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GATEWAY THEORY & Cannabis studies completed

We found that marijuana use within itself wasn't a risk factor for use of other drugs," said lead author Joseph Palamar, an assistant professor in the New York University Langone Medical Center's department of population health. "People do generally use marijuana before other drugs, but that doesn't mean marijuana is a cause of [using] those other drugs." source WebMD

Undated - News - The myth of marijuana's gateway effect

1996 - Study - Marijuana and the gateway theory

1997 - Study - Cannabis use - A gateway to other drugs? The case of Amsterdam  

1998 - FAQ - Does cannabis lead to taking other drugs?

2001 - Study - Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect.

2002 - Study - Reassessing the gateway effect

2003 - Letter - Twin study fails to prove 'gateway' hypothesis

2003 - Study - Is cannabis a stepping-stone for cocaine?

2004 - Study - Endogenous cannabinoids are not involved in cocaine reinforcement

2005 - Study - Cannabis use when it's legal

2006 - News - Study questions marijuana as gateway drug

2006 - News - No 'smoking' gun: Research indicates teen marijuana use does not predict drug, alcohol abuse

2006 - News - Gateway to nowhere? The evidence that pot doesn't lead to heroin 

2008 - News - Study of 4000 indicates marijuana discourages use of hard drugs.

2009 - Study - Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances

2009 - Study - Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats

2009 - News - Claim #13: marijuana as a "gateway" to the use of other drugs 

2009 - News - The surprising effect of marijuana on morphine dependence

2009 - News - Active ingredient in cannabis eliminates morphine dependence in rats

2010 - Study - Evaluating the drug use "gateway" theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO (World Mental Health Surveys)

2010 - News - Marijuana as a gateway drug: The myth that will not die

2010 - News - Risk of marijuana's 'Gateway Effect' overblown

2010 - News - Teen pot smoking won't lead to other drugs as adults

2011 - Study - Previous exposure to delta9-tetrahydrocannibinol enhances locomotor responding to but not self-administration of amphetamine.

2012 - Study - Alcohol as a gateway drug: A study of U.S.A 12th graders

2012 - Study - Does the "gateway" sequence increase prediction of cannabis use disorder development beyond deviant socialization? Implications for prevention practice and policy.

 Hardcover Books  

 Shattered SpiritsJournal of Cannabis Therapeutics Studies in Endogenous, Herbal & Synthetic CannabinoidsAddictionCannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic PotentialEffects of a synthetic cannabinoid on the reinforcing efficacy of self-administered ethanol in rats.Cannabinoids in Nature and Medicine

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Does the "gateway" sequence increase prediction of cannabis use disorder development beyond deviant socialization? Implications for prevention practice and policy

Drug Alcohol Depend. 2012 Jun;123 Suppl 1:S72-8. doi: 10.1016/j.drugalcdep.2012.01.015. Epub 2012 Feb 25.

Source

Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, United States. [email protected]

Abstract

BACKGROUND:

This study was conducted to test whether non-normative socialization mediates the association between transmissible risk measured in childhood and cannabis use disorder manifested by young adulthood, and whether the sequence of drug use initiation ("gateway", i.e., consuming legal drugs before cannabis, or the reverse) increases accuracy of prediction of cannabis use disorder.

METHODS:

Sons of fathers with or without substance use disorders (SUDs) related to illicit drugs were tracked from 10-12 to 22 years of age to model the association between transmissible risk for SUD, socialization (peer deviance), order of drug use initiation ("gateway" or reverse sequence), and development of cannabis use disorder. Path analysis was used to evaluate relationships among the variables.

RESULTS:

Non-normative socialization mediates the association between transmissible risk measured during childhood and cannabis use disorder manifest by young adulthood. The sequence of drug use initiation did not contribute additional explanatory information to the model.

CONCLUSIONS:

The order of drug use initiation does not play a substantial role in the etiology of cannabis use disorder.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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Alcohol as a Gateway Drug: A Study of US 12th Graders

  1. Tristan Kirby MPH
  2. Adam E. Barry PhD

Source: Wiley Online Library

BACKGROUND: The Gateway Drug Theory suggests that licit drugs, such as tobacco and alcohol, serve as a “gateway” toward the use of other, illicit drugs. However, there remains some discrepancy regarding which drug—alcohol, tobacco, or even marijuana—serves as the initial “gateway” drug subsequently leading to the use of illicit drugs such as cocaine and heroin. The purpose of this investigation was to determine which drug (alcohol, tobacco, or marijuana) was the actual “gateway” drug leading to additional substance use among a nationally representative sample of high school seniors.

METHODS: This investigation conducted a secondary analysis of the 2008 Monitoring the Future 12th-grade data. Initiation into alcohol, tobacco, and other drug use was analyzed using a Guttman scale. Coefficients of reliability and scalability were calculated to evaluate scale fit. Subsequent cross tabulations and chi-square test for independence were conducted to better understand the relationship between the identified gateway drug and other substances' use.

RESULTS: Results from the Guttman scale indicated that alcohol represented the “gateway” drug, leading to the use of tobacco, marijuana, and other illicit substances. Moreover, students who used alcohol exhibited a significantly greater likelihood of using both licit and illicit drugs.

CONCLUSION: The findings from this investigation support that alcohol should receive primary attention in school-based substance abuse prevention programming, as the use of other substances could be impacted by delaying or preventing alcohol use. Therefore, it seems prudent for school and public health officials to focus prevention efforts, policies, and monies, on addressing adolescent alcohol use.

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Previous exposure to delta9-tetrahydrocannibinol enhances locomotor responding to but not self-administration of amphetamine

Authors

Cortright JJ, Lorrain DS, Beeler JA, Tang WJ, Vezina P

Institution

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.

Source

The Journal of pharmacology and experimental therapeutics 337:3 2011 Jun pg 724-33

Abstract

Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ(9)-tetrahydrocannibinol (Δ(9)-THC) on behavioral and biochemical responding to amphetamine.

Rats in different groups received five exposure injections of vehicle or one of five doses of Δ(9)-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ(9)-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug.

Moreover, exposure to 3.0 mg/kg i.p. Δ(9)-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ(9)-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc.

Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ(9)-THC (5 × 3.0 mg/kg i.p.).

Previous exposure to this dose of Δ(9)-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.).

Thus, unlike amphetamine exposure, exposure to Δ(9)-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ(9)-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration.

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  • Teen Pot Smoking Won't Lead to Other Drugs as Adults

    By
    WebMD Medical Reference
    Reviewed by Laura J. Martin, MD
     
     

    Sept. 2, 2010 -- New research finds little support for the hypothesis that marijuana is a "gateway" drug leading to the use of harder drugs in adulthood.

    Teens in the study who smoked marijuana were more likely to go on to use harder illicit drugs, but the gateway effect was lessened by the age of 21, investigators say.

    Harder drugs in the study referred to illicit drugs that include analgesics, cocaine, hallucinogens, heroin, inhalants, sedatives, stimulants, and tranquilizers.

    The study is published in the September issue of the Journal of Health and Social Behavior.

    Failure to graduate from high school or find a job were all bigger predictors of drug use in young adulthood than marijuana use during adolescence, says study researcher Karen Van Gundy, who is a sociologist at the University of New Hampshire.

    She adds that the findings have implications for policymakers on the front lines in the war on drugs.

    "If we overly criminalize behaviors like marijuana use among teens, this could interfere with opportunities for education and employment later on, which, in turn, could be creating more drug use," she tells WebMD.

    Marijuana's Gateway Effect Goes Away

    Van Gundy says she did not set out to disprove the idea that marijuana is a gateway drug when she and co-researcher Cesar J. Rebellon examined survey data from 1,300 mostly male Hispanic, white, and African-American young adults who attended south Florida public schools in the 1990s. The participants were followed from enrollment in the sixth or seventh grade until they reached their late teens or early 20s.

    "Most of the previous research has examined early drug use among people with serious drug problems," she says. "These people do tend to progress from alcohol and marijuana use to other drugs."

    When the teens in the study were followed forward into young adulthood, however, a different picture emerged.

    "We were somewhat surprised to find the gateway effect wasn't that strong during the transition to adulthood," Van Gundy says. "It really didn't matter if someone used marijuana or not as a teen."

    Specifically, the study found illicit drug abuse in young adulthood to be much more closely linked to stress during the teen years and whether or not the young adults were employed.

    "Assuming and occupying conventional roles, such as 'worker,' may close the marijuana gateway by modifying and redirecting substance use trajectories," the researchers write.

     

    The findings suggest anti-drug efforts aimed at keeping kids in school and providing employment opportunities may have the biggest positive impact on drug use in adulthood, Van Gundy says.

    Urban sociologist and drug-use researcher Lesley Reid agrees.

    An associate professor of sociology at Georgia State University in Atlanta, Reid's research has focused on the gateway effect of so-called club drugs like ecstasy and cocaine among heavy drug users in their 20s.

    She says most of these heavy users do start with alcohol and marijuana and progress to harder drugs.

    "Obviously, we don't see this age effect among these heavy users," she tells WebMD. "But in the general population most people do outgrow behaviors like drug use and other delinquent behaviors."

    'Gateway' Pioneer Critical of Study

    But Columbia University sociologist Denise B. Kandel, PhD, whose research early in the decade found marijuana to be a gateway drug, calls the new research highly flawed and the conclusions "ill founded."

    She tells WebMD that the design of the study did not allow the researchers to properly test the hypothesis that marijuana is a gateway drug.

    Kandel does not disagree with the conclusion that social position in young adulthood plays a big role in drug use during this time. But she says the researchers fail to consider the potential impact of early marijuana use on social position.

    "Using marijuana as a teen can certainly have an impact on whether or not someone fails to graduate from high school or gets a job," she says. "And this increases the risk of persistent illicit drug use."

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    Risk Of Marijuana's 'Gateway Effect' Overblown

    Source: RedOrbit

    New research from the University of New Hampshire shows that the "gateway effect" of marijuana ““ that teenagers who use marijuana are more likely to move on to harder illicit drugs as young adults ““ is overblown.

    Whether teenagers who smoked pot will use other illicit drugs as young adults has more to do with life factors such as employment status and stress, according to the new research. In fact, the strongest predictor of whether someone will use other illicit drugs is their race/ethnicity, not whether they ever used marijuana.

    Conducted by UNH associate professors of sociology Karen Van Gundy and Cesar Rebellon, the research appears in the September 2010, issue of the Journal of Health and Social Behavior in the article, "A Life-course Perspective on the ‘Gateway Hypothesis.’ "

    "In light of these findings, we urge U.S. drug control policymakers to consider stress and life-course approaches in their pursuit of solutions to the ‘drug problem,’ " Van Gundy and Rebellon say.

    The researchers used survey data from 1,286 young adults who attended Miami-Dade public schools in the 1990s. Within the final sample, 26 percent of the respondents are African American, 44 percent are Hispanic, and 30 percent are non-Hispanic white.

    The researchers found that young adults who did not graduate from high school or attend college were more likely to have used marijuana as teenagers and other illicit substances in young adulthood. In addition, those who used marijuana as teenagers and were unemployed following high school were more likely to use other illicit drugs.

    However, the association between teenage marijuana use and other illicit drug abuse by young adults fades once stresses, such as unemployment, diminish.

    "Employment in young adulthood can protect people by ‘closing’ the marijuana gateway, so over-criminalizing youth marijuana use might create more serious problems if it interferes with later employment opportunities," Van Gundy says.

    In addition, once young adults reach age 21, the gateway effect subsides entirely.

