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Carl Olsen's Marijuana Archive
Substance Abuse: The New Paradigm
by Jon Gettman

Part 1 of 2.

Author:  U.S. Congress, Office of Technology Assessment

Title: Biological Components of Substance Abuse and Addiction -
Background Paper

Date:  September, 1993

Source:  Washington, DC: U.S. Government Printing Office(OTA-BP-BBS-
117), 68 pgs.  $4.25 + postage from GPO (202) 512-1800.

        This OTA paper reviews medical research through 1992
regarding the effects of various drugs of abuse on the brain, and by
way of excellent references, provides a guide to the scientific
literature for the interested public.  The paper provides:

        A discussion of the basic concepts of neuropharmacology,
including the brain reward system, adaptive responses such as
tolerance, dependence, and sensitization, and how the abuse liability
of various drugs is evaluated and compared.

        A discussion of the specific effects on the brain of cocaine,
amphetamines, caffeine, nicotine, phencyclidine, alcohol,
barbiturates, benzodiazepines, opiates, cannabis and Lysergic Acid

        A discussion of research on inherited traits that may
increase the risk of drug abuse, primarily reviewing studies on
alcoholism, with some mention of opiate-related research.


        Research on several drugs of abuse has converged on a single
point -- their impact on the release of the neurotransmitter dopamine
and their subsequent influence on human behavior through the brain
reward system dominated by that neurotransmitter.

        The paper reports on the current attributes used for
evaluating the abuse potential of drugs. OTA reports that no research
indicates that cannabis (marijuana) shares these attributes. OTA
fails to discuss the ramifications of such a finding.


        "The capacity to produce reinforcing effects is essential to
any drug with significant abuse potential, whereas tolerance and
physical dependence most commonly occur but are not absolutely
required to make such a determination . . . The predominant feature
of all drugs with significant abuse potential properties is that they
are self-administered . . . Animal models of self-administration
provide a powerful tool that can give a good indication of the abuse
liability of new or unknown drugs."  OTA 1993 pg. 5.

        "While marijuana produces a feeling of euphoria in humans, in
general, animals will not self-administer THC in controlled studies.
Also, cannabinoids generally do not lower the threshold needed to get
animals to self-stimulate the brain reward system, as do other drugs
of abuse."  OTA 1993 pg. 34.


        The executive summary explains that susceptibility to drug
abuse is influenced by such factors as the biological response to a
drug, a person's psychological makeup, and the drug's availability.

Author:  U.S. Congress, Office of Technology Assessment

Title:  Technologies for Understanding and Preventing Substance Abuse

Date:  September, 1994

Source Washington, D.C.: U.S. Government Printing Office, (OTA-EHR-
597) 260 pgs.  $15.00 + postage from GPO (202) 512-1800.

        Several committees of Congress asked the Office of Technology
Assessment (OTA) to study the socioeconomic, psychological,
physiological and genetic foundations for substance abuse and
addiction.  OTA's report on the Biological Components of Substance
Abuse and Addiction was published in 1993 (see above); this is the
companion report that reviews social science research that has
implications for prevention efforts.

        This report provides an extensive discussion of available
data and the limitations of the studies that produce it.  Like its
predecessor, it is a comprehensive guide to current research and its
varying interpretations.

        This report does not address treatment or law enforcement

        There are not root causes for drug abuse, but risk and
protective factors that influence the possibility of abuse within
different sub populations in different settings.  Research into
Necessary Preconditions, Individual Factors, and Activity Settings is
reviewed, and policy options for prevention funding are discussed in

        Appendices review the history of drug control policy in the
U.S., existing federal prevention programs, and provide a list of
original research papers contracted for this study and extensive


        This paper re-presents the material from the 1993 OTA report.
With regard to marijuana, while more research strides were made
between the publication of the two papers, even less is reported
about the biological basis for cannabis use than in the 1993 paper.

        Four models for considering prevention issues are reviewed, a
Public Health Model, a Medical Model, a Criminal Justice Model, and
the over-generalized approach of mass communications.

        Leading indicators of drug use are criticized  for several
limitations, including the government's credibility, over-looked
populations, measuring use but not abuse, and little opportunity to
conduct multi-variate analysis.

        Teenage use of "legal" drugs precedes use of marijuana.

        The statistical results of 242 studies have been analyzed to
sort risk factors into 11 major categories (50 sub categories), and
to establish strong, moderate, and weak relationships between risk
factors and school age drug use.

        Analysts are beginning to find the differences between drug
use and abuse more interesting than the differences between legal and
illegal drugs.

