districts where opium production has now ceased)---_
87
Union of Soviet Socialist Republics------------------------------------
1s
Viet-Nam--------------------------------------------------------------
1
Yugoslavia-------------------------------------------------------------
11
Mr. SouRwINE, Doctor, I would like to ask you this : from what you
have already said, I take it that, you must have it fair number of
samples from each country that produces opium in order to make the
procedure of identification reasonably accurate?
Dr. BRAENDEN. Yes; that is right.
Mr. SounwINri. I note from this list, your authenticated samples
list, that has just, gone in the record that, for instance, you have 620
samples from India, 87 froth Turkey, 48 from Iran, 18 from the Soviet
Union, but only one from Vietnam and only one from, China. One
sample is really not enough to make serious identification possible?
Dr. BRAENDEN. No.
Mr. SouRWINE. Would it be posible to determine the geographic
origin. of morphine base by it simil iar procedure?
Dr. BRAENDEN. No; it would not, but one could do some work in that
direction by linking the, well, the samples together. It would be the
same situation with counterfeit money, where we would know where
the samples turned up, but we would not know where it was made. But,
also, this would be the same thing as with counterfeit money where
you know where the money trams up, but you do not know where the
press is.
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Mr. SOURWINE. Understood. Would it be possible to determine the
geographic origin of the opium from which a specific batch of heroin
has been defined ?
Dr. BRAENDEN. No.;This would be even more difficult.
Mr. SourwINE. I have no more questions, Mr. Chairman, except
perhaps I should ask this catchall. Doctor, is there any other aspect
of your current narcotics research that you would tell us about?
Dr. BRAENDI:NY. There is one aspect which could be of interest to
you. That is the question of Papaver bracteatum, and this is the ques-
tion of poppy thebaine. This is a poppy which grows wild in Iran,
in the mountains north of Iran, and it contains thebaine, appreciable
amounts of thebaine, but no morphine. Now, thebaine can be trasferred
into codein, and codein is really what is used of the opium poppy. And
90 percent of the morphine which is produced in the world is trans-
fered to codein. So, if this plant, if it really is what it looks like, and
if it would be economical, this would probably lead to a cutting down
of the leading production of opium to one-tenth of what it is now, and
still the requirements of the country could be met. Thebaine is not an
addictive.
Mr. SouxwrNr:. You; say there is a kind of poppy that would pro-
duce codein but would not produce opium, or at least would produce
only a small amount of opium.?
Dr. BRAENDEN. No, it is not quite like that. It produces a substance
which ono can use for making codein but it does not produce morphine
or any other addiction-producing substance.
Mr. SouRwiNH:. I understand, sir.
Dr. BrL&ENDEN. So, this is really an interesting field, and we have now
in cooperation with the Department of Agriculture of the United
States, we have planted this, the seeds of this plant in various parts
of the world, in Scandinavia, in Turkey, and also over in Thailand.
And it is going to be'produced now, or cultivated. This could give
the farmers a cash crop, I mean the opium farmers a cash crop with-
out changing too much their way of cultivation, because this will also
be a poppy, you see.
Thank you, Mr. Chairman.
Senato. GURNEY. Well, thank you, Dr. Braenden. You have shed a
lot of light on the very, troublesome subject of drugs, and it is a world-
wide problem, of course, now. We appreciate very much your corning;
here this morning before the subcommittee and giving us the benefit
of your knowledge. Thank you.
Mr. SouRwINE. Mr. Chairman, these other witnesses were scheduled
to testify. They are Eugene T. Rossides, John E. Ingersoll, and Nelson
Gross. We have their statements, which should be made part of the
record. May they be ordered printed as though read?
Senator GTRNsr. So ordered.
(Because of the length of the above mentioned, the statements of
Messrs. Rossides, Ingersoll, and Gross were ordered printed in a sepa-
rate )'olume.)
The subcommittee will recess, subject to the call of the Chair.
(Whereupon, at 11:55 a.m., the hearing was recessed, subject to the
call of the Chair.)
(Seven' articles dealing with the injurious effects of cannabis were
subsequently ordered into the record. Because the articles are lengthy
and technical, each is preceded by an editorial summary.)
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APPENDIX
[From Drugs and Society, Jan. 9, 1972, pp. 17-20]
GUIDE TO DRUGS
(By Prof. W. D. Paton)
Editorial summary
1. "Little is known about the composition of the smoke
from cannabis cigarettes, save that about 25 to 50 percent of
the TIIC content is delivered to the respiratory tract."
2. "The cannabinoids are extremely fat-soluble and corre-
spondingly inso]uable in water. They and their metabolites
therefore persist in the body; thus, 24 hours after a dose of
labelled TIC a rat has eliminated, as metabolites in urine
and feces, about 10 percent of the dose, a rabbit about 45 per-
cent and a man about 25 percent."
3. "Cannabis has not been found to produce fetal deformi-
ties and fetal resorption in animals (rats, rabbits and ham-
sters) in doses (per unit or bodyweight) ranging down to that
used in man. The effect has been shown to be dose-related .
and is exerted at all small fraction of the dose liable to kill
the mother." In this respect it resembles Thalidomide and
other human teratogens. [A teratogen is a substance which
causes fetal deformities.]