    "While marijuana use may serve as a gateway to other illicit drug use in adolescence, our results indicate that the effect may be short-lived, subsiding by age 21. Interestingly, age emerges as a protective status above and beyond the other life statuses and conditions considered here. We find that respondents ‘age out’ of marijuana’s gateway effect regardless of early teen stress exposure or education, work, or family statuses," the researchers say.

    The researchers found that the strongest predictor of other illicit drug use appears to be race-ethnicity, not prior use of marijuana. Non-Hispanic whites show the greatest odds of other illicit substance use, followed by Hispanics, and then by African Americans.

    On the Net:

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    Marijuana as a Gateway Drug: The Myth That Will Not Die

     Of all the arguments that have been used to demonize marijuana, few have been more powerful than that of the “gateway effect”: the notion that while marijuana itself may not be especially dangerous, it ineluctably leads to harder drugs like heroin and cocaine. Even Nick Kristof — in a column favoring marijuana legalization — alluded to it this week in the New York Times. In what is known as the “to be sure” paragraph, where op-ed writers cite the arguments of opponents, he wrote:

    I have no illusions about drugs. One of my childhood friends in Yamhill, Ore., pretty much squandered his life by dabbling with marijuana in ninth grade and then moving on to stronger stuff. And yes, there’s some risk that legalization would make such dabbling more common.

    The idea that marijuana may be the first step in a longer career of drug use seems plausible at first: when addicts tell their histories, many begin with a story about marijuana. And there’s a strong correlation between marijuana use and other drug use: a person who smokes marijuana is more than 104 times more likely to use cocaine than a person who never tries pot, according to the National Institute on Drug Abuse. (More on Time.com: 7 Tips for California: How to Make Legalizing Marijuana Smart)

    The problem here is that correlation isn’t cause. Hell’s Angels motorcycle gang members are probably more 104 times more likely to have ridden a bicycle as a kid than those who don’t become Hell’s Angels, but that doesn’t mean that riding a two-wheeler is a “gateway” to joining a motorcycle gang. It simply means that most people ride bikes and the kind of people who don’t are highly unlikely to ever ride a motorcycle.

     cientists long ago abandoned the idea that marijuana causes users to try other drugs: as far back as 1999, in a report commissioned by Congress to look at the possible dangers of medical marijuana, the Institute of Medicine of the National Academy of Sciences wrote:

    Patterns in progression of drug use from adolescence to adulthood are strikingly regular. Because it is the most widely used illicit drug, marijuana is predictably the first illicit drug most people encounter. Not surprisingly, most users of other illicit drugs have used marijuana first. In fact, most drug users begin with alcohol and nicotine before marijuana — usually before they are of legal age.

    In the sense that marijuana use typically precedes rather than follows initiation of other illicit drug use, it is indeed a “gateway” drug. But because underage smoking and alcohol use typically precede marijuana use, marijuana is not the most common, and is rarely the first, “gateway” to illicit drug use. There is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.

    Since then, numerous other studies have failed to support the gateway idea. Every year, the federal government funds two huge surveys on drug use in the population. Over and over they find that the number of people who try marijuana dwarfs that for cocaine or heroin. For example, in 2009, 2.3 million people reported trying pot — compared with 617,000 who tried cocaine and 180,000 who tried heroin. (More on Time.com: See photos of cannabis conventions)

    So what accounts for the massive correlation between marijuana use and use of other drugs? One key factor is taste. People who are extremely interested in altering their consciousness are likely to want to try more than one way of doing it. If you are a true music fan, you probably won’t stick to listening to just one band or even a single genre —  this doesn’t make lullabies a gateway to the Grateful Dead, it means that people who really like music probably like many different songs and groups.

    Second is marijuana’s illegality: you aren’t likely to be able to find a heroin dealer if you can’t even score weed. Compared with pot dealers, sellers of hard drugs tend to be even less trusting of customers they don’t know, in part because they face greater penalties. But if you’ve proved yourself by regularly purchasing marijuana, dealers will happily introduce to you to their harder product lines if you express interest, or help you find a friend of theirs who can.

    Holland began liberalizing its marijuana laws in part to close this particular gateway — and indeed now the country has slightly fewer young pot-smokers who move on to harder drugs compared with other nations, including the U.S. A 2010 Rand Institute report titled “What Can We Learn from the Dutch Cannabis Coffeeshop Experience?” found that there was “some evidence” for a “weakened gateway” in The Netherlands, and concluded that the data “clearly challenge any claim that the Dutch have strengthened the gateway to hard drug use.” (More on Time.com: Is Marijuana Addictive? It Depends How You Define Addiction)

    Of course, that’s not the gateway argument favored by supporters of our current drug policy — but it is the one supported by science.

    More on Time.com:

    Best of ‘Stoner Cinema’

    The Marijuana Number That Was Too Good to Check

    Is Drug Use Really on the Rise?

     

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    Evaluating the drug use "gateway" theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO World Mental Health Surveys.

     
    The publisher's final edited version of this article is available at Drug Alcohol Depend
    See other articles in PMC that cite the published article.

    Abstract

    Background

    It is unclear whether the normative sequence of drug use initiation, beginning with tobacco and alcohol, progressing to cannabis and then other illicit drugs, is due to causal effects of specific earlier drug use promoting progression, or to influences of other variables such as drug availability and attitudes.

    One way to investigate this is to see whether risk of later drug use in the sequence, conditional on use of drugs earlier in the sequence, changes according to time-space variation in use prevalence. We compared patterns and order of initiation of alcohol, tobacco, cannabis, and other illicit drug use across 17 countries with a wide range of drug use prevalence.

    Method

    Analyses used data from World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures carried out in 17 countries throughout the world.

    Results

    Initiation of “gateway” substances (i.e. alcohol, tobacco and cannabis) was differentially associated with subsequent onset of other illicit drug use based on background prevalence of gateway substance use. Cross-country differences in substance use prevalence also corresponded to differences in the likelihood of individuals reporting a non- normative sequence of substance initiation.

    Conclusion

    These results suggest the “gateway” pattern at least partially reflects unmeasured common causes rather than causal effects of specific drugs on subsequent use of others. This implies that successful efforts to prevent use of specific “gateway” drugs may not in themselves lead to major reductions in the use of later drugs.

    Keywords: tobacco, alcohol, illicit drugs, gateway, WHO World Mental Health Surveys

    1.0 Introduction

    Community epidemiological research, concentrated in North America and Oceania, has documented a common sequence of drug use initiation that begins with tobacco and alcohol use, followed by cannabis and then other illicit drugs. This pattern was originally described as the “gateway pattern”, with use of an earlier drug in this sequence predicting progression to use of later ones (e.g. cannabis and other drugs) (Grau et al., 2007; Kandel et al., 1986a; Kandel and Faust, 1975; Kandel, 1984; Kandel et al., 1986; Kandel et al., 1992; van Ours, 2003; Yamaguchi and Kandel, 1984).

    Some commentators have argued that the gateway pattern is due to a causal effect of earlier substance use on use of later substances (Fergusson et al., 2006b; Rebellon and Van Gundy, 2006).

    A variety of pathways have been proposed, some more reductionist than others. One suggestion for a gateway effect of cannabis use on subsequent opioid use, for example, is that cannabis alters the opioid system in the brain, leading to a change in hedonic processing that promotes subsequent opioid use (Ellgren et al., 2007).

    If true, such causal effects of earlier substances in the gateway sequence on subsequent use of later substances would suggest that efforts to prevent use of specific earlier drugs might help reduce initiation of the later ones.

    However, the gateway pattern observed in epidemiological data is also consistent with the existence of one or more unmeasured common causes, such as a risk-taking predisposition and latent propensity to use drugs as just one of a range of risk behaviours, rather than a causal effect of earlier gateway drugs (Morral et al., 2002).

    If common causes account for the gateway pattern, then we would not expect prevention of use of specific earlier drugs in the sequence to cause a reduction in use of later substances. Debate about these possibilities continues (Fergusson et al., 2006a; Hall, 2006; Morral et al., 2002; Schenk, 2002).

    One approach to investigating this issue that has not been pursued in the past is to examine data on time-space variation in use of drugs earlier and later in the gateway sequence.

    An analogous approach was presented by Weiss et al. (1988) in their evaluation of cocaine use among hospitalised drug users: cocaine use was strongly related to mood disorder in cohorts studied in 1980-82, but when cocaine use was more common (1982-86) the association between mood disorder and cocaine was reduced. Similarly, the association between nicotine dependence and psychiatric disorders has become stronger in more recent US cohorts as smoking has become less common; a pattern that is thought to be related to changes in social norms, such that nicotine dependence is a more powerful marker of “deviance” now than when smoking was much more normative in the past (Breslau, 2004).

    These studies suggest that the association between cocaine and tobacco use and mood disorders may not be a simple causal one; and perhaps that the prevalence of drug use might impact upon associations with other variables. Conversely, if associations between the use of a drug and other outcomes (such as psychiatric disorders or other drug use) were causal, we would expect changes in prevalence of one drug to have no impact on associations with later outcomes (e.g. cannabis use would remain similarly associated with other illicit drug use, but there would be lower levels of those later outcomes).

    The Weiss et al. analysis is compelling: it could be taken to suggest that the pharmacological effects of cocaine were less important in predicting adverse outcomes than sociocultural meanings of use (i.e., a shift from being a rarely used drug, perhaps perceived as dangerous, with those using it high risk-takers; to later use by a considerably larger proportion of the population). This implies that some external (sociocultural) factors influenced changes in prevalence of use, with the difference in prevalence due to reasons that would not be expected to influence the outcomes under study (other than through exposure to cocaine).

    This assumption is formalised in the econometric method of instrumental variables analysis, in which a causal determinant of a putative risk factor is found, which can be assumed not to have any direct causal effect on an outcome other than through the risk factor (Pearl, 2000).

    When such an instrument is found, it can be used to estimate the magnitude of the causal effect of the risk factor on the outcome in such a way as to separate out any bias due to reciprocal causation or unmeasured common causes. The classic case in economics was the use of information about forest fires in Northwest USA, and railroad strikes, to influence the price of lumber, which in turn influenced the number of new housing starts. This allowed the effects of economic stimulation on interest rates to be estimated, independent of the effects of the interest rate on economic stimulation (Angrist & Krueger, 2001).

    Assuming that time-space variation in the prevalence of drug use results at least in part from instrumental variables, we can study the extent to which variation in use of early “gateway” drugs predicts subsequent change in use of later drugs in the gateway sequence.

    We know, for example, that US tobacco use dropped dramatically in the 1990s, due to a combination of public education campaigns and aggressive taxation policy, influences that would not be expected to have any direct effect on use of cannabis or other illicit drugs other than through the effect of reducing tobacco use.

    Was this reduction in tobacco use accompanied by the reduction in use of illicit drugs that would be predicted by the gateway theory? We are unaware of any direct analysis of epidemiological data aimed at answering that question.

    We present this type of analysis here. Rather than focus on a single country in a single time period though, we present cross-national comparisons, combining information about between-country differences with information about within-country through-time variation, to examine broad patterns of association.

    No attempt is made to measure explicit instrumental variables. Instead, we work on the implicit assumption that the time-space variation in prevalence of earlier so-called gateway drugs (alcohol, tobacco and cannabis) reflects factors that would not be expected to influence use of later drugs directly.

    This makes the comparison of time-space variation useful for making preliminary inferences about the potential effects of interventions to specifically reduce use of drugs early in the “gateway” sequence upon use of drugs later in the sequence.

    Cross-national data can provide some information on this issue, as the prevalence of licit and illicit drug use varies dramatically across countries and cultures. If the “gateway sequence” was consistent across diverse countries, this would provide support for a more strongly causal interpretation of the sequence.

