HomeMy WebLinkAboutCOM 0093.013 1998-2000O
Aloha County Council Chair Ayikaki and council
Greetings to new council members and Mahalo for your attention to my testimony.
What the county is doing is perpetuating a un -reviewed program and disobeying the
county charter. RECEIVED
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What the county should be doing is protecting the privacy rights of citizens. Dat y'Y ----
County Coundl
Article I sect. 6 of the Hawaii Sate Constitution was enacted specifically to allow the
private use of Cannabis in the home
The county should prohibit the prosecutor and police from spending county tax dollars on
cannabis crimes
Rather should the prosecution of cannabis crimes be placed at the lowest order of priority
especially with regard to the medical or religious use in the privacy of the home
I will submit to the council a suggested resolution or ordinance requiring the Prosecution
of cannabis crimes to be placed at the lowest order of priority only arresting someone on
the occasion of other crimes thus freeing the police to concentrate on solving real crimes
like the death of Dana Ireland.
I have for your benefit supplied a number of pieces of information some of which is
referenced in my testimony. Should any of you have any questions regarding this
material please ask me.
In the last meeting on mandatory program review I witnessed Prohibitionist and
bureaucrats deliver a number of misconceptions and outright lies to the council and the
public.
The first such misconception is that eradication is necessary to increase the public safety
Eradication has acted to drive the cost of Hawaii Cannabis from $100 to over 500 Dollars
per ounce
increasing the value to a cost greater than gold also increases the likely hood that greed
driven profiteers might use violent means to secure their crop
in 1989 when warren price was attorney general he pegged the value of Hawaii's
Cannabis crop at 10 billion Dollars. What Hawaii drug law enforcement advocates failed
to tell legislators is that the nearly 10 per cent of Hawaii Islands population who grew this
cannabis were adding hundreds of millions of dollars in tax revenues through the 4%
sales tax. The impact of green harvest was a short fall in state revenues that resulted in the
budget cuts and raised taxes of the last four years.
ODMM No. 73.1-5
File No. POS
Ref. Tot Presented COOAc,�
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Another lie told the public is that Cannabis is a dangerous drug, this in the face of
government subsidies to tobacco farmers and tax revenues generated from alcohol and
tobacco
I heard expert testimony in my trial for the religious freedom to use Cannabis to the effect
that the death toll due to alcohol and tobacco in the united states stands at 500,000 per
year while the death toll due to Cannabis ingestion stands at zero for the last 5000 years
of recorded history and will remain at zero for the next 5000 years because it is
impossible to ingest a amount of cannabis large enough to be fatal
I have heard testimony from the American Cancer Society in these chambers to the effect
that smoking Cannabis is as harmful or potentially more cancer causing than tobacco.
a study by Donald Tashkin shows that in the long term Cannabis smoking does not
deteriorate lung capacity and respiratory response in fact a strict interpretation of his
numbers show that Cannabis smokers had a slightly better rate of decline in lung capacity
and respiratory response than did the control group which smoked nothing at all. Even
more illuminating is the finding that smokers of Cannabis and tobacco had a 58% better
response than did tobacco only smokers.
If Cannabis is cancer causing this would show up as a higher mortality rate than non
Cannabis smokers yet in a Kaiser Permanente study of -65,000 patients, current women
Cannabis smokers died from all cancers at a rate 44% less than non-smokers
men did less well but also had a 25% lower rate of mortality due to Cancer than did their
counterparts
I gained 3 recommendations for Medical Cannabis on my repatriation to California the
state of my birth this past spring.
One of the conditions for which I suffer is asthma I am a life long sufferer from this
debilitation I have a study before you from the Veterans administration which shows that
Cannabis expands the airways by 44% this medicinal effect allows me to live in relative
comfort downwind of the worlds most active volcano now approaching its 16a' year of
continuous vog producing eruption.
Mahalo and Aloha
Rev. Dennis [Jesus in me
loves Jesus in you] Shields
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US: Column: Dumping DARE A Good Start
Newshawk: Jerri Merritt
Pubdate: Tues, 8 Dec 1998
Source: Denver Post (CO)
Contact: letters@denverpost.com
Website: http://www.denverpost.coin/
Copyright: 1998 The Denver Post
Columnist: Diane Carman, Denver Post Staff Columnist
dcarman@denverpost.com
DUMPING DARE A GOOD START
Dee. 8 - It's only a baby step, the tiniest movement toward rational public
policy. A handful of cities have dared to dump the DARE program.
Like most aspects of the war on drugs, DARE has been a colossal waste of
money. A study commissioned by the U.S. Justice Department found the
program's effectiveness at keeping kids off drugs to be "statistically
insignificant."
Basically, the war on drugs makes the war on poverty look like a
resounding success. And we all know the war on poverty was our
domestic Vietnam.
Since 1971, the U.S. has spent an estimated $1 trillion on the war on
drugs.
In that time, illegal drug use has mushroomed and black-market prices
have soared. In this country, commerce in illegal drugs is estimated to be
a $150 billion -a -year industry. The U.N. estimates illegal drugs. account
for 10 percent of the world's trade - all tax-free.
While marijuana laws are enforced with enthusiasm in the U.S., the
percentage of adolescents using marijuana is twice as high here as in the
Netherlands, where the substance is legal.
Columbia University, meanwhile, determined that education and
treatment of substance abusers is seven times more cost-effective than
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US: Column: Dumping DARE A Good Start O
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arrest and incarceration. Still, among industrialized countries in the
world, the U.S. lags far behind in spending on treatment programs - and
way, way ahead in incarceration.
Instead of paying the annual cost of $2,000 to $5,000 per addict for
outpatient treatment or up to $15,000 for long-term inpatient programs,
we spend $25,000 to $50,000 a year to jail addicts, leaving their complex
medical and psychological problems untreated.
More than 400,000 Americans are in prison on drug charges. Among
federal prisoners, 65 percent are doing time for nonviolent, drug-related
convictions. One in nine American schoolchildren has at least one parent
in prison.
The patently racist drug laws deliver their harshest penalties to inner-city
crack addicts and dealers, while giving much lighter sentences to the
well-heeled snorting cocaine in Beverly Hills and Cherry Hills Village and
Washington, D.C. It takes possession of 500 grams of powdered cocaine to
incur the same mandatory five-year sentence as possession of 5 grams of
crack cocaine.
Thanks largely to the U.S. war on drugs, the economies of Colombia,
Bolivia and Peru are so dependent on black-market cocaine trafficking
that no amount of American foreign aid can compensate for the revenues
that would be lost if production were curtailed.
The failures in the war on drugs have been so spectacular and so
thoroughly documented that it's clear the only reason it continues is that
Americans have been brainwashed by self-interested political leaders and
the tidal wave of propaganda, of which DARE represents but a trickle.
If we really cared about protecting our children from the scourge of drug
addiction, we'd demand that the government abandon the war on drugs
and employ some of the cheaper and vastly more effective programs under
way in other countries.
We'd demand that leaders stop wasting our money on ill-conceived prison
programs and spend it giving our kids preparation for the kind of future
that makes wasting their lives on drugs unthinkable.
Checked -by: Richard Lake
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US CA: Study Highlights
Newshawk: General Pulaski
Pubdate: Sat, 19 Dec 1998
Source: San Jose Mercury News (CA)
Contact: _Letters@simercury.com
Website: http://www.simercury.com/
Copyright: 1998 Mercury Center
Author: Associated Press
STUDY HIGHLIGHTS
The annual Monitoring the Future study has examined teen drug use and
attitudes since 1975. The anonymous survey was administered early this
year to nearly 50,000 teenagers in 422 randomly chosen classrooms by the
University of Michigan's Institute for Social Research.
ANY DRUG: Nearly 30 percent of eighth -graders have tried an illegal
drug at least once. It was 45 percent for 10th -graders, 54 percent for high
school seniors. This was the first year the figure had dropped for the older
two groups and the second yearly drop among eighth -graders.
MARIJUANA: This most widely used drug was tried by 22 percent of
eighth -graders, 40 percent of 10th -graders and nearly half of
12th -graders. Use among eighth -graders dropped for a second year; use
among other teens dropped after several years on the rise.
STIMULANTS: Use has declined for two years among eighth -graders and
for one year among 10th -graders, and is level among 12th -graders. About
7 percent of eighth -graders used amphetamines in the past year. It was
11 percent of 10th -graders and 10 percent of 12th -graders.
HALLUCINOGENS: All grades showed declines, though they were not
statistically significant.
INHALANTS: Popular with younger teens, use began gradually declining
three years ago.
HEROIN: Stable use across all grades and increasingly viewed as risky.
loft
19/9916Q a.nz nnrt
-WS CA: Sturly Highlights O Ihttf'rw.mapinc.org/drugnewe/v98.n1185.aU3.litnit/all
11 11
COCAINE: Small increases in use of crack cocaine in younger grades.
ALCOHOL: Continued stable use among eighth- and 10th -graders. After
increasing among 12th -graders last year, it was stable among them, too.
About seven in 10 sophomores said they had drunk alcohol, and one-third
of seniors reported being drunk in the last month.
CIGARETTES: A drop from last year's all-time high among high school
seniors, with 22.4 percent smoking daily. That still was higher than the
low point of 17.2 percent in 1992. Black teens continue having the lowest
smoking rates, with just under 15 percent of black seniors saying they
smoked in the past month.
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IIS. body'K,0~ Ila Own Medical Marijuana O httww.mapu.c.org/drugmtw elvO8.n 1187.a l0.html/all
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US: Body Has Its Own Medical Marijuana
Newshawk: General Pulaski
Pubdate: 17 Dec 1998
Source: Florda Times -Union (FL)
Contact: mailto:iaxstaff@iacksonville.com
Website: http://www.times-union.com/
Forum: http://cafe._iacksonville.com/cafesocietv.html
Copyright: The Florida Times -Union 1998
BODY HAS ITS OWN MEDICAL MARIJUANA
WASHINGTON -- Amid this year's clamorous battles to legalize medical
marijuana stands this little-known fact: Our brains and bodies are flooded
with a natural form of the drug.
Called cannabinoids, this family of compounds blocks pain, erases
memories and triggers hunger. Studies show they may also regulate the
immune system, enhance reproduction and protect the brain from stroke
and trauma damage.
Discovered in humans just a few years ago and, until recently, virtually
unstudied, the compounds have become one of the looming mysteries of
the nervous system.
Already, scientists are testing cannabinoids with hopes of harnessing the
medical power of marijuana to treat pain without its high, smoke or
political baggage.
A key challenge is separating the curing power of the compounds from
their mind -altering side effects.
Because cannabinoids are so numerous in the brain, they also could help
explain the workings of some of our body's most complex, and least
understood, systems.
"It's obviously important because there's so much of it. And we never
knew it existed before," said J. Michael Walker, a Brown University
psychologist who has conducted some of the first studies of how
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US: Body tlas Its Own Medical Martj"ana O
cannabinoids block pain.
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There has always been evidence, from the intoxicating effects cannabis
evokes in smokers, that it contains powerful compounds.
The sticky, flowering buds of the plant have been harvested as medicine
for centuries.
Now, scientists are beginning to understand just what natural
cannabinoids might be doing in the human body.
For example:
Cannabinoids have been found to both suppress and enhance the body's
defenses against diseases and tumors, a duality that has researchers
puzzled. "It's a science clearly in flux," said Thomas Klein, an
immunologist at the University of South Florida.
While pot warnings -- "This is your brain on drugs" -- have long
spotlighted the drug's damaging effects on the brain, research last
summer from the National Institute of Mental Health shows cannabinoids
protect brain cells from stroke or trauma damage.
Last year, scientists at the Neurosciences Institute in San Diego showed
that cannabinoids block the formation of new memories in slices of animal
brain tissues. This power to forget might keep the brain from filling up or
getting overwhelmed with unimportant memories.
Researchers' largest hopes are focused on using a synthetic form of
cannabinoids to block pain, including chronic nerve pain that can't be
adequately blocked with existing drugs.
Animal studies show cannabinoids can block other kinds of pain almost
before they begin -- stopping the pain signals before they reach the spinal
cord or brain, working as well as morphine.
Checked -by: Mike Cogulski
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US CO: Column: The Dire Consequences Of DARE
Newshawk: cohippllevellers.org (Colo. Hemp Init. Project)
Pubdate: Fri, 4 Dec 1998
Source: Boulder Weekly (CO)
Contact: bweditor@tesser.com
Website: http://www.boulderweekly.com/
Author: Wayne Laugesen (Wayne@Laugesen.com)
THE DIRE CONSEQUENCES OF DARE
Epp and Beckner are right (and we don't say that often)
Police Chief Mark Beckner and Boulder County Sheriff George Epp
recently dumped the local chapters of DARE, a national mistake known as
Drug Abuse Resistance Education. They should be applauded for their
bold actions, which hopefully will put Boulder at the leading edge of an
overnight national trend.
Publicly, Beckner says he has nothing against DARE, which every year
dispatches police officers to preach against the evils of drug use to 35
million fifth graders nationally. The police chief allows that the program
wasn't meeting the community's needs. Epp criticizes DARE for lacking
flexibility. They're being polite.
The truth: DARE led to an increase in drug abuse among teenagers.
I suspected that in 1996 when the U.S. Department of Health and Human
Services issued a report showing a rise in teen drug use of 78 percent
US CO: -Column: The Dire consequences Of D
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between 1992 and 1995 on the heels of DARE's most prolific years of
growth. Some high profile potheads at Boulder's Sacred Herb
Church -where toking joints once served as communion -also felt strongly
that DARE was leading children to drugs. And who would know better, I
thought.
Shortly after the HHS report broke, I conducted some research, which
involved contacting the people who know DARE best -its founders.
I called psychologist William Hansen, whose research formed the basis for
DARE. Hansen was a professor of psychology at the University of
Southern California when DARE was started in 1983 by then -Los Angeles
Police Chief Darryl Gates, whose son was addicted to drugs. Hansen said
the LAPD took an anti-drug model he had developed while it was in its
infant stages and ran with it. More than a decade later, Hansen observed,
DARE was still using the exact same model, even though he himself had
scrapped it as one of many unsuccessful attempts to develop a workable
anti-drug program for schools. "DARE was misguided as soon as they
adopted our material, because we were off base," Hansen told me. "It's
outdated material that does not work."
I called Bill Colson, the world-renowned psychologist who co-authored 17
books with the late Carl Rogers, former president of the American
Psychological Association. In the '60s and '70s, Colson and Rogers, along
with renowned psychologist Abraham Maslow, developed and popularized
psychological practices known as "experimental education," "humanistic
psychology," and "self -actualization." Their theories formed the foundation
for Hansen's research.
Like Hansen, Colson, Rogers and Maslow all eventually said "oops,"
regarding the theories DARE was founded upon.
"DARE is rooted in trash psychology," Colson told me two years ago. "We
developed the theories that DARE was founded on, and we were wrong.
Even Abe Maslow wrote about these theories being wrong before he died."
Which is true, said Boulder psychotherapist Ellen Maslow, Abraham
Maslow's daughter. She called DARE "nonsense" in 1996, saying the
program represented widespread misinterpretation of humanistic
psychology.
Ellen Maslow said her father's vision of humanistic psychology was
misunderstood by public educators, who bent and twisted it and ended up
R �F9 i"ronino c.no nar
US C(: Colutim: The Dire Consequences Of' ,s
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making childhood "self-esteem" a central focus of public education.
Self-esteem is a central focus in DARE, and Ellen Maslow says it has led
to narcissism and self-indulgence.
Other critics of self-esteem are easy to find these days. "Saddam Hussein
and Stalin had great self-esteem," Norm Resnick, a psychologist and
national radio talk show host told me. "Children need authoritative
guidance. Self-esteem alone doesn't translate into making good decisions."
Still not convinced DARE was all bad, I contacted psychologist Richard H.
Blum at Stanford University School of Medicine. At the time, Blum was
heading the single largest ongoing study of drug education in the United
States, published as "Drug Education: Results and Recommendations.
"Basically, we have found again and again that drug education in schools
causes kids to take on drugs and alcohol sooner than they would without
the education," Blum told me.
Colson summed it up best. "As they get a little older, they become very
curious about these drugs they've learned about from police officers. The
kids start thinking, 'I don't want to say no.' Then they say, 'Didn't that
police officer tell me it's my perfect right to choose?' And thus, they choose
to experiment."
By now police departments must know this. But DARE is first and
foremost about money. According to Hansen, taxpayers spend about $125
per DARE pupil. "What this does is channel a lot of money to police
departments, and that's why they like it," Hansen says.
Responding to Boulder's abandonment of the program, DARE spokesman
Ralph Lockridge had the gall to suggest we need more of it. The program
should be broadened to include high school students, not just fifth graders,
he claims.