4. Although only it small proportion of casual cannabis
users progress to heroin or other opiates, progression is much
commoner with heavy users, while the vast majority of opiate
users have had prior experience with cannabis. The progres-
sion can be explained pharmacologically by the fact that can-
nabis increases suggestibility, and shares with heroin (al-
though in milder form) the ability to produce euphoria and
analgesia.
5. "There seems no rational basis for drawing a line be-
tween cannabis on the one hand and LSD, the amphetamines
or the potent opiates, on the other."
Cannabis sativa is a widely distributed plant producing fibre oil (from its
seeds) and resin in varying proportions according to its variety and the con-
ditions of cultivation. The resin is produced mainly in the flowering tops.
Marijuana, made from the dried plant, contains a good deal of other plant
material mixed with the resin ; in hashish the resin is more or less concentrated..
The term `cannabis' will be used to refer to any preparation of the crude material..
Cannabis differs from the other drugs discussed in this series in always being
a mixture of substances. Of the scores of chemical compounds that the resin
contains, the most important are the oily cannabinoids, inclading tetrahydro-
cannabinol (T'HC), which is the chief cause of the psychic action. Samples of
resin vary greatly in the amounts and proportions of these cannabinoids accord-
ing to their country of origin ; and as the sample ages, its TIIC content declines.
(209)
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210
As a result, the TIIC content of samples can vary from almost zero to eight per
cent. Pure TIIC is unstable unless kept in the dark under nitrogen, but is better
preserved in the undamaged plant. One result of these facts is that the dose of
TIIC taken, unless under laboratory control, is far more uncertain than with
other drugs.
In addition to the candabinoids are certain water-soluble substances, including
a small amount of an atropine-like substance (which may contribute to the dry
mouth), and some acetylcholine-like substances (which may contribute to the
irritant effect of the smoke).
Little is known about the composition of the smoke from a cannabis cigarette,
save that about twenty five to fifty percent of the TIIC content is delivered to
the respiratory tract.
THC and other cannabinoids are now fairly easily detectable in small amounts
by gas-liquid chromatography. But once THC enters the body, it is hard to trace,
unless it has been labelled for research purposes with a radioactive atom-partly
because it is taken up by the tissues, partly because it undergoes a series of still
incompletely understood. conversions. The products of these conversions are
found in 'the urine, but a urine or blood test suitable for forensic or research
use is still not available.: This is a serious handicap to clinical investigation and
means, that there is no way of establishing how much (if any) cannabis a subject
has taken.
The cannabinoids are extremely fat-soluble, and correspondingly insoluble in
water. They and their metabolites therefore persist in the body ; thus twenty
four hours after a dose of labelled TIIC, a rat has eliminated, as metabolites in
urine and feces, about 10 per cent of the dose, a rabbit about forty five per cent,
and a man about twenty five per cent.
It.ea.etiQns are very varied, and they are much influenced by the behavior of
the group. Euphoria is common, though not invariable, with giggling or laughter
which can seem pointless to an observer. Sensations become more vivid, especially
visual, and contrast and: intensity of color can increase, although no change in
acidity occurs. Size of objects and distance are distorted. Time as experienced
becomes longer than clock time; thus a subject asked to say when sixty seconds
has elapsed responds too early, but if asked to say how long some period of time
was, overstates it; sense of time can disappear altogether, leaving a. sometimes
distressing sense of timelessness. Recent memory and selective attention are im-
paired; the beginning of a sentence may be forgotten before it is finished, and
the subject is very suggestible and easily distracted. Psychological tests such as
mental arithmetic, digit-symbol substitution, and pursuit meter tests show im-
pairment} the effect being greater as the task becomes more complex. The vivid-
ness of sensory impressions and distractibility gives rise to imagery and fantasy ;
this can progress with increasing dose from mere fanciful interpretation of actual
sensations to hallucination in the sense of vivid sensory impressions lacking an
external basis. These effects may be accompanied by feelings of deep insight and
truth. They are similar In type, though often more intense, to those experienced
in liypnagogic imagery or while recovering from an anaesthetic.
It seems likely that these effects of cannabis can be explained if it removes a
restraining `gate' on the inflow of sensory information. Normally, considerable
selection takes place, and familiar stimuli or those judged irrelevant are ignored.
A dis-inhibitory action of cannabis, lifting this gate, would allow the `flood of
sensation' so often reported. Further,. it is believed that time sense depends on
the frequency of sensory impressions ; an increased flow would therefore give
the feeling that more time had elapsed. Finally, it is known that the process of
memory involves at least three processes : entry into a sensory `register' and
passage into a short-term 'store'; rehearsal of information either consciously
or unconsciously, leading to consolidation and transfer to a longer-term store ;
and retrieval. It appears that retrieval is not impaired by cannabis (longstand-
ing memories often form: the basis of the imagery), and entry seems normal ; but
conversion of short-term to long-term memory is known to be interfered with by
a flow of additional sensory impressions, just as a telephone number is likely to
be forgotten if someone speaks to you just after you have heard it. It is likely that
the flow of sensory impressions under cannabis interferes with the consolidation
of recent information in? a similar way. Once memory is impaired, concentration
becomes less effective, since the object of attention is less well remembered.
