1. Addictive Qualities of Popular Drugs In 1994, for an article in the New York Times, Dr. Jack E. Henningfield of the National Institute on Drug Abuse and Dr. Neal L. Benowitz of the University of California at San Francisco ranked six substances based on five problem areas.

Withdrawal: Presence and severity of characteristic withdrawal symptoms. Reinforcement: A measure of the substance's ability, in human and animal tests, to get users

to take it again and again, and in preference to other substances. Tolerance: How much of the substance is needed to satisfy increasing cravings for it, and the level of stable need that is eventually reached. Dependence: How difficult it is for the user to quit, the relapse rate, the percentage of people who eventually become dependent, the rating users give their own need for the substance

and the degree to which the substance will be used in the face of evidence that it causes harm. Intoxication: Though not usually counted as a measure of addiction in itself, the level of intoxication is associated with addiction and increases the personal and social damage a substance may do. "Is Nicotine Addictive? It Depends on Whose Criteria You Use." New York Times, Aug. 2, 1994.

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2. General Criteria for Drug Dependence, Including Nicotine Dependence "The 1988 Surgeon General’s report lists the following general 'criteria for drug dependence,' including nicotine dependence (USDHHS 1988, p. 7): "Primary Criteria

"• Highly controlled or compulsive use

"• Psychoactive effects

"• Drug-reinforced behavior "Additional Criteria

"• Addictive behavior, often involves:

"– stereotypic patterns of use

"– use despite harmful effects

"– relapse following abstinence

"– recurrent drug cravings

"• Dependence-producing drugs often produce:

"– tolerance

"– physical dependence

"– pleasant (euphoriant) effects "These criteria are consistent with those for a diagnosis of dependence provided in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) (American Psychiatric Association [APA] 2000) and the International Classification of Diseases, Tenth Revision (ICD-10) (Table 4.1) (World Health Organization [WHO] 1992). The diagnosis of dependence using these diagnostic systems depends on the person experiencing a specific number of these symptoms. The relevance of some of these symptoms to nicotine addiction may be questionable because the DSM criteria are used across different drugs of abuse. For example, one symptom of addiction is that a great deal of time is spent in activities necessary to obtain the substance or recover from its effect. This criterion may not be as relevant to the diagnosis of nicotine addiction compared with other abused substances." US Department of Health and Human Services. "How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General." Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010, pp. 105-106.

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3. Addictive Potential Of Various Drugs Including Marijuana, Heroin, Amphetamines, LSD "Of the people who sample a particular substance, what portion will become physiologically or psychologically dependent on the drug for some period of time? Heroin and methamphetamine are the most addictive by this measure. Cocaine, pentobarbital (a fast-acting sedative), nicotine and alcohol are next, followed by marijuana and possibly caffeine. Some hallucinogens—notably LSD, mescaline and psilocybin—have little or no potential for creating dependence." Gable, Robert S., "The Toxicity of Recreational Drugs," American Scientist (Research Triangle Park, NC: Sigma Xi, The Scientific Research Society, May-June 2006) Vol. 94, No. 3, p. 208.

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4. Risk of Heroin Dependence After Onset of Use "When observed within approximately 1 to 12 months after heroin onset, an estimated 23% to 38% of new heroin users have become dependent on heroin. Rank-order correlation and post hoc exploratory analyses prompt a hypothesis of recently increased odds of becoming dependent on heroin. "Seeking estimates for comparison, we found 3 published studies on how often heroin dependence was found among people who have used heroin at least once in their lifetime. The National Comorbidity Survey (1990-1992) estimate was 23% dependence rate (with a standard error [SE] of 5%); National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002) estimate (SE) was 28% (4%); and National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013) estimate (SE) was 25% (2%).4,6 These 3 values yield a random-effects meta-analysis summary of 26%, with a 95% CI of 22% to 29%, which clearly overlaps this study’s overall finding of 23% to 38% of all participants becoming heroin dependent soon after first heroin use." Rivera OJS, Havens JR, Parker MA, Anthony JC. Risk of Heroin Dependence in Newly Incident Heroin Users. JAMA Psychiatry. Published online May 30, 2018. doi:10.1001/jamapsychiatry.2018.1214