"It's sort of like teaching someone 17 piano lessons in the fifth grade and
expecting them to remember anything without any reinforcement when
you test them in high school," Lockridge told the Sunday Camera.
This man obviously suffers from excessive self-esteem disorder.
In truth, DARE's expectation is far sillier than Lockridge's piano analogy
suggests. He'd be accurate to say: "It's like teaching students 17 piano
lessons in the fifth grade and then expecting them to never touch a
,-,a 12/22/98 5:48 PM
US CU: 6o1unm+J'he Dire Consequences of D0
keyboard."
O
Despite their public politeness, 1 suspect Sheriff Epp and Chief Beckner
have figured all this out and no longer wish to sponsor a program that
spawns young drug addicts.
Unfortunately, both men have suggested some other program might
replace DARE. They should think about the lack of success
world-renowned psychologists have had in finding a way to introduce the
subject of drugs without it backfiring.
In school, students are supposed to learn. 'Peach them math, they'll use
math. Teach them reading, they will read. Teach them about drugs, they
will toke up.
We ought to celebrate the local dumping of DARE. Then take the
opportunity to urge the school district and local law enforcement to reject
drug education in schools. Let individual guardians of children figure out
the complex issue of adolescent drug abuse on an individual basis.
Here's a proposition for the Boulder Police Department, Sheriff Epp and
the Boulder Valley School District: Dare to have no drug intervention
program at all. Let's call it DIRE -Drug Intervention Resistance Endeavor.
The goal will be zero tolerance for drug education in public schools.
The results will be astounding. Fewer children will use drugs, more
classroom time will be spent on legitimate education, and police will be
able to focus on crime.
Checked -by: Don Beck
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8 of 9 ioiooioa a.na DTR
.4,
Objectives. The purpose of this
study was to examine the relation-
ship of marijuana use to mortality.
MethoA The study population
comprised 65 171 Kaiser Perman-
ente Medical Care Program enroll-
ees, aged 15 through 49 years, who
completed questionnaires about
smoking habits. including marijuana
use, between 1979 and 1985. Mortal-
ity follow-up was conducted through
1991.
Results. Compared with nonuse
or experimentation (lifetime use six
or fewer urns), current marijuana
use was riot associated with a signifi-
cantly increased risk of non -acquired
immunodeficiency syndrome (AIDS)
nxxtality in men (relative risk [RR1 =
1.12, 95%confidence Interval [CU =
0.89, 1.39) or of total mortality in
women (RR = 1.09.95%CI = 0.80,
1.48). Curran marijuana use was
asstxiated with increased risk of
AIDS mortality to men (RR = 1.90.
95% CI = 133.2.73), an association
that probably was no(causal but most
likely represented uncontrolled con-
founding by male homosexual behav-
ior. Tlus interpretation was supported
by the lack of association of mari-
juana use with AIDS mortality in
men from a Kaiser Pennanente A[DS
database.. Relauve risks for ever use
of marijuana were similar.
Conclusions. Marijuana use in a
prepaid health care -based study co-
hon had little effect on non -AIDS
monabty in men and on total mortal-
ity to women. (Am J Public Health.
1997;87:585-590)
Marijuana Use and
rtality
Stephen Sidney, AID, Jerome E. Beck DrPll, Irene S. Tekawa. MA,
Charles P. Quesenberry Jr, PhD, and Gary D. Friedman, AID
Introduction
Marijuana is the most commonly
used illegal drug to the United States.
Over 65 million Americans (31% of the
US population aged 12 and older) 'are
estimated to have used marijuana': its
mean retail sales value In the United
States is approximately $10 bdlion.t
Despite its longstanding popularity and
increasing use among youth in recent
years.' i we still know little about long-
term health risks associated with mari-
juana use. Harvard policy analyst Mark
Kleiman recently concluded that "aside
from the almost self-evident proposition
that smoking anything is probably bad for
the lungs, the quarter century since large
numbers of Americans began to use
marijuana has produced remarkably little
laboratory or epidemiological evidence of
serious health damage done by the
drug."*P251i Similar appraisals of the
health effects of cannabis were offered in
the two most comprehensive reviews
tram the 19805.1.6 More currently, Hall
and coauthors concluded that while there
are no well-established health or psycho-
logical effects of chronic cannabis use, the
following were considered to be probable
major adverse effects. respiratory diseases
associated with smoking as the method of
administration, including chronic bronchi-
tis and premalignant histopathological
changes In the lung, development of a
cannabis dependence syndrome: and subtle
forms of cognitive unpannent.'IPmi
The only other large-scale study of
marijuana use and mortality was per-
formed In a cohort of 45 540 male
Swedish conscripts, aged 18 through 2�0
years at baseline and followed for 15
years.' In this study. the relative risk (RR)
for monality associated with marijuana
use (more than 50 tinies) was 1.2 (95%
confidence interval [C11 = 0.8, 1.9) after
adjustment for social background.
We report here the findings of a
study of the relationship of marijuana use
to mortality in a cohort of over 65 000
'members of a large prepaid health plan.
Data on marijuana use in this cohort were
collected before the "war on drugs"
escalated in the latter half of the 1980s.
which may have resulted in underreport-
ing of illegal drug use.° Mortality is one of
several health outcomes being studied:
other endpoints Include cancer incidence
and outpauent utilization for respiratory
illnesses and Injuries. We hypothesiztd
that marijuana use would be assmiated
with increased risk of respiratory disease
and injury.
Methods
Study Population
A cohort of 65 171 men and women
aged 15 through 49 years (mean age. 33
years) completed detailed self-adminis-
tered research questionnaires on tobacco.
marijuana. and alcohol use from mid -
1979 through 1985. The subjects were
undergoing multiphasic health checkups
in the San Francisco (until 1980) and
Oakland Kaiser Permanente facilities.
Monahty was followed dough Decem-
ber 31. 1991, for a mean length of 10.0
years.
Stephen Sidney. Irene S Tekawa Charles P
Quewnbemy. Jr, and Gary D Friedman are with
the Division of Research. Kaiser Permanente
,Medical Care Program (Northern California
Region). Oakland. Calif. Jerome E. Beck is with
the School of Public Health. University of
California. Berkeley.
Requests for reprints should be sent to
Stephen Sidney. MD. Division of Research.
Kaiser Permanente Medical Care Prugram 3505
Broadway. Oakland. CA 94611.
This paper was accepted June 28, 1996.
April 1997. Vol. 87. No. 4 American Journal of Public Health 585
O
..� O >larpuana UWarwl Vorti lily
TABLE 2 -Relative Risk of Death lot Ever Users and Current Users of Marijuana, by Sex and Cause of Death: Kaiser
Permanente Medical Care Program Members (n = 65 171), Oakland and San Francisco, June 1979 through
December 1985
Ever Users
Current Users
No Deaths in
Nonsmokers/
Nonsmokers/
Reference
Full Model- Occasional Dnnkersb
Full Model- Occasional Drinkers
Group
Cause of No.
No
(Nonusers)
Death Deaths
RR (95% CI) RR (95% GI)
Deaths°
RR (950,16 CI) RR (95% CI)
Experimenters)
Men
AIDS 152
1 80 (1.29. 2.52) 2 34 (1 32, 4 14)
104
1.90 (1 33, 2 73) 1.91 (1.02, 3.55)
55
Non -AIDS 266
1.11 (092, 1.34) 1.25 (0 82, 1.89)
153
1 12(089. 1.39) 1.15 (0 67, 1.97)
315
Neoplasms 45
0.78(052. 1.18) 0.46(0 15, 1.41)
30
0 97 (0.61, 1.55) 0.75 (0.21, 2 69)
90
Circulatory disease 60
1.08 (0.75. 1.55) 1.36 (0 58. 3 19)
37
1.22 (0.80. 1.87) 1.80 (0 68, 4 73)
102
Injury/poisoning 92
1.24 (0.87, 1.75) 1.65 (0.84, 3 23)
47
0 99 (0.65, 1.50) 1.23 (0 51, 2.95)
72
Other causes 69
1.47 (0.98, 2 22) 1.71 (0 62. 4 68)
39
1.39 (0.86, 2.24) 0 68 (0.14, 3.45)
51
Unknown 12
.. ...
8
...
7
Total 430
1.28 (1.09, 1.50) 1.58 (1.14, 2.16)
265
1.33 (1 11, 1.59) 1.50 (1.01, 2 22)
377
Women
Neoplasms 36
0 82 (0.54, 1.22) 0.70 (0.31, 1.58)
19
0 86 (0 51, 1.45) 0 56 (0 17, 1.90)
155
Circulatory disease 13
0.68 (0.35, 1.33) 0.34 (0.(14, 2.90)
10
0.96 (0.46, 2.02) 0 70 (0 08. 5.95)
64
Injury/poisoning 28
1.39 (0.79, 2 44) 1 40(065, 3 04)
19
1.86 (0 99, 3.51) 2.04 (0 85, 4.91)
38
Other causes^ 16
0.76 (0.39, 1.46) 0.40 (0.05, 3.35)
10
0.95 (0.45, 2.04) 0 84 (0 10, 7 23)
50
Unknown 4
... ...
3
...
4
Total 97
0.90 (0.69, 1.16) 0.81 (0.49, 1 34)
61
1.09 (0.80, 1.48) 1.03 (0 55, 1 90)
311
Note. RR = relative risk, Cl = confidence Interval. we
•Adjusted for age, race. education, marital status, obesity, cigarette smoking,
and alcohol use.
bAdlusted for age, race, education, mantal status. and obesity
9nctudes 3AIDS deaths.
dNo. deaths In current users is included in no. deaths in ever users
Service Cornnussmn, and the Railroad
Retirement Board. While Social Security
numbers were avadable for about two
thirds of the study cohort, only 27 of 1215
deaths (2.2170 were ascertained by out-of-
state search. Since ca s of death were
unavailable for oui-of-state deaths, these
deaths were included in analyses of total
mortality but excluded in subcategory
r nronaluy analyses.
The overall age-specific mortality
rates of this group were about three
quarters as large as the corresponding
1987 United States rates.)' a discrepancy
we attribute to the probable better health
and predominantly employed status of our
Insured population and to our inability to
ascemmn mortality lin subjects without
Social Security numbers who had left
California.
ArUAsis
SAS programs were used for slatistl-
cal analyses." Cox propottional hazards
models were used to examine the joint
effect of sociodemographhc characteristics
and use of marijuana, tobacco, and
alcohol on mortality risk; esumutei of
relauve risks and associated 95`'e conh-
dence intervals were obtained from these
models.16 Age -squared temis were en-
tered into Cox proportional hazards mod-
els to detennme whether there was a
nonlmrar relationship between age and
mortality and were Included when signifi-
cant. Interactions between marijuana and
tobacco use and between marijuana and
alcohol use were tested In the selected
models (total mortality. AIDS mortality
[men only], non -AIDS mortality [men
onlyl, and morality from mjuries/poison-
mgs) by including cross -product terms In
our profxinional hazards modek. None of
the Interactions were statistically signlfi-
cant(P < .05).
Results
Soctalenhugraphic characteristics of
the sample are shown in Table I. The
cohort comrsted of 389c nonusers. 20`rr
experimenters, 201b former users, and
22% current users.11he percentage of ever
users was highest in the 20- through 29 -
yew -old agc group. Ever use of marijuana
was inure common among men than
among women and was highest among
Whites. Never -manned men and women
were about twice as likely to be ever users
as their marred counterparts. Soclolenm-
graphic patterns were generally smular
for current marijuana use.
Current marijuana users were twice
as likely as never users to be current
tobacco cigarette snickers and nearly 2.5
tines as likely to be alcohol drinkers. The
percentage of current snmukern was 'It2
for never marijuana users. 31"2 fur
experimenters. 32% liar former users. and
42'%e for current users. The corresponding
percentages of those amsummg one ser
more drink per Jay were I o<2. '752. 3 1'; ,
and 3917. While few marijuana users were
nonusers of alcohol. a substantial propur-
lion of ever marijuana users 125rr of men.
30% of wonmem) and current manjuana
users (22% of nhen. 28% of women) were
nonsmokers of tubacco crgaremes and
occasional (less than once per month)
drinkers.
We compared risks of mortality as-
sociated w uh ever and current use Manse
to never or experimental use of marijuana
There were 807 deaths arnong men and
408 deaths among women lin this cohort.
Ne performed analyses for total mortal-
ity. AIDS (men only). neoplasms, clrcula
Anil 11)97 Vni V pan a ' i Amrnrar Intimal nl Pnhhr Ilrallh i97
Stil.n.i eI ,1.
TABLE 3—Rlsk of Mortality Associated with Current Cigarette, Alcohol, and Mari)uana Use: Kaiser Permanente Medical
Care Program Members (n = 65 171), Oakland and San Francisco, June 1979 through December 1985
Current Marijuana Use,
Current
Consumption of Three or
Cigarette Smokmga
More Alcoholic Drinks per Day° At Least Once a Week Daily
RR (95% CI)
RR (95% Cl) RR (959, Cl) RR (959. CI)
Men
AIDS 1 64 (1 15, 2 34)
0 94 (0.60, 1 47) 2 09 (1 42. 3 06) 1.65 (0 97, 2 82)
Non -AIDS 1.76 (1.40, 2.20)
1.21 (0 94, 1 56) 1.17 (0 91, 1 51) 1 31 (0.93, 1.84)
Total mortality 1.75 (1 45, 2.11)
1 13 (0.91, 1 40) 1.46 (1 19, 1 79) 1 43 (1.08, 1 90)
Women. Total mortality 1.58 (1.25, 2 01)
1.90 (1 31, 2 76) 1.23 (0.84, 1.80) 1 44 (0 80, 2.56)
Note The model was adjusted loi age, race, education, mautal status obesity, cigarette smoking and alcohol use, RR = relative risk, CI =
confidence Interval.
-Relative to nonsmoking
°Relative to occasional alcohol use
°Relative to nonuser/experimental user status
tory disease, injury or poisoning. "other
causes" of mortality, and total non -AIDS
mortality (inch only) (Table 2).
A4arijuana List, in Relation
m Morlah1v
For men, ever use of marijuana was
associated with a sigmficand increased
nsk of local mortality (28%) and AIDS
mortality (80%) and a nonsignificant (P>
.05) increase (I I%) in risk of non -AIDS
mortality. Relative risks associated with
ever marijuana use for these mortality
catcgones were similar or higher in
nonsmokers/occasional drinkers (a group
in which marijuana use could be evalu-
ated without uncontrolled confounding by
cigarette and substantial alcohol use). Of
note was the nearly significant 47% in-
crease in "other causes" of mortality,
exanunatton of which revealed higher
proportions of deaths from infectious
diseases and from alcohol and drug abuse
in ever users than in never users/
expcnnlcnters. Current marijuana use was
also associated wilt a significantly in-
creased risk in men of total mortality
(33%1) and AIDS mortality (9017().
ht women, there were no significant
increases or decreases in mortality risk
associated with ever or current marijuana
use. Current use was associated with a
nearly significant 8617, increase in mortal-
ityfrom injury or poisoning. which could
not be attributed to any specific category
of Injury
Relative risks associated with man-
juana use among nunsrnokers/occaslonal
drinkers were generally similar to those
for the complete cohort, suggesting that
increased risks in the complete cohort
were not an artifact resulting from incom-
plete control of the effects of cigarette
smoking or alcohol use. The results of an
analysts of mortality excluding subjects
who died wWtm the first 5 yeah of
follow-up (data not shown) were similar
to the overall results shown to Table 2.
suggesting that the overall results were
uncompromised by the possibility that
serious illness occumng before the multi-
phasic health checkup affected subjects'
decision to use marijuana.
Duration of use in current marijuana
users was not consistently related to the
risk of AIDS mortality in men or to total
mortality to women, and had an inverse
tendency in relationship to total and
non -AIDS mortally 1n men (data not
shown). A continuous duration -of -use
variable was not significant when added
to the full models for each mortality
outcome.
Nfanjuana use at Icast once a week
was associated with slightly higher rela-
tive risks of moilahty than less frequent
use. The addition of frequency of use
improved the fit of the model (P<.05)
only for total mortality u1 men (RR = 1.25,
9517, Cl = 0.97. I.62, for total mortality
among those who used less than once a
week and RR = 1.46, 957 Cl = 1.19.
1.79, among Wosc whu used at (cast once
a week, relative to nonuscrs/expennlcnt-
ers).
AIDS Morialin
The vast nlajonty of AIDS deaths
(1721207 = 83%) occurred among never
manned inch. Current marijuana use was
nearly twice as high in never manned asin
manned rnen jlablc 1). raising the ques-
tion of whether analytic control for
mantal status was insufficient to adjust for
confounding hfcstyle factors, particularly
male homosexual behavior.