With this may go an insensitivity to danger or the consequences of actions.
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A striking phenomenon is the intermittent wave-like nature of these effects-a
subject may return towards normal, or bring himself `down' for a period. This in-
termittancc effects mood, visual impressions, time sense, spatial sense, and other
functions : it represents, incidentally, one of the many experimental difficulties
in analyzing cannabis action. The effect of a single dose usually ends with
drowsiness or actual sleep.
The effects can also be unpleasant, especially by inexperienced subjects, par-
ticularly timelessness and the feeling of loss of control of mental processes. Feel-
ings of unease, sometimes amounting to anguish, occur, and may well have some
physical basis-perhaps associated with the acceleration of the heart rate. There
is also, especially in the habitual user, a tendency to paranoid thinking. High or
habitual use can be followed by a psychotic state ; this is usually reversible,
quickly with brief periods of cannabis use, but more slowly after sustained
exposures.
Cannabis smoked or taken by mouth produces reddening of the eyeballs (prob-
ably the forerunner of the general dilation of blood vessels and fall of blood pres-
sure with higher doses), unsteadiness (particularly for precise movements), and
acceleration of heart rate. The latter effect can be substantial, and although the
insolubility of the cannabinoids in water makes intravenous abuse difficult, cardiac
failure would be a serious risk with such use. The smoke produces the usual
smoker's cough, and the tar from reefer cigarettes is as carcinogenic in animal ex-
periments as cigarette tobacco tar. Although increase in appetite is commonly
experienced, no explanation for it exists, and cannabis use does not have any
striking effect on the blood sugar. In animals, with chronic administration of
substantial doses, food intake is reduced and weight loss occurs.
An important finding in animals is that cannabis prolongs sleeping time after
a dose of a barbiturate such as pentobarbitone (Nembutal). This has been shown
to be due to an impairment of the ability of the liver to break down (metabolise)
the barbiturate, as a result of inhibition of the microsomal enzymes. The import-
ance lies in the fact that many drugs used in medicine are also dealt with by
these enzymes; and it is to be expected that their functions will be impaired in
the case of any recent or habitual cannabis user. The effect is not due to TIIC
itself, but mainly to another constituent of the resin, cannabidiol. One hopes that
cannabis users seeking medical treatment would inform their doctors accord-
ingly the main danger would be of overdosage or of overprolonged action.
A recent report has concerned the loss of brain substance, as measured by the
technique of air encephalography, in a group of ten young heavy cannabis users.
The enlargement of the ventricles of the brain is of the type that occurs in old
age, or in middle years with chronic alcoholics. The work needs confirmation,
since although the subjects had taken hundreds of doses of cannabis, they also
had a number of doses of LSD or amphetamines, and occasionally heroin. One is,
however, bound to take it seriously, since cannabis, the main drug used by the
patients, is cumulative, with a very high affinity for fat, and able to impair
cell division by lymphocytes in tissue culture.
Cannabis has been found to produce fetal deformities and fetal resorption
in animals (rats, rabbits and hamsters) in doses (per unit weight) ranging
down to that used in man. The effect has been shown to be dose-related, and
(unlike the teratogenic effect in animals of many drugs, but like thalidomide
and other known human teratogens) is exerted at a small fraction of the dose
liable to kill the mother. It is not clear what the effect in the human is, and it is
to be hoped that it is the human equivalent of fetal resorption (miscarriage)
rather than teratogenicity. Tests for chromosome damage have been negative, so
that there is no evidence for a heritable genetic defect ; but the same tests showed
an impairment of cell division, and it may well be this, applied to the developing
fetus, which causes the reduction deformities. The teratogenic effects appear
to be due to some factor other than THC in the resin.
There is much debate about the connection between cannabis and criminality.
A reasonable view, covering other aspects of behavior, is that cannabis may accen-
tuate a particular mood or facilitate a train of action and such a process could well
explain the case of violence described. A similar position could hold about the
connection with sexual behavior. But here two other contrasting factors enter;
the alteration in time sense would change the apparent duration of sexual inter-
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2
course ; and the predisposition to fantasy may replace actual activity with im-
ages of it. There is, too, the unexplored possibility that the circulatory effects of
cannabis Include a mild genital engorgement.
More important, however, is likely to be the effect of repeated use described
as the "amotivational syndrome". This term dignifies a still imprecisely charac-
terized state, ranging from a feeling of unease and sense of not being fully ef-
fective, up to a gross lethargy, with social passivity and 'deterioration. It is dif-
ficult to assess, when personal traits and intellectual rejection of technological
civilization are also taken into account. Yet the reversibility of the state, its as-
sociation with cannabis use, and its recognition by cannabis users make it impossi-
ble to ignore.