        Commercially marketed prevention programs, such as DARE,
require extensive evaluation studies.  To date, the few evaluation
studies that have been done do not indicate success at prevention of
drug abuse.


On the Brain Reward System:

        "Most drugs of abuse, either directly or indirectly, are
presumed to affect the brain reward system.  Inducing activity in the
brain reward system gives drugs of abuse positive reinforcing actions
that support their continued use and abuse."  OTA 1994 pg. 45.

        "The rewarding properties of stimulant drugs such as cocaine
and amphetamines are due directly to the effects of the chemical
dopamine. Opiates, on the other hand, indirectly stimulate dopamine
by activating other chemical pathways, which in turn increases
dopamine activity.  All of these drugs have reinforcing properties.
Phencyclidine (PCP) is also a strong reinforcer but its relationship,
in any, to activity in the dopamine pathway has yet to be
established.  Other drugs are either weak reinforcers or have not
been shown to support self-administration in animal experiments.
Nicotine stimulates dopamine neurons; however, its effect is modest
when compared with cocaine or amphetamine.  Likewise, caffeine is a
weak reinforcer, but the precise mechanisms of its reinforcment are
unclear.  Finally, cannabis and lysergic acid diethylamide (LSD) also
produce positive effects that clearly support their use."  OTA 1994
pg. 47.

On the Stepping Stone and Gateway Drug Theories:

        "While study results vary somewhat, the sequence most often
reported is that alcohol and cigarette use come first, followed by
marijuana use and then by the use of other illicit substances."  OTA
1994 pg. 74.

        "(T)he criminalization of marijuana may have caused some
marijuana users to move on to other illicit substances through
contact with the subculture of illicit users."  OTA 1994 pg. 74.

        In one study, "delinquency and youthful sexual activity
tended to precede the use of marijuana and hard liquor. . . The early
use of so-called gateway drugs, such as beer and cigarettes, may
contribute to later problem behaviors, while the later use of
marijuana, hard liquor, and other illicit substances may be more the
result of extended participation in problem behaviors"  OTA 1994 pg.

        "Because many individuals who use substances do not go on to
substance abuse, and because one level does not guarantee use at a
higher level, these stages are descriptive but not predictive."  OTA
1994 pg. 80.

On National Surveys:

        "Drug measures focus on use, rather than abuse or addiction.
The common measures of drug use employed by the Household and Seniors
Surveys - lifetime, past year, and past month use-are insufficiently
refined to distinguish between casual and dependent use."  OTA 1994
pg. 38.

On learning from those who use drugs without abuse:

        "What prevents some individuals from progressing from initial
use to abuse to addiction? . . . Studying those individuals who do
not progress from use to addiction may provide insights and lessons
about how to prevent progression among those who do progress."  OTA
1994 pg. 75

        "But what about those individuals who live in stressful and
chaotic conditions - who are constantly exposed to many of these risk
factors - yet who do not develop substance abuse problems?"  OTA 1994
pg. 115.

On the Public Health Model for understanding abuse and addiction:

        "The legality or illegality of a drug is an artificial
barrier that is not as relevant as the health-related considerations
stemming from all types of drug use.  Rather than using
legal/illegal, the public health approach categorizes drugs by such
characteristics as addictive potential and long-term health risks. .
.Dealing with the drug problem primarily as a moral problem is
considered inappropriate and counterproductive (as part of the public
health model)." OTA, 1994 pg. 29.

On Ethnographic studies of Marijuana Use:

        "Differences in marijuana smoking may also be partially
attributable to gender.  In a recent review, it was shown that men's
marijuana smoking was tied more to the  availability of the drug,
while women's smoking was affected to a greater degree by social
influences, such as weekday versus weekend smoking, and the smoking
of their male partners. Women have also been shown to increase their
marijuana smoking during periods of anger and other unpleasant
dispositions."  OTA 1994 pg. 90.

        "Most of the ethnographic research on marijuana use has been
conducted outside the United States.  Much of it was initiated in the
1960's and 1970's . . .In Jamaica, for example, anthropologists Vera
Rubin and Lambros Comitas directed a research team of 45 . . .Their
controversial findings were that none of the deleterious social or
medical consequences believed by many to be associated with the drug
in the United States could be found among Jamaican users."  OTA 1994
pg. 124.


        The findings OTA reports on marijuana are very exciting
because of their possible impact on marijuana's legal status under
federal law, however that is just one application of the technologies
of this report, and but one measure of this report's significance.

        This is the most valuable report on substance abuse in the
United States since the second report of the National Commission on
Marihuana and Drug Abuse in 1973.