To address dos question, the study
cohort was linked to the Northern Califor-
nia Kaiser Pennanente Medical Care
Program AIDS Database, which revealed
214 men with a diagnosis of AIDS after
deiemtinanon of tier marijuana use
status The prevalence of current mari-
juana use at the unlc of the checkup (5(, i, )
in these AIDS pauenLs was substanna0%
higher than the prevalence to unmarried
men in the total studs cohort (3871.
For these _214 AIDS patients, current
marijuana use was associated with a
nonsignificant decrease to relative risk for
total mortality IRK = 0.78. 95'n Cl =
0.47, 1.30) and for AIDS mortality
(RR = 0.71, 9511, Cl = 0.41, 123). As-
suming that most of the unmanned nlcn
who developed AIDS were homosexual
or bisexual. these ftndmgs supponexl the
hypoflbcsis that the presalence of man-
juana use was higher in homosexual and
bisexual men In the cuhon. it group at high
risk for AIDS nurnehty. Therefore, male
homosexual (chas Ior. a critical confound
ing variable. could not he controlled lot In
complete cohort nlomahn analyses.
Comparative Ri.;O of lobarco,
Alcohol, and Afar ijuana Use
The relative risks of total monaluy In
men and women. and of AIDS and
non -AIDS mortality in men, associated
with current cigarette smoking, consump-
tion of three or more dnnks per day. and
current marijuana use are shown in Table
3 Except for AIDS mortality. the risks
588 Amencan Journal of Public Health Apnl I9'/7. Vol 87. No 4
9
associated with marijuana use were lowOer
than those for tobacco cigarette smoking.
Compared with consurmpuon of duce or
more drinks per day, manjuma use was
associated with a higher risk of total
mortality and AIDS mortality in men and
a lower risk of total mortality in women.
Discussion
The main overall findings were an
increased risk of total mortality associated
with marijuana use in men but not in
women. The increased risk of total
mortality In men was explained by the
strong relationship between manjuana use
and AIDS mortality. Marijuana use was
unassociated with non -AIDS mortality in
men.
The question of the effect of mun-
juma use on AIDS mortality is an
important one. Marijuana use has been
advocated as a therapeutic adjunct to
ameliorate the nausea and loss of appetite
commonly associated with the wasting
syndrome in AIDS.10 We have provided
substantial evidence that tire increased
risk of AIDS mortality in the total study
cohort probably resulted from uncon-
trolled confounding by homosexual behav-
ior. Other studies have reported a substan-
tially higher prevalence of manjuana use
in homosexual and bisexual men, support-
ing the hypothesis that marijuana use is a
marker for homosexuality or bisexual-
lly. i e -m
There are several other potential
explanations for the Increased risk of
AIDS In manjuana users. Marijuana
smoking might theoretically place AIDS
patients at increased risk of infection
because of its irritative effects on the
respiratory system or because of infec-
tious contanunants (e.g., fungi) in man-
juma. Other potential explanations in-
clude marijuana as a marker of hieh-nsk
sexual behavior or Intravenous drug use:
Initiation of marijuana use as a result of
having HIV or AIDS, rather than preced-
ing the disease: and possible mrunimosup-
pressive propenes of marijuana
The use of alcohol and nonmedical
psychoactive drugs, including marijuana,
is associated with risky sexual behavior
such as unprotected intercourse."' but
methodological limitations have made It
impossible to determine causality." Man-
juma use may serve to a ceruun extent as
a marker of intravenous drug use. How-
ever, the relative risk of AIDS mortality
associated with marijuana. use did not
dinunish when the analysts was limited to
men who were nonsmokers of tobacco
April 1997. Vol. 87. No. 4
OMarijuana Lw anal Noruh y
and occasional alcohol drinkers, a sub
group unlikely to contain many parenteral
drug users Additional evidence against
marijuana as a marker for parenteral drug
use was the finding of only one case of
infective eridocardlus in Kinser Pemtan-
care hospitalization records of the AIDS
decedents.
The lack of increased mortality
during the first 5 years of follow-up
suggests that therapeutic use of marijuana
at baseline for AIDS-related symptoms
has little. if any, explanatory effect on the
association between marijuana use and
AIDS. Furdwrrnore, the majority of AIDS
patients initiated marijuana use long
before the onset of clinical disease, nearly
two thirds (6517c) of AIDS patients re-
ported uuuadon before 1976, when HIV
infection in the San Francisco Bay area
was either nonexistent or negligible.=
While marijuana and its psychoac-
tive cannabanuids possess known immu-
nosuppressive qualities, there is no consen-
sus as to whether typical doses result in
clinical immunosuppression in humans.'-
Marijuana use has been associated with a
higher prevalence of seropositivity for
HIV in sonic cross-sectional studies of
homosexual and bisexual men. 1124 but it
has nor been shown to be an independent
predictor of serocunversion?r nor does it
increase the risk of AIDS in seropositive
men.='
The nearly significant increase in
mortality risk from injury or poisoning for
female current marijuana users was consis-
tent with our hylxrthesns that marijuana
use Is a nsk factor for death due to injury.
Marijuana is known to decrease psycho-
motor performance; some studies have
implicated its use to mutor vehicle
crashes."K"-" Marijuana use is also
strongly associated with alcohol use,
another major risk for accidental death.
There were too few deaths to meaning-
fully study die odier main hypothesis. that
marijuana use would be associated with
increased respiratory disease mortality.
Another study perforated on a subgroup
of this cohort showed that daily or
near -daily manjumta users who were not
tobacco cigarette smokers had a 19%
higher risk of outpatient visits for respira-
tory disorders than nonusers of both
substmces.'°
The major limitations of this study
Include Its reliance on self-report for
ascerunment of matlju:ma use .talus: the
Inability to study changes in marijuana
use status during follow-up: a lack of
lengthy follow-up Into the geriatric age
range (m=ruuu lullow-up, 12.5 years:
maximum age reached. 63 years): a lack
of information regarding other illegal
drug use. and potential underascertain-
ment of mortality (noted earlier). Esu -
males of manju:ma use were similar to
diose obtained during this period by the
National Household Survey on Drug
Abuse, the most authoritative source of
illegal drug use information for US
adults.= The lack of longitudinal data
regarding use status is common to many
cohort studies. It seems unlikely that
"ever" marijuana use status would have
changed substantially over titre, because
relatively few adults in this cohort are
likely to have initiated marijuana use
during follow-up in a period (the 1980s)
when there was a marked secul,u decline
In self-reported marijuana use in the
United States.' It is possible that relation-
ships between marijuana use and mortal -
ay might be found with longer -tens
follow-up or later in life It is likely that if
information on subjects' use of other
illegal drugs had been available, adjust-
ment for other drug use would have
lowered the relative risk estimates for
marijuana use.
As noted earlier, relatively few ad-
verse clinical health effects front the
chronic use of marijuana have been
documented in humans.lip"' The cnminal-
ization of marijuana use may itself be a
health hazard. since it may expose the
consumer to violence and criminal activ-
ity.'" While reducing the prevalence of
drug abuse is a laudable goal, we nwst
recognize that marijuana use is wide-
spread despite the lung -term, multibillion
dollar War on Drugs. Therefore, medical
guidelines regarding its prudent use should
be esiabhshed. akin to the commonsense
guidelines that apply to alcohol use.
Unfortunately, clinical research on prnen-
tml therapeutic uses for marijuana has
been difficult to accomplish in the United
States, despite reasonable evidence for the
eflicacv of tcuahydrmannabmol (1 -HC)
and nianjuma as antiemetic and antiglau-
coma agent -5 and the suegcstive evidence
for then efficacy In the treatment of
other medical conditions- mcludme
AIDS.-"'n�]n]i
In sununary, flus study showed little.
If any, effect of marijuana use on nun -
AIDS mortihty to men and on total mor-
tality In women. The Increased risk of
AIDS mortality In male marijuana users
probably did not reflect a causal relation-
ship. but most likely represented uncon-
trolled confounding by male homosexual
behavior. The risk of mortality associated
with manjuana use was lower than that
Arnencan Joumal of Public Health 589
.- - $Wr.cs 5-•t al. O
5utxaateJ with tobacco ugarcnc stook
ins. ❑
AcknoH ledbmenls
Tlu, rc,eanh uas supported by gram 901
DA(K.(iFt
from the National Institute on Drug
Abuse Or Friedman is supported in pan h)
gram R35 C.A49761 front the National Cancer
Irnumte The collection of data on alcohol u,e
ua< Supf.med hs a grant from The Alcoholic
Beserace Mrdnal Rcscarch Foundation IBalu-
more. Sid 1.
The aulinrs acknowledge Chnsuanna
Willuuns. Sic,c Wlhon. and Marianne Sadler
for computer prugranunmg and Leo Hurley for
consultation meaning the use of the K.u,et
Permancnre AIDS damba-sc
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V)0 Amencan Jtwntal of Public Health April 1997. Vol. 87. No.4
Heavy Habitual M rijuana Smoking Doe's Not Cause
an Accelerated Decline in FEV, With Age
DONALD Is. TASHKIN, MICHAEL S. SIMMONS, DUANE L SHERRILL, and ANNE H. COULSON
Depenments of Medicine and Epidemiology, UCIA Schools ol'Medkine and Public Health, Los Angeles;
and Division of Respiratory Sciences, University of Arizona College of Medicine, Tucson, Arizona
To assess the possible role of daily smoking of marijuana in the development of chronic obstructive .
pulmonary disease (COPD), we evaluated the effector habitual use of marijuana with or without tobacco
on the age-related change in lung function (measured as FEVs) in comparison with the effect of non-
smoking and regular tobacco smoking. A convenience sample of 394 healthyyoung Caucasian adults
(68% men; age: 33 t 6 yr; mean 3 SD) Including, at study entry, 131 heavy, habitual smokers of mariju-
ana alone, 112 smokers of marijuana plus tobacco, 65 regular smokers of tobacco alone, and 86 non-
smokers of either substance were recruited from the greater Los Angeles community. FEV1 was mea-
sured in all 394 participants at study entry and In 25S subjects (6S %) on up to six additional occasions
at Intervals of l, 1 yr (1.7 t 1.1 yr) over a period of 8 yr. Random -effects models were used to estimate
mean rates 2f decline in FEVs and to compare these rates between smoking groups. Although men
showed a significant effect of tobacco on FEV1 decline (p G 0.05), in neither men nor women was
marijuana smoking associated with greater declines In FEVs than was nonsmoking, not was an addi-
tive effect of marijuana and tobacco noted, or a significant relationship found between the number
of marijuana cigarettes smoked per day and the rate of decline in FEVI. We conclude that regular
tobacco, but not marijuana, smoking is associated with greater annual rates of decline in lung function
than Is nonsmoking. These findings do not support an association between regular marijuana smoking
and chronic COPD but do not exclude the possibility of other adverse respiratory effects.Tashkin DP,
Simmons MS, Sherrill DL, Coulson AH. Heavy habitual marijuana smoking doer not cause an
accelerated decline In FEVI with age. "r WPM Carr esu Mrs) 1se7:uusu..lu.
Marijuana remains the most commonly smoked illicit substance
In American society (I, 2). After more than a decade of declin-
ing prevalence of marijuana use in the United States, an upswing
in its usehas recently been demonstrated, especially among young
individuals (1, 2). Because the constituents or marijuana smoke
are similar In many respects to those or tobacco (3, 4), it is possi.
bit that habitual smoking of marijuana may lead to some of the
same respiratory erfats that derive from regular tobacco use.
This possibility is supported by several animal and cellular studies,
which have shown that chronic exposure to marijuana smoke
can Injure respiratory tissue (5-9). Although earlier studies in
humans yielded conflicting data about the association between
heavy marijuana smoking and clinical evidence of respiratory
illness (10-14), more recent clinical studies have demonstrated a
relationship between habitual marijuana use and symptoms of
chronic bronchitis (15, 16). Moreover, histopathologic studies have
revealed epithelial alterations in biopsies from proximal bronchi
(Recatved N odginol form Ap61 3, 1996 and in revised form rune 25, 1996)
Suppomd by Grant No. ROl D.A03019 from the National Insdtums of
HsafWNauonal Institute m Drug Abuse.
Correspondence and request$ for reprp,u should be addressed to Donald P.
Taihkin. M.D. Department of Medicine, VCtA School'of MedKlne, los An-
gelese CA 90095-1690.
AM I Vspir Crit Care Med vol 135. pp 141-148. 1997
of marijuana smokers (goblet -cell metaplasia, reserve -cell hyper-
plasia, squamous metaplasia) (17, 18) that are consistent with
symptoms of mucus hypersecretion.
In contrast to the concordance of findings in recent studies
with respect to the impact or regular marijuana smoking on
chronic respiratory symptoms, cross-sectional studies or mariju•
ana users in Los Angeles (I5) and of smokers of nontobacco (pre.
sumably and hereafter referred to as marijuana) in Tucson (16)
have revealed conflicting effects on lung function. The Los An-
geles study (15) failed to demonstrate any relationship between
marijuana use and impairment in tests of lulls function, includ-
ing sensitive indices of small airways dysfunction, whereas the
Tucson study (16) demonstrated obstructive ventilatory defects
additive to those attributable to regular tobacco use Recent anal-
ysis of longitudinal data from the Tbcson study (19) estimated
significant decrements in FEV, in continuing male (but not fe.
male) marijuana smokers �a I yr after marijuana smoking was
first reported. Moreover, these decrements were twice as large
as the estimated decrements in continuing tobaccosmokers, and
the effects of both habits were additive. The latter data suggest
that marijuana smoking might be a significant risk factor for
Progressive airflow obstruction.
To further evaluate the possibility that continuing marijuana
smoking might lead to progressive declines in lung function not
consistently apparent in cross-sectional studies, we invited non-
smokers and smokers of marijuana and/or tobacco who were
participants In a cohort study of the pulmonary effects of habitual
142 O
AMERICAN JOURNAL OF RESPIRATORY AND CWTICAL CARE MEDICINE VOL to 1997
marUuaoa use (15) to undergo repeat lung function testing on
up to six additional occasions at Intervals of at least I The
we also fitted A second random<ffccts model in which tobacco and
me"j'"
yr.
Present report presents the results of the analysis of this longitu-
nes status were constant ewvariabla, rather than t6nc-depesedent,
For this analysis, each subject was classified as a never or continuing
dinal study of lung function.
smoker oreaa substance uparstely, based on whether the subject was
either A nonsmoker or a smoker or that substance at each and every
Lino, respectively. Otherwise, subjects were classified as inlerrrjuent
METHODS
smokers for that substance
The initial sample consisted of healthy volunteers 25 to 49 yr of age,
including 144 heavy, habitual smokers of marijuana alone (MS), 133
regular smokers or both marijuana and tobacco (MTS), 70 smokers or
tobacco only (TS), and 97 nonsmokers (NS) of any substance (11). Sub-
jects were Initially recruited from the general Los Angeles area through
newspaper and radio announcemenis from 19831hrough 1985. Criteria
for study entry have been pnwiou* reported (I5). Specifically excluded
were persons who reported current or previous intravenous drug use or
smoking of other illicit substances (eg.. crack cocaine, phencyclidine,
methamphetamine, heroin, and opium) more than 12 times In thdr Ilves
or within the previous 6 mo. Persons with significant occupational ex-
posures to substances potentially hazardous to rapbatory health, or with
a history of Chronic respiratory Illness, were also excluded.
Eligible subjects completed a detailed respiratory and drug use ques-
tionnaire adapted from the American Thoracic Society/National Han,
Lung and Blood Institute (ATS/NHLBI) questionnaire (20) and the Na.
bona) Institute on Drug Abuse (NIDA) nationwide survey on drug abuse
(21). An extensive battery of pulmonary function testa was also per.
formed. Details of the testing procedures, methods of Calculation, And
comparison with expected reference values used in the study haw been
described previously (15). A subsd of these participants (36 MS, 42 MTS,
267%and 40 NS) also underwent f4booptic broncbascopy, bronchoal-
veolar lavage (RAL), and bronchial mucosal biopsies at variable times
following pulmonary function testing. Results of the broachoscopic
studies have been reported previously (17, 18, 22. 23).
Since 1985, extensive efforts haw been made to reeootad at least
annually, by mall and telephone, all 446 participants who had under-
gone Initial testing in 1923 through 1985. Mail was scot under a US.