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5. Probability of Transition From First Use to Dependence For Various Substances "In a large, nationally representative sample of US adults, the cumulative probability of transition to dependence was highest for nicotine users, followed by cocaine users, alcohol users and, lastly, cannabis users. The transition to cannabis or cocaine dependence occurred faster than the transition to nicotine or alcohol dependence. Furthermore, there were important variations in the probability of becoming dependent across the different racial-ethnic groups. Most predictors of transition were common across substances. "Consistent with previous estimates from the National Comorbidity Survey (Wagner and Anthony, 2002a), the cumulative probability of transition from use to dependence a decade after use onset was 14.8% among cocaine users, 11.0% among alcohol users, and 5.9% among cannabis users. This probability was 15.6% among nicotine users. Furthermore, lifetime cumulative probability estimates indicated that 67.5% of nicotine users, 22.7% of alcohol users, 20.9% of cocaine users, and 8.9% of cannabis users would become dependent at some time in their life." Catalina Lopez-Quintero, et al., "Probability and Predictors of Transition From First Use to Dependence on Nicotine, Alcohol, Cannabis, and Cocaione: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)," Drug and Alcohol Dependence, 2011 May 1; 115(1-2): 120-130. doi:10.1016/j.drugalcdep.2010.11.004

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6. Estimated Prevalence of Substance Use Dependence or Addiction in the US by Race/Ethnicity, According to NSDUH "In 2015, approximately 20.8 million people aged 12 or older had an SUD in the past year, including 15.7 million people who had an alcohol use disorder and 7.7 million people who had an illicit drug use disorder (Figure 27). An estimated 2.7 million people aged 12 or older had both an alcohol use disorder and an illicit drug use disorder in the past year (Figure 28). Thus, among people aged 12 or older in 2015 who had an SUD in the past year, nearly 3 out of 4 had an alcohol use disorder, and about 1 out of 3 had an illicit drug use disorder. About 1 in 8 people aged 12 or older who had SUDs in the past year had both an alcohol use disorder and an illicit drug use disorder. "Of the 7.7 million people aged 12 or older who had a past year SUD related to their use of illicit drugs, 4.0 million had a past year disorder related to their use of marijuana, and 2.0 million people had a disorder related to their misuse of prescription pain relievers (Figure 27). Smaller numbers of people in 2015 had disorders in the past year related to their use of cocaine or heroin. "The 20.8 million people who had SUDs in 2015 (Figure 27) represent 7.8 percent of people aged 12 or older (Figure 29). This percentage of people in 2015 who had SUDs corresponds to about 1 in 13 people aged 12 or older. An estimated 1.2 million adolescents aged 12 to 17 had SUDs in 2015, which represents 5.0 percent of adolescents, or about 1 in 20 adolescents. In 2015, 5.3 million young adults aged 18 to 25 had SUDs; this number of young adults with SUDs represents 15.3 percent of young adults, or about 1 in 7 young adults. An estimated 14.2 million adults aged 26 or older in 2015 had SUDs, which represents 6.9 percent of adults aged 26 or older, or about 1 in 15 adults in this age group." Center for Behavioral Health Statistics and Quality. (2016). Key substance use and mental health indicators in the United States: Results from the 2015 National Survey on Drug Use and Health (HHS Publication No. SMA 16-4984, NSDUH Series H-51), pp. 21-22. Retrieved from http://www.samhsa.gov/data/

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7. Alternative Analysis of the Relative Risk from MDMA Use "Nutt et al. (2007) attempted to compare the relative dangers of the main types of psychosocial drug, using a series of subjective rating scales. Heroin and cocaine were graded as the two most harmful drugs, whereas Ecstasy/MDMA emerged as one of the least harmful (18th out of 20). Unfortunately, it was unclear how this low harm rating score for Ecstasy/MDMA was given, as they cited no empirical research studies or reviews. Instead, Nutt et al. (2007) suggested that: ‘for drugs which have only recently become popular e.g. Ecstasy or MDMA, the longer term health and social consequences can only be estimated from animal toxicology at present’. Nutt et al. (2007) noted that the most pleasurable drugs tended to be the most problematic, and on the ‘intensity of pleasure’ scale, heroin and cocaine were given maximum scores of 3.0. In contrast, Ecstasy/MDMA was given an ‘intensity of pleasure’ score of 1.5, which was lower than cigarette smoking at 2.2. It is unclear why Ecstasy was rated as less pleasurable than smoking a cigarette, although the low pleasure score contributed to its low harm score.