    Alternatively, if there was variation in both levels and associations across countries, this would support the putative influence of other variables on the association. Some limited data exist on this issue.

    Specifically, two studies in New Zealand (Wells and McGee, 2008) and the United States (Degenhardt et al., 2009) found that violations of the normative order of substance initiation, although uncommon, were more common among more recent cohorts, who also had a higher prevalence of drug use.

    They also found that “violating” this sequence was not associated with increased dependence risk. Rather, it was prior cumulative exposure to total drugs, and an earlier onset of initiation, that were significant predictors of transition to dependence.

    These results argue against the hypothesis that use of specific “gateway” drugs has a causal effect on subsequent initiation of use of later ones.

    It would be useful to extend these results to a larger set of countries with a wider range of variation in drug use to consider the consistency of the order of initiation of drug use, and observe whether associations between use of one drug and initiation of another are consistently observed.

    The current paper presents the results of such an extension using the World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures that were carried out in 17 countries throughout the world. The aims of this study are to:

    1. examine the prevalence of drug use by age 29 years across age cohort and country;
    2. consider if differences in prevalence are associated with differences in associations with drug use later in the “gateway” sequence;
    3. examine whether violations of the “gateway“ sequence vary according to age cohort and country differences in prevalence of drug use earlier in the sequence;
    4. examine whether the specific order of initiation of drug use predicts later development of drug dependence.

    2. Method

    2.1 Sample

    WMH surveys were carried out in seven countries classified by the World Bank (World Bank, 2003) as developing (Colombia, Lebanon, Mexico, Nigeria, Peoples’ Republic of China, South Africa, Ukraine) and ten classified as developed (Belgium, France, Germany, Italy, Japan, Israel, Netherlands, New Zealand, Spain, and United States of America).

    The total sample size was 85,088, with individual country sample sizes ranging from 2372 (the Netherlands) to 12,992 (New Zealand). The weighted average response rate across countries was 69.9%, with country-specific response rates ranging from 45.9% (France) to 87.7% (Colombia). All surveys were based on probability household samples of adults that were either representative of particular regions of the country (in China, Colombia, Japan, and Mexico) or nationally representative (other countries). Table 1 presents sample characteristics for the WMHS.

    Table 1
    WMH Sample Characteristics

    All interviews were conducted face-to-face by trained lay interviewers. Each interview had two parts. All respondents completed Part I, which contained core mental disorders, while all Part I respondents who met criteria for any core mental disorder plus a probability sub-sample of approximately 25% of other Part I respondents were administered Part II.

    The Part II interview assessed correlates, service use, and disorders of secondary interest to the study. The assessment of substance use patterns was included in Part II.

    The Part II survey data were weighted to adjust for the over-sampling of people with mental disorders and for differential probabilities of selection within households, as well as to match samples to population socio-demographic distributions, making the weighted Part II samples representative of the populations from which they were selected.

    Standardised interviewer-training procedures, WHO translation protocols for all study materials and quality control procedures for interviewer and data accuracy were consistently applied across all WMH countries in an effort to ensure cross-national comparability. These procedures are described in more detail elsewhere (Alonso et al., 2002; Kessler et al., 2004; Kessler and Üstün, 2004). Informed consent was obtained before beginning interviews in all countries.

    Procedures for obtaining informed consent and protecting human subjects were approved and monitored for compliance by the Institutional Review Boards of the organizations coordinating the surveys in each country.

    2.2 Measures

    Mental and substance disorders were assessed with Version 3.0 of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) (Kessler and Üstün, 2004), a fully structured lay-administered interview designed to generate research diagnoses of commonly occurring DSM-IV disorders (American Psychiatric Association [APA], 1994).

    Participants were separately asked if they had ever used tobacco, alcohol, cannabis and other illicit drugs. A report of ever using a drug was followed with questions about age of first use (“How old were you the very first time you ever smoked even a puff of a cigarette, cigar, or pipe?”; “How old were you the very first time you ever drank an alcoholic beverage – including either beer, wine, a wine cooler, or hard liquor?”; How old were you the first time you used marijuana or hasish?”; “How old were you the first time you used cocaine?”; “How old were you the first time you used one or more of the drugs on page Y in your reference book such as heroin, opium, glue, LSD, peyote, or any other drug?”), age-of-onset (AOO) of first regular use, lifetime occurrence of symptoms of abuse/dependence, and AOO of abuse-dependence.

    Exceptions were that AOO of tobacco use, nicotine dependence and drug dependence were not assessed in Belgium, France, Germany, Italy, the Netherlands, and Spain; AOO of tobacco use and nicotine dependence were not assessed in Japan and New Zealand; nicotine dependence was not assessed in Israel and South Africa.

    2.2.1 Order of onset and violations of the gateway progression

    Different onset orders, as determined by retrospective age-of-onset reports were evaluated. Violations of the gateway progression were defined as:

    • Violation 1: First use of cannabis before both alcohol and tobacco;
    • Violation 2: First use of other illicit drugs (cocaine, heroin, opium, glue, LSD, peyote, or any other drug) before alcohol and tobacco;
    • Violation 3: First use of other illicit drugs (cocaine, heroin, opium, glue, LSD, peyote, or any other drug) before cannabis.

    For countries that did not assess age of onset of tobacco use, in order to be a violation that included use of cannabis or other illicit drugs before “both alcohol and tobacco”, respondents must have reported either never having used tobacco, with a later age of onset of alcohol use; or never having used both tobacco and alcohol prior to use of illicit drugs.

    In order to examine whether a less stringent text of the gateway sequence may have produced different results, we examined use of cannabis before either alcohol or cannabis use (i.e. before the use of one of these drugs). Although violations of this sort were more common, the pattern of findings was similar (Supplementary Tables 1a, 2a, 3)1.

    2.3 Analysis methods

    Cumulative prevalence of drug use and gateway violations by age 29 were estimated for each country and cohort, with standard errors derived using the Taylor series linearisation (TSL) methods implemented in SUDAAN to adjust for the effects of weighting and clustering on the precision of estimates.

    When p-values are reported or indicated, they are from Wald tests obtained from TSL design-based coefficient variance-covariance matrices (α = 0.05; two-tailed). Regression models were then carried out to examine the significance of age cohort associations (defined by interview age 18-29, 30-44, 45-59, and ≥60) with drug use and with each of the three gateway violations within each country.

    The associations of the onset of substances earlier in the gateway sequence with the subsequent first onset of the later drug in the sequence were estimated using discrete time survival analysis with person year as the unit of analysis within country and controlling for person year and sex. Person-years were restricted to those <=29 to make cross-cohort comparisons.

    Discrete-time survival models pooled across countries were run to include the interaction between use of each gateway drug category and the prevalence of gateway drug use within each country. Covariates included, gender, age cohort, and country. Odds ratios and 95% confidence intervals for the interaction term are presented, to evaluate whether the strength of the association between gateway drug use and initiation of subsequent drugs in the sequence differs according to background prevalence of use within each country.

    3. Results

    3.1 Cross-national and cohort differences in drug use

    Drug use by age 29 years by age group at interview is presented in Table 2 for all 17 countries. South Africa had the lowest level of alcohol use, with 40.6% of the total sample reporting any use by age 29 years, followed by Lebanon (52.8%), Nigeria (55.6%) and Israel (55.7%). Tobacco use was relatively rare in South Africa (32.4%) and Nigeria (16.1%). Cannabis use was very low in Nigeria (2.8%), Japan (1.6%), and the People’s Republic of China (0.3%). Despite relatively low rates of alcohol and tobacco use, South Africa showed moderate prevalence of cannabis use (8.5%) relative to the remaining countries (cross-country median 9.8%). In Japan, the use of other illicit drugs by age 29 years was more prevalent than cannabis (Table 2). Age cohort differences in drug use were common: most countries showed increases in prevalence of use of all drugs among younger cohorts.

    Table 2
    Prevalence of drug use by age 29 years, according to age group at interview. Data from the World Mental Health Surveys (n = 54,068).

    3.2 Cross-national and age cohort differences in associations between order of initiation of drug use and later other drug use

    With few exceptions, substances earlier in the “gateway” sequence predicted drug use later in the sequence (Table 3). However, the strength of these associations differed across countries. For example, cannabis use was less strongly associated with later illicit drug use (cocaine and other illicit drugs) among young adults (18-29yrs) in the Netherlands than it was in Belgium, Spain and the United States.

    Table 3
    Association between the initiation of a drug and the later use of other drugs by 29 years, according to country and age cohort

    Discrete-time survival models pooled across countries revealed a significant interaction between the initiation of alcohol/tobacco and prevalence of alcohol/tobacco use predicting the subsequent initiation of other illicit drugs (OR=32.7, CI 8.3-129.0), suggesting that alcohol/tobacco initiation was associated more strongly with the subsequent onset of other illicit drug use in countries/cohorts with higher rates of alcohol/tobacco use.

    Conversely, cannabis initiation was more strongly associated with the subsequent onset of other illicit drug use in countries/cohorts with lower rates of cannabis use (OR=0.3, CI 0.2-0.6). There was no significant interaction effect of the onset of alcohol/tobacco and the prevalence of alcohol/tobacco use in a country upon later cannabis initiation.

    3.3 Cross-national and cross-cohort differences in violations to the gateway sequence

    Estimated prevalence of violations to the gateway sequence among drug users in each of the 17 countries is presented in Table 4 (and Supplementary Tables 1 and 2). Cannabis users in South Africa, a country with the lowest rates of both alcohol and tobacco use, showed the highest rate of violating the typical gateway sequence, with 16.3% never using both alcohol and tobacco as of the age of first cannabis use.

    This rate was one and one third to more than 10 times higher than that seen among cannabis users in countries where alcohol and/or tobacco use was prevalent (Supplementary Table 1, 1a).

    Among other illicit drug users, Japan had the highest rate of violating the gateway sequence, with 52.5% failing to use both alcohol and tobacco as of the onset of other illicit drug use (Supplementary Table 2, 2a). Nigeria had the second highest rate, with 51.8% failing to have used both alcohol and tobacco as of the onset of other illicit drug use. In comparison, within countries where rates of alcohol and/or tobacco were highest, the use of other illicit drugs before both alcohol and tobacco was rare (Germany 0.6%, New Zealand 0.2% and Ukraine 0.0%; Supplementary Table 2, 2a).

    Table 4
    Percent of those using other illicit drugs4 by age 29 years who had NOT already used cannabis before beginning other illicit drug4 use, by country and age at interview

    Cannabis was rarely used before other illicit drugs by most other illicit substance users in countries where cannabis use was rare (Japan 83.2%, Nigeria 77.8%, Table 4). In countries where rates of cannabis use were highest, violations to the gateway sequence were uncommon (U.S. 11.4%, New Zealand, 12.7%).

    Further analyses were conducted to consider whether violations to the “gateway” sequence of initiation predicted the later onset of dependence among users of each drug type (Table 5, Supplementary Table 3).

    Discrete-time survival models pooled across all countries (controlling for country in models) revealed that violations to the “gateway” sequence of initiation largely did not predict the onset of any drug dependence in a given year. Rather, it was the number of drugs used, and an earlier onset of exposure to drugs overall, that predicted transition to dependence (Table 5,Supplementary Table 3a).

    Early onset mental disorders (both internalising and externalising) were also important predictors of the development of dependence.