Postal Service arrangement that pronleled the tender with Identification
of the address to which the mail was delivered. Participants who were
lost to follow-up (cit-, unddivered mail with no forwarding address) were
traced through work telephone numbers, contacts with Individuals Iden -
ti fled by the subject as Likely to know his or be whereabouts, Stale depart-
ment of motor vehicle rosters, voter registration fila, the U.S. Social
Security forwarding syuem, and commercial credit seambes. A field visit
to the last known residence of a participant was utilind it necessary.
The National Death Index (NDI) was used to identify deaths In the study
group NDI searches were run eaeb year for individuals not known to
be alive at the end of that year. For deaths of study subjects identified
by the NDI, death eoreineatu and hospital and pathology records were
requested to determine the mum of death.
Recontacted particiPeats were Invited to undergo subsequent rounds
or examinations at periods of 3 I yr, Including an interval respiratory
and drug use interview and at least forced expiratory spirometry. Tro
experienced technicians who were sou -trained In the study procedures
Performed the Initial And follow-up pulmonary function tats. The same
pulmonary function equipment and testing procedures were used through-
out the study (I5). Questionnaires were administered by trained later -
viewers.
Data Analysis
For FEV„ random-erfects modeling was used to estimate the rate of
decline In lung function with age in relation to snacking status fm mariju.
ana or tobacco at any point In time, with smoking staters as a time -
dependent covariable (24, 23). Other potential covar(ables were height
(constant) and intensity of use of marijuana (joints/day) and tobacco
(cigarettes/day), the tobaao-marijwna interaction, and former smok-
ing of each substance, which were all assessed at each survey (time.
dependent). The model Also included data from subjects with only one
measurement These single observations contribute to the estimate of
the Intercept but do not affect the slope csdmatt The advantage of this
model is that it allows for one or more changes in smoking status ower
flue. Analyses were performed rot men and women scpamtdy.
RESULTS
Of the 446 eligible subjects Initially enrolled in the study, 394
underwent measurements of lung function. Demographic char-
acteristics, smoking status, and FEV, of the 394 study participants
with evaluable lung function are shown in Table I by smoking
category at the lime of study entry (Visit 1). The tobacco -only
smokers were slightly older than subjects in the other smoking
categories (P <0.05). The marijuana smokers were heavy daily
smokers (mean of more than 3.5 joints/d), w ^ as the tobacco
smokers smoked an average of nearly I to 1.5 packs of cigarettes
Per day. The combined smokers of marijuana plus tobacco
smoked less tobacco than did the tobacco -only smokers (p <
0.03), whereas the current intensity and lifetime amount of
marijuana smoking was not significantly different between the
dual and maiijuaaa-only smokers. The mean age and tobacco
consumption of the female subjects in each smoking category
were similar to those of the male subjects in the same category.
Baseline % predicted FEV, did not differ across smoking cate-
gonm
Table 2 shows the number of longitudinal assessments by gen-
der. The mean interval between consecutive visits was 1.7 d: 1.1
(SD) yr, with minimum and maximum intervals of approximately
I and 8 yr, respectively. The mean interval between the first and
last visit for each subject was 4.9 t 2.0 yr. Nearly two-thirds
of the cohort (255/394) were festal on two or more occasions.
Nearly all of those not retested bad moved out of the area or
were otherwise lost to follow -u0. The proportion of male and
female subjects who underwent morethan one set of lung func-
tion tests was similar, and the proportion of subjects who were
tested more than once (MS 66.7%; MTS 56.391s; TS 64.65o; NS
73.3%) did not differ significantly from those who did not un.
dergo follow-up testing by baseline smoking category (p> 0.09;
chi-square analysis). Moreover, within each smoking category,
no significant differences were found in the age, baseline smok-
ing characteristics, or baseline FEV, of the subjects who were
studied only once and those with multiple tests, except that MTS
in the follow-up group were slightly lighter tobacco smokers (16.0
cigarettes/d) than MTS who were studied only once (21.7 ciga.
rettes/d) (p < 0.05).
Fourteen participants were known to have died during the
follow-up period, including 8 MTS, 2 MS, 3T& and 1 NS. Known
causes of death included acquired immune deficiency syndrome
(AIDS) (1 MS, 1 MTS, and 2 TS); violence (3 MTS); suicide (1
MTS); drug overdose (1 MTS); breast cancer (1 MTS and I NS);
and asphyxiation from aspirated food (1 TS).
The number of subjects in each smoking category who re.
mained "continuing smokers" of each substance or temporarlly
quit (or started) smoking a particular substance during the follow-
up period Cintermittent smokers") is shown in Table 3. More
than 80% of smokers of marijuana with or without tobacco con-
tinued to smoke marijuana throughout the follow-up period, and
RPPmsxjmately 90% of (obacco-ordy smokers continued to smoke,
Whereas; 75% of dual smokers of tobacco and mar))uana Con.
tinued to smoke tobacco. Relatively few subjects in any smoking
category began smoking either tobacco or marijuana during
follow-up. Although most smokers of marijuana (nitially (587e
of MS and 67% of MTS), including those who quit smoking
ashkin, Simmons, Shwill, rt o7., Marii`and Annual Change in FEV, - O
° TABLE 1
OEMOGRAINIC AND SMOKING CNAIIAMKD-nC3 Or SUBJECTS AT VISrr 1
N Mean ,lye Tob4Or9 mariiYana
KVI
3uolects (W) V) (evorm4V4) u -M (141+11/.31
C01,101-
(%,+M
Ms 101130 31.5to.s• 0-0200 3.410.6 4.1 it0.6
Mrs 61131 13.630.5 16.4*1.31 16.011.31
36.2611.9
108*1,4
3.630.3
TS 33/32 36.7*0.94 27.111.7 21A 11.9 0.010.0
43.1139
OA 10.0
10611.1
NS 53/33 32.0a0.6 0.1*00 0.010.0 0.040.0
0.020.0
106*1.9
10911,41
Definition d *bb1^4&tioiv. M o nyle r+remeN; Ms a n,, n usn, smoke MT3 + man)uana pun tobavo vnoken; TS+,Ob4crn
•ar�c NS • norunwiew jamas/d a number d nsCo,n'
t IWraeQuiVelMU) per � iW"'Yr v nYmbe, d
sm,k.
)OVIb Co,
Eay a nYmMr d Jean unoked.
lomLeq,ry
Itnu) per
SLM.
37
S
1 Signi6carey bvwr then T3 (p < 11.01).
_
1 slgvfw try NOMr Von Wier 0n&* ra6 WWW (p < 0.05).
marijuana, reduced their daily amount of marijuana use, others
(31% of MS and 2617, of MIS) Increased their use•, the resultant
average reduction In use was relatively small (0.7 and 1 joint
among MS and MTS, respectively). Among initial tobacco smok-
ers, including those who subsequently quit smoking tobacco, 49%
of IS and 36% or MTS reduced their daily number of cigarettes,
whereas 190/6 of TS and 34176 of MTS increased their dally use
of tobacco; the mean changes in IS and MTS were reductions
of 4.8 end 0.8 cigarettes/d, respectively.
Figure I shows the estimated decline in FEV, with age by
smoking status derived from the random -effects model for men
(Figure IA) and women (Figure III), with smoking status for
tobacco and marijuana, and the lobaceo-marijuana interaction
entered as a tinwdependent covariable. In men, tobacco smok-
ing, but not marijuana smoking, was associatod with a signifi-
cantly steeper decline in FEV, compared with nonsmoking, in-
dicating an accelerated decline In lung function with increasing
age for tobacco smoking but not for marijuana smoking com-
pared with nonsmoking. Similar findings were observer! In women,
although the slope difference for tobacco did not achieve statisti-
cal Lign)ficance. A negative interaction was found between mariju-
ana and tobacco smoking in men but not in women (Figure )A;
Table 4).
When the Intensity of marijuana smoking on FEV. decline
with age was examined in men, no differences were noted be-
tween even quite heavy marijuana smoking (14:, 3 joints/d) and
nonsmoking of marijuana (Figure 2A). Similar findings were
noted in women. In contrast, the amount of tobacco smoked was
significantly correlated with decline In FEV, with age (Figure
2E), although a dose -response relationship for tobacco was not
demonstrated in women.
Figure 3 shows the effect of the continuity of marijuana
smoking among men who were nonsmokers of tobacco (Figure
3A) or continuing tobacco smokers (Figure 3$), with marijuana
smoking status (never, continuing, intermittent) as a constant
covariable. Neither the continuing nor the intermittent mariju-
ana smokers exhibited any significantly different rates ordecline
in FEV, as compared with neva smokers ormarijuana. This lack
TABLE 2
NUMBER OF SUBJECTS WrTH ONE OR MORE ygn-S
Visit No. 1 k 3 4 s 6 1 Tdd
Mak TB 49 36 23 2) 21 14 266
Female 41 24 11 16 IS 9 6 126
TOW_ 139 73 ss 41 $6 30 A 394
143
of a marijuana effect "a independent or the effect of tobacco,
as indicated by the similarity of the findings for the different
categories of marijuana smokers (never, continuing, later mit-
tent) when the analyses were confined to tither never tobacco
smokers (Figure 3A) or condnuing tobacco smokers (Figure 38).
Similar observations were noted in women. The slopes for all
categorles of marijuana smokers are steeper among the contin-
uing tobacco smokers than among the never tobacco smokers,
As a consequence of the effect of tobacco (not marijuana) on
the rate of decline in FEV,.
In contrast to marijuana, the continuity of tobacco smoking
did affect the rate of decline in lung function, with a consistent
gradient of increasing decline from never through intermittent
to continuing tobacco smoking, as shown for men in Figure 4.
Table 4 shows the results of random -effects models, which
are plotted in Figures 1 through 4;1 tests were used to determine
whether the slope coefficients differed from zero, The listed
coefficients represent the decline in FEV, with age for each of
the rererc= groups, and for the nonrefefenee groups they rep-
resent the rate of decline relative to each reference group. For
oiample, the results for Figure ]A Indicate that the reference group
(nonsmokers) had a 253 ml/yr tate of decline, whereas Mari.
Juana smokers had a 30.8 ml/yr rate of decline, or a difference
of 5.5 ml/yr (as shown in Table 4) from the reference group. MTS
had a decline 10.5 ml/yr greater than did NS, which Is the sum
of the marijuana and tobacco terms and their interaction (which
is zero for all groups except MTS). Slight differences from the
figures arc due to round -off error. According to the model for
Figure 2A, FEV, in marijuana smokers declined only 0.036 ml/yr
faster than in nonsmoker of marijuana for each joint per day
regularly smoked. In Figure 3A (never smokers or tobacco only),
FEV, in intermittent and continuing smokers of marijuana de-
clined 0.97 and 194 ml/yr faster than in never smokers of mari-
juana, respectively.
TABLE 3
CONFINUrrY OF SMOKING STATUS
Nymber of Subjects in Fxh Category
lmdal
Marquarsa Tobacco
--- W
Status
n
Cm4nuing thfil nNMt Continuing
Intermittent
MS
67
71 16
MIS63
Ts
—
17 40
6
23
NS63
42
37
S
_
2
. 1�4
A e.00
4.10
Is 4.00
7.60
3.00
2.60
MALES
AMERICAN )OURNAL Of RESPIRATORY AND 11. 1. CARE MEDICINE
a0 36 a0 46 e0 6s ae
AGE (pa)
-� NS ..... Ta Ms M•-- MTS
Anthill daWM
E FEV, Oral 2" 114 70.1 31.3
FEMALES
B 400
P.04
VOL 153 1997
7.10
7.00
250
I
t.ao 1 so u
ae a7 70 67 60
ACE (yrs)
AM4 dadar Ne ..•-. 78 us -- u78
N FEV, V* 96A 314 28.4 tat
Figure 7. Declines In FEVI (in liters) with age (in years) by smoking status at any measurement time, estimated from linear random -effects
model In man (A) and women (B). Slope coeffici9nts for annual decline in FEV1 (in milliliters) for each smoking status are shown at bottom
of each panel. The model Includes terms for tobacco and marijuana smoking status and tobacco -marijuana Interaction.
DISCUSSION
Data from the present prospective study of 255 nonsmokers and
smokers of marijuana and/or tobacco (Including approximately
ISO heavy habitual smokers of marijuana with or without tobacco
smoking at study Initiation) who were tested on 2 to 7 separate
occasions Over a maximum span of 9 yr extend the results of
an earlier cross-sectional survey of lung function in 394 smok-
ing and nonsmoking young adults, which failed to show any im-
pact of heavy, habitual marijuana smoking leverage of> 3 joints,
0r joint -equivalents, per day) on lung fsolctton. Longitudinal find -
Ings froln this FOIIOw-up study fail to demonstrate that habitual
daily smoking of marijuana in amounts as much as 3 joints (or
jointequivalcnts) per day is associated with greater age-related
rates or decline in FEV, than is nonsmoking (Figures 1, 2A and
3). These results are )B contrast to the accelerated annual rate
of decline In lung function that occurs in regular tobacco smokers
Of comparable age (Figures 1, 2B. and 4). Moreover, no additive
effects of marijuana and tobacco on the age-related decline in
lung function were notal. A negative interaction between mariju•
ane and tobacco, however, was noted (Table 4), as suggested by
TABLE 4
RANDOM EFFECTS MODELS
SLOPE COEFFICIENTS FOR VARIABLES BY ALE
Figure
'9 Variable
31001!COttkiem
(SE)t
1A NOnfmOkec'
_25.3.
t
P Valut
MariTobacco
mo
0.98
0.33
Mar(luana-tobacco Interaction
-31.0 (8.S)
-26.0 (10.0)
3.66
o,o002s
16 Nonsmokers. -
-29.8
2.36
0.011
Martfuans
Tobacco
3.3 (7.3)
0.46
0.65
Marijuana_tobacco or, letweul
-6.8 (7,])
7.1 (0.23
9.8)
9.8)
120
2A Nonsmokcn of marijuana•
0.72
0.47
Marauana amount
25 Nmsmalan of tobacco-
-0.036 (0.37)
0.099
'0.92
Tobacco /OwYM
3A and B Nonsokers•
m
-245
'066 (0.19)
3.4)
0.00063
Tobacco
-2.45
Mar(jWna -
4
-13D(3.7)
^097 (316)
3.50
0.00049
Nonsmokers-
-23.5
0.27
0.78
- Tobacco
-13.0 (3.7)
3.56
fkekrence grpup. ibpa <wlrKknt irrdlutn diMrenca Imm selennct yroYo.
Slap. cot6kknu
0.00039
-^
em ml per Feet of tFtenet Y, FFV,,
An modem W4kKk a Inco 10, negin (nM shown).
Unlb of curlew amokug Nnamb marl(yani a mrmber of loms,(Or
day. TY -cltptndent smO3ing sutw terms lot
loudepuvaknu) per del, tobaCto a numbe
m.trna en
uaand lubu (Fiyun
N0. MCNivaM.robec<o eaetadton term is I lot MTs, 6 (wall 09,ars.
unomn¢ 1 e <unmYy rrhm r of tp.raltrl pe
IA and E): 0. OO, NrrenYy r
COrdtenpth~M atewuh
i hums (Fgt 7 er d 4p 1 e tyv'r anroked,
T • V4n une"' smo4n¢
3 • <nwin"Ou- atr ou rg. Ser lotto,
N
�� • -.� I uL- klb : Jb Ym
/ashkln, Simmons, Sheriil, [f of.; Mu0 and Annual Charge in FEVs
A
s.00
4.60
3.00
2.60
AGE (yr&)
Arvala a6dIN NOeA4WANA ----- 1{X2NT{pA1 140INTSMAY
M "V, (fit 331 3aS all
O P-05
145
6.00
4.50
4.00 ,
IL I
3.601
&00
I
2.60
00 36 40 IS s0 as So
AGE
An" 6{rfM NOTOaACCO •••-• to CIG/DAY 27 CI%DAY
Y FEV, 04- Saa 40A 411.3
Figure 2. Oeclines in FEVs (In liters) with age (in years) by intensity of smoking marijuana (A) or tobacco (8), estimated from random -effects
model In man. Slope coefficients for annual dgdine in FEVs (in milliliters) for smokers of 0, 1.5, 3.0 joints/d (A) or 0, 18, and 27 tobacco
cigarettesid (6) are shown at the bottom or the figure.
the similarity or the annual rate of decline in FEV, in the com-
bined smokers of marijuana and lobacco and in the nonsmok-
Ing control subjects, in contrast to the accelerated rate of decline
found among the tobacco -only smokers (Figure IA). Although
the dynamics of recruiting the different smoking groups were
similar, we cannot exclude the possibility that the results in the
dual smokers of marijuana and tobacco might have been in-
fluenced by an inadvertent sampling bias. Nonetheless, overall,
the findings in the present study do not support an association
between even heavy, regular marijuana smoking and the devel-
opment of chronic obstructive pulmonary disease (COPD).