"Another question concerned drug injections, with Nutt et al. (2007) noting that ‘The potential for intravenous use is taken into account in the Misuse of Drugs classification and was treated as a separate parameter in our exercise’. Cocaine and heroin were given maximum scores of 3.0, whereas Ecstasy/MDMA was given a score of 0. Again, this did not accord with the empirical literature. In their survey of 329 recreational Ecstasy/MDMA users, Topp et al. (1999) reported that 54 (16%) had injected Ecstasy. MDMA injecting may be atypical and only occurs amongst the more experienced Ecstasy users, although this pattern would also describe cocaine. Most cocaine users never inject, and it is only found with experienced users. Hence, the injection score for MDMA should be similar to that for cocaine. Many of the other Ecstasy harm values in Nutt et al. (2007) were surprisingly low. With revised values based on the empirical literature, MDMA rises to the fifth most harmful drug (Parrott, 2009b)." Parrott, Andrew C., "Human Psychobiology of MDMA or 'Ecstasy': An Overview of 25 Years of Empirical Research," Human Psychopharmacology: Clinical and Experimental, 2013; 28:289-307. DOI: 10.1002/hup.2318

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8. Ranking of Substances by Potential for Harm "Method: Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance." "Findings: MCDA [multicriteria decision analysis] modelling showed that heroin, crack cocaine, and methamphetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places." Nutt, David J Nutt; King, Leslie A; Phillips, Lawrence D, "Drug harms in the UK: a multicriteria decision analysis," The Lancet (London, United Kingdom: November 1, 2010) Vol. 376, p. 1558.

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9. Estimated Prevalence of Cannabis Dependence "Some 4.3 percent of Americans have been dependent on marijuana, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR; American Psychiatric Association, 2000), at some time in their lives. Marijuana produces dependence less readily than most other illicit drugs. Some 9 percent of those who try marijuana develop dependence compared to, for example, 15 percent of people who try cocaine and 24 percent of those who try heroin. However, because so many people use marijuana, cannabis dependence is twice as prevalent as dependence on any other illicit psychoactive substance (cocaine, 1.8 percent; heroin, 0.7 percent; Anthony and Helzer, 1991; Anthony, Warner, and Kessler, 1994)." Budney A, Roffman R, Stephens R, Walker D. Marijuana dependence and its treatment. Addiction Science and Clinical Practice. 2007;4(1):4–16.

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10. Admissions to Treatment for Marijuana in the US According to the Substance Abuse and Mental Health Service's Treatment Episode Data Set, in 2015 in the US there were 213,001 admissions to treatment with marijuana reported as the primary substance of abuse out of the total 1,537,025 admissions to treatment in the US for those aged 12 and older for all substances that year. This is the lowest number of marijuana admissions and total treatment admissions in at least a decade: marijuana admissions peaked in 2009 at 373,338, and total admissions peaked in 2008 at 2,074,974. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2005-2015. National Admissions to Substance Abuse Treatment Services. BHSIS Series S-91, HHS Publication No. (SMA) 17-5037. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2017, Table 1.1A, p. 47.

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11. Difficulties in Assessing "Problem" Marijuana Use "The issues of measurement and conceptualization described above in relation to efforts to screen for problematic or harmful cannabis use highlight the shortcomings of ‘one-size-fits-all’ approaches to screening. Our examination of the existing literature and of cannabis users from a general population study and from a mixed-methods study of adult, stable, socially integrated users suggests that many cannabis users who may otherwise meet the criteria for being at moderate risk for problematic use are nonetheless able to successfully integrate cannabis use into everyday life with few associated problems. Indeed, our findings advocate that regular use of small amounts of cannabis does not appear to increase an individual’s likelihood of experiencing problems, and it does not threaten one’s ability to function well and perform expected roles. Even so, the tools used to assess potentially harmful cannabis use invariably serve to classify almost all ‘regular’ users as problematic users." Asbridge M, Duff C, Marsh D, C, Erickson P, G, Problems with the Identification of ‘Problematic' Cannabis Use: Examining the Issues of Frequency, Quantity, and Drug Use Environment. Eur Addict Res 2014;20:254-267.

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