        The title is very important, and very revealing:
"Technologies for Understanding and Preventing Substance Abuse and
Addiction."  Ideas, theories, programs, policies, and though
unmentioned, laws as well, are all technologies.  They are all
subject to evaluation, or assessment, by conventional standards.  The
drug war has reached a critical, and perhaps terminal stage where it
has been going on long enough for empiricism to take over from
theory.         This report represents the end of the "Just Say No!"
monopoly on prevention efforts, one of the driving forces behind
marijuana prohibition. Effectiveness is replacing strength as the
standard of evaluation.

        OTA recognizes a prevention program market that receives one
fourth of the funds given to local jurisdictions under the Drug Free
Schools and Communities Act.  Three programs "have captured a sizable
share" of the market, DARE, Quest: Skills for Living; and Here's
Looking at You 2000. Only DARE has been evaluated sufficiently for
conclusions to be drawn about the program.

        DARE is one of the better funded prevention programs and is
delivered to 5 million students at a cost of $10 each.  Of the
studies reviewed by OTA on DARE's effectiveness, "the average
reductions in substance use were very small.  Use among control
schools and DARE schools was roughly equal." (OTA, 1994 pg. 150-151)
While the program has important strengths, school-based prevention
technologies "have not been refined and tested enough to demonstrate
their effectiveness."

        OTA commissioned a study involving 9930 statistical analyses
from 242 separate studies reporting relationships between substance
use by school age youths and its postulated causes, and OTA only
summarizes the findings of this study in this report.  Tobacco,
alcohol, and marijuana accounted for 82% of the completed analyses.

        Only four variables were held to have strong relationships to
school-age drug use.  "1)  prior and concurrent use of substances, 2)
substance use by peers and friends, 3) perceived peer attitudes about
substance use, and 4) offers to use substances."  (OTA 194 pg. 147)
Of the 15 variables with moderate relationships to substance use, 7
were social variables involving resistance skills, peer pressure, and
beliefs about consequences.

        These findings need to be examined in more detail, but they
should be of immense help in evaluating the theoretical basis for
many prevention programs which lack performance data for evaluation.

        The significance for policy discussions is that these
findings suggest that availability itself is probably the greatest
contributing factor to school-age drug use.

        The role of tobacco and alcohol marketing, and the role of
head shops is discussed in the context of the availability of drugs
as a necessary precondition for abuse.

        Distinctions are made between use, abuse, and addiction.  OTA
is straightforward that substances differ in their abuse liability,
and the line between use and abuse varies.  The goals of prevention
programs vary between attempting to prevent initial use, delay
initial use, or reduce or control continued use.  While there is a
progression to the use of various drugs, OTA reports that these
stages are descriptive, not predictive. There is considerable
evidence that expectations play an influential role in drug use and

        Ethnographic studies and anthropology have begun to make
important contributions to understanding substance abuse.  Four
social contexts are recognized: a drug focused subculture, drug use
as part of a larger lifestyle or identity, normal, recreational use
among specific partners or peers, and use in social isolation.
(Interestingly, medical marijuana use is provided as an example of
drug use in social isolation.  Sad, true in too many cases, and

        However, "most of the ethnographic research has concentrated
on drug-focuses subcultures or on crime-related subcultures.  There
are too few studies on other populations . . . (for example) no
significant ethnographic studies of student drug use in almost two
decades.  The drug problem has been defined in the public mind and
among some funding sources as a problem of poor minority communities.
. . Drug use and drug users are defined as the "other," different
from the rest of society.  Ethnographers have paid relatively little
attention to the relationship between culturally approved drug use
(e.g., caffeine, nicotine, alcohol, psychoactive prescription drugs)
and illicit drug use."  (OTA 1994 pg. 128-129)

        The elements of notable prevention programs include:
promoting social and life skills, strengthening families, promoting
healthy peer interaction, indirect and participatory approaches to
substance use, and alternative activities.

        A considerable amount of material covered by OTA is not
reviewed here.  This includes a review of all major drug use
indicators and considerable discussion of the demographic differences
in drug use by people of different genders and races.  Relationships
between individual risk factors and aggressiveness, delinquency,
physical and sexual abuse, and mental disorders are also discussed.

        Technologies are problem solving tools that have benefits and
limitations.  This article has touched on a few of the technologies
that are most relevant to marijuana law reform:  the brain reward
system, the gateway drug sequence, the public health model, the
isolation of primary causes of school-age drug use, the use of
ethnographic studies, the elements of successful prevention programs
and learning about drug abuse from drug use.  These are all tools
that provide new ways to address, solve, and explain old problems.

        Advocates of marijuana law reform must become familiar with
the latest findings in these and other areas, otherwise arguments for
reform will become increasingly irrelevant as the context of public
policy discussions evolves.