These findings are at variance with the results of a previous
longitudinal study in which data were analyzed fromastratified
random sample (n - 856) of young adult residents (age 6 40
NEVER TOBACCO SMOKERS
A a.00
Clio[ i
4.00 r
3.50
3.00
2.60' 30 36 40 46 6o so t
IWAVUAN4t AGA loss)
A.nYaI tladv NEVER -••-- RITaANnTENT coNnNylba
IN FE'11, Owl; aha na eaa
Yr) of Tucson, Arizona (19). The latter sample, which included
leu than 100 self-reported smokers of nontobacco (marijuana)
either alone or with tobacco at study entry, had lung function
measured in 210 4 surveys conducted every 2 yr over a maximum
span of 8 yr. In the latter study, the estimated annual decline
in FEV, attributed to marijuana smoking reported at least dur-
ing the initial survey was 142 ml/yr, which was equivalent to ap-
proximately 501a of the predicted FEV„ in contrast to an expected
rate of decline of approximately I0/4 of predicted FEV, In non-
smokers. In the same study, moreover, the annual decrement in
FEV, among the marijuana smokers was twice as large as the
estimated annual decline due to current tobacco cigarette smok-
ing (68 ml), and theeffects of smoking both types of substances
were additive (19).
a A.00
4.50 r
4.00 F
�
3.50-
3.00
a.so
CONTINUING TOBACCO SMOKERS
30 33 40 45 SO 66 e0
eAAlxA1114 AGE tyro)
MrbY tlmr NMR ••--- INTERWMIT eONTINUU/a
F FN, ally 60.2 1 4011
Y4
Figure I. Declines In FEVI (in liters) with age (in years) by continuity of marijuana smoking (never, Intermittent, and continuing), estimated
from linear random -effects model among male never tobacco smokers (A) and continufng tobacco smokers (a). Slope coefficients for annual
electing in FEVI (in milliliters) In never, intermittent, and continuing marijuana smokers are shown at boftam of each panel.
,146 O AMERICAN JOURNAL OF RESPIRATORY Arvp CRITICAL CARE MEDICINE
5.00
4.60
? 4.00
3.60
0.09
960
30 as w Ma a0 as ev
r0a�iooa AGE (yrs)
MEVER ----- wrEAMITTEMT COM NU1Ma
AMUW esmnE
n Fev, tell: ass su Es.e
figure 4. Declines In FEV, (in liters) with age (in years) by continuity
of tobacco smoking (never, intermittent and continuing), estimated
from random effects modal In men. Slope coefficients for annual de-
cline in FEVs (in milliliters) for never, Intermittent and continuing
tobacco smokers are &hewn at the bottom of the figura.
The reason for she discrepancy between the results of these
two longitudinal studies is unclear. One possible reason might
be due to population sampling differences, since the randomly
selected Tucson sample was more likely to be representative of
the marijuana smoking population as a whole than was the Los
Angeles convenience sample, which may have selectively under.
recruited "sicker" smokers. Other possible reasons for these
discrepant results include differences in environmental or oc.
cupational exposures, concomitant substanceabuse (aside from
tobacco, such as crack cocaine, phencyclidine, or heroin), inLen-
sity and continuity of marijuana smoking, and other host char.
acteristics, such as allergy and concomitant illness. With regard
to possible confounding by differences in intensity and/or con-
tinuity of marijuana use, It is noteworthy that the marijuana
smokers in the present study were particularly heavy current users
(mean of over 3 joints/d) and reported heavy lifetime use (mean
of 43 to 56 joint -yr, defined as the number of joints per day limes
the number of years smoked), and most (82% or MTS and 73%a
of MS) continued to smoke marijuana during the entire follow-
up period. In contrast, the marijuana smokers in the Tucson co-
hort were much lighter smokers (< I joint/d, on average), and
reported a much lower lifetime intensity of use (mean of 9.3
marijuana joint -yr, when calculated as the number ofjoints per
day times she number of years smoked) (19). Although the authors
do nes specify the continuity of marijuana use in their cohort
of ever marijuana users, continuing or quitting marijuana smok-
ing did not influence the decrements in Jung function estimated
from thew model. Thus. differences in current and lifetime amount
of marijuana use, or in continuity of use during the course of
follow-up, do not appear to account for the discrepant results
of the two studies, since one would not expect the more intense
and prolonged use among the Lot Angeles marijuana smokers
to have rtsulled In the much lower rate of decline in FEV, rela-
tive to nonsmoking (and even tobacco smoking) than that which
was observed in the Tucson study.
Specifically excluded from the present study were individuals
with preexisting chronic chest disease, Including asthma or a his-
tory of intravenous drug abuse or of smoking substances other
than tobacco and/or marijuana. Moreover, only a small minority
of the follow-up sample from this cohort (12.6%s) initiated cock
P..06
VOL 155 1997
cocaine smoking during the follow-up period, and none initi-
ated intravenous drug abuse. Asthma or other chest Ulness was
not listed as an exclusionary criterion for participation in the
Tucson study (16, 19). It is unlikely, however, that the presence
of these Illnesses would have accounted for the difrerentially
grater rate of loss of lung function in the marijuana smokers
compared with the nonsmoking or tobacco smoking participants
in the Tucson study (19). Although a higher rate of Initiation of
smoking or other illicit substances (e.g., crack cocaine, which
would be included as a nontobacco substance) by the nontobaceo
smokers in tbeTucson follow-up sample might have contributed
to the observed excessive rates of decline among these smokers,
it is of interest that habitual crack smoking has generally not
been associated with impairment in spirometric indices, at least
in cross-secdonel studies (26, 27).
Although a "healthy smoker" effect might have accounted for
the absence of an abnormally rapid decline in lung function in
the marijuana smoking volunteers for the Los Angeles study, this
possibility seems unlikely, since tobacco -smoking participants
in the some study did exhibit accelerated declines in FEV 1, and
one would not expect that a "healthy smoker" effect would be
confined only to the marijuana smokers. Additional evidence
against a "hcallhy smoker" effect in the Los Angeles marijuana
smokers Is their relatively high prevalence of symptoms of chronic
and acute bronchitis at Visit 1, which was comparable with the
prevalence of these same symptoms in the tobacco smokers in
the same study (I5), as well as in the nonlobacco (marijuana)
smokers in the Tucson study (16).
A weakness of the present study is the relatively low follow-
up rate (65%a), raising the possibility of a difrerential loss to
Follow-up of the sicker participants, who might have exhibited
grater rates of decline in lung Function over time. Although the
latter possibility cannot be excluded, the fact (hat nearly all
participants who could be contacted and did not move out of
the area returned for retesting, that follow-up rates were com-
parable across smoking categories, and that baseline lung
function was similar in those who did and those who did not
undergo follow-up rating diminishes the likelihood or this ex-
planation for the lack of a demonstrable impact of continuing
marijuana smokingoo lung -function decline, particularly since
an accelerated decline in FEV, was detected in the tobacco.
smoking participants.
Other potential confounding influences (hat might have af-
fected the results of this longitudinal study of lung function
change include systematic differences in technician or equipment
performance. However, the same equipment was used through-
out the entire study, and all tests were performed by two highly
experienced technicians who adhered to a rigorous daily calibra-
tion and quality control protocol (28), and were cross -trained
in spirometry using the Same Instrument. hforeover, any instru-
ment drift or intertechnician variability in test performance would
not be expected to differentially influence the results only in the
marijuana smokers, since subjects in all smoking categories were
tested at similar times throughout the follow-up period.
Our failure to rind evidence or progressive lung dysfunction
in the continuing marijuana smokers who we followed contrasts
with our own observations that the proportion of these smokers
who reported symptoms of chronic bronchitis was comparable
with that of the tobacco smokers in The same cohort (15), and
that many of the continuing marijuana smokers have shown
as extensive histopathologic altcmijons on bronchial mucosal
biopsies as the tobacco -only smokers (17, I8). However, these
similarities between the effects of habitual smoking of mariju-
ana and tobacco on chronic respiratory symptoms and proximal
bronchial histopathology do not necessarily imply similar con-
sequences with respect to bronchiolar and alveolar injury that
might lead to smoking-related obstructive small airways disease
/ aahk+n, Simmons, Sheriff, er 01.: r',u Jna and Annual Change in FN, O
) 147
l/
r end/or emphysema. Although ryn Jim s of chrome bronchitis
are believed to be related histopathologically to hypertrophy or
marijuana smoke than they wccc amutomcd to which would
submucosal bronchial mucous gland; AtteratiQm in ciliated bran-
' chial epithelial cells, and hyperplasia of mucus
not have progressed at the same rate with much more prolonged
exposure in the face of emerging adaptive mechanisms.
-secreting goblet
cells (29), these symptoms of mucus hypersecretare not
thought to be necessarily lini
ked to the
Conclusion,
In nclusion, findings from the present long-term, follow-up
study of heavy, habitual marijuana smokers argue
progressive damage to
and narrowing of peripheral airways that accompany the evolu-
lion of smoking-related chronic obstructive airways disease (30),
against the
concept that continuing heavy use Of marijuana is a significant
risk factor for the development of COPD. These negative find -
ings,
It is possible that the contrasting effects of marijuana and
tobacco smoking in the present study on
however, do not imply that regular marijuana smoking is
free of harmful pulmonary effects. Habitual marijuana
Progreasive changes in
lung function might be due to the marked disparity in the quan-
tity of the two substances that were smoked: an
smok-
ing is associated with a higher than expected prevalence of symp-
toms of chronic bronchitis (15, 16), as well as a higher incidence
average of 4.1
joints/d in the marijuana -only smokers versus 27.5 cigarettes/d
the Although the precise amount
oracute bronchitis (15). Moreover, other evidence suggests that
marijuana ouy be an important risk factor for the development
M anatobacco-onlyskedsmokers. of
marijuanasmoked cannot be accurately determined because of
the uncertain reliability of self-reported usage
of respiratory infection (9, 35), and possibly respiratory maljg-
nancy (36). Further studies are required to document the
and the common
practice of sharing joints, it is highly likely that the amount of
real re -
spiratory risks of this commonly smoked substance.
actual usage of marijuana was far less than that of tobacco, On
the other hand, differences in fdlralion of smoke through the
" b"ekd9"emV The authors thank Mr. Enoch tee for his technical asdstame
and Mr, John Dennand for his assistance in tracking and I
more densely packed tobacco cigarettes (in which cellulose filters
°cab"9 Pa tQwnu.
were generally incorporated) and the more loosely packed, filter -
less marijuana joints, whlchareusuall sm ked
length, approximately double the tar yield of themarmuajoint References
ian
(18), Moreover, differences in smoking topography (larger Cu. I. Johnnone, L. D., P. M. O'Malley, and J. G. Bachman. 1994. National
mulative puff volumes and inhaled volumes of marijuana smoke survey results on drug use from The Monitoring the Future Study,
and a d fourfold longer smoke retention time for marijuana than 1975-93, Volume I. Secondary School Students. Nations) Institute
On for tobacco), added to the differences in smoke filtration, may PrlmtinggOffi see Waslhinnggton P1DC No,
9°-Jao9. V.S. Governmem
result in a fourfold greater retention of tar in the lungs of martin• 2. Johnstone, L. D., P. M. O%a&y, and J. G. Bachman. 1994. National
ana smokers compared with smokers of a comparable quantity survey results on udy
drug use from The Monitoring the Future St,
orwhole tobacco (31). This amplification of the exposure of the 1975-93, Volume fl. CoOcge Students end Young Adults. National
lungs to the smoke of marijuana narrows the gap between a ;a six. lustiluu on Drug Abuse, NIH Publication No.94-3810. U -S. Gores,
fold greater quantity or reported u went Printing Office, Washington, DC.
sage of to perhaps 3. Hoffmann, D., D. K. &unoemann, G. B. Gori, and E. L. Wynder.
the
only approximately twofold greater exposure of the lungs to x975. Qct the arcinogcnidty of maty' G.
B. smoke. Ree. Adv. Wynder. the smoke from tobacco compared with marijuana. Thus, quart. them. 9:63-81.Ph
titative differences alone may not entirely explain the disparity 4. N°`rotnY• M., F. Meru, D. Weider, M. Fetal, and T. Saeed. 1982. Fnc-
in longitudinal rates of decline in lung function between the two donation and capillary gas chro
ofsmokers. "utographk mass spectrometric char -
[he
twi?videncethatQualitativedifrerencesbetwm "t t'40"0fthttunalcvmponenuInnurijuanaandtobaccosmoke
the two types Of smoke may be more important thanuantita- condensates. 1. CAromarogr. 238:141.150.
live differences with res P q 5• Roy, P. E., F. Magnan -Lapointe, N. D. Huy, and M. Bourn. 1976.
pect to the development of COPA de- Chronic Inhalation of marijuana and tobaao In dogs: Pulmonary
rives from animal studies In which morphologic and physiologic pathology. Ra. Commun. Cham, Por 10bitil- PhorIn dog 1Pulmo317.
evidence of emphysema was found in rats exposed for 6 mo to 6. Fleischman, R. w„ D. W. Hayden, M. C. Braude, and H. Rosenkranz.
tobacco smoke, but not in rats exposed for the same period to 1975. Chronic marihuana inhalation toxicity in rats.
smoke from a comparable quantity of marijuana (32), Phonriecaf. 34:467-478, Totkol. Apps.
Peripheral deposition of inhaled particles in the lura depends 7. Fleischman' R. W., J. R. Baker, and H. Roscnkrantz. 1979. Pulmo
largely on particle size If particulates in marijuana smoke were n9arry a noal-vg i changes in rats exposed to marijuana smoke for one
substantially larger than those in tobacco smoke, it could be ar- 8. Fligid, S. E. G., T. F. BeeisnD. P. Tashkln M O. Pause, A. C. Scallct,
gued that these particulates do not reach the small airways and S- V Ali, J. R. galley. and W. Slikker, Jr. 1991. Marij nano cxpoaurc
alveoli as efficiently as the submicronic panicles In tobacco "it Pulmonary alterations in mates. Phormptpl. 8rothem.8ahay.
smoke, and are therefore less likely to cause tissue injury at those 40:617-642'
sites primarily affected in COPD. On the 9. Huber, G. L.. V. B. Pochay, W. Pereira, j. W. Shea, W C. Hind$,
other hand, obacc - M. in past, and O. C. Sorobbacte 1980. Mad)uana, tctrahydrocan•
notate measurements Of particles in marijuana and tobacco nabinol, and pulmonary anr;bactcrial Qcfcnsn. Chess 11:403-4I0.
smoke, made with laser Doppler velocimetry techniques, have to. Rubin, V., and L. Comius. 1975. Rnpl dt fcn m on and 403-41 l -
confirmed that the mass median aerodynamic diameter of the oar• fn oanja In Jamaica; q Medica! Anthropological cal Study of
particles from the two types otsmoke are comparable (approxi_ Chronic Marihuana use. Mouton, the Hague. g7_IO2.
mately 0.5 µm) (33), thus refutiog this argument. If. Cl opra,as. 1973, Stud es Mouton,
The Has
The results of the present 8 -yr study also contrast with find• runt use in 124 cases. 1171, !. Addirr. 3:1015-1026. tem Mari_
from a short-term prospective study(34) that demonstrated 13 Hlmv ct on United Slsuero5eturityaJn Herrings of the Committee on
an accelerated decline in FEV, (approximately 3% of baseline) 1 Hashish Epidemic and lis
Or-
in 28 heals J Y 'h eJ Judiciary, United States Sena It U.S. Government Printing Of-
hy male marijuana smokers over only 8 to 9 wk of Washington, DC. 147-154.
much heavier than usual exposure (mean of S joints/d, compared 13. Herrnnda-Rishm s, l., E. W. Swenson, and W. J, Co
with their customary use Of an average of I joint/ ervation of pulmonary function in regular , heavy, ong_t 1976. Pre•
after cessation of this unusuallyhu �t One month ana smokers (Abstract). Am. Rev. ea r, long-term:joo-
vy use, the latter subjects to,, aoulouaou.ia, J. C., C. P. PanaNue Du. I13(So. A.):100.
exhibited a rdurnof their FEVs to baseline. Although it is diffi• chronic
a, n. Acts
cult to explain the discrepancy end C. SteAnia, 1976. £flints of ch onich �a"v sit. P ry between these two prospective tua in 44 users compared with 38 control Amt. sK.. Y. Acad. e on l&i.
studies, it is possible that the participants In the Short-term study 2g2c168-172.