ESCALATION THEORY
Attention has mainly concentrated on progression from cannabis to heroin
or other opiates. Although only a very small proportion of casual users progress,
it is much commoner with heavy users, and the vast majority of opiate users
have prior experience of cannabis. Although it is often said that there is no
pharmacological basis for such progression, this in fact exists, since cannabis
increases suggestibility and shares with heroin (though in milder form) the
ability to produce euphoria and analgesia.
But the situation is a more general one. It seems probable that amphetamine
use also predisposes to heroin use; and the overlap in actions between cannabis
and LSD makes intelligible the observed progression to LSD. The role of prior
use of "soft" drugs, or use of drugs by "soft" techniques in predisposing to more
serious abuse needs much more study, particularly by methods which can estab-
lish objectively the actual amount of drug used. Although it can only be one of
many factors, it could be important in the prevention of serious abuse.
TOLERANCE AND DEPENDENCE
Tolerance to the behavioral effects of cannabis and of TIIC in animals has
now been repeatedly demonstrated. As with the fat-soluble barbiturates, the
first few doses may cumulate, masking the underlying development of insensi-
tivity to the drug's effects. It is not clear whether the tolerance results from
increased destruction of the drug or a resistance at the cellular level.
In man, the evidence is largely and anecdotal and uncontrolled (this applies
to Weil and Zinberg's data, since the experimental subjects but not the naive
were told what they were to receive). There is limited evidence that THC
disappears somewhat faster from the blood users as compared with naive sub-
jects. Perhaps the best evidence is still that in the Laguardia report, where it
was found that a three times higher close was required to produce a given
degree of ataxia in users than in non-users. Withdrawal symptoma of morphine
or barbiturate type do not occur : but after heavy use, depression, anxiety, sleep
disturbance, tremor and; other symptoms develop, and many users find it very
difficult to abandon cannabis use. In studies on self-administration by monkeys,
spontaneous use did not occur, but once use was initiated, drug-seeking be-
havior developed. Subjects who have become tolerant to LSD or opiates as a
result of repeated dosage respond normally to be cross-tolerance between can-
IN CONCLUSION
The salient fact about cannabis is that it is a mixture of substances, whose
psychically active principle is highly fat-soluble. It seems likely that for the
foreseeable future it will be the crude material that is used. The outstanding
problem, therefore, is that of the effects of chronic use, not only of TIIC but
of the other constituents. The significance of toratogenesis, of microsomal
inhibition, of the amotivational syndrome, and of the observations on brain
damage needs clarifying. Hitherto, dependence-liability has rested largely on
assertion, but definite evidence should. be forthcoming. Methods of measurement
of the cannabinoids or their products in blood or urine should also be to hand
before too long. One can say, at last, that "work is in progress."
Many general points have been omitted. But three final comments are needed.
First, no comparison has been attempted with other drugs such as alcohol which,
because of the peculiarities of cannabis, is in any case complicated. But it
must be emphasized that such a comparison requires a major effort of the
imagination. To estimate the probable result of treating cannabis like alcohol
one must suppose it to be as readily available, with equivalent advertisement
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and promotion, in an equivalent range of potencies, and used by a comparable
proportion of the population. It is peculiarly difficult to extrapolate in this
way, given only our knowledge of widespread use of relatively weak crude
material in the USA, of less common use of more active material in this country,
and poorly characterized endemic use in developing countries. Second, too much
stress has been laid on reports such as those by the Indian Hemp Commission :
these were relevant to knowledge of the day and the social conditions of a
subject country with a low expectation of life, but not to modern conditions
in which society and its members expect so much of each other.
Finally, cannabis occupies a fascinating position in the debate of what society
should tolerate, and the outcome of the debate will be important. Despite the
damage done in later life by alcoholism, it is possible to draw a line between
it and cannabis : there seems no rational basis for drawing a line between
cannabis on the one hand and LSD, the amphetamines or the less potent opiates
on the other.
The older literature is rapidly becoming scientifically obsolete and much new
information is appearing in current journals. Recent reports include :
The Use of Cannabis.-W110 Technical Report Series No. 478. Geneva 1971.
Marihuana and Health.-A Report to Congress. Washington 1971.
The Botany and Chemistry of Cannabis.- (Proceedings of a conference or-
ganized by the Institute for the Study of Drug Dependence). Ed. C R B Joyce
and S H Currey. Churchill, London 1970.
Marihuana: Chemistry, Pharmacology and Patterns of Use.-Annals of NY
Acad Sci Vol 191 (1971).
[From the Lancet, Dec. 4, 1971 I
CEREBRAL ATROPHY IN YOUNG CANNABIS SMOKERS
A. M. G. Campbell
Department of Neurology, Bristol Royal United Hospitals
M. Evans
Department of Psychiatry, Whitchurch Hospital, Cardiff
J. L. G. Thomson
Department of Radiology, Frenchay Hospital, Bristol
M. J. Williams
Department of Medicine, Bristol Royal Infirmary
Editorial szumnnary
1. "Personality changes and mental illness have been re-
ported in chronic cannabis smokers over a period of 3-11
years. Addicts often have impairment of recent memory,
vegetative symptoms, and a tendency to reversed sleep
rhythm suggesting organic brain damage."