    Table 5
    Multivariable predictors of onset of dependence by drug type. Pooled analyses from the WHO World Mental Health Surveys

    4. Discussion

    The present paper examined the extent and ordering of licit and illicit drug use across 17 disparate countries worldwide. This comparison, using surveys conducted with representative samples of the general population in these countries, and assessment involving comparable instruments, allowed for the first assessment of the extent to which initiation of drug use follows a consistent pattern across countries.

    Previous studies, concentrated in high income countries with relatively high levels of cannabis use, have documented: a common temporal ordering of drug initiation; an increased risk of initiating use of a drug later in the sequence once having initiated an earlier one; and the persistence of the association following controlling for possibly confounding factors (Kandel et al., 2006).

    The present study supported the existence of other factors influencing the ordering and progression of drug use because 1) other illicit drug use was more prevalent than cannabis use in some countries, e.g. Japan; 2) the association between initiation of “gateway” drugs (i.e. alcohol/tobacco and cannabis), and subsequent other illicit drug use differed across countries, in some instances according to background prevalence of use of these gateway drugs; and 3) cross-country differences in drug use prevalence corresponded to differences in the prevalence of gateway violations.

    Higher levels of other illicit drug use compared to cannabis use were documented in Japan, where exposure to cannabis and tobacco/alcohol was less common. In this case, a lack of exposure and/or access to substances earlier in the normative sequence did not correspond to reductions in overall levels of other illicit drug use. This finding is contrary to the assumption that initiation reflects a universally ordered sequence in which rates of drug use later in the sequence must necessarily be lower than those earlier in the sequence (Kandel, 2002). This has not previously been reported as research has been traditionally conducted in countries where use of tobacco, alcohol and cannabis is relatively common.

    As expected by a model in which environmental factors such as access and/or attitudes toward use of a drug play some role in the order of substance initiation, gateway substance use was differentially associated with the subsequent onset of other illicit drug use in countries/cohorts based on background prevalence of gateway substance use (i.e. alcohol/tobacco more strongly associated with the subsequent onset of other illicit drug use in countries/cohorts with higher rates of alcohol/tobacco use and cannabis initiation more strongly associated with the subsequent onset of other illicit drug use in countries/cohorts with lower rates of cannabis use).

    Thus, while previous studies have consistently documented that the use of an earlier substance in the gateway sequence predicts progression to use of later substances (Grau et al., 2007; Kandel et al., 1986; van Ours, 2003; Yamaguchi and Kandel, 1984), the present analyses conducted across diverse countries and cohorts showed that the strength of associations between substance use progression may be driven by background prevalence rather than being wholly explained by causal mechanisms.

    Further, differences in patterns of gateway violations seen across countries in the WMHS provided evidence in support of the likely influence of access and/or attitudes toward substance use in shaping order of initiation.

    The most common gateway violation was that of other illicit drug use before cannabis. Higher levels of other illicit drug use before cannabis were related to lower levels of cannabis use in these countries (Japan and Nigeria).

    Similarly, first use of other illicit drugs before alcohol and tobacco was found to be most prevalent in Japan and Nigeria, countries with relatively low rates of alcohol and tobacco use compared to other WMHS countries (Degenhardt et al., 2008). In contrast, use of cannabis before alcohol and tobacco was extremely rare in countries with some of the highest rates of cannabis use, such as the US and New Zealand. Cannabis users in the US were also much more likely to progress to other illicit drug use than those in the Netherlands. Taken together, cross-country differences in drug use prevalence corresponded remarkably well with differences in the prevalence of gateway violations.

    What are the implications of these findings for our understanding of the relationship between the initiation of drug use and potential adverse drug-related outcomes later in life?

    First, consistent with other discussions of early onset drug use (Iacono et al., 2008) it may be more useful to discuss early onset drug use (regardless of the type of drug used) rather than focusing on any particular type of drug since: the order of onset is clearly not the same for all users; the order varies to some extent across countries and across cohorts born in different periods; and since changes in the order of onset do not seem to affect risk for later dependence.

    Rather, consistent with a number of lines of observational evidence, many involving prospective study designs (see Iacono et al., 2008), the risk for later development of dependence upon a drug may be more affected by the extent of prior use of any drug and the age of onset at which that use began. This was lent support in this study through the finding that the number of early onset mental disorders (prior to age 15 years) was an important moderator of risk for developing dependence.

    The finding that adolescents with externalising and internalising disorders were at elevated risk of developing drug dependence is consistent with prospective cohort studies, which have found that early onset drug use and mental health problems are risk factors for later dependent drug use (Toumbourou et al., 2007), and that comorbid mental health problems escalate risk of developing dependence once drug use begins.

    It also suggests that, rather than focusing on specific patterns of initiation, or on the use of particular drugs in order to prevent transitions to other specific drug use or dependence, prevention efforts are probably better targeted at all types of drug use, particularly among young people who are already dealing with other challenges or risk behaviours, since it may be this group that is most at risk of developing problems later on.

    4.1 Limitations

    As with all cross-sectional survey research (it needs to be noted that the WMHS surveys were not explicitly designed to answer the current research question), there are several limitations that should be considered. First, this study found cohort differences in substance use within various countries as well as cohort differences in the order of onset of use.

    Although this may reflect actual cohort differences, they may also reflect response biases. Retrospective reporting of age of first substance use is subject to error, given that respondents are being asked about events that, for older persons, may have occurred decades ago.

    Longitudinal studies have found that estimates of the age of first use do tend to increase upon repeat assessment (i.e. as people age) (Engels et al., 1997; Henry et al., 1994; Labouvie et al., 1997), but not that the order of reporting of initiation changes. Further, background prevalence rates used here do not necessarily map to actual differences in consumer demand, supply and/or attitudes toward drug use.

    There might be differential social stigma and legal practices in each country affecting self-reported drug use. Attempts were made to ensure truthful, honest answers were provided by participants in these surveys in four major ways.

    First, pilot testing in each country was carried out to determine the best way to describe study purposes and auspices in order to maximize willingness to respond honestly and accurately.

    Second, in countries that do not have a tradition of public opinion research, and where the notions of anonymity and confidentiality are unfamiliar, we contacted community leaders in sample sites to explain the study, obtain formal endorsement, and have the leaders announce the study to community members and encourage participation.

    The announcements were most typically made by religious leaders as part of their weekly sermons, although there are other cases, such as the formal community leaders in each neighbourhood in Beijing and Shanghai, where secular community leaders who were given presents by the study organizers made formal announcements and encouraged members of their neighbourhood to participate in the survey.

    Third, interviewers were centrally trained in the use of non-directive probing, a method designed to encourage thoughtful honest responding.

    Finally, especially sensitive questions were asked in a self-report format rather than an interviewer-report format, although this could be done only for respondents who could read. These methods were doubtlessly not completely effective in removing cross-national differences in willingness to report, though, so it is important to recognise the possible existence of remaining differences of this sort in interpreting cross-national differences in results.

    It needs to be noted that the comparisons used in this paper were very conservative for several reasons. The first reason reflects the use of “country” as the unit of comparison. Different countries are comprised of differing ethnic, religious and other social groupings, which are highly likely to affect the prevalence of drug use.

    We were not able to directly control for these groupings in a consistent way across countries. Future research might examine whether some of the differences in the levels of use and possibly in the order of initiation might be related to ethnicity and religious affiliation.

    The second reason reflects the measurement of drug use. We selected any use of a drug as the prior exposure variable when considering the gateway sequence of initiation. It could be argued that we did not use the same criteria as Kandel in her original conceptualization of the “gateway pattern” of drug use initiation; we did examine two versions (which made little difference) – no use of both alcohol and tobacco, and no use of one or the other of these. Future work might examine the relationship between onset of regular use to examine whether the same relationships still hold as observed in the analyses presented here.

    Finally, our conclusions are limited by the fact that we did not measure instrumental variables explicitly, nor were we able to conduct the kinds of analysis required to better examine potential causal effects of preventing the use of drugs “early” in the “gateway” sequence.

    A more focused approach could also be used to study one place and interval of time to measure explicitly a single instrumental variable, such as a change in cigarette taxation rates, to estimate the effects of cigarette use on later substance use. This was examined for the relationship between tobacco use and physical health, using cigarette price as the instrumental variable (Leigh & Schembri, 2004). The next step in this line of research should consequently be to undertake focused analyses.

    Despite these limitations, the present study is the first to describe cross-national associations between substances in the order of initiation of drug use, based on largely comparable sampling strategies and assessment tools. The most notable advantage of the WMHS is that these surveys represents 17 large, nationally representative and regionally diverse samples, and cover a wide range of ages and hence birth cohorts, over a period of changing drug markets and country specific social norms related to drug use.

    4.2 Conclusions

    The present study provided suggestive evidence to suggest that drug use initiation is not constant across contexts and cultures. Although cannabis is most often the first illicit drug used, and its use is typically preceded by tobacco and alcohol use, the variability seen across countries, which is related to the background prevalence of such drug use, provides evidence to suggest that this sequence is not immutable. Violations of this sequence are not associated with the development of dependence; rather, it seems to be the age of onset and degree of exposure to any drugs that are more important predictors.

    Supplementary Material

    01

    Footnotes

    *Supplementary data for this report can be accessed with the online version of this paper at doi:xxx/j.drugalcdep.xxx …

    1Supplementary tables are available with the online version of this paper at doi.xxx/j.drugalcdep.xxx …

    Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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    Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances


    Does cannabis lead to taking other drugs?

    Originally from the ISDD faq (http://www.isdd.co.uk) in 1998. However this information is apparently no longer online (2010) and the cannabis page is now little more than a promotion of the FRANK campaign.
    ______________

    This is the so-called 'escalation' hypothesis. In the mid-80s research from the US revived interest in this idea; specifically it was claimed that cannabis use tends to lead to heroin use, but the arguments are similar for progression to illicit drugs other than heroin.

    Most people who use heroin will have previously used cannabis (though only a small proportion of those who try cannabis go on to use heroin). This could be because cannabis actually does (at least for some people) lead to heroin use, but there are alternative explanations.

    For instance, it could be that heroin and cannabis use are both caused by something else in the individual's personality or background that the researchers have not taken into account. Also the studies suggesting cannabis might lead to heroin have been done in Western societies at a time when cannabis is more freely available than heroin. This could mean people tend to use cannabis first simply because they come across it first.

    Even if cannabis use did lead to heroin use, there would remain the crucial issue of exactly how this happened. The assumption is that if cannabis leads to heroin, then more cannabis use would result in more heroin use - an argument against legalizing cannabis. But the reverse could be the case. For instance, it could be that cannabis use involves people in the buying of illegal drugs, making it more likely that they will meet with an offer of heroin, an offer which some will accept. In this example it would be the illegality of cannabis use rather than cannabis use itself that led most directly to heroin use. The implication is that some heroin use might be prevented by legalizing cannabis, even if this meant more widespread cannabis use.

    This example illustrates the fact that the mechanism of any link between cannabis and heroin may be as important as whether or not such a link exists in the first place.

    All that can be said definitely is that

    1. Cannabis use generally precedes the use of other illegal drugs.

    2. Cannabis use does not necessarily (or even usually) lead to the use of other illicit drugs.

    The unsatisfactory state of affairs with respect to the escalation theory is typical of our knowledge about other ill-effects sometimes said to be caused by cannabis. There is evidence suggesting a number of undesirable consequences of regular use (mental illness, poor motivation, decreased fertility, impaired development in adolescents) but no evidence to either convincingly refute or confirm these suggestions.

