Gateway drug effect

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The gateway drug effect (alternatively, stepping-stone theory, escalation hypothesis, or progression hypothesis) is a comprehensive catchphrase for the often observed effect that the use of a psychoactive substance is coupled to an increased probability of the use of further substances. Possible reasons for the connection include environmental influence, impulsive people seeking both soft and hard drugs (meaning people who use one drug are likely to use another drug due to personality and that it's not the initial drug that leads to the use of another drug), [1] alterations in the brain due to earlier substance exposure, as well as similar attitudes of people who use different substances, and therefore experience a "common liability to addiction". [2] In 2020, the National Institute on Drug Abuse released a research report which supported allegations that marijuana is a "gateway" [3] to more dangerous substance use; one of the peer-reviewed papers cited in the report claims that while "some studies have found that use of legal drugs or cannabis are not a requirement for the progression to other illicit drugs [...] most studies have supported the "gateway sequence"." [4] However, a 2018 literature review conducted by the National Institute of Justice, which analyzed 23 peer-reviewed research studies, concluded "that existing statistical research and analysis relevant to the "gateway" hypothesis has produced mixed results", [5] and that "no causal link between cannabis use and the use of other illicit drugs can be claimed at this time." [5]

Contents

History

While the phrase gateway drug was first popularized by anti-drug activists such as Robert DuPont in the 1980s, the underlying ideas had already been discussed since the 1930s by using the phrases stepping-stone theory, escalation hypothesis, or progression hypothesis. [6] [7]

The scientific and political discussion has intensified since 1975 after the publications of several longitudinal studies by Denise Kandel and others. [8] [9] [10]

In 2019, a research report by the National Institute on Drug Abuse determined that marijuana use is "likely to precede use of other licit and illicit substances", and cited a longitudinal study in which "adults who reported marijuana use during the first wave of the survey were more likely than adults who did not use marijuana to develop an alcohol use disorder within 3 years; people who used marijuana and already had an alcohol use disorder at the outset were at greater risk of their alcohol use disorder worsening." [3] They further claimed that marijuana use "is also linked to other substance use disorders including nicotine addiction." [3] While stating that their "findings are consistent with the idea of marijuana as a "gateway drug"", [3] they conceded that "the majority of people who use marijuana do not go on to use other, "harder" substances", [3] and that "cross-sensitization is not unique to marijuana. Alcohol and nicotine also prime the brain for a heightened response to other drugs and are, like marijuana, also typically used before a person progresses to other, more harmful substances." [3]

On the other hand, the 2018 report issued by the National Institute of Justice states "that the current state of research on this issue is limited, and the studies that have been conducted suffer from difficulties in collecting information and applying the findings to a larger population. The report further notes that although many of the reviewed studies found statistically significant associations between cannabis use and the users' later use of other illicit drugs, there is currently no conclusive evidence that cannabis use caused the later use of harder illicit drugs." [5]

Sequence of first-time use

General concept

The concept of gateway drug is based on observations that the sequence of first-time use of different drugs is not random but shows trends. On the basis of established techniques of longitudinal studies such trends can be described precisely in terms of statistical probability. As to the interpretation of the observed trends, it is important to note the difference between sequence and causation. Both may – but need not – be coupled, a question which is subject of further research, e.g., by physiological experiments. [11]

From a sample of 6,624 people who had not used other illegal drugs before their cannabis consumption the overall probability of later use of other illegal drugs was estimated to be 44.7%. Subgroup analyses showed that personal and social conditions, such as gender, age, marital status, mental disorders, family history of substance use, overlapping illegal drug distribution channels, alcohol use disorder, nicotine dependence, ethnicity, urbanicity, and educational attainment influenced the height of probability. [12] [13]

A study of drug use of 14,577 U.S. 12th graders showed that alcohol consumption was associated with an increased probability of later use of tobacco, cannabis, and other illegal drugs. Adolescents who smoked cigarettes before age 15 were up to 80 times more likely to use illegal drugs. [14] Studies indicate vaping serves as a gateway to traditional cigarettes and cannabis use. [15]

Large-scale longitudinal studies in the U.K. and New Zealand from 2015 and 2017 showed an association between cannabis use and an increased probability of later disorders in the use of other drugs. [16] [17] [18]

Students who regularly consume caffeinated energy drinks have a greater risk of alcohol use disorder, cocaine use and misuse of prescription stimulants. The elevated risk remains after accounting for prior substance use and other risk factors. [19]

A meta-analysis of 2018 came to the conclusion that the use of electronic cigarettes increases the risk of later use of conventional cigarettes. [20]

Associations aside from first-time use

The role of cannabis use in regard to alcohol use and Alcohol Use Disorder (AUD) is still not fully understood. Some studies suggest better alcohol treatment completion for those who use cannabis, while other studies find the opposite. [21] A 2016 review of 39 studies which examined the relation between cannabis use and alcohol use found that 16 studies support the idea that cannabis and alcohol are substitutes for each other, 10 studies found that they are complements, 12 found that they are neither complementary nor substitutes, and one found that they are both. [22]