(34) experienced a temporarily steep step -decline in their lung 15. Tashkin, D. P„ A. H. Cwhan, V. A. Clark, M. Simmons, L. B. Bour.
function, after daily exposure of their airways to much more quq S.Duann,G.H.Spiv
ey, and He , Gone1987. RespiratorysYmp•
roma and h+"a function In heavyaabitual, ary uaokvs or mar(juana alone,
Antineoplastic Activity c0clinnabinolds' ' O
A. E. Munson, L. S. Harris, M. A. Friedman, W. L. Dewey, and R. A. Carchman 3
SUMMARY—Lewis lung adenocarclnoms growth was retarded
by the oral administration of Ar -tetrahydrocannabinol (Ar -THC),
A` -tetrahydrocannabinol (A' -THC), and cannabinol (CBN), but
not cannabidiol (CBD). Animals treated for 30 consecutive days
with A' -THC, beginning the day after tumor Implantation,
demonstrated a dose-dependent action of retarded tumor
growth, Mice treated for 20 consecutive days with As -THC and
CON had reduced primary tumor size. CBD showed no Inhlbl•
tory effect on tumor growth at 14, 21, or 28 days. A' -THC,
A' -THC, and CON Increased the mean survival time (36% at
100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, re•
spectively), whereas CBD did not. .11 -THC administered orally
dally until death In doses of 50, 100, or 200 mg/kg did not
Increase the life -spans of (C578L/6 x DBA/2)Fl (BDF,) mice
hosting the L1210 murine leukemia. However, As -THC admin-
Istered dally for 30 days significantly Inhibited Friend leu.
kemia virus -Induced splenomegaly by 71% at 200 mg/kg as
compared to 90.2% for actinomycin D. Experiments with bone
marrow and Isolated Lewis lung cells Incubated In vitro with
AP -THC and Aa -THC showed a dose-dependent (10.1-10,1)
Inhibition (80-20%, respectively) of titillated thymidine and
11C.uridine uptake Into these cells. CBD was active only In
high concentrations (10-1),—) Nall Cancer Inst 55: 597-602,
1975.
Investigations into the physiologic processes affected
by file psychoactive constituents of marihuana fpr-tetra-
Ipdrocannabinol (A'-TFIC) and A'.tctrahydroc-innabinol
(Y.TIIC)j purified from Cannabis sntiva are extensive
(1). l to vever, only recently have aaseuspts been made to
elucf(bae the biochemical basis for their cytotoxic or,
cytostatic activity. Lcuchfcnbciger ct al. (2) demon.
strated that human lung culhtcs exposed to marihuana
smoke showed alterations in DNA synthesis, scull the
appealance of anaphase bridge%. 7.inunernil" 111d Afc-
Clean ()), s(ildying macromolecular synthesis in Tc7in-
hynrenn, indicated shit VCly IOIv coriceintr.1tioil% of 69.
TIM inhibited RNA, DNA, and plotein synthesis alld
produced c tolysis. Stenchever et a). (1) showed an in-
a'case in the number of damaged or broken chromo-
somes in chronic users of marihuan-i. As-7'IIC adminis-
tered iv inhibited bone marrow Icukopoicsis (3), and
KOlodny et al. (0) reported that marihuana may impair
a
scostcrouc secretion -incl spermatogenesis. Fursherniore,
Nahas et al. (7) showed that in chronic marihuana users
dleie is a decrease(] IyrnphocJ'te reactivity to mitogens as
measured by thymidine uptake. These and other (8)
observations suggcsf that marihuana (;1':I-IIC) interferes
with s•it'll cell biocllentical processes, though no definite
nicchani.snt has yet been esmblishcd. A preliminary re.
POI -1 hon this laboratory (9) indicated that file ability of
-%'--I'IIC to interfere with normal cell functions might
prove efficacious against neoplasms. -Fhis report repre-
sents an effort to test various cannabinoids in several
in vivo and in vitro Unnor systems to determine the
kinds of tumors that arc sensitive to Thcsc coollsoanlds
and reveal their possible biochemical sites of action(s).
MATERIALS AND METHODS
The tumor systems used sverc the Lcwis lung adcno-
k-r
carcinoma, leukemia L1210, and B -tropic Friend leu-
kemia.
!n vivo spslcnis.-1-CIvis Will; tumor; For the mainte-
nance of file "wets lung carcinoma, approximately
1 -mm' pieces of tunior were transplanted into C57BL/6
mice wall a 15 -gauge trocar. !n experiments involving
chemotherapy, 14- to 18 -day-old tumors were excised,
cleared of (debris and necrotic tissue, and cut into small
fragments (== I nima). Tumor tissue was tile,, placed in
0.25;, trypsin in Dulbecco's medium with 100 U penicil-
"11/1111 and 100 pg streptomycin/ml. After 90 minutes'
incubation at 22° C. trypsin action leas stopped by file
ad(lition of complete mediuni containing heat-inacti.
entad fetal calf serum (final concentration, 20;). Cells
sverc washed two tinges in complete medium, entnnerated
in a Cot ]it
counfcr (Model Z13,) or on a hcmocytometcr,
and resilsperl(lc(I in serum -free medium at a concentra-
liou of 5x 104 cells/nil. Next I x 104 cells were injected
fun into the right hind gluteus muscle, and (]rugs admin.
isicred as described in "Results." Standard regimens pro.
vided for 10 consecutive (gaily doses beginning 21 hours
after tumor inoculation. Body weights were recorded be.
fore tumor inoculation -incl weekly for 2 weeks. Tumor
si7c was measured weekly for the duration of the cx(,cri-
ment and converted to mg tumor weight, as described
by Mayo (/0).
Friend leukemia: B -tropic Friend leukemia ,virus
(FIA') was maintained in IIAI,B/c "lice, and dnlg evalu-
ation performed in the sante animals. Pools of virus wcic
plep-ired floor like plasma of mice given FLV and stored
at -700 C. In cxperinients with FLV, 0.2 nil of a 1/20
dilution of plasma (derive(] from FI,V.infected mice) in
medium seas inoctllated if) into BA1.11/e mica Cannabi-
noids sverc administered orally daily for 10 consecu.
tive da)s beginning 2.1 hours after virus inoculation.
T%venf)'-four hours after the last drug administration, the
mice wcrc killed by cervical dislocation, and the spleens
removed and svcigllcd. \rice not given FLV wcrc treated
as described above, to e%•aluate possible drag induced
spleuomcgaly.
1.1210 leukemia: The murine leukemia L1210 was
nrlinlained in DBA/2 mice by w'eckly transfers of 101
cells derived from the peritoneal cavity. In these experi-
orenss. IOa leukemia cells sverc inoculated ill into
(C57ISI./6 X DBA/2)17, (IIDF,) mice, and the ,,)ice sverc
treated (gaily for 10 consecutive (la)s beginning 21 hours
after tunsor cell inoculation. Mean survival time %vas
used as an index of drug activity.
!n villa c"fl J)slerns.—Lewis lung tumor: We obtained
isolated I.e%vis lung tumor cells by subjecting I-mrns sec-
tions of utmor to 0.25:. trypsin at 220 C and stirring for
60-90 minutes. After tr)psinization, the cells were centri-
1 Recci%ed December 26, 1974; accepted pfay 30, 1975.
'Supported by Public Ifeallh Senicc grant DA00190 frnin the
\3(101131 tnrtitu(t on Drug Abuse. Ilcalth Scniccs k kfnnal
Ilcalth Adruinirtntion; by a gnat from the Alexander and \lar
garc( stcaart 'fruit Fun(; and by an imtilulional grant from lbe
Anierican Cancer Society.
a Deparlinent or rhatmacology and the klCl'/l'CU Cancer Cen.
ler, Stedical C0IIc9e of Virginia. Virgil li3 ICV/VCU Can er Cen.
III)', Ridwlond, Va. 23298,
JOURNAL OF TIIE NATIONAL CANCER INSTITUTE, VOL, 53, NO. S, SF.r'r F.%IRER 1975
Fitz FT TtilstF( PgGFS)
597
MUNSON ET AL.
fuged (1,000 rpm for 10 min) and washed twice in Dul-
becco's medium containing 207. heat -inactivated fetal calf
serum. They were then reconstituted to l01 cells/nd in
Dulbecco's medium containing, for every 500 nil, 5 nal of
200 mm glutamine, 5,000 U penicillin, and 5,000 pg strep.
tomycin. Tumor cells (3–G ml) were dispensed into 25an1
Erlenmeyer flasks and preincubated with either the drug
or the drug vehicle for 15 minutes in a Dubnofl metabolic
shaker at 370 C in an atmosphere of 5 Co. -95% O..
After preincubation, 10 pl tritiated thymidine (1H -TDR)
(10 pCi, 57 Ci/mmole; New England Nuclear Corp., Bos.
ton, Mass.) was added to each flask and incubated for smri-
ous times, after which Ia111 aliquots were removed -incl
placed in 10x75.inm test tubes containing 1 1111 10 0
trichloroacetic acid (TCA) at 4e C. The TCA-precipi-
fated samples were then filtered on 0.•15-p Millipore fil.
ters and washed twice with 5 ml of 10'. TCA at 4° C.
True filters were transferred to liquid scintillation vials
and counted in a toluene cocktail containing Liquifluor
(New England Nuclear Corp.) (4 liters toluene to 160 nil
Liquifluor). Samples were then counted in a liquid
scintillator.
Bone marrow: Bone marrow cells were derived from
the tibias and fibulas of BDF, mice. One nil Dulbecco's
medium containing 1 U heparin/ml was forced through
each boric by n I -nil syringe with a 26.gauge needle. 7'he
cells were washed three times, nucleated cells stere enu-
merated on a henlocytonleter, and cell viability was ascer-
tained by trypan blue exclusion. Cell number was ad-
justed to 101 cells/ml with heparin -flee Dulbecco's
medium mol incubated at 4e C for 15 minutes. ]tone
marrow cells were then dispensed (3-5 ml) Into 25-m1
Erlenmeyer flasks containing the lost drug or the drug
vehicle. This preincubation period was followed by the
addition of 10 pl 'H -TDR and the procedures done as
outlined for the isolated Lewis lung cells.
L1210: L1210 cells were derived from DBA/2 mice as
described above. They were obtained from DBA/2 mice
and inoculated 7 days before the experiment by the
peritoneal cavity being flushed with 10 nil Dulbecco's
medium containing heparin (5 p/ml). 7 -he cells were
washed three times in medium, and the final medium
wash dill not contain heparin. The cells were resus-
pended at 101 cells/ml and treated as described above.
Cells were routinely counted with a hemocytonleter for
tire determination of cell viability with trypan blue; for
Lewis lung tumor and L1210 cells, a Coulter apparatus
(Mode ZB,) was also used.
All other reagents were of the highest quality grade
available. Actinomycin I), 5.Ouorouracii (5 -FU), and
cytosine arabinoside (ara-C) were provided by the Drug
Development Branch, National Cancer Institute (NCI).
Cannabinoids.—The struc!ures of the four cmnpounds
are shown in text -figure 1. All occur naturally in nrari.
huana and were chemically synthesized. _Hicse drugs
were provided by the National Institute on Drug Abuse
or the Sheehan Institute for Research, Cambridge, Massa-
chusetts. In clue preparation of the drugs, the cannabi.
noids were complexed to albumin or solubilired in
Enudphor-alcohol. Boih lrepnrations produced similar
antitumor activity. With a�bunlin, the cannabinoids were
prepared in the following planner: A stock solution of
150 mg cannabinoid per ml absolute ethanol was made.
Six mi of this solution was placed in a 200-m! flask. The
ethanol was evaporated off under a stream of nitrogen
and 2,100 mg lyophilized bovine serum albumin (LISA)
added. After the addition of 20 ml distilled water, the
CH3
OH
C5H I I (n )
O9 -THC, Z -THC
CH3
� OH
i
CSHII(n)
112 -THC, LI(6)-THC
CH3 CH3
\ OH \ OH
� I i
\ C5H11(n) \ \ I C5H11(n)
OH
Cannabinol (CBN) Cannabidiol (CBD)
'rrxT-rrcear I.—SlraClllrer of lha four major canuabinoide.
subswnces were stirred with a lass rod in a sonicator
until a good suspension was achieved. Sufficient distilled
water was then added to make the desired dilution. Con.
centrations were routinely checked with a gas chromat.
ograph. When Enndphor-alcohol was used as the velli.
cle, the desired amount of cannabinoid was sonicated
iu a solution of equal volumes by absolute ctluanol and
Eniulphor (EI -620: GAF Corp., New York, N.Y.) and
then diluted with 0.15 N NaCl for a final ratio of 1:1:4
(ethanol: Ensulphor: NaCl).
RESULTS
Effects of Cannabinoids on Murine Tumors
W- THC, As -THC, and cannabinol (CBN) all inhibited
primary Lewis lung t unor growth, whereas cannabidiol
(CBD) enhanced tumor growth. Oral administration of
25, 50, or 100 mg Ar-THC/kg inhibited primary tumor
growth by 48, 72, and 757t,, respectively, when measured
12 days frost tumor inoculation (table I). On day 19,
mice given Ar -THC had a 34% reduction in primary
tumor size. On clay 30, primary tumor size was 76'/,that
of controls and only those given 100 mgg Ar-THC/kg had
a significant increase in survival time (36 ,).
Mice treated with W -THC showed a slight weight loss
over the 2 -week period (average loss. 0.3 g at 50 mg/kg
and 0.1 g at 100 nig/kg). This can be compared to cyclo.
phosphamide, which caused weight loss approaching 20'.
(table 2).
Al' -THC activity was similar 10 that of Ar -THC when
administered orally daily until death (table 2). However,
as with Ar -THC, primary tumor growth approached con-
trol values after 3 weeks. When measured 12 days post
tumor inoculation, all doses (50-400 mg/kg) of Aa-TIIG
inhibited primary tumor growth between 40 and 60"6.
Significant inhibition was also seen on day 21, which ara+
comparable to cyclophosphamide -treated mice. Although
this was not the optimum regimen for cyclophosphamide,
it was the (>ositive control protocol provided by the NCI
(1/). All mice given W -THC survived significantly longer
than controls, except those treated with 100 mg/kg. Mice
given 50, 200, and 400 mg/kg Ar -THC had an increased
life -s an of 22.6, 24.6, and 27.2%, respectively, as corn*
parol to 33;, for mice treated with 20 mg cyclophus-
R
OANTICANCER ACTIVITY OF CANNABIN0
599
- TABLE 1. E,ffed of de -THC on lumor growth and survival time of mite hosting Lewis lung
carcinoma
Treatment Daae Body weight Tumor weights (g) at
mg/kg 'change (g) a 12 drays r 19 days • 30 days • Mime ean (days)al
life -spam, 0o
Control (BSA 7.5%) ...... - }1.5 892}150 3,456+252 5,8&9}673 25.8+1.3
(8) (3)
p,•TIIC................. 25 }0.9 468+)107 s 2,363+146 it 4,337:L270 s 30.3+2.0
17.4
(8) (8)
p•-TIIC................. 50 -0.3 253( ,118 it 2,168 a 4,8511 27.4+O.G
6.2
8}95
p••T11C................. iW -0.1 221( )98' 2,30362d
362. 4,6067)
.6 35.0+1.1 a
36
07+312+
• Croups of mice were Inctu Is ted Im wi lb 1 X106 Lewis lung tell. and treated orally for 10 days with A•-TIIC.
. whole body weight changes after 10 day. of treatment.
• Post tumor Implants; tumor welahte aero der,,'d Isom measurement of major and minor sate. Calum are means tee;
I P <0.05 number of mice .ry Indicated in pormrM1nn.
a compared to control.,
TABLE 2. Efferl of C'-TIIC on tumor growth and survival time of BDFI mire hosting Leun's hep carcinoma
Tumor weights (g) at
Treatment Dane Hod) weight
Mean nnrvival
mg/kg change (g) a 12 days • 21 days • time (Jaya)
Increased
life
-span,
Control (BSA 7.5%) .......... - -1.6 621+30 4,880+380 30.5+0.9
(3O) (30)
da•TIIC..................... 50 -0.9 238+411 it 3,104+274 s 37.4+1.7 s
22.6
,1•-TIIC..................... IW -3.4 1114:00 s 2,299:236 s 34.3+1.9
12.4
(7) (7)
Gr•THC...................... 200 -I.6 174+53 • 3,188+389 s 38.0+1.9 a
24.6
pr-TIIC................... _ (6) (6)
_ 4W -3.3 235+78 a 3,194+413 a 38.8+1.2 is
27.2
Cyclophosphamide..._...__._;20 -4.0 (6)0 s 2,949+194 J 40.6+1.8 s
33.0
(8)
Pyran copolymer ............. 50 -1-0.3 122+38 it 1,876+174 • 42.5+3.3 s
39.3
(8) (8)
• Groupe of male BDF, mice were Inorulated in, with 101 Lew l• lune orcinoma ,If. and treated mittly Jelly with d%Ti IC until des lh. Cydophoeph.mide and p) an
torol)n,rr were administered Its for 10 constitutive days healnnb9t
24 hours after tumor Inoeula0on.
s 1% hole body weight change, after 10 day of treatment.