    The illegality of cannabis and the fact that most cannabis users do not approach treatment services makes detailed follow-up studies of cannabis users difficult, and laboratory studies cannot duplicate real life situations. Certainly, widespread cannabis use in the UK and other countries has not been accompanied by correspondingly widespread demand for medical, psychological or social help with cannabis-related problems - but it will never be possible to prove that such problems might not materialize in the future or be found if research techniques improved.

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    Is cannabis a stepping-stone for cocaine?

    Abstract

    This paper uses a unique dataset on the inhabitants of Amsterdam, to study the dynamics of the consumption of cannabis and cocaine. People are most likely to start using that drugs at ages 18-20 and 20-25. An analysis of the starting rates shows some evidence of cannabis being a "stepping-stone" for cocaine. However, the fact that some individuals use both cannabis and cocaine has to do mostly with correlation through (unobserved) personal characteristics and not with cannabis causing the use of cocaine.

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    Study Questions Marijuana As Gateway Drug

    A study of drug use among young men suggests that those who used marijuana before trying alcohol or tobacco were about as likely to develop an addiction problem as those who drank or smoked before using marijuana, according to researchers who say the findings run counter to the “gateway” theory underlying much of U.S. drug policy.

    The Pittsburgh Post-Gazette reported Dec. 5 that researchers from the University of Pittsburgh School of Pharmacy found that about a quarter of the 200 young men studied used marijuana before trying alcohol or tobacco. “This is actually quite novel, this idea,” said lead researcher Ralph E. Tarter. “It runs counter to about six decades of current drug policy in the country, where we believe that if we can't stop kids from using marijuana, then they're going to go on and become addicts to hard drugs.”

    Neil Capretto, medical director of the Gateway Rehabilitation Center in Aliquippa, Pa., said some addicted patients' first drug was heroin, not alcohol or marijuana. He said the study “really shows the complex nature of addiction. What they're showing here is what we've been seeing in practice for years.”

    Capretto added that most people who use marijuana never go on to use harder drugs. “If we could push a button and all the marijuana would go away, by no means will that stop the drug problem in this country,” he said.

    The researchers did find, however, that marijuana users tended to have less parental supervision, live in neighborhoods where the drug was easily available, and were more apt to be behaviorally deviant, less involved in school, and to hang out with people that their parents didn't like.

    The study, funded by the National Institute on Drug Abuse, was published in the December 2006 issue of the American Journal of Psychiatry.

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    Study of 4000 indicates marijuana discourages use of hard drugs.

    A ground-breaking study of 4117 marijuana smokers in California1 reveals that the 'Gateway Theory' probably had it backwards. Instead of enticing young people to use other drugs, this study suggests that marijuana may have the opposite effect.

    This first-ever clinical examination of a large number of medical marijuana applicants depicts a population that is remarkably normal. The percentages earning bachelors' degrees and doctorates are nearly identical to the national numbers. They are, in the main, productive citizens with jobs, homes and families who smoke marijuana weekly or daily – and have in some cases for decades.

    For the vast majority of these applicants, their use of cannabis ultimately led to a decrease in the use of tobacco, alcohol, and hard drugs. Asked to compare their current alcohol consumption with their lifetime peak, over 10% claimed to be abstinent and nearly 90% claimed to have cut their drinking in half.

    They also report using cannabis as self medication for stress and anxiety – with fewer side effects than the legal pharmaceutical alternatives.

    As children, a significant percentage of the male applicants had been treated for ADHD (Attention Deficit Hyperactivity Disorder). Today their routine morning use of minimal amounts of cannabis strongly suggests that it enhances their ability to concentrate by allowing them to focus on one problem at a time.

    As one construction company estimator said, "After two hits and my morning coffee, I'm the best estimator in the company."

    Common Sense for Drug Policy
    www.CommonSenseDrugPolicy.org

    www.DrugWarFacts.org

    www.ManagingChronicPain.org

    www.MedicalMJ.org

    www.TreatingDrugAddiction.org
    [email protected]

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    Reassessing the gateway effect


    © 2002 Society for the Study of Addiction to Alcohol and Other Drugs
    Addiction,
    97, 1493–1504
    Blackwell Science, Ltd
    Oxford, UK
    ADDAddiction
    0965-2140© 2002 Society for the Study of Addiction to Alcohol and Other Drugs
    Original Article
    Andrew R. Morral et al.Marijuana gateway effect
    Correspondence to:
    Andrew Morral
    Senior Behavioral Scientist
    Drug Policy Research Center
    1200 South Hayes Street
    Arlington, VA 22202-5050
    USA
    Tel:+1 703 413 1100, ext. 5119
    E-mail: [email protected]
    Submitted 16 October 2001;
    initial review completed 12 April 2002;
    final version accepted 4 June 2002
    FOR DEBATE

    Andrew R. Morral, Daniel F. McCaffrey & Susan M. Paddock

     ABSTRACT

    Aims


    Strong associations between marijuana use and initiation of hard drugs
    are cited in support of the claim that marijuana use
    per se increases youths’ risk of initiating hard drugs (the ‘marijuana gateway’ effect). This report examines whether these associations could instead be explained as the result of a common
    factor—drug use propensity—influencing the probability of both marijuana and other drug use. 


    Design
    A model of adolescent drug use initiation in the United States is constructed
    using parameter estimates derived from US household surveys of drug
    use conducted between 1982 and 1994. Model assumptions include:
    (1) individuals have a non-specific random propensity to use drugs that is normally
    distributed in the population; (2) this propensity is correlated with the risk
    of having an opportunity to use drugs and with the probability of using them
    given an opportunity, and (3) neither use nor opportunity to use marijuana is
    associated with hard drug initiation after conditioning on drug use propensity.


    Findings
    Each of the phenomena used to support claims of a ‘marijuana gateway
    effect’ are reproduced by the model, even though marijuana use has no
    causal influence over hard drug initiation in the model.


    Conclusions
    Marijuana gateway effects may exist. However, our results demonstrate
    that the phenomena used to motivate belief in such an effect are consistent
    with an alternative simple, plausible common-factor model. No gateway
    effect is required to explain them. The common-factor model has implications
    for evaluating marijuana control policies that differ significantly from those
    supported by the gateway model.....read full article (PDF)

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    Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect.

    Source:

    Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, UMR 8600 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, 4, Avenue de l'Observatoire, 75270 Paris Cedex 06, France.

    Abstract

    Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Delta9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism.

     This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Delta9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo [3H]diprenorphine binding to opioid receptors in total mouse brain.

    The repetitive pretreatment during 3 weeks of Delta9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Delta9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm.

     Taken together, these behavioral and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.

    PMID:
    11359533
    [PubMed - indexed for MEDLINE]

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    Marijuana And The Gateway Theory

    Source: NORML Report, NOV 1996

    Since the earliest stages of marijuana prohibition, critics have maintained that one of marijuana's greatest dangers is its potential to be used as a gateway to harder drugs. Currently, this notion serves as one of the key facets of the prohibitionist argument. Ironically, there exists little scientific data to support this theory.

    Depending on society's hard-drug of choice throughout the past century, prohibitionists have consistently branded marijuana as the inevitable gateway. For example, marijuana prohibitionist and one of the chief proponents of the gateway theory, Gabriel Nahas, has claimed: "It appears that the biochemical changes induced by marijuana in the brain result in drug-seeking, drug taking behavior, which in many instances will lead the user to experiment with other pleasurable substances. The risk of progression from marijuana to cocaine to heroin is now well documented."

    According to much of the scientific literature, however, this assessment could not be further from the truth.

    One of the first major studies to debunk the gateway theory was commissioned by New York City Mayor Fiorello La Guardia in 1938. The six year study, conducted by a team of scientists from the New York Academy of Medicine, was the most comprehensive, extensive marijuana fact-finding mission since the Indian Hemp Drug Commission released its monumental approximately 50 years earlier. Released in 1944 as "The LaGuardia Report," the study found that:

    "The use of marijuana does not lead to morphine or heroin or cocaine addiction. ...The instances are extremely rare where the habit of marihuana (sic) smoking is associated with addiction to these narcotics."

    In 1972, President Richard Nixon appointed a panel of politicians and leading addiction scholars to examine federal policy regarding marijuana. The commission, headed by former Pennsylvania governor Raymond P. Schafer, contracted a study of 105 middle class California marijuana smokers to investigate marijuana's alleged gateway potential. According to the commision's findings,

    "With the exception of marihuana (sic) and hashish, no drug was used by more than 25 percent of this population and this use was almost exclusively experimental."

    This led the commission to conclude that,

    "incidence of other drug use was relatively low, [even among] frequent marihuana users."

    Regarding the patterns of use among adolescent marijuana users, the commission stated that,

    "a majority of [high school marijuana users] have used no other illicit drug, and they tend to be experimental or intermittent users of marihuana (sic)."

    The issue of marijuana's purported gateway effect was explored yet again several years later in a federally contracted study for the Center for Studies of Narcotics and Drug Abuse of the National Institute of Mental Health. Directed by Drs. Vera Rubin and Lambros Comitas of the Research Institute for the Study of Man and conducted in Jamaica, the study was hailed as "the first intensive multidiscplinary study of marijuana use to be published." Summarizing the findings of the study in the July 4, 1975 issue of Science Magazine, Dr. Erich Goode of the State university of New York at Stony Brook wrote:

    "One of the more interesting findings to emerge from this study relates to the 'stepping-stone' hypothesis. ... Nothing like that occurs among heavy, chronic ganja smokers of Jamaica. No other drugs were used, aside from aspirin, tea, alcohol, and tobacco. The only hard drug use known on the island is indulged by North American tourists."

    A fourth federally contracted study reaffirmed this conclusion some years later. Conducted by the Institute of Medicine of the National Academy of Sciences (NAS) and released in 1982, the 15-month study analyzed the habits of American marijuana smokers and offered one of the most comprehensive and balanced analyses ever compiled regarding marijuana and its effects. In regards to marijuana's gateway potential, the study concluded that, "There is no evidence to support the belief that the use of one drug will inevitably lead to the use of any other drug."

    Although never fully laid to rest, the much maligned gateway theory returned to prominence in the early 1990s driven by statements made by the Center on Addiction and Substance Abuse (CASA) and it's head Joseph Califano. Armed with statistics from the 1991 National Household Survey on Drug Abuse, CASA announced that marijuana users are 85 times more likely than non-marijuana users to try cocaine.

    However, as pointed out by NORML board members Drs. John P. Morgan and Lynn Zimmer, this figure is close to meaningless. It was calculated by dividing the proportion of adolescent marijuana users who have ever used cocaine by the proportion of cocaine users who have never used marijuana. The high risk factor is a product not of the fact that so many marijuana users use cocaine, but that so many cocaine users used marijuana previously.

    "It is hardly a revelation that people who use one of the least popular drugs are likely to use the more popular ones -- not only marijuana, but also alcohol," noted Morgan.

    Perhaps more damning than any other indictment of the "gateway" hypothesis is that it fails to hold up in the face of the federal government's own statistics regarding drug use. For example, as marijuana use increased in the 1960s and 1970s, heroin use declined; while cocaine use was increasing in the early 1980s, marijuana use was declining. Over the past 20 years, marijuana use rates have fluctuated dramatically while the use of hallucinogens has hardly changed at all.

    Most importantly, federal statistics indicate that although nearly 66 million Americans over age 12 have experimented with marijuana at some point in their lifetime, less than one-third of them have ever tried cocaine. Moreover, less than 16 million Americans admit to having ever experimented with LSD, less than 7 million have ever tried methamphetamines, and only 2.5 million have ever graduated to heroin. In sum, federal statistics conclude that the overwhelming majority of American marijuana users do not move on to harder drugs.