2. A study of ten youthful patients with histories of
consistent cannabis use over a period of 3-11 years showed
serious brain atrophy, comparable to the atrophy that nor-
mally takes place between ages 70 and 90.
3. The brains of monkeys given isotope-labelled canna-
binols intravenously showed concentration of the drug in
the frontal lobes and cortex and other brain sectors near the
third and lateral venticles. After 24 hours, the drum had
spread uniformly throughout the brain. The fat solubility of
the cann'abinols make it likely that they would accumulate in
the nervous tissues, including the brain, because of their high
fat content.
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4., Chronic abuse of cannabis and LSD produce symptoms
similar to those of encephalitis lethargica-an inflammation
of the lining of the brain characterized by extreme lethargy.
Among these symptoms are, reversal of sleep rhythms, hal-
lucinations, loss of memory, inability to work, and a falling
off of moral character.
5. "For many years the production of cerebral atrophy
in boxers was not. realized. We would suggest that a similar
state of affairs is happening in relation to drug abuse. Far
too much attention has been paid to psychological and be-
havioral. disturbances without relating these to the possi-
bility of permanent damage to the brain."
Evidence of cerebral atrophy was demonstrated by air encephalography in ten
patients with histories of consistent cannabis smoking over a period of 3-11
years. The average age of the patients was 22 years ; all were males. Ampheta-
mines and lysergide (L.S.D.) had also been taken, but in much smaller amounts.
Measurements of the lateral and third ventricles were significantly different
from those in thirteen controls of a similar age-group.
Personality changes and mental illness have been reported in chronic cannabis
smokers of previously normal personality [1]. Addicts often have impairment of
recent memory [2], vegetative symptoms, and a tendency to reversed sleep rhythm
suggesting organic brain damage. If organic brain damage were confirmed, this
would clearly lead to a different approach to the problem of increasing drug
abuse.
This study was prompted by the finding of cerebral atrophy on air encephalog-
raphy in four young patients referred to one of us (A. M. G. C.) for neurological
investigation of headache,; memory loss, or behavior change. A common factor
in all four histories was prolonged heavy cannabis smoking. Amphetamines and
lysergide (L.S.D.) had also been taken, but in very much smaller amounts. Since
no recognized cause of the cerebral atrophy was apparent, neurological and
radiological investigation of other cannabis smokers seemed indicated.
Patients
The first four cases were unselected routine admission for investigation of neu-
rological symptoms. The next five were under treatment by one of us (M. E.) for
drug abuse, and were referred for detailed investigations of cerebral function,
including air encephalography. They were selected because of known long-stand-
ing cannabis smoking ; two, bad been attending a drug-addiction center for some
time and the other three were the next cases which presented to psychiatric
outpatients with histories of long-standing cannabis smoking. The tenth patient
was admitted as all emergency with a drug overdose and had a 6-year history of
drug abuse with heavy cannabis intake. All these cases were given a full clinical
examination and were investigated by air encephalography.
It was fully explained to the patients that the test was to assess possible brain
damage with a view to ultimate prognosis, and our patients willingly consented
to this investigation, which was done under local anesthesia and sedation.
Controls
One of the main difficulties in estimating the size of the cerebral ventricles
by air encephalography is the choice of controls. Most published series include
patients of all ages ; however, the ventricles enlarge with age [3]. The mean age
of our patients was 22 years. To obtain normal values for the age range 15-25
years we reviewed the X-ray films and notes of all cases investigated by air
encephalography in our neuroradiological unit in which the findings had been
reported at the time as normal. We excluded all those with abnormal neurological
signs, a raised cerebrospinal-fluid (C.S.F.) protein, or other abnormal features.
In this way we obtained thirteen controls; their ease-notes indicated that these
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had originally been referred because of symptoms such as headache, loss of con-
sciousness, or syncope. Subsequent follow-up on all of these patients had not
revealed the development of any neurological illness. A typical control air enceph-
alogram is shown in fig. 1. Particular attention should be paid to the shape of
the lateral ventricles anteriorly, especially the sharpness of the lateral and
inferior angles and the upward and inward curve of the floor of the body and the
posterior part of the frontal horns.
Of the thirteen controls, seven were female and six male. The series of ten
drug-taking patients were all male. However, air-encephalograms on the female
controls were not significantly different from those of the male controls.
Radiology
The standard air-encephalography technique was used in all cases. About 25 ml.
of air was injected into the lumbar subarachnoid space with the patient in the
sitting position, under basal sedation. Just enough cerebrospinal fluid for routine
laboratory testing was removed. Films of the patient's head were taken in this
position, and again with the patient supine and prone. Routine views of the tem-
poral horns were also taken. Measurements of the anterior ends of the lateral
ventricles were taken from films obtained in the anteroposterior position with
the patient supine. Measurements of the lateral ventricular size were carried
out using three standard di:.cnieters, and an accurate area measurement was also
obtained by using a planimeter, an instrument that mechanically integrates a
trace of the perimeter of an object into the .objeet. [31 These measurements are
illustrated in fig. 2:
"A" is the widest transverse diameter of the frontal horn.