• Post tumor implants; tumor weight .ere derired from measurement of major and minor tumor see \•dun .re mmmfa,p number
std in porentAne,.
of min are Indi.
• P <0.05 as compared to eentro6.
TABLE 3.-F.jfert of CIIN on tumor prou•th and sunirnl time in BDFI mire holing Leuis lung rarrinoma
Tumor weighl. (g) titTrenlmeut Dire Bodyecighl \Icon sun•ivnl
Inrreacd
mg,4 change (g) a 14 tiny. • 24 +trays • time (days)
life -span, �
Cuutrol(BSA 7.5%) .......... +3.3 1,288+146 5,520+506 26.6+1.3
(21) (21)
CIIS....................... 25 -0.6 1)(I5+140 it 0,74:1+376 29.0+1.2
12
(x) (�)
CI{N....................... 511 -0,G 875+115 e .5,709+291 :1.9.7+1.6
27 e
CIL\....................... IW (G) (G)
-2.G 296+984 4,843+4G2 27.8+0.9
3.5
(7) (7)
• G1e11p, of mice Inoculated his with 1 X10• Leal, lung 1111. and I ... led orally daily with )••TIIC or CBN until death.
. \%'hole body .d,lrt changes titer 10 day, of treatment.
• Post tumor Implant; tumor .debt were derhed from measurement of major and
nt„1 m pmenthwrr. minor tumor ate. Falun ase mnro r, tanumber of mice are inJl-
'
• P <0A3 as compared to comets.
phamide/kg. Pyran copolymer, an immun0Ootentia(or was observed on clay 21; however, these animals (lid stir.
(12) when administered at 50 nig/kg, also significantly \•ive 27 longer.
increased the survival time of the animals (39.3";). MID, administered at 25 or 200 nig/kg daily until
CBN, administered by gavage (fail)• until cic:ull, dcnl•
death, showed no ulmor•inhibitory properties as mea\•
onstrated antitumor activity against the Lewis lung carci• ured by primary Lewis lung tumor size or survival time
soma when evaluated on day 1.1 post tumor inoculation (table 4). In this experiment. CBD -treated slice showed
I (table 3). Primary tumor growth wits inhibited by 775; at enhance(1 primary tumor growth. However, the control
doses of 100 mg/kg on (lay 14 but only by I I"; on da) 24- rumor giow'th rate in this experiment was decreased as
At 50 mg/kg, MIN inhibited)rinlary tumor growth by compared to the previous studies.
only 32",; when measured on Say 14, and no Inhibition Survival time of BDF, "lice hosting 1.1210 leukemia
r
0081�l�/3gel•0001302.0a/0 Vol. 38, No. t
pµ�UucaLar.�ce L acvlewa prL.hd in U S.A.
.nal Cogyritht® 19M by The American Society for Pharmacology and Ezperimeatel l-herapautin
'.her
21: Health Aspects of Cannabis*
:ate
•�•- LEO E. EiOLLISTER
J.
f Veterans Administration Medical Center and Stanford University School o/ Medicine, Palo Alto, California
:ter-
hys.
I. Introduction.................................................................................
aoa,.........................................2
II. Acute and chronic effects of cannabis in humans . - - - • • • • • • • - 2
.............................................. 3
• A. Acute studies............... ...........
rugs B. Chronic studies..............:...................................................•
Ar- . "......................................................
H. , �. possible adverse effects of cannabis on health 3
A. Immunity..................................................................................4
feted : B. Chromosomal damage.................................. .
..........................................4
(top C. Pregnancy and fetal development................... 5
onal5
D. Cell metabolism ....................... . ........ .
E. Psychopathology.......................................................... ...................5
ergs....................................
rroa 1. Acute panic reaction ............... .
2. Toxic delerium ....................... .....................6
3. Acute paranoid states .................
...............................
4. Psychoses........................................
5. Flashbacks ..............................................................7
.
6. Violence........................................
7. Amotivational syndrome .............................................
psychomotor .................
impairment .........................................8
8. Resldualpsy P ......8
9. Brain damage............................................................................8
F. Tolerance and dependence ................•--•
•...........................
1. Cross tolerance...........................................................................9
? 2. Physical dependence ...............................
G. Endocrine and metabolic effects ......... ....................................................70
,, , , , , , , , ,,, , , ,
.........................
H. Lung problems ........' • • ..
10
t I. Cardiovascular problems .................................................
J. Eye problems................................. . 11
K. Contamination of cannabis .......... • - - .
..................................•,....................................11
....
L. Possible accumulation of drug..........................................12
i M. Effects on driving an automobile........................................................ 13
t IV. Therapeutic uses...................................... .............. .......................
............Z�
A. Antiemetic for patients in cancer therapy....................................... • • • .14
l B. Glaucoma..........................................................
.....:..........14
Analgesia...............::................................................
1s
Muscle relaxant............................................ 15
;c
E. Anticonvulsant..... ...............................................'...........__..........
Bronchial asthma...................:......................................................15
t... G Insomnia..........................................._............
........................................t__...........1
H. Miscellaneous uses ............................................................. ..16
1. Hypertension .................................................. .::.......
............
2. Abstinence syndromes due to central nervous system depressants ....................... • • • • • • • • 1
3. Antineoplastic activity........................................
.............16
4. Antimicrobial action ...............................................................16
Migraine..................................................... ...................:... ..16
Appetite stimulant.............................................. ,........17
_ 7. Alcoholism .................... 17
V. Summary ..........................................
This article is otie of a sense of five stimulated by a symposium held in Conjunction with the Fall Meeting of the American Society of
Pharmacology, and Experimental Therapeutics at Louisville, August 18-20. 1982; The aeaistence gf William L. Dewey as consulting editor is
tretetblly acknowledged.
.nstil.
,d the
irable
td for
;vould
lbbits
d eye
over.
ration
pres-
ll eye
ect is
of the
but it
)they
or 8-
also
have
gable
tnna-
ested
Ips in
ffects
lctive
iY, a
com-
oten.
in to
con-
ltion.
rtely,
-term
that
acids
y the
coma
mna-
nuch
mna-
The
glau-
aften
ve to
may
igs,
rg of
ed to
ag of
mg)
was
dose,
ither
OHEALTH ASPECTS OF CANNABIY
dose of codeine (129). THC given i.v. in doses of 44 µg/
kg to patients undergoing dental extraction produced an
analgesic effect, which was less than that achieved from
doses of 157 ug of diazepam per kg i.v. Several of these
patients actually preferred placebo to the dose of 22 µg
of THC per kg because of anxiety and dysphoria from
the latter drug (139).
The apparent paradox is that THC both increases at:d
decreases pain. Traditionally, aspirin -like drugs, which
work peripherally by inhibiting the synthesis of prosta-
glandins, are used to treat pain derived from the integu-
ment. The initial mental stimulation from THC might
increase sensitivity to this kind of pain. Visceral pain,
such as that of cancer patients, is usually treated by
opiates, which have both peripheral and central sites of
action. Recent evidence suggests that opiates may act
directly on pain pathways in the spinal cord as well as
reducing the affect that accompanies pain. Cannabis
could conceivably modify the affective response. Thus,
when the two types of pain are distinguinshed from each
other, the apparent paradox is solved.
THC, nantradol, and nabilone shared some properties
with morphine in the chronic spinal dog model. Latency
of the skin twitch reflex was increased, and withdrawal
abstinence was suppressed. Naltrexone did not antago-
nize these actions, suggesting that they are not mediated
through opiate receptors (56). Levonantradol i.m. was
compared with placebo in postoperative pain, and a
significant analgesic action was confirmed. No dose -
response relationship was observed, and the number of
side effects from levonantradol was rather high (89). It
seems unlikely that any THC homolog will prove to be
an analgesic of choice, when one considers the present
array of very effective new analgesics of the agonist.
antagonist type. It is too early to be sure, however.
D. Muscle Relaxant
Patients with spinal cord injuries often self -treat their
muscle spasticity by smoking cannabis. Cannabis seems
to help relieve the involuntary muscle spasms that can
be so painful and disabling in this condition. A muscle
relaxant or antispastic action of THC was confirmed by
an experiment in which p.o. doses of 5 or 10 mg of THC
were compared with placebo in patients with multiple
sclerosis. The 10 -mg dose of THC reduced spasticity by
clinical measurement (135). Such single small studies
can only point to the need for more study of this potential
use of THC or possibly some of its homologs. Diazepam,
cyclobenzaprine, baclofen, and dantrolene, which are
used as muscle relaxants, all have major limitations. A
new skeletal muscle relaxant would be most welcome.
E. Anticonuulsant
One of the first therapeutic uses suggested for cannabis
was as an anticonvulsant. Such an effect was documented
experimentally many years ago (112). Subsequent studies
in various animal species have validated this action. THC
15
in cats temporarily reduced the clinical and electro -
graphic seizure activity induced by electrical stimulation
of subcortical structures (175). Mice were protected by
cannabidiol against maximal electroshock seizures but
not against those caused by pentylenetetrazole. Its profile
of activity more resembled that of phenytoin than that
of THC (170). THC and cannabidiol both potentiated
the anticonvulsant effects of phenytoin against electri-
cally induced seizures in mice. The two cannabinoids in
combination produced the most effect (29). Kindling
involves the once -daily appliction of initially subconvul-
sive electrical stimulation to culminate in generalized
convulsive seizures. THC given chronically to rats pre-
vented the kindling effect (174).
Clinical testing has been rare, despite all these various
lines of evidence supporting an anticonvulsant effect of
cannabinoids. Better control of seizures following regular
marijuana smoking was reported in a not very convincing
single case (39). Fifteen patients not adequately con-
trolled by anticonvulsants were treated with additional
cannabidiol in doses of 200 or 300 mg or placebo. Can-
nabidiol controlled seizures somewhat better than the
addition of placebo (25). Cannabidiol has little if any
psychoactivity, making it a good candidate for this use.
F. Bronchial Asthma
A general study of the effects of marijuana on respi-
ration revealed a bronchodilating action in normal vol-
unteer subjects. Marijuana smoke was calculated to de-
liver 85 or 32 µg of THC per kg. A fall of 38% in airway
resistance and an increase of 44% in airway conductance
occurred in the high -dose group. The low-dose group
showed lesser changes, but they were still significant as
compared with baseline. The sensitivity of the respira-
tory center to carbon dioxide was not altered by either
dose, indicating no central respiratory depression (172).
Asthma was deliberately induced by either inhalation
of metbacholine or exercise in asthmatic patients. They
were then treated with inhalation of placebo marijuana,
of saline, of isoproterenol, or of smoke derived from
marijuana containing 1 g of THC. Both marijuana smoke
and isoproterenol aerosol effectively reversed both meth-
acholine- and exercise-induced asthma, while saline and
placebo marijuana had no effect (160). Aerosols of
placebo -ethanol, of THC (200 µg) in ethanol, or of sal-
butamol (100 pg) were tasted in another study of ten
stable asthmatic patients. Forced expiratory volume in
1-5 forced vital capacity, and peak flow rate were meas-
ured on each occasion. Both salbutamol and THC sig-
nificantly improved ventilatory function. Improvement
was more rapid with salbutamol, but the two treatments
were equally effective at the end of 1 h (181).
Both 'delta -8 and delta-9-TIIC have broncbodilating
effects, while neither cannabinol nor cannabidiol has
such actions. Thus, this action resides only in the psv-
choactive material. No evidence of tolerance to this effect
developed over 20 days of continual administration (58).
HOLLISTER
some mental symptoms resembling those of THC.
the latter are less than from THC in proportion
efinite sep&ra'
blood
harma ological effects hasctd
not really been at
P
(106).
Effective antihypertensive drugs have been one
outstanding achievements of pharmacology over t.l
30 years. A new antibypertensive based on orth.
hypotension, perhaps the least desirable mode of
ing blood pressure, is hardly very enticing (8). Th -
seems hardly worth pursuing further.
2. Abstinence Syndromes due to central nervous
depressants. Synhezyl, the first THC homolog
synthesized, was tested as a treatment for with(
reactions from opiates and alcohol with little evide
efficacy. Withdrawal symPtoms experienced by ra
lowing morphine pellet implantation, followed b
sequent injection of naloxone, were reduced by
Cannabidiol, without any direct effect itself, augn
the action of THC (79)•
is This relatively weak effect of cannabir►oids in
dependence is unlikely to be of clinical use. Deto
tion programs using methadone have been bighl:
cess
C. Insomnia ful and acceptable. d
THC does not differ from conventional hypnotics in 3. Antineoplastic cuhv(tti- Both the delta have
an
SOMF
reducing rapid eye movement (REM) sleep (136). THC 9 -THC isomers, as well un R nabinoltumors in an
in doses ranging from 61 to 258 µg/kg Produces in normal neoplastic effect on transplanted
4 slee and decrements in well as on tumors in vitro (125). THC may r
subjects increments in stage p general ability to reduce the synthesis of nucleic
REM sleep, but without the characteristic roti rebound. Waccount for the reported immunosuppri
which follows chronic treatment with hyp a bLichts �ywell. Many agents are available that i.
THC was administered p.o. as a hyr subjeholiccts
solution nucleic acid synthesis, so the possibility that T1
in doses of 10, 20, and 30 mg, our subjects fell asleep other cannabinoids might be advantageous seems I
faster after having MOO alterations coy fsollowi with unlikely.
"high." Some degree of "hangover" the day
4. Antimicrobial action. Both THC and car►r:a
noted from larger doses (42). Another sleep laboratory inhibit and kill staphylococci and streptococci in vi
study showed that a dose After
four
r t of THC given
decreased REM sleep After four to six nights of use, concentrations of 1 to 5µg/tnl (11, 3). Such cotncentri
are well above those reported for use of THC is
in
abrupt discontinuation of THC produced a mild insom- aVen at the highest tolerated doses. Thus,
nia but not marked REM rebound (52). REM rebound �� � have little practice] application•
may not be apparent after low doses of THC. However,
5. Migraine. This indication has not been st
very high p.o. doses (70 to 210 mg) d by mark d sleep 6.
syystematically in recent years, although it has a
during treatment and were followed by In one patient I treated, the mental e
rebound after witbdrawal (48). history.
The sleep produced by THC does not seem to differ sought socially caused the patient to abandon treat
y hypnotics. Side Innumemble successful treatments for migraine
much from that of most
currently used s t been reperted at one time or another.
effects before sleep induction as well as the hangover a Appetite stimulant. Most antipsychotic agent
effects make the drug less acceptable than cu-rrently elite, but few other drugs do- TI
popular benzodiazepines. It seems unlikely that THC stimulate app
will supplant existing hypnotics in the treatment of compared with ethanol and dextroamphetawule
duced a variable response on appetite, both in fe(
insomnia. The majority had increased appetit
16
The treatment of asthma is much more chronic•, further
studies of tolerance will be needed. bronchoconstriction
Some patients might expe io produced mild and
following THC. Doses of 10 mg p.
inconsistent bronchodilator effects Wellas
of significant six
central nervous system effects. One p
studied developed severe bronchial constriction (1). Mild
but significant functional impairment, predominantly smokers
involving large airways, was found in 74 regular
of cannabis. Such U'pa'rment who rawas not detectable in
arly smoked tobacco
individuals of the same ageg�
(64).
THC would best be administered by aerosol for this
purpose, but whether effective doses would avoid the
mental effects is uncertain. The mechanism of action by
which THC increases airway conductance may be differ-
ent from the usual beta-adrenergic stimulants. Resist-
ance to repeated applications of beta-adrenergic stimu-
lants does occur. Another type of bronchodilator might
help some patients. The recent introduction of highly
effective steroid aerosols, such as beclomethasone, mee
that need to a considerable extent.
H. Miscellaneous Uses
1. Hypertension. Orthostatic by occasio
follows use of THC (5). A dimethylheptyl side -
derivative has more profound and nd showed onstant a ec
blood pressure. In man, this comec
po h —di
orthostatic hypotensive effect, as well as tau Y
fasted subjects.
nay food consumption as compared with placebo (80)
orexia nervosa might be helped by an appetite stim,
chain resumed appetite -stimulating prop
to on A test of the presumed
t�
arked of THC in
h anorexia ne
a and 4 -week period- THC ranged between a
.nstil-
!d the
irable
!d for
Mould
ibbitz
a eye
over.
ration
pres-
d eye
ect is
if the
but it
)they
or 8-
s also
have
trable
inna-
ested
Ips in
ffects
.ctive
iY, a
com-
oten.
in to
con-
ttion.
rtely,
-term
that
noids
h the
roma
mna-
nuch
Luna -
The
glau-
aften
ve to
may
igs.
rg of
ed to
ag of
mg)
was
dose,
ither
O HEALTH AS OF CANNAH1'.
dose of codeine (128)• THC given i.v. in doses of 44 µg/
kg to patients undergoing dental extraction produced an
analgesic effect, which was less than that achieved from
doses of 157 ug of diazepam per kg i.v. Several of these
patients actually preferred placebo to the dose of 22 µg
of THC per kg because of anxiety and dysphoria from
the latter drug (139).