    It is worth noting that many scientists and physicians within our own government now dismiss the validity of the "gateway theory." For example, the 1995 guidebook: Marijuana: Facts for Teens, published by the U.S. Department of Health and Human Services (HHS), states unequivocally that, "Most marijuana users do not go on to use other drugs."

    In addition, similar 1996 literature from the HHS reasons that the minority of marijuana users who do graduate to harder drugs do so not because of marijuana use, but because of marijuana prohibition. "Using marijuana puts children and teens in contact with people who are users and sellers of other drugs," states Marijuana: What Parents Need to Know. "So there is more of a chance for a marijuana user to be exposed and urged to try more drugs."

    Further support for this theory is provided by the Netherlands where marijuana is allowed to be purchased openly in government-regulated "coffee shops" designed specifically to separate young marijuana users from illegal markets where harder drugs are sold. As a result, just 1.8 percent of Dutch youth report having tried cocaine and 75 percent of adult cannabis users do not report other drug use.

    Consequently, it seems that when the cannabis markets are effectively separated from the harder drugs, marijuana is clearly a "terminus" rather than a gateway drug.

    Although the gateway theory still remains a staple in prohibitionist rhetoric, the facts indicate it to be a blatant falsehood. Moreover, any correlation between marijuana use and hard drug use can be linked to federal policies that place marijuana in the same underground markets as hard drugs like cocaine and heroin. Consequently, politicians who voice concern about marijuana being a possible gateway to harder drugs should review the facts and support policies that would effectively separate marijuana from the black market.

    CITATIONS

    1 Nahas, G. Keep Off the Grass. Paul S. Eriksson, Middlebury, Vermont, 1985.

    2 The Marihuana Problem in the City of New York: Sociological, Medical, Psychological, and Pharmacological Studies by the Mayors Committee on Marihuana. The Jaques Cattell Press, Lancaster, Pennsylvania, 1944, p. 25.

    3 Ibid., p. 13.

    4 Marihuana: A Signal of Misunderstanding: First Report of the National Commission on Marihuana and Drug Abuse. U.S. Government Printing Office, Washington, D.C., 1972, pps. 45-46.

    5 Sullivan, Walter. "Marijuana Study by U.S. Finds No Serious Harm." New York Times: July 5, 1975.

    6 Goode, Erich. "Effects of Cannabis in Another Culture." Science Magazine: July 1975, pp. 41-42.

    7 Marijuana and Health: Report of a Study by a Committee of the Institute of Medicine. National Academy Press, Washington, D.C., 1982, p. 47.

    8 Drs. Morgan, John and Zimmer, Lynn. "The Myth of Marijuana's Gateway Effect." NORML's Active Resistance, Spring 1995, p. 9.

    9 Ibid.

    10 Drs. Morgan, John and Zimmer, Lynn. Exposing Marijuana Myths: A Review of the Scientific Evidence. Open Society Institute, New York City, 1995, p. 14.

    11 Preliminary Estimates from the 1995 Household Survey on Drug Abuse. U.S. Department of Health and Human Services. Washington, D.C. August 1996, p. 56.

    12 Marijuana: Facts for Teens. U.S. Department of Health and Human Services. Washington, D.C. 1995, p. 10.

    13 Marijuana: What Parents Need to Know. U.S. Department of Health and Human Services. Washington, D.C. 1995, p. 11.

    14 Drs. Morgan, John and Zimmer, Lynn. Exposing Marijuana Myths: A Review of the Scientific Evidence.

    15 Cohen, Peter, et al. Cannabis Use, A Stepping Stone to Other Drugs? 1996.

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    Endogenous cannabinoids are not involved in cocaine reinforcement

    oi:10.1016/j.euroneuro.2004.04.003 | Copyright © 2004 Elsevier B.V. and ECNP. All rights reserved.  

      Permissions & Reprints

     

    Heidi M. B. Lesscher, Emily Hoogveld, J. Peter H. Burbach, Jan M. van Ree and Mirjam A. F. M. GerritsCorresponding Author Contact Information, E-mail The Corresponding Author

    Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Stratenum, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands

    Received 27 January 2004; 
    accepted 6 April 2004. 
    Available online 15 June 2004.

    Abstract

    The endogenous cannabinoid system is a relatively novel discovered system consisting of cannabinoid CB1 receptors, which are expressed both in the periphery and in the central nervous system, peripheral cannabinoid CB2 receptors and endogenous cannabinoids, which are anandamide and 2-arachidonyl glycerol.

    The cannabinoid CB1 receptors have recently been implicated in rewarding aspects of not only the cannabinoid drug Δ9-tetrahydrocannabinol (Δ9-THC), but also of other drugs of abuse, including cocaine. The present study was designed to further investigate the role of CB1 receptors in reward-related effects of cocaine. Using the CB1 receptor selective antagonist SR141716A, the involvement of CB1 receptors in cocaine reinforcement was determined by intravenous cocaine self-administration.

    In addition, the effects of the CB1 receptor selective antagonist SR141716A upon the development of cocaine-induced behavioural sensitization were investigated.

    SR141716A did not affect cocaine reinforcement nor did it affect the development of behavioural sensitization to the locomotor stimulant effects of cocaine. These findings suggest that CB1 receptors are not involved in acute cocaine reinforcement nor in cocaine-induced behavioural sensitization.

    Author Keywords: Addiction; Mice; Behaviour; Cannabinoid; Cocaine

    Article Outline

    1. Introduction
    2. Experimental procedures
    2.1. Animals
    2.2. Effects of SR141716A upon intravenous cocaine self-administration
    2.3. Effects of SR141716A upon cocaine-induced behavioural sensitization
    2.4. Statistical analysis
    3. Results
    3.1. Effects of SR141716A upon intravenous cocaine self-administration
    3.2. Effects of SR141716A upon cocaine-induced behavioural sensitization
    4. Discussion
    Acknowledgements
    References
    European Neuropsychopharmacology
    Volume 15, Issue 1, January 2005, Pages 31-37
     


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    No 'Smoking' Gun: Research Indicates Teen Marijuana Use Does Not Predict Drug, Alcohol Abuse

    ScienceDaily (Dec. 4, 2006) — Marijuana is not a "gateway" drug that predicts or eventually leads to substance abuse, suggests a 12-year University of Pittsburgh study. Moreover, the study's findings call into question the long-held belief that has shaped prevention efforts and governmental policy for six decades and caused many a parent to panic upon discovering a bag of pot in their child's bedroom.



    The Pitt researchers tracked 214 boys beginning at ages 10-12, all of whom eventually used either legal or illegal drugs. When the boys reached age 22, they were categorized into three groups: those who used only alcohol or tobacco, those who started with alcohol and tobacco and then used marijuana (gateway sequence) and those who used marijuana prior to alcohol or tobacco (reverse sequence).

    Nearly a quarter of the study population who used both legal and illegal drugs at some point -- 28 boys -- exhibited the reverse pattern of using marijuana prior to alcohol or tobacco, and those individuals were no more likely to develop a substance use disorder than those who followed the traditional succession of alcohol and tobacco before illegal drugs, according to the study, which appears in this month's issue of the American Journal of Psychiatry.

    "The gateway progression may be the most common pattern, but it's certainly not the only order of drug use," said Ralph E. Tarter, Ph.D., professor of pharmaceutical sciences at the University of Pittsburgh School of Pharmacy and lead author of the study. "In fact, the reverse pattern is just as accurate for predicting who might be at risk for developing a drug dependence disorder."

    In addition to determining whether the gateway hypothesis was a better predictor of substance abuse than competing theories, the investigators sought to identify characteristics that distinguished users in the gateway sequence from those who took the reverse path. Out of the 35 variables they examined, only three emerged to be differentiating factors: Reverse pattern users were more likely to have lived in poor physical neighborhood environments, had more exposure to drugs in their neighborhoods and had less parental involvement as young children. Most importantly, a general inclination for deviance from sanctioned behaviors, which can become evident early in childhood, was strongly associated with all illicit drug use, whether it came in the gateway sequence, or the reverse.

    While the gateway theory posits that each type of drug is associated with certain specific risk factors that cause the use of subsequent drugs, such as cigarettes or alcohol leading to marijuana, this study's findings indicate that environmental aspects have stronger influence on which type of substance is used. That is, if it's easier for a teen to get his hands on marijuana than beer, then he'll be more likely to smoke pot. This evidence supports what's known as the common liability model, an emerging theory that states the likelihood that someone will transition to the use of illegal drugs is determined not by the preceding use of a particular drug but instead by the user's individual tendencies and environmental circumstances.

    "The emphasis on the drugs themselves, rather than other, more important factors that shape a person's behavior, has been detrimental to drug policy and prevention programs," Dr. Tarter said. "To become more effective in our efforts to fight drug abuse, we should devote more attention to interventions that address these issues, particularly to parenting skills that shape the child's behavior as well as peer and neighborhood environments."

    Indeed, according to the study, interventions focusing on behavior modification may be more effective prevention tactics than current anti-drug initiatives. For example, providing guidance to parents -- particularly those in high-risk neighborhoods -- on how to boost their caregiving skills and foster bonding with their children, could have a measurable effect on a child's likelihood to smoke marijuana. Also, early identification of children who exhibit antisocial tendencies could allow for interventions before drug use even begins.

    Although this research has significant implications for drug abuse prevention approaches, Dr. Tarter notes that the study has some limitations. First, as only male behaviors were studied, further investigation should explore if the results apply to women as well. Also, the examination of behaviors in phases beyond alcohol and marijuana consumption in the gateway series will be necessary.

    Other study authors include Michael Vanyukov, Ph.D., and Maureen Reynolds, Ph.D., and Levent Kirisci, Ph.D., also of the University of Pittsburgh School of Pharmacy; and Duncan Clark, M.D., Ph.D., of the University of Pittsburgh School of Medicine. The research was funded by the National Institute on Drug Abuse.

     

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    CLAIM #13: MARIJUANA IS A "GATEWAY" TO THE USE OF OTHER DRUGS

    Advocates of marijuana prohibition claim that even if marijuana itself causes minimal harm, it is a dangerous substance because it leads to the use of "harder drugs" such as heroin, LSD, and cocaine.

    THE FACTS

    Most users of heroin, LSD and cocaine have used marijuana. However, most marijuana users never use another illegal drug.

    Over time, there has been no consistent relationship between the use patterns of various drugs. 

    As marijuana use increased in the 1960s and 1970s, heroin use declined. And, when marijuana use declined in the 1980s, heroin use remained fairly stable.

    For the past 20 years, as marijuana use-rates fluctuated, the use of LSD hardly changed at all.

    Cocaine use increased in the early 1980s as marijuana use was declining. During the late 1980s, both marijuana and cocaine declined. During the last few years, cocaine use has continued to decline as marijuana use has increased slightly.

    In 1994, less than 16% of high school seniors who had ever tried marijuana had ever tried cocaine - the lowest percentage ever recorded. In fact, as shown below, the proportion of marijuana users trying cocaine has declined steadily since 1986, when a high of more than 33% was recorded.

     


    Proportion of Marijuana Users Ever Trying Cocaine

    High School Seniors, 1975-1994 

    1975: 19%	1980: 27%	1985: 31%	1990: 22%
    1976: 19% 1981: 28% 1986: 33% 1991: 22%
    1977: 20% 1982: 27% 1987: 30% 1992: 18%
    1978: 22% 1983: 28% 1988: 26% 1993: 17%
    1979: 25% 1984: 29% 1989: 23% 1994: 16%

     


    In short, there is no inevitable relationship between the use of marijuana and other drugs. This fact is supported by data from other countries. In the Netherlands, for example, although marijuana prevalence among young people increased during the past decade, cocaine use decreased - and remains considerably lower than in the United States. Whereas approximately 16% of youthful marijuana users in the U.S. have tried cocaine, the comparable figure for Dutch youth is 1.8 percent. Indeed, the Dutch policy of allowing marijuana to be purchased openly in government-regulated "coffee shops" was designed specifically to separate young marijuana users from illegal markets where heroin and cocaine are sold.