"B" is the oblique diameter from the lateral angle to the junction of the floor
of the body of the lateral ventricle with t.lie medial wall.
"C", a line at right angles to B, 5 mm. from its lateral extremity, gives a
measure of the lateral angle of the ventricle.
"D" is the transverse diameter of the third ventricle, the posterior width being
taken from the film with the patient sitting up, and the anterior width from
the film with the patient supine.
"Ii" is the area of the shadow of the posterior part of tine frontal horn of the
lateral ventricle (indicated in fig. 2 by the shaded area, and shown in fig. 3 for
all cases).
Other Investigations
C.S.F. obtained at air encephalography was examined under the microscope
and analysed for protein, Wassermann reaction, and Lange curve. The c.s.F.
pressure was normal in all cases. Skull and chest X-rays were taken in all cases.
Venous blood was tested for haemoglobin, leucoaytecount, crythrocyte-sedimen-
tation rate, urea, electrolytes, and liver function. Results were normal except
Case 1
An unemployed steel erector, aged 22, complained of generalized headache over
recent months. He had had a probable epileptic fit at age 13 but had not been
investigated or treated. It was not known whether he had suffered any birth
injury, and there was no family history of epilepsy. At age 18 he was in hospital
for 3 days because of a head injury. 3 weeks later he had a grand-real epileptic
attack, with four similar attacks in the next year. The head injury would seem
to have exacerbated pre-existing epilepsy.
He had smoked cannabis regularly and frequently since the age of 10. L.S.D.
had been taken about twenty times, but he did not admit to taking ampliet
amine.
On examination lie seemed restless, anxious, suspicious, irritable, and
despondent. There were no abnormal neurological signs.
)llectroencephalography was outside normal limits, displaying minimal fea-
tures in all areas. There were no focal abnormalities.
At air encephalography diameters A and B were within the normal range, but
diameters C were increased and the back ends of the lateral ventricles were some-
what "square" (fig. 4). The third ventricle diameter D was towards the upper
limit of normal. The area measurement B was increased on both sides.
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Casa 2
An 18-year-old unemployed salesman was admitted for investigation of change
in behavior and impairment of recent memory. He said he was becoming
increasingly aggressive and could not understand his own behavior. There had
been frequent generalized headache over the previous month. He was an adopted
son and his own family history was unknown. At the age of 1 year he had whoop-
ing-cough and at 13 he had hepatitis, but neither produced neurological com-
plications.
Drug abuse started when he was 14, amphetamines being passed to him by a
fellow choirboy. Within; a year he was smoking cannabis regularly and fairly
heavily three times a week, and continued to do so. He had taken L.S.D. about
twenty times and heroin four times, but discontinued the amphetamines after
the first year. Ile abandoned A-level studies at a technical college and there-
after could only work as a salesman for a short time.
On examination he was excited, exhibited pressure of speech, poor memory,
and lack of insight. There were no abnormal physical signs.
At air encephalography diameters A and C (especially C) were increased on
both sides. The width of the third ventricle posteriorly was outside normal
limits, and the trigone of the left lateral ventricle was rather "square". The
area measurement E was also increased on both sides, left more than right (fig. 5).
E.E.G. was normal.
-I
l1
Tig. 2--- Mcnsuarcments We.d In n8ses8in5 ventricular ei-zo (gra
text).'
Areas in sq.cm. Shown in table.
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CONTROLS
F G Fi J K L (!!
A C
2 3 4 5 6 7 10
CASES
Pig. 3-Outlines of the areas (E) measured by plnnographic method (sec table).
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218
Case 3
A 21-year-old computer operator was admitted for investigation of frequent
headaches of a year's duration. He also complained of poor concentration. There
was no history of birth injury or other significant illness. At age 8 he had had a
minor head injury and was unconscious for half-an-hour but did not require
hospital admission.
He had smoked cannabis regularly since the age of 15, had taken L.S.D. twice
and amphetamines about ten times. Since leaving grammar school he had fre-
quently changed his work, but after his marriage a few months before admission
he had stopped taking drugs, and had stayed in the same job.
On examination he was anxious, morose, and withdrawn. Ile was unable to
give a clear account of his symptoms, about which he seemed very concerned.
There were no abnormal physical signs.
At air encephalography the diameters A, B, and C of the left lateral ventricle
were well outside normal limits (fig. 6). The width of the third ventricle was
outside normal limits also, both anteriorly and posteriorly. The trigonal region
was "square" on the left side, the left temporal horn dilated, and the surface
sulci rather prominent. The area measurement E was increased on the left side.
Case It
An unemployed laborer aged 24, son of an academic, complained of depression
and left :frontote.mporal headaches over the previous 10 months. He also had
attacks of photophobia, not necessarily associated with the headache. During
the previous year he had twice briefly lost his sense of awareness. Ile had not
fallen, convulsed, or lost consciousness, and witnesses described him as looking
vacant for a few moments. There was no significant past illness, but it was
not known whether he had suffered any birth injury nor if there was a family
history of epilepsy. 3 years previously he had been involved in a motor accident
when he had a blow on the head, losing some teeth but without loss of conscious-
ness. Since leaving grammar school, aged 17, he had held many jobs for short
periods.