The apparent paradox is that THC both increases and
decreases pain. Traditionally, aspirin -like drugs, which
pork peripherally by inhibiting the synthesis of prosta-
glandins, are used to treat pain derived from the integu-
ment. The initial mental stimulation from THC might
increase sensitivity to this kind or pain. Visceral pain,
such as that of cancer patients, is usually treated by
opiates, which have both peripheral and central sites of
action. Recent evidence suggests that Opiates may act
directly on pain pathways in the spinal cord as well as
reducing the affect that accompanies pain. Cannabis
could conceivably modify
he affective
fect Ve�respo from each
when the two types of pain Bu
other, the apparent paradox is solved.
THC, nantradol, and nabilone shared some properties
with morphine in the chronic spinal dog model. Latency
of the skin twitch reflex was increased, and withdrawal
abstinence was suppressed. Naltrexone did not antago-
nize these actions, suggesting that they are not mediated
through opiate receptors (56). Levonantradol i.m. was
compared with placebo in postoperative pain, and a
significant analgesic action was confirmed. No dose -
response relationship was observed, and the number of
side effects from levonantradol was rather high (89). It
seems unlikely that any THC bomolog will prove to be
an analgesic of choice, when one considers the present
array, of very effective new analgesics of the agonist -
antagonist type. It is too early to be sure, however.
D. Muscle Relaxant
Patients with spinal cord injuries often self -treat their
muscle spasticity by smoking cannabis. Cannabis seems
to help relieve the involuntary muscle spasms that can
be so painful and disabling in this condition. A muscle
relaxant or antispastic action of THC was confirmed by
an experiment in which p.o. doses of 5 or 10 mg of THC
were compared with placebo in patients with multiple
sclerosis. The 10 -mg dose of THC reduced spasticity by
Clinical measurement (135). Such single small studies
can only point to the need for more study of this potential
use of THC or possibly some of its homologs. Diazepam,
cyclobenzaprine, baclofen, and dantrolene, which are
used as muscle relaxants, all have major limitations. A
new skeletal muscle relaxant would be most welcome.
E Anticonvulsant
One of the first therapeutic uses suggested for cannabis
was as an anticonvulsant. Such an effect was documented
experimentally many years ago (112). Subsequent studies
in various animal species have validated this action. THC
15
in cats temporarily reduced the clinical and electro -
graphic seizure activity induced by electrical stimulation
of subcortical structures (175). Mice were protected by
carnabidioi against maximal electroshock seizures but
not against those caused by pentylenetetrazole. Its profile
of activity more resembled that of phenytoin than that
of THC (170). THC and cannabidiol both potentiated
the anticonvulsant effects of phenytoin against electri-
cally induced seizures in mice. The two cannabinoids in
combination produced the most effect (29). Kindling
involves the once -daily appliction of initially subconvul-
sive electrical stimulation to culminate in generalized
convulsive seizures. THC given chronically to rats pre-
vented the kindling effect (174).
Clinical testing has been rare, despite all these various
lines of evidence supporting an anticonvulsant effect of
cannabinoids. Better control of seizures following regular
marijuana smoking was reported in a not very convincing
single case (39). Fifteen patients not adequately con-
trolled by snticonvulsants were treated with additional
cannabidiol in doses of 200 or 300 mg or placebo. Can-
nabidiol controlled seizures somewbat better than the
addition of placebo (25). Cannabidiol has little if any
psychoactivity, making it a good candidate for this use.
F. Bronchial Asthma
A general study of the effects of marijuana on respi-
ration revealed a bronchodilating action in normal vol-
unteer subjects. Marijuana smoke was calculated to de-
liver 85 or 32 pg of THC per kg. A fall of 38% in airway
resistance and an increase of 447a in airway conductance
occurred in the high -dose group. The low-dose group
showed lesser changes, but they were still significant as
compared with baseline. The sensitivity of the respira-
tory center to carbon dioxide was not altered by either
dose, indicating no central respiratory depression (172).
Asthma was deliberately induced by either inhalation
of methacholine or exercise in asthmatic patients. They
were then treated with inhalation of placebo marijuana,
of saline, of isoproterenol, or of smoke derived from
marijuana containing 1 g of THC. Both marijuana smoke
and isoproterenol aerosol effectively reversed both meth-
acholine- and exercise-induced asthma, while saline and
placebo marijuana had no effect (160). Aerosols of
placebo -ethanol, of THC (200 µg) in ethanol, or of sal-
butamol (100 µg) were tested in another study of ten
stable asthmatic patients. Forced expiratory volume in
I forced vital capacity, and peak flow rate were meas-
ured on each occasion. Both salbutamol and THC sig-
nificantly improved ventilatory function. Improvement
was more rapid with salbutamol, but the two treatments
were equally effective at the end of 1 h (181).
Both 'delta -8 and delta-9-TIiC have bronchodilating
effects, while neither cannabinol nor cannabidiol has
such actions. Thus, this action resides only in the psv-
choactive material. No evidence of tolerance to this effect
developed over 20 day's of continual administration (58).
18OHOLLISTER
1
cannab,nel and live or tilled gram negative bacteria. Inlet. Immun. 17:
60. FLEISCHMAN. R W.. HAYDEN, D. W., ROSEmwrta R, H.
J�WA
20. BnAUNKTLIN, GD., HURTERJ.E.,SGARE9.JR,AND GRGR9, S. J.
hormone concentrtion in manic.via
AND B
C.: Teratelo a evelu. ® tion of re. Ter colo ydrvemebinol ii
dUdinga rerea of lh<limrnve. TentOlo 121Prwoncy 47`50,
uun. Lite Sci. 33: 19:r
HIM.
51. FRANK, L, LE3SIN,
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P.. TYRRELL, HANN, P.. AND SWA S,
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PP, 673-W- Raven Pre&, New York, 1976.
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• A•
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n
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N., SEIPP. C..
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:D patients with Chemothenp�
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bAlm.l9, 4: 2
14: 261-2
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61 Gaprw, K„ Awn RMN, hl.;
I
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H .HO
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US: Natuial Form Of Marijuana In Humans A;-'—.Ical Mystery htty��,%, mapmc.org/drugnews/v98.n1184.a03.html/all
' . ,.. .
Me _ ..., ... ..
21ia'Awazeness'Project` ,
US: Natural Form Of Marijuana In Humans A Medical
Mystery
Newshawk: Steve Young
Source: Chicago Tribune (IL)
Pubdate: 18 Dec 1998
Section: Sec. 1A
Contact: tribletter@aol.com
Website: http://www.chicaotribune.com/
Forum: http://www.chicavotribune.com/interact[boards/
Copyright: 1998 Chicago Tribune Company
Author: Usha Lee McFarling
NATURAL FORM OF MARIJUANA IN HUMANS A MEDICAL
MYSTERY
WASHINGTON -- Amid this year's clamorous battles to legalize medical
marijuana stands this little-known fact: Our brains and bodies are flooded
with a natural form of the drug.
Called cannabinoids, after the euphoria -inducing plant Cannabis sativa,
this family of compounds blocks pain, erases memories and triggers
hunger. Newer studies show they also may regulate the immune system,
enhance reproduction and even protect the brain from stroke and trauma
damage.
Discovered in humans just a few years ago and, until recently, virtually
unstudied, the compounds have become one of the looming mysteries of
the nervous system, and a field of exploding scientific interest.
Scientists are testing cannabinoids with hopes of harnessing the medical
power of marijuana to treat pain without its high, smoke or political
baggage. A key challenge is separating the curing power of the
compounds from their mind -altering side effects.
"That's the holy grail of this field," said Steven Childers, a pharmacologist
at the Wake Forest University School of Medicine in Winston-Salem, N.C.
Because cannabinoids are so numerous in the brain, they also could help
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explain the workings of some of our body's most complex, and least
understood, systems.
"It's obviously important because there's so much of it. And we never
knew it existed before," said J. Michael Walker, a Brown University
psychologist who has conducted some of the first studies of how
cannabinoids block pain.
"It could help us understand movement, it could help us understand
memory, it could help us understand pain. We don't really know how any
of these things work."
There has always been evidence, from the intoxicating effects cannabis
evokes in smokers, that it contains powerful compounds.
The sticky, flowering buds of the plant have been harvested as medicine
for centuries. Five thousand years ago, Chinese physicians used the plant
to treat malaria, absent-mindedness and "female disorders."
African tribes used it to treat snakebite and the pain of childbirth. Indian
physicians prescribed it for headaches.
Sifting through the plant's chemical stew in the early 1960s, Israeli
pharmacologist Raphael Mechoulam discovered more than 60
cannabinoids in marijuana, including the famous and psychoactive
compound THC.
In 1992, a team led by Mechoulam and William Devane trumped that
discovery by showing that humans produced their own cannabinoids.
They called the substance anandamide (Sanskrit for "eternal bliss").
Our brains contain receptors that interact with the anandamide we
produce. In an accident of nature and chemistry, compounds in pot are
shaped similarly and therefore trigger similar but more potent effects.
The same is true of the plant drugs nicotine and cocaine.
Now, scientists are beginning to understand just what natural
cannabinoids might be doing in the human body.
"We're opening doors now we couldn't even have predicted existed," said
Childers, president of the International Cannabinoid Research Society.
2 of 4 1 oiowun o-1 a e nn
U5: l�atuial Form Of Marijuana In HumansU cal Mystery
For example:
htt/--Nvw.mapiiie.org/drugnews/v98.nll84.a03.11tiul/alI
- - This week Herbert Schuel and Lani J. Burkman of the University of
Buffalo reported that cannabinoids help control the exquisite synchrony of
timing during reproduction by slowing anxious sperm if they try to
approach an egg before it's ready for fertilization. This may also explain
why heavy pot users, both men and women, are sometimes infertile.
- - Cannabinoids have been found to both suppress and enhance the body's
defenses against diseases and tumors, a duality that has researchers
puzzled. "It's a science clearly in flux," said Thomas Klein, an
immunologist at the University of South Florida. "The more we learn, the
more confused we are."
- - While pot warnings --"This is your brain on drugs" --have long
spotlighted the drug's damaging effects on the brain, research last
summer from the National Institute of Mental Health shows cannabinoids
protect brain cells from stroke or trauma damage.
- - Last year, scientists at the Neurosciences Institute in San Diego
showed that cannabinoids block the formation of new memories in slices of
animal brain tissues. This power to forget might keep the brain from
filling up or getting overwhelmed with unimportant memories.
Cannabinoid research in animals already has scientists considering drugs
that might be quite powerful in exploiting an untapped chemical system
within the brain to solve an array of medical problems.
"While no one wants a drug that disrupts memory, maybe you could boost
memory by blocking cannabinoids," said Billy Martin, a professor of
pharmacology at the Medical College of Virginia and one of a handful of
people who have studied cannabinoids since the 1970s.
Researchers' largest hopes are focused on using a synthetic form of
cannabinoids to block pain, including chronic nerve pain that can't be
adequately blocked with existing drugs.
Animal studies show cannabinoids can block other kinds of pain almost
before they begin, stopping the pain signals before they reach the spinal
cord or brain, working as well as morphine. That power suggests they
could be substituted for morphine, which is addictive and must be used in
increasing doses over time.
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Cannabinoids enhance morphine's power; combining the drugs could
vastly reduce the dosages needed to kill pain, offsetting problems of
addiction and drug tolerance. Cannabinoids also counteract nausea,
another plus for patients with cancer and AIDS.
"It might be possible to manipulate levels of the body's own cannabinoids.
You could create drugs like Prozac that block the body's reuptake of
cannabinoids or inhibit their breakdown so they stay active longer," said
Andrea Hohmann, who previously worked with Walker and now
researches pain at the National Institute of Dental and Craniofacial
Research.
Checked -by: Richard Lake
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Mon, 21 Dec 1998 iI 30 lines]
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New Zealand: Cannabis Laws Should Be Rew" htt�;w.mapinc.org/drugnews/v98.n 1184.a07.html/all
' p Media Awareness Project `�„�►
6ttp//w'N'K'mapinc.org(<.-
New Zealand: Cannabis Laws Should Be Reviewed
Newshawk: hadorn@dnai.com (David Hadorn)
Source: The Press (New Zealand)
Contact: editorial@press.co.nz
Website: httn://www.press.co.nz/
Copyright: 1998 The Christchurch Press Company Ltd.
Pubdate: Friday, 18 Dec 1998
CANNABIS LAWS SHOULD BE REVIEWED
The Government should review the legal status of cannabis, Parliament's
health select committee has recommended.
In its report on its inquiry into the mental health effects of cannabis,
tabled in Parliament yesterday, the committee says that the effectiveness
of the present policy on cannabis requires examination, given the high
level of use in New Zealand.
"It is acknowledged that cannabis prohibition enforced by traditional
crime control methods has not been successful in reducing the apparent
number of cannabis users," the report says.
"That the police are open-minded on the issue of decriminalisation of
cannabis is an indication that thinking on the subject is changing . . .
Methods other than prohibition certainly deserve consideration."
The committee concluded that the negative mental health effects of
cannabis appeared to have been overstated.
Occasional cannabis use posed few risks to the mental health of most
adult users, and the weight of available evidence suggested that even
long-term, heavy use of cannabis did not produce severe or gross
impairment of cognitive function, the committee found.
Checked -by: Richard Lake
1 of 2 12/22/98 9:16 AM
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1997 Marijuana Arrests Ilit 695,000
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1997 Marijuana Arrests Hit 695,000 -- A New Record;
Percentage Of Marijuana Arrests For Simple Possession Ties 1979 Record
Analysis By Richard Cowan
1997 marijuana arrests
hit a new record of 695,201 38% of
1997's 1,583,600 total "drug" arrests.
the total number of marijuana arrests under Clinton to approximately 2,800,000.
This year's 87% of marijuana arrests for simple possession was equaled only in 1979.
Marijuana arrests almost reached the 717,000 combined total number of arrests for the violent
crimes of murder, rape, robbery, and aggravated assault. .
the FBI reports that the
Police solved only about half of all violent crimes and were able to solve only 14 percent of the
burglaries and car theftsl
1997 Marijuana Arrests Hit. 695,000 ..Record// ualysia By Richard Cowan hlLp:!/www.ma; ��,;u ews.cum/1997_mariluana_arrests _ hit_695.htm
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it is very likely that both real crimes and marijuana arrests are greatly
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Australian �'t tidy Of 2,5001njuted D..
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Swediehibitioniats Report Il°
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Australian Study Of 2,500 Injured Drivers Showed Those Who Used Marijuana
Less Likely To Have Caused Accident Than Even Drug -Free Drivers —
But How Do The Swedish Prohibitionists Report It?
Drivers who use marijuana are less likely to cause road accidents than drunk
drivers or even drug-free drivers, a study has found.
the most comprehensive of its kind in the world
blood samples from
2500 drivers injured in accidents in South Australia.
In their attempt to define whether cannabis and other drugs played a large role in road
accidents, researchers used information from the police report on each crash to determine
whether the injured driver was culpable.
Drug-free drivers caused the accidents in 53.5 per cent of cases.
Injured drivers with a blood-alcohol concentration of more than 0.05 per cent were culpable in
nearly 90 per cent of accidents they were involved in.
Drivers with cannabis in their blood were less likely to cause an accident with a
culpability rate of 50.6 per cent.
Au trahan :tudy Of 2,50j) Inured 11... Swedirr—%dtibttionists Reporl. It? http: .mari)uananews.cum/austraban_study_oC_`L.hLm
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EARLY 25% OF ALL SOUTH AUSTRALIAN MOTORISTS INVOLVED IN NON-FATAL CRASHES
ESTED POSITIVE FOR DRUGS
compulsory -acquired blood samples of 2.500 drivers hospitalised after such
is the largest survey of its kind in the world.
rcyclists are more likely than car drivers to test positive for cannabis, and more than a
of drivers who tested positive for alcohol, had blood alcohol levels over three times th
limit. Alcohol remains the leading cause of road accidents.
Copyright HNN and Medstriims Multimedia AB
Freedom has nothina to fear from the truth.