     

     

     

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    Gateway To Nowhere? The Evidence That Pot Doesn't Lead To Heroin

    Ryan Grim, Slate , 21st July 2006

    Earlier this month, professor Yasmin Hurd of the Mount Sinai School of Medicine released a study showing that rats exposed to the main ingredient in marijuana during their adolescence showed a greater sensitivity to heroin as adults. The wire lit up with articles announcing confirmation for the "gateway theory" — the claim that marijuana use leads to harder drugs.

    It's a theory that has long seemed to make intuitive sense, but remained unproven. The federal government's last National Survey on Drug Use and Health, conducted in 2004, counted about 97 million Americans who have tried marijuana, compared to 3 million who have tried heroin (166,000 had used it in the previous month).

    That's not much of a rush through the gateway. And a number of studies have demonstrated that your chances of becoming an addict are higher if addiction runs in your family, or if heroin is readily available in your community, or if you're a risk-taker. These factors can account for the total number of heroin addicts, which could make the gateway theory superfluous.

    On close inspection, Hurd's research, published in the journal Neuropsychopharmacology, doesn't show otherwise. For the most part, it's a blow to the gateway theory. To be sure, Hurd found that rats who got high on pot as adolescents used more heroin once they were addicted. But she found no evidence that they were more likely to become addicted than the rats in the control group who'd never been exposed to delta-9-tetrahydrocannabinol, or THC, marijuana's main ingredient.

    Hurd began with two groups of rats. The first was administered THC every three days during their early adolescence (beginning at 28 days old) to approximate the sporadic marijuana use of American teens. The second group was given no drugs.

    Then, at mid-adolescence (56 days), both groups began a heroin regime. Hurd started by giving the rats a low dose of the harder drug. None of them got hooked. So, she doubled the fix. Each cage was equipped with an active and an inactive bar. Depressing the active bar when a white light was on gave the rats a hit of heroin; if they hit the bar regularly, that indicated addiction. Rats in both groups hit the active bar at least twice as often as they did the inactive one, which means they became addicted at roughly the same rate.

    The difference between the groups came post-addiction: For the first 15 heroin sessions, both sets used generally equal amounts of heroin. Then the control rats leveled off. But the pot rats kept taking more of the drug, leveling off at about a 25 percent higher dosage. This increased use was evidence of their greater sensitivity to heroin.

    Hurd says that because the marijuana-exposed rats demonstrated this heightened sensitivity, she expected them to be more motivated in pursuing the drug. But they weren't. The control rats paced their cages and repeatedly pressed the active bars even when the light indicating availability wasn't on. The pot rats, on the other hand, figured out that the heroin was available only at certain times, and that pacing and tapping the bar incessantly wasn't worth the trouble. When heroin was available, the marijuana rats took more of it. But when it wasn't, they chilled in the corner.

    Extrapolate the study to human behavior, Hurd says, and it suggests that teenagers who smoke pot are no more likely than other kids to become addicted to heroin. (Her study doesn't speak to whether they'd be more likely to try the drug.) If teens do get hooked on the hard drug, though, they may develop a stronger addiction.

    Hurd's results come on the heels of another marijuana finding that's not what the drug's opponents want to hear. Donald Tashkin, a UCLA medical with funding from the NIH's National Institute on Drug Abuse, looked at more than 1,200 people with cancers typically associated with cigarette smoking and a control group of more than 1,000 people without cancer. To his surprise, he found no link between marijuana and increased risk of cancer, even among the heaviest pot smokers. The results of Tashkin's study, the largest of its kind that's been done, will soon appear in the journal Cancer Epidemiology Biomarker and Prevention.

    There are a couple of plausible explanations for Tashkin's finding. Research finds that smoking less than a pack of cigarettes a day leads to only a slightly higher cancer risk than not smoking at all. It's two packs a day that triggers a much higher risk. Two packs is the equivalent of 10 joints—more marijuana than almost anyone smokes. Tashkin speculates that the risk threshold for pot might be too high to measure in the United States. "One would have to repeat the study in a society such as Jamaica," he says.

    Another possibility, according to Tashkin, is that marijuana's cancer-fighting elements and its carcinogens counteract each other. Animal studies have shown that THC has an inhibitory effect on a number of cancers. Marijuana also contains dozens of active cannabinoids, several of which have been shown to block cancer cell growth.

    Tashkin's findings do not mean that marijuana is harmless. In previous work, he has shown that pot smoke leads to chronic and acute bronchitis at the same elevated rate as tobacco smoke. He is currently studying the drug's relationship to pneumonia. But his latest results about cancer risk, like Hurd's on the gateway theory, make pot seem more rather than less benign. The federal government has announced the results of Tashkin's past studies with press conferences and subway ads. Don't look for any this time around.

     

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    Cannabis use when it's legal

    Jan C. Van Ours
    Tilburg University - Department of Economics; Institute for the Study of Labor (IZA); Centre for Economic Policy Research (CEPR)


    January 2005

    CentER Discussion Paper No. 2005-12

    Abstract:     
    This paper uses information about prime age individuals living in Amsterdam, to study whether the use of alcohol, or tobacco stimulates the use of cannabis, i.e., whether alcohol or cannabis are stepping stones for cannabis. The special element of the study is that it concerns the use in an environment where not only alcohol and tobacco but also cannabis is a legal drug. It turns out that alcohol and cannabis are intertemporal substitutes, while tobacco and cannabis are intertemporal complements. Only tobacco is a stepping stone for cannabis use.

     

    Number of Pages in PDF File: 32

    Keywords: Alcohol, tobacco, cannabis, stepping stone

    JEL Classifications: C41, D12, I19

    Working Paper Series

    Date posted: February 21, 2005  

    Contact Information

    Jan C. Van Ours (Contact Author)
    Tilburg University - Department of Economics ( email )
    P.O. Box 90153
    Tilburg 5000 LE
    Netherlands
    +31 13 466 2880 (Phone)
    +31 13 466 3042 (Fax)
     
    Institute for the Study of Labor (IZA)
    P.O. Box 7240
    Bonn D-53072
    Germany
     
    Centre for Economic Policy Research (CEPR)
    77 Bastwick Street
    London EC1V 3PZ
    United Kingdom
     
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    The Myth of Marijuana's Gateway Effect

    by John P. Morgan, M.D. and Lynn Zimmer, Ph.D.


    The Partnership for a Drug-Free America, in cooperation with the National Institute on Drug Abuse (NIDA) and the White House Office of Drug Control Policy, recently announced a new anti-drug campaign that specifically targets marijuana. Instead of featuring horror tales of marijuana-induced insanity, violence and birth detects, this campaign is built upon the premise that reducing marijuana use is a practical strategy for reducing the use of more dangerous drugs.

    The primary basis for this "gateway hypothesis" is a recent report by the center on Addiction and Substance Abuse (CASA), claiming that marijuana users are 85 times more likely than non-marijuana users to try cocaine. This figure, using data from NIDA's 1991 National Household Survey on Drug Abuse, is close to being meaningless. It was calculated by dividing the proportion of marijuana users who have ever used cocaine (17%) by the proportion of cocaine users who have never used marijuana (.2%). The high risk-factor obtained is a product not of the fact that so many marijuana users use cocaine but that so many cocaine users used marijuana previously.

    It is hardly a revelation that people who use one of the least popular drugs are likely to use the more popular ones -- not only marijuana, but also alcohol and tobacco cigarettes. The obvious statistic not publicized by CASA is that most marijuana users -- 83 percent -- never use cocaine. Indeed, for the nearly 70 million Americans who have tried marijuana, it is clearly a "terminus" rather than a "gateway" drug.

    During the last few years, after a decade of decline, there has been a slight increase in marijuana use, particularly among youth. In 1994, 38 percent of high school seniors reported having ever tried the drug, compared to about 35 percent in 1993 and 33 percent in 1992. This increase does not constitute a crisis. No one knows whether marijuana use-rates will continue to rise. But even if they do, it will not necessarily lead to increased use of cocaine.

    Since the 1970s, when NIDA first began gathering data, rates of marijuana and cocaine use have displayed divergent patterns. Marijuana prevalence increased throughout the 1970s, peaking in 1979, when about 60 percent of high school seniors reported having used it at least once. During the 1980s, cocaine use increased while marijuana use was declining. Since 1991, when data for the CASA analysis were gathered, marijuana use-rates have increased while cocaine use-rates have remained fairly steady.

    The over-changing nature of the statistical relationship between use-rate for marijuana and cocaine indicates the absence of a causal link between the use of these two drugs. Therefore, even if the proposed Partnership campaign were to be effective in reducing marijuana use it would not guarantee a proportional reduction in the number of people who use cocaine. To the extent anti-drug campaigns are effective, they seem to be most effective in deterring those people who would have been fairly low-level users. There is no reason to believe that anti-marijuana messages of any sort would deter many of those marijuana users -- currently 17 percent of the total -- who also develop an interest in cocaine.

    Nor is there reason to believe that the Partnership's new campaign will actually reduce the overall number of marijuana users. For a decade now, American youth have been subjected to an unparalleled assault of anti-drug messages. They have seen hundreds of Partnership advertisements, on television and in the print media. They have been urged to "just say no" by rock stars, sports heroes, presidents and first-ladies. They have been exposed to anti-drug educational programs in the schools. Yet this is the same generation of young people that recently began increasing its use of marijuana. It seems unlikely that many of them will be deterred by hyperbolic claims of marijuana's gateway effect, particularly when it contradicts the reality of drug use they see around them.

    If the creators of American drug policy are truly interested in reducing the risk of marijuana users using other drugs, they should take a closer look at Holland, where drug policy since the 1970s has been guided by a commitment to diminishing any potential gateway effect. Wanting to keep young marijuana users away from cocaine and other "hard drugs," the Dutch decided to separate the retail markets by allowing anyone 18 years of age or older to purchase marijuana openly in government-controlled "coffee shops" which strictly prohibit the use and sale of other drugs.

    Despite easy availability, marijuana prevalence among 12 to 18 year olds in Holland is only 13.6 percent -- well below the 38 percent use-rate for American high school seniors. More Dutch teenagers use marijuana now than in the past; indeed, lifetime prevalence increased nearly three-fold between 1984 and 1992, from

    4.8 to 13.6 percent. However, Dutch officials consider their policy a success because the increase in marijuana use has not been accompanied by an increase in the use of other drugs. For the last decade, the rate of cocaine use among Dutch youth has remained stable, with about .3 percent of 12-18 year olds reporting having used it in the past month.

    In the United States, the claim that marijuana acts as a gateway to the use of other drugs serves mainly as a rhetorical tool for frightening Americans into believing that winning the war against heroin and cocaine requires waging & battle against the casual use of marijuana. Not only is the claim intellectually indefensible, but the battle is wasteful of resources and fated to failure.