Ile gave a 4-year history of drug-taking, but denied taking amphetamines. He
smoked cannabis regularly four times a week, L.S.D. had been taken on about
thirty occasions, and mescaline and `Mandrax' (diphenhydramine and metha-
qualone) occasionally.
On examination he was unkempt, withdrawn, and uncommunicative. Ile was
emotionally flattened, and at times his thoughts were disjointed. There were no
abnormal physical signs.
At air encephalography the diameters A, B, and C of the left lateral ventricle
were all slightly increased (fig. 7). The width of the third ventricle was within
normal limits. The left trigonal region was rather "square". The area measure-
ment E was increased on the left side.
E.E.G. was normal.
Case 5
A 20-year-old clerk complained of loss of concentration and memory loss for
recent events over the previous 10 months. He had become irritable and depressed
and volunteered to being increasingly inefficient and careless at work. His birth
had been normal, and there was no history of significant illness or trauma.
Ile had started taking amphetamines at school when 14 years old, and within
a year was smoking canhabis. This had become the main drug of dependence,
although he had taken others, including two doses of L.S.D. Cannabis had been
smoked once or twice daily over the past 18 months.
On examination he was mentally retarded, thinking with obvious difficulty,
and with poor memory for recent events. There were no other abnormal neuro-
logical signs.
At air encephalography the diameters A and B were within normal range, but
the diameters C were slightly increased. The width of the third ventricle was at
the upper', limit of normal. The area measurement E was within normal limits.
Case d
A 22-year-old unemployed man complained of difficulty in recalling recent
events, and also of periods of amnesia with occasional headaches. He described
permanent alteration of vision after some years of drug abuse, with alteration
of bright lights into colors : "On a sunny day I have a lot of extra color with-
out drugs-that's very nice". There was no history of birth injury, trauma to
the head, or significant past illness.
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fie had a 7-year history of drug abuse, starting with cannabis and ampheta-
mine at age 15. Cannabis remained the chief drug, although he had also taken
a large amount of L.S.D. and occasional barbiturates. Ile left school aged 15 Navy.
Since
then and then had 4 months sea viand1has notl~orked for the past 4 yearshad been
Over
unable to hold any job ob for long, .
the previous 18 months his mental state had rapidly deteriorated, with inter-
mittent confusional states and paranoid psychosis. There seemed to be a striking
difference between the bright lively youngster of 14 who was interested in fish-
ing and shooting and was able to strip down and maintain a motorcycle, and
the retarded, slothful, emotionally labile, and intolerant man of 22.
Ile had no abnormal neurological signs.
At air encephalography the diameters A and B were within the normal.
range but the C diameters were increased (fig. 8). The width of the third
ventricle was towards the upper limit of normal, and the right temporal horn
was larger than the left. The area measurement E was increased on both sides.
Case '7
A 26-year-old unemployed clerk complained of poor memory and frontal head-
ache. He described several brief episodes over recent months during which he
noticed a sensation of heat in the head, pounding in the temples, and loss of
vision followed by visual hallucinations. There was no history of birth injury
or any subsequent trauma to the head. Ile had had eczema at age 2 and had
been treated with sedatives off and on for several years.
He first smoked cannabis at age 15, but stopped while in the Army for 4 years.
Ile described regular and heavy dependence on cannabis over the past 2 years.
A large amount of L.S.D. had been taken but not much barbiturate or ampheta-
mine.
Abnormal traits were characterized by superficial personal relationships,
failure to develop any continuing interest, and inability to learn from experience
or to apprehend any long-term consequence of his behavior. There were no
abnormal neurological signs.
At air encephalography the diameters A and B were within the range of
normal, but the C diameters were slightly increased. The width of the third
ventricle was towards the upper limit of normal. The surface sulci frontally were
rather prominent. The area measurement E was towards the upper limit of
normal.
E.E.G. showed paroxysmal slow activity in all areas with no focal abnormal-
ities, and the background pattern was normal.
Case S
A 28-year-old man had been severely psychiatrically disabled with a schizo-
phrenic illness marked by episodes of excitement and confusion for over 5 years.
There was no history of birth injury or other significant past illness.
At age 16 he started taking amphetamines, having left his work as a clerk and
joined a group of potato pickers. At this time he also started drinking alcohol
heavily. When 17 he smoked cannabis for the first time, and had continued
taking it as the preferred drug since then. With money received as compensation
for a facial injury he financed a visit with friends to a Spanish island, where lie
drank a lot of wine, smoked cannabis heavily, and took five doses of L.S.D.
despite the fact that it produced devastating reactions. He remained there for
6 months and was probably in a very confused and hallucinated state most of
that time, 6 months later he was admitted to Whiteburch Hospital with a schizo-
phreniform reaction, and he has been under continual treatment since then.
At recent examination there were no abnormal neurological signs, but over
the previous 6 years there have been frequent episodes of apparently spontaneous
wide dilatation of the pupils.