 Interview with Professor Raphael Mechoulam, Codiscoverer of THC

The International Journal of the Addictions, 21(4&5), 579-587, 1986.

        The interview was conducted by Stanley Einstein in Jerusalem
on January 14, 1985.

        Mechoulam provides a brief history of research preceding his
isolation of THC with Yehiel Gaoni in 1964, and discusses some of the
possible therapeutic applications that can be derived from

        "Probably the major barrier has been the unwillingness, or
fear, by companies to develop drugs that are based on cannabis.  They
are afraid, as I said before, of notoriety.  They were afraid that
they would get into a jam of sorts.  So for the first ten years after
our discoveries, essentially no work has been done whatsoever on the
pharmaceutical properties of cannabis.  Even afterwards the work that
was done, was done very, very timidly and very slowly.  Even when
work done at a scientific level it was stopped at the corporate-
administrative level . . . Most industries and governments do not
know how to make use of scientists and scientific ideas."  pg. 587.

 Renee C. Wert & Michael Roulin

The Chronic Cerebral Effects of Cannabis Use

I  Methodological Issues and Neurological Findings

II Psychological Findings and Conclusions

The International Journal of the Addictions, 21(6), 605-642, 1986.

        (I) "On the basis of available research, it was concluded
that there is no evidence that marijuana produces gross structural
cerebral changes and little evidence that it leads to functional
impairment, although subtle impairment cannot be ruled out." pg. 605.

        (II) "Evidence from both American and cross-cultural studies
suggests that marijuana probably does not produce chronic cerebral
impairment, although subtle impairment cannot be ruled out." pg. 629.

        This paper summarizes what research had determined about
marijuana's effects on the brain by the early 1980's.

        This paper also marks a transition in the focus of research
from brain damage to brain function.

 Leo E. Hollister

Health Aspects of Cannabis

Pharmacological Reports, 38(1), 1-20. 1986.

        This article reviews a) the acute and chronic effects of
cannabis in humans b) the possible adverse effects of cannabis on
health and c) the therapeutic uses of cannabis.  This article is
cited frequently and is considered one of the most authoritative
analyses of cannabis-oriented research to date.  Subsequent research
has tended to support Hollister's conclusions, particularly in regard
to tolerance and dependence.

        "Tolerance is not a problem when doses are small, or
infrequent, or where the pattern of use of the drug is not prolonged.
Tolerance only becomes a major factor with high, sustained, and
prolonged use of the drug . . . Large doses of THC are required over
long time periods for tolerance to develop.  As most social use of
the drug does not meet these requirements, neither tolerance nor
dependence has been a major issue in its social use."  pg. 9.

 William A. Devane, Francis A. Dysarz III, M. Ross Johnson, Lawrence
S. Melvin, and Allyn C. Howlett

Determination and Characterization of a Cannabinoid Receptor in Rat

Molecular Pharmacology, 34:605-613.  1988.

        Prior to this study, "one reason for our lack of insight
concerning the actions of cannabinoid drugs in the (Central Nervous
System) is that a clearly defined cellular mechanism(s) for this
class of drugs has remained elusive."  pg. 605.

        It had long been suspected that the effects of cannabis were
mediated by receptors in the brain, but until this study the
technology to determine and characterize these receptors did not
exist.  Prior research had established criteria for a
pharmacologically distinct cannabinoid receptor; this study met those
criteria by using autoradiographic binding of a potent isomer of THC
to tissues from a rat brain.

 Miles Herkenham, Allison B. Lynn, Mark D. Little, M. Ross Johnson,
Lawrence S. Melvin, Brian R. De Costa, and Kenner C. Rice.

Cannabinoid Receptor Localization in Brain

Proceedings of the National Academy of Science USA, 87:1932-1936.

        Herkenham's research team applied the technology developed by
Howlett's team to locating cannabinoid receptors in guinea pig, rat,
dog, monkey and human brains.

        Receptors are most dense in the basal ganglia, hippocampus,
and cerebellum, and are sparse in the lower brainstem areas
controlling heart and lung functions.  "High densities of receptors
in the forebrain and cerebellum implicate roles for cannabinoids in
cognition and movement." (pg. 1932.)

        Addressing recent interest in dopamine release in the brain,
Herkenham notes that:  "The presence of cannabinoid receptors in the
ventromedial striatum suggests an association with dopamine circuits
thought to mediate reward.  However, reinforcing properties of
cannabinoids have been difficult to demonstrate in animals.
Moreover, cannabinoid receptors in the basal ganglia are not
localized on dopamine neurons."  pg. 1936.

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