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 causes are biological alterations in the brain due to the earlier substance exposure and similar attitudes of people who use different substances across different substances (common liability to addiction). In 2020, the National Institute on Drug Abuse released a study backing allegations that marijuana is a "gateway" to more dangerous substance use, though not for the majority of people who use substances. A literature review by the United States Department of Justice found no conclusive evidence that the link is causal. 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. Examples of trends 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. 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. Studies indicate vaping serves as a gateway to traditional cigarettes and cannabis use. 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. Students who regularly consume caffeinated energy drinks have a greater risk of alcohol use disorder, cocaine use and misuse