At air encephalography the diameters A and B were within the normal range
but the C diameters were increased. The width of the third ventricle was outside
normal limits, particularly posteriorly. The left temporal horn was dilated and
the surface sulci over the left hemisphere were prominent. The area measurement
B was increased on both sides.
F.E.G. was normal.
Case 9
This 21-year-old man complained of poor concentration and memory over the
past year. He had no significant past illness, head injury, or birth trauma.
Ile started taking amphetamines when 14 years old and was soon smoking
cannabis and taking barbiturates. From the age of 17 he had occasional L.S.D.
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220
and intravenous morphine, but cannabis and barbiturates had remained the
main drugs. The recent clinical picture was that of an excited overactive state
with periods of confusion. He seemed to have a blurred and telescoped view of
his drug-taking history.
On neurological examination he was found to have some clumsiness of fine
movement, of the left hand.
Serum-aspartate-aminotransferase was raised to 37 I.U. There was no history
of jaundice or excessive alcohol intake, and no evidence of hepatomegaly.
At air encephalography the diameters A, B, and C were well within normal
limits. The width of the third ventricle was also within normal range. The left
temporal horn, however, was much dilated. The area measurement E was well
within normal limits.
Case 10
This 26-year-old man was admitted as an emergency with an overdose of L.S.D.
He had been unemployed for several years after only a year at university, where
he had become less able to continue his work after starting taking drugs. There
was no history of birth injury, significant past illness, or trauma.
He gave a 7-year history of drug addiction, starting with amphetamines and
cannabis at age 19. By the time of admission lie was taking large amounts of these
drugs as well as occasional L.S.D. He admitted to being in a perpetual state of
confusion and carelessness, and complained of poor memory.
On examination after recovery from the acute episode of L.S.D. intoxication,
it was noted that he had persistent clumsiness of fine movement of the left hand,
but no other neurological signs.
At air encephalography;the diameters A and B were within the normal range
but the diameters C were increased. The width of the third ventricle was towards
the upper limit of normal. The right temporal horn was a little dilated. The area
measurement E on the right side was towards the upper limit of normal.
An E.E.G. showed abnormal slow activity in the temporal lobes on both sides.
RESULTS
Descriptions of individual air encephalograms have been given with the case
histories. Comparison of the diameters of the lateral and third ventricles showed
that, between the control and the drug-abuse groups, the diameters A and B were
not statistically different. But the diameters C and D and the area measurement
E showed more striking changes, and these were statistically significant. The
table shows the measurements and distribution of C, D, and E for the controls
and the drug-abuse group. We could not measure D in one control where the
posterior diameter of the third ventricle was not well enough shown. The areas
E measured by planimetry!are shown in fig. 3.
Besides these differences in the bodies and frontal horns of the lateral ventri-
cles there were other isolated abnormal features in the drug addicts. Temporal-
horn dilatation was found' in five of the cases, and in one of those the dilatation
of the horn was the sole abnormality found (case 9). The trigonal region of the
lateral ventricles as seen in the prone films was also considered abnormally
"square" in three of the cases (see fig. 4), and surface air showed dilated sulci
(>3 mim.) in two of the ;cases in the frontal region. There were none of these
abnormalities in the control group.
Study of the diameters A, B, and C and area B showed that on average the
left lateral ventricle is slightly larger than the right in both the control and the
drug-abuse groups, but that this difference is magnified in the drug-abusers. This
asymmetry is not uncommon, but has never been satisfactorily explained. Its
relationship to left-sided cerebral dominance is of interest, and in this respect
it should be noted that all. our patients were right-handed.
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MEASUREMENTS C AND D AND AREA MEASUREMENT E FOR THE CONTROL AND DRUG-ABUSE GROUPS
Controls:
A
3
4
3
3
1.8
2.4
B
4
4
3
4
2.6
3.7
C
3
3
4
5
1.6
1.2
D
4
4
4
4
1.8
1.8
E
5
5
4
7
1.4
1.6
F
7
8
4
6
3.4
3.0
G
6
6
5
6
3.2
3.1
H-----------------------------------------
7
7
5
7
3.0
2
4
3.1
2
8
------------------------------------------
5
5
7
6
.
3
.
1
3
-----------------------------------------
5
5
4
4
3.
2
9
.
2
6
K -------------------------------------
4
4
3
3
.
2
.
2
3
L--------------------------------------
----
4
5
4
5
.9
1
.
1
8
M-----------------------------------------
5
5
3
3
.6
.
Cases:
1
7
8
5
6
4.6
5.8
2
9
9
5
8
4.0
4.4
3
4
9
8
8
2.6
4.9
4
5
10
4
5
2.9
4.1
5
6
6
7
6
3.2
3.0
6
9
9
6
6
4.0
4.3
7
6
6
7
7
3.2
3.4
8
8
8
8
10
4.3
4.6
9
5
5
4
5
2.1
2.2
10
---------------------------------------
6
6
6
6
3.4
2.4
--
Mean of controls--------------------------------
4.8
5.0
4. 1
4.7
2.5
2.9
Mean of cases-----------------------
6.5
7.6
6.0
6.7
3.4
3.1
L
P----------------------------------------------