    Received by Iowa NORML from the National Organization for the Reform of Marijuana Laws (NORML), 1001 Connecticut Avenue, N.W., Suite 1010, Washington, D.C. 20036, on Tuesday, February 7, 1995. For more information, call Allen St. Pierre, NORML Assistant Director, at (202) 483-5500, or e-mail NORML at [email protected]

     

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    Twin study fails to prove 'gateway' hypothesis

    by Dr Andrew Byrne

    Original paper

    Dear Colleagues,

    Twin studies can be informative in causation theories. These authors state that in addition to having close or identical genetic make-up: ".. twin pairs, having been reared in the same household, would be expected to be highly concordant for environmental experiences." Thus most twins are exposed to alcohol, tobacco and other drugs at much the same age.

    In their lead item in JAMA, Lynskey et al. find that for the exceptional minority of twin pairs (~300 out of 4000) in whom 'cannabis use before age 17' was discordant, that subsequent reported drug abuse/dependency was 2 to 5 times more prevalent in the early cannabis users. The authors find that this association lends weight to causation while admitting it is 'not possible to draw strong causal conclusions' of the 'gateway' theory. It is intriguing that they would address causation when this is a retrospective, cross-sectional study, a design which is not able to determine causation.

    Since twins who used cannabis in the same year were eliminated, conclusions based on their similarities of upbringing must be guarded. These twins demonstrated at least one major difference in their environment and/or decision making on at least one occasion during adolescence. Whatever caused this may also explain the higher reported rates of other drug use, quite independent of any theoretical 'chemical priming' or 'gateway' effect.

    These results are all derived single follow-up telephone interviews with an unknown party over matters relating to illegal drug use, child sex abuse and other personal issues up to 15 years earlier. Some may have chosen to (falsely) deny childhood cannabis use and then to also deny adult abuse or dependency. Others may have had faulty recollection for such distant events, making the findings less secure.

    A certain minority of young people use hard drugs prior to using cannabis (around 1 - 2% from household surveys). Such subjects should be of considerable interest to those addressing the so-called 'gateway' theory. Lynskey et al. however, having found that up to 17 of their subjects used hard drugs before being exposed to cannabis, chose to exclude them from their study.

    Another problem with this study is that the drug abuse/dependence findings are so high that they may indicate an atypical sample. For 'any illicit drug abuse/dependence' the prevalence was 33-48%; for 'alcohol dependence' it was 30-43% ['non cannabis by age 17' group first percentage followed by 'early users group' %]. Alcoholism is only thought to affect around 5% of adult males in the general population.

    The authors state that their findings "..were consistent with early cannabis use having a causal role as a risk factor for other drug use and for any drug abuse or dependence." But further, they state: "While the findings of this study indicate that early cannabis use is associated with increased risks of progression to other illicit drug use and drug abuse/dependence, it is not possible to draw strong causal conclusions solely on the basis of the associations shown in this study." A 'causal' link between early cannabis use and later hard drug use remains unlikely on balance (National Academy of Science review) - and it is hard to imagine that a study of this nature could clarify the issue, no matter how well it was performed and analysed.

    An associated editorial by Kandel teases some of the matters out while still seeming to assume that all cannabis use is problematic and needs to be discouraged by any effective means. Her own work from 19 years ago showed the strong association between alcohol/tobacco and illicit drug use.

    Kandel indicates three factors necessary to prove the gateway hypothesis: (1) sequencing, (2) association and (3) causation. As she points out, the third is the hardest to prove.

    In discussing the modern calls for prescribed cannabis, Kandel states that there is no empirical knowledge on whether medical cannabis will lead to problems. But cannabis products were widely prescribed in the first half of the 20th century without apparent problems arising (eg. tincture of cannabis). She says that it is a 'curious phenomenon' that morphine used for medical purposes 'does not lead to addiction'. Could it be equally 'curious' that medical cannabis does not do so either?

    And unlike Lynskey et al., Kandel does not address the known non- chemical associations between cannabis and hard drug use. Having found from personal experience that drug education about cannabis was unreliable, young people may then reason that information about heroin and cocaine being dangerous is also unreliable. Similarly, having broken the law on cannabis, they may then have less compunction about breaking laws relating to other drugs. There is at least anecdotal evidence that some heroin addicts first used heroin when their dealer could not supply cannabis, amphetamine or other drugs of current choice. To his credit, Lynskey writes: ".. access to cannabis use may provide individuals with access to other drugs as they come into contact with drug dealers. ... [Dutch decriminalization of cannabis] may have been partially successful as rates of cocaine use among those who have used cannabis are lower in the Netherlands than in the United States." [One wonders what criteria the authors would need for 'complete' success of Dutch cannabis policy!]

    Citations: Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PAF, Nelson EC, Statham DJ, Martin NG. Escalation of Drug Use in Early-Onset Cannabis Users vs Co-twin Controls. JAMA (2003) 289:427-433

    Kandel DB. Does Marijuana Use Cause the Use of Other Drugs? JAMA (2003) 289; 4: Editorial

     

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    The Surprising Effect Of Marijuana On Morphine Dependence

    Posted on: Monday, 6 July 2009, 11:33 CDT

    Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth. This has been shown by a study carried out by Valérie Daugé and her team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / INSERM) in the journal Neuropsychopharmacology. The findings could lead to therapeutic alternatives to existing substitution treatments.

    In order to study psychiatric disorders, neurobiologists use animal models, especially maternal deprivation models. Depriving rats of their mothers for several hours a day after their birth leads to a lack of care and to early stress. The lack of care, which takes place during a period of intense neuronal development, is liable to cause lasting brain dysfunction. Valérie Daugé's team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / Inserm) analyzed the effects of maternal deprivation combined with injections of tetrahydrocannabinol, or THC, the main active principle in cannabis, on behavior with regard to opiates.

    Previously, Daugé and her colleagues had shown that rats deprived of their mothers at birth become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent

    . In addition, there is a correlation between such behavioral disturbances linked to dependence, and hypoactivity of the enkephalinergic system, the endogenous opioid system.

    To these rats, placed under stress from birth, the researchers intermittently administered increasingly high doses of THC (5 or 10 mg/kg) during the period corresponding to their adolescence (between 35 and 48 days after birth). By measuring their consumption of morphine in adulthood, they observed that, unlike results previously obtained, the rats no longer developed typical morphine-dependent behavior. Moreover, biochemical and molecular biological data corroborate these findings. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC.

    Such animal models are validated for understanding the neurobiological and behavioral effects of postnatal conditions in humans. In this context, the findings point to the development of new treatments that could relieve withdrawal effects and suppress drug dependence.

    The enkephalinergic system produces endogenous enkephalins, which are neurotransmitters that bind to the same receptors as opiates and inhibit pain messages to the brain.

     

     

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    Active Ingredient In Cannabis Eliminates Morphine Dependence In Rats

    ScienceDaily (July 15, 2009) — Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth.  The findings could lead to therapeutic alternatives to existing substitution treatments


    .

    Cannabis plant. Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth. (Credit: iStockphoto/Guillermo Perales)

    In order to study psychiatric disorders, neurobiologists use animal models, especially maternal deprivation models. Depriving rats of their mothers for several hours a day after their birth leads to a lack of care and to early stress. The lack of care, which takes place during a period of intense neuronal development, is liable to cause lasting brain dysfunction.

    The study was carried out by Valérie Daugé and her team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / INSERM).

    Valérie Daugé's team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / Inserm) analyzed the effects of maternal deprivation combined with injections of tetrahydrocannabinol, or THC, the main active principle in cannabis, on behavior with regard to opiates.

    Previously, Daugé and her colleagues had shown that rats deprived of their mothers at birth become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent. In addition, there is a correlation between such behavioral disturbances linked to dependence, and hypoactivity of the enkephalinergic system, the endogenous opioid system.

    To these rats, placed under stress from birth, the researchers intermittently administered increasingly high doses of THC (5 or 10 mg/kg) during the period corresponding to their adolescence (between 35 and 48 days after birth). By measuring their consumption of morphine in adulthood, they observed that, unlike results previously obtained, the rats no longer developed typical morphine-dependent behavior. Moreover, biochemical and molecular biological data corroborate these findings. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC.

    Such animal models are validated for understanding the neurobiological and behavioral effects of postnatal conditions in humans. In this context, the findings point to the development of new treatments that could relieve withdrawal effects and suppress drug dependence.

    The enkephalinergic system produces endogenous enkephalins, which are neurotransmitters that bind to the same receptors as opiates and inhibit pain messages to the brain.



    Story Source:

    The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by CNRS (Délégation Paris Michel-Ange).

    Journal Reference:

    1. Morel et al. Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats. Neuropsychopharmacology, 2009; DOI: 10.1038/npp.2009.70

    Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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    Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats

    Original Article

    Neuropsychopharmacology (2009) 34, 2469–2476; doi:10.1038/npp.2009.70; published online 24 June 2009

     

    Lydie J Morel, Bruno Giros and Valérie Daugé

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
    2. Centre National de la Recherche Scientifique (CNRS), UMR 7224, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
    3. UMPC Université Paris 06, 9 quai Saint Bernard, Paris, Ile de France, France
    4. Department of Psychiatry, Douglas Hospital Research Center, McGill University, boulevard Lasalle, Verdun, QC, Canada
    5. Université Paris Descartes, 12 rue de l’Ecole de médecine, Paris, Ile de France, France

    Correspondence: Dr V Daugé, Physiopathologie des maladies du système nerveux central, INSERM UMRs 952, Université Pierre et Marie Curie, 9 quai St-Bernard, Paris, ile de france, 75005, France, Tel: 331 44 27 61 09, E-mail: [email protected]

    Received 16 April 2009; Revised 19 May 2009; Accepted 21 May 2009; Published online 24 June 2009.

    Abstract

    Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated.

    Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35–49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and μ-opioid receptors were quantified in the striatum and the mesencephalon.

    Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate–putamen nucleus, without any modification for preference to oral morphine consumption.

    In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and μ-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.

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    Cannabis Use - A Gateway to other Drugs? The Case of Amsterdam

    Peter COHEN & Arjan SAS

     Cannabis use, a stepping stone to other drugs?
    The case of Amsterdam

    Arjan Sas
    Does smoking reefer lead to using other drugs, in daily practice usually described as cocaine and heroin? Raising the possibility that the answer to this question might be affirmative, is known as the stepping stone hypothesis. Recently this hypothesis has been raised again in slightly other terms: cannabis use as a “gateway” to other allegedly more dangerous drugs. Gabriel Nahas summarizes the evidence in support of the theory which connects marijuana use to other drug use in the preface to 1990’s 5th edition of Keep Off the Grass:

    “It appears that the biochemical changes induced by marijuana in the brain result in a drug-seeking, drug taking behavior, which in many instances will lead the user to
    experiment with other pleasurable substances. The risk of progressing from marijuana to cocaine or heroin is now well documented”


    In this article we will investigate the adequacy of the stepping stone hypothesis for Amsterdam, in population that has been relatively free to try and use cannabis for at least 20 years. The method used is different from the one chosen by Kandel et al. (Denise B. Kandel et al. 1992, 1993, 1995). Kandel’s database is a sample from students in New York State in schools from grade 10 and 11, which she has
    followed from 1971 to 1990. In another study she reports data from a student survey in the same area, grades 7 to 12 in 1988. She clearly finds temporal patterns in drug use, although she remarks that “the notion of stages in drug behavior does not imply that these stages are either obligatory or universal....”
    (Kandel et al., 1992, 453). Entry into a particular stage is a common and perhaps even necessary, although not a sufficient prerequisite for entry into the next higher stage. (Kandel et al., 1992, 454). In this article we will confirm her conclusions with a high level of detail. We show evidence that a large majority of cannabis users in Amsterdam do not enter the next higher stage and that for those who do, current or frequent drug use other than cannabis is very rare....please visit here for free pdf for conclusion to this study

     

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