A study involving self-reported data from a sample of 27,461 people examined the relationship of cannabis use and AUD. These respondents had no prior diagnosis of AUD. Of the 27,461 people, 160 had reported cannabis use within the past year. At the end of a three-year period, it found that those who had previously reported cannabis use were associated with a five times greater odds of being diagnosed with AUD than those who had not. After adjustment for select confounders (age, race, marital status, income, and education), these odds were reduced to two times greater risk. Another sample of self-reported data from 2,121 persons included only those who had already been diagnosed with AUD. In this sample, it was found that those who had reported cannabis use in the past year (416 people) were associated with 1.7 greater odds of AUD persistence three years later. After adjustment for the same confounders as before, these odds were reduced to 1.3. [23] [24]

Causes

Because a sequence of first-time use can only indicate the possibility – but not the fact – of an underlying causal relation, different theories concerning the observed trends were developed. The scientific discussion (state of 2016) is dominated by two concepts, which appear to cover almost all possible causal connections if appropriately combined. These are the theories of biological alterations in the brain due to an earlier drug use and the theory of similar attitudes across different drugs. [2] [25] [26]

Alterations in the brain

Adolescent rats repeatedly injected with tetrahydrocannabinol increased the self-administration of heroin (results based on 11 male rats [27] and >50 male rats [28] ), morphine (study based on 12 male rats) [29] and also nicotine (34 rats). [30] There were direct indications that the alteration consisted of lasting anatomical changes in the reward system of the brain. [27] [28] Because the reward system is anatomically, physiologically, and functionally almost identical across the class of mammals, [31] [32] [33] the importance of the findings from animal studies for the reward system in the human brain in relation to the liability to the use of further drugs has been pointed out in several reviews. [34] [35] [36] [37]

In mice, nicotine increased the probability of later consumption of cocaine, and the experiments permitted concrete conclusions on the underlying molecular biological alteration in the brain. [38] The biological changes in mice correspond to the epidemiological observations in humans that nicotine consumption is coupled to an increased probability of later use of cannabis and cocaine, [39] as well as other drugs. [40]

In rats, alcohol increased the probability of later addiction to cocaine and again relevant alterations in the reward system were identified. [41] [42] These observations thus correspond to the epidemiological findings that the consumption of alcohol in humans is coupled to a later increased risk of a transition from cocaine use to cocaine addiction. [43] [44]

Controlled animal and human studies showed that caffeine (energy drinks) in combination with alcohol increased the craving for more alcohol more strongly than alcohol alone. [45] These findings correspond to epidemiological data that people who consume energy drinks generally showed an increased tendency to take alcohol and other substances. [46] [19]

Personal, social and genetic factors

According to the concept of similar attitudes across different drugs (common liability to addiction), a number of personal, social, genetic and environmental factors can lead to a generally increased interest in various drugs. The sequence of first-time use would then depend on these factors. [2] [47] Violations of the typical sequence of first-time drug usage give credit to this theory. For example, in Japan, where cannabis use is uncommon, 83.2% of the people who used illicit substances did not use cannabis first. [2] The concept received additional support from a large-scale genetic analysis that showed a genetic basis for the connection of the prevalence of cigarette smoking and cannabis use during the life of a person. [48]

The results of a twin study presented indications that familial genetic and familial environmental factors do not fully explain these associations, and are possibly only relevant for sequences of some drugs. In 219 same-sex Dutch identical and non-identical twin pairs, one co-twin had reported cannabis use before the age of 18 whereas the other had not. In the cannabis group the lifetime prevalence of later reported use of party drugs was four times higher and the lifetime prevalence of later reported use of hard drugs was seven times higher than in the non-cannabis group. The authors concluded that at least family influences – both genetic and social ones – could not explain the differences. The study noted that, besides a potential causal role of cannabis use, non shared environment factors could play a role in the association such as differing peer affiliations that preceded the cannabis use. [49] [50]

Another twin study (of 510 same sex twin pairs) also examined the association of earlier cannabis use and later hard drug use. Like other studies it examined later drug use differences between siblings where one sibling had used cannabis early and the other had not. The study examined identical twins (who share approximately 100% of their genes) and non-identical twins (who share approximately 50% of their genes) separately and adjusted for additional confounders such as peer drug use. It found, after confounder adjustment, that the associations with later hard drug use existed only for non-identical twins. This suggests a significant genetic factor in the likelihood of later hard drug usage. The study suggested that a causal role of cannabis use in later hard drug usage is minimal, if it exists at all, and that cannabis use and hard drug use share the same influencing factors such as genetics and environment. [51] [50]

See also

Related Research Articles

<span class="mw-page-title-main">Recreational drug use</span> Use of drugs with the primary intention to alter the state of consciousness

Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants, stimulants, and hallucinogens.

