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

Source: Wiley Online Library

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.

Links

Source: RedOrbit

By Maia Szalavitz

 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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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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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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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
info@csdp.org

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© 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: morral@rand.org
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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PMID:

11359533

[PubMed - indexed for MEDLINE]

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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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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. Gerrits, 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   Top      Home

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.

 

 

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.

 

 

 

 

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.

 

 

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   Top      Home

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 natlnorml@aol.com

 

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

 

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.

 

 

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

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