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.