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 Diethylamide. 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. Significance: 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. Excerpts: "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. Discussion: 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 issues 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 conclusion. 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 references. Significance: 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. Excerpts: 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. 78. "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. Discussion: 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 abuse. 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 unnecessary.) 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 cannabinoids. "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 Brain 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. 1990. 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.