<span class="mw-page-title-main">Substance abuse</span> Harmful use of drugs

Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, medical, and criminal justice contexts. In some cases, criminal or anti-social behavior occurs when the person is under the influence of a drug, and long-term personality changes in individuals may also occur. In addition to possible physical, social, and psychological harm, the use of some drugs may also lead to criminal penalties, although these vary widely depending on the local jurisdiction.

Self-medication, sometime called do-it-yourself (DIY) medicine, is a human behavior in which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions, for example headaches or fatigue.

<span class="mw-page-title-main">Cannabis (drug)</span> Psychoactive drug from the cannabis plant

Cannabis, also known as marijuana or weed among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various traditional medicines for centuries. Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis, which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, such as cannabidiol (CBD). Cannabis can be used by smoking, vaporizing, within food, or as an extract.

Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.

<span class="mw-page-title-main">Tobacco and other drugs</span> Association between tobacco and other drug use

An association between tobacco and other drug use has been well established. The nature of this association remains unclear. The two main theories, which are not mutually exclusive, are the phenotypic causation (gateway) model and the correlated liabilities model. The causation model argues that smoking is a primary influence on future drug use, while the correlated liabilities model argues that smoking and other drug use are predicated on genetic or environmental factors.

<span class="mw-page-title-main">Polysubstance dependence</span> A type of substance use disorder

Polysubstance dependence refers to a type of substance use disorder in which an individual uses at least three different classes of substances indiscriminately and does not have a favorite substance that qualifies for dependence on its own. Although any combination of three substances can be used, studies have shown that alcohol is commonly used with another substance. This is supported by one study on polysubstance use that separated participants who used multiple substances into groups based on their preferred substance. The results of a longitudinal study on substance use led the researchers to observe that excessively using or relying on one substance increased the probability of excessively using or relying on another substance.

<span class="mw-page-title-main">Long-term effects of cannabis</span> Overview of long-term effects of the consumption of cannabis

The long-term effects of cannabis have been the subject of ongoing debate. Because cannabis is illegal in most countries, clinical research presents a challenge and there is limited evidence from which to draw conclusions. In 2017, the U.S. National Academies of Sciences, Engineering, and Medicine issued a report summarizing much of the published literature on health effects of cannabis, into categories regarded as conclusive, substantial, moderate, limited and of no or insufficient evidence to support an association with a particular outcome.

<span class="mw-page-title-main">Substance use disorder</span> Continual use of drugs (including alcohol) despite detrimental consequences

Substance use disorder (SUD) is the persistent use of drugs despite the substantial harm and adverse consequences to one's own self and others, as a result of their use. In perspective, the effects of the wrong use of substances that are capable of causing harm to the user or others, have been extensively described in different studies using a variety of terms such as substance use problems, problematic drugs or alcohol use, and substance use disorder. The National Institute of Mental Health (NIMH) states that "Substance use disorder (SUD) is a treatable mental disorder that affects a person's brain and behavior, leading to their inability to control their use of substances like legal or illegal drugs, alcohol, or medications. Symptoms can be moderate to severe, with addiction being the most severe form of SUD". Substance use disorders (SUD) are considered to be a serious mental illness that fluctuates with the age that symptoms first start appearing in an individual, the time during which it exists and the type of substance that is used. It is not uncommon for those who have SUD to also have other mental health disorders. Substance use disorders are characterized by an array of mental/emotional, physical, and behavioral problems such as chronic guilt; an inability to reduce or stop consuming the substance(s) despite repeated attempts; operating vehicles while intoxicated; and physiological withdrawal symptoms. Drug classes that are commonly involved in SUD include: alcohol (alcoholism); cannabis; opioids; stimulants such as nicotine, cocaine and amphetamines; benzodiazepines; barbiturates; and other substances.

<span class="mw-page-title-main">Addiction</span> Disorder resulting in compulsive behaviours

Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behaviour that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in addiction's development. Classic signs of addiction include compulsive engagement in rewarding stimuli, preoccupation with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification, coupled with delayed deleterious effects.

<span class="mw-page-title-main">Cannabis use disorder</span> Continued use of cannabis despite clinically significant impairment

Cannabis use disorder (CUD), also known as cannabis addiction or marijuana addiction, is a psychiatric disorder defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and ICD-10 as the continued use of cannabis despite clinically significant impairment.

Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction; the contribution from epigenetic risk factors to the total risk is unknown. Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time can result in an addiction. In other words, anyone can become an individual with a substance use disorder under particular circumstances. Research is working toward establishing a comprehensive picture of the neurobiology of addiction vulnerability, including all factors at work in propensity for addiction.

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<span class="mw-page-title-main">Denise Kandel</span> American medical sociologist and epidemiologist

Denise Kandel is an American medical sociologist and epidemiologist, Professor of Sociomedical Sciences and Psychiatry at Columbia University and Head of the Department of Epidemiology of Substance Abuse at the New York State Psychiatric Institute. She is known for her epidemiological longitudinal studies on the sequence of first-time use of various legal and illegal drugs, carried out beginning in the 1970s and continuing until at least 2016.

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