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Substance use disorders involve substances that directly activate the brain's reward system. Dopamine is the primary neurotransmitter involved in this reward system, although gamma-aminobutyric acid (GABA), endogenous opioids and cannabinoids, and other neurotransmitters play a role depending on the specific substance (Substance use disorders involve substances that directly activate the brain's reward system. Dopamine is the primary neurotransmitter involved in this reward system, although gamma-aminobutyric acid (GABA), endogenous opioids and cannabinoids, and other neurotransmitters play a role depending on the specific substance (1). The activation of the reward system typically causes feelings of pleasure; the specific characteristics of the pleasurable feelings evoked vary widely depending on the substance. These drugs or substances are divided into 10 different classes that have different, although not completely distinct, pharmacologic mechanisms (1, 2). (See table Ten Drug Classes Commonly Associated With Substance-Related Disorders.)
Ten Drug Classes Commonly Associated With Substance-Related Disorders
CaffeineCaffeine |
Hallucinogens (eg, LSD, phencyclidine, psilocybin, 3,4-methylenedioxymethamphetamine [MDMA]), psilocybin, 3,4-methylenedioxymethamphetamine [MDMA]) |
Inhalants (volatile hydrocarbons [eg, paint thinner, certain glues]) |
Opioids (eg, fentanyl, morphine, oxycodone)(eg, fentanyl, morphine, oxycodone) |
Sedatives, hypnotics, and anxiolytics (eg, lorazepam, secobarbital)(eg, lorazepam, secobarbital) |
Stimulants (eg, amphetamines, cocaine) |
Other (eg, anabolic steroids) |
This classification is not based on whether a drug is legal (eg, alcohol, caffeine), illicit (eg, hallucinogens), or available by prescription (eg, morphine, lorazepam). This classification is not based on whether a drug is legal (eg, alcohol, caffeine), illicit (eg, hallucinogens), or available by prescription (eg, morphine, lorazepam).
The term "narcotic" is both a legal and a colloquial term. Originally, it referred to drugs that caused narcosis (insensibility or stupor), particularly opioids (eg, opium, opium derivatives). However, the term is currently used so indiscriminately (eg, the U.S. government classifies the stimulant drug cocaine as a narcotic) that it retains little scientific or medical meaning.The term "narcotic" is both a legal and a colloquial term. Originally, it referred to drugs that caused narcosis (insensibility or stupor), particularly opioids (eg, opium, opium derivatives). However, the term is currently used so indiscriminately (eg, the U.S. government classifies the stimulant drug cocaine as a narcotic) that it retains little scientific or medical meaning.
Psychological, behavioral, and physiologic changes can result from the use of substances (intoxication) and their subsequent cessation (withdrawal). Substance use can also result in psychiatric disorders (eg, depression, psychosis, anxiety, or neurocognitive disorders) (3–5).
Substance use disorders involve a pathologic pattern of behaviors in which patients continue to use a substance despite experiencing significant problems related to its use. There are also physiologic manifestations, including changes in neural circuitry (1, 6). The term "substance use disorder" is more accurate, clearly defined, and has fewer negative connotations than "addiction," "abuse," or "dependence."
Drugs in the 10 classes vary in how likely they are to cause a substance use disorder. The likelihood that a substance will be misused or lead to a substance use disorder depends upon a combination of factors, including the following (7):
Route of administration
Rate at which the drug crosses the blood-brain barrier and stimulates the reward pathway
Time to onset of effect
Ability to induce tolerance and/or withdrawal symptoms
Scheduled drugs (controlled substances)
In the United States, medications classified as controlled substances are regulated by the Drug Enforcement Administration (DEA). (See table Some Examples of Controlled Substances). Controlled substances are divided into 5 schedules (or classes) on the basis of their potential for promoting a substance use disorder, whether there is an accepted medical use, and their ability to be used safely under medical supervision. The schedule classification determines how a substance must be controlled.
Schedule I: These substances have a high potential for misuse, no medical use recognized by the United States DEA, and a lack of accepted safety. They can be used only under government-approved research conditions.
Schedule II to IV: These medications have progressively less potential for misuse (going from schedule II to IV). They have an accredited medical use. Prescriptions for these medications must bear the physician’s federal DEA license number.
Schedule V: These substances have the least potential for misuse. Some Schedule V medications do not require a prescription.
State schedules may differ from federal schedules.
Some Examples of Controlled Substances
USDEA Schedule | Examples |
|---|---|
I* | Heroin, LSD, marijuana, ecstasy, GHB, peyote |
II | Methamphetamines and amphetamine derivatives, opioids, meperidine, cocaine, barbiturates with high potential for misuse (eg, pentobarbital)Methamphetamines and amphetamine derivatives, opioids, meperidine, cocaine, barbiturates with high potential for misuse (eg, pentobarbital) |
III | Anabolic steroids, codeine, ketamine, testosterone, barbiturates with moderate potential for misuse (eg, butalbital)Anabolic steroids, codeine, ketamine, testosterone, barbiturates with moderate potential for misuse (eg, butalbital) |
IV | Benzodiazepines, chloral hydrate, modafinil, zolpidem, barbiturates with lower potential for misuse (eg, phenobarbital)Benzodiazepines, chloral hydrate, modafinil, zolpidem, barbiturates with lower potential for misuse (eg, phenobarbital) |
V | Cough suppressants containing small amounts of codeine, diphenoxylate/atropine, pregabalinCough suppressants containing small amounts of codeine, diphenoxylate/atropine, pregabalin |
* Cannot be prescribed. | |
GHB = gamma hydroxybutyrate; LSD = lysergic acid diethylamide; MDMA = methylenedioxymethamphetamine; USDEA = United States Drug Enforcement Agency | |
See also the complete list USDEA controlled substances. | |
References
1. Volkow ND, Michaelides M, Baler R. The Neuroscience of Drug Reward and Addiction. Physiol Rev. 2019;99(4):2115-2140. doi:10.1152/physrev.00014.2018
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. American Psychiatric Association Publishing; 2022:543-553.
3. Tucker JS, Huang W, Green HD Jr, Pollard MS. Patterns of Substance Use and Associations with Mental, Physical, and Social Functioning: A Latent Class Analysis of a National Sample of U.S. Adults Ages 30-80. Subst Use Misuse. 2021;56(1):131-139. doi:10.1080/10826084.2020.1843059
4. Fiorentini A, Cantù F, Crisanti C, Cereda G, Oldani L, Brambilla P. Substance-Induced Psychoses: An Updated Literature Review. Front Psychiatry. 2021;12:694863. Published 2021 Dec 23. doi:10.3389/fpsyt.2021.694863
5. Melugin PR, Nolan SO, Siciliano CA. Bidirectional causality between addiction and cognitive deficits. Int Rev Neurobiol. 2021;157:371-407. doi:10.1016/bs.irn.2020.11.001
6. McNally GP, Jean-Richard-Dit-Bressel P, Millan EZ, Lawrence AJ. Pathways to the persistence of drug use despite its adverse consequences. Mol Psychiatry. 2023;28(6):2228-2237. doi:10.1038/s41380-023-02040-z
7. Allain F, Minogianis EA, Roberts DC, Samaha AN. How fast and how often: The pharmacokinetics of drug use are decisive in addiction. Neurosci Biobehav Rev. 2015;56:166-179. doi:10.1016/j.neubiorev.2015.06.012
Drugs Mentioned In This Article
