Untangling the Jargon: Substance Use Disorder, Addiction, and Dependence, What’s the Difference?

In the 1980s, a group of researchers attempted to revise the guidelines which psychologists used to diagnose patients, the DSM-III. Debates quickly ensued when researchers discussed the current term “dependence”. The clinicians on the committee favored using the word “addiction” or “addictive disorder” because they felt that it encompassed the behavioral changes they noticed in patients with this disorder. The non-clinicians on the team felt that the stigma surrounding the term addiction was too great and that the term “dependence” would be more objective and fitting. At the end of the committee meetings, the term “dependence” won by a single vote (review by O’Brien & Volkow, 2006; review by O’Brien, 2011). This language was carried on into the DSM-III-R and the DSM-IV within a section labeled “Substance-Related Disorders”, but has since been changed in the DSM-5 the within the revised section of “Substance-Related and Addictive Disorders” (O’Brien, 2011).

“Dependence” should not be used as a euphemism for “addiction” for multiple reasons. The two are not interchangeable, using them as such has created problems for laymen and physicians even today. This blog post is an attempt to clarify the distinction between dependence, addiction, and substance use disorder.

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What is a “substance use disorder”

Substance use disorders lie under the branch of “Substance-Related and Addictive Disorders” in the DSM-5. They range from mild, marked by having only 2-3 symptoms, to moderate, having 4-5 symptoms, or severe having 6 or more out of 11 symptoms. Substance use disorder encompasses 10 recognized classes of drugs: 1) alcohol, 2) caffeine, 3) cannabis, 4) hallucinogens, 5) inhalants (hallucinogens), 6) opioids, 7) sedatives, 8) hypnotics and anxiolytics, 9) stimulants, and 10) tobacco, and other (or unknown) substances (DSM-5). As seen in Figure 1, symptoms of SUD can include desire and inability to stop using the drug, disruption of function in daily life due to the drug, and biological changes resulting from drug use, such as increased tolerance and presence of withdrawal symptoms, which are signs of dependence. The criteria is modified if the patient takes these drugs under medical supervision. Having a substance use disorder does not necessarily mean having dependence as well or vice versa. Recall, the patient needs to have at least 2 of these 11 symptoms to have a mild SUD– these two symptoms don’t have to include symptoms of dependence.

Figure 1: Diagnostic criteria of Substance Use Disorder in the DSM-5

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What is Dependence?

A review by O’Brien and Volkow states that dependence is distinct from drug seeking behavior (O’Brien & Volkow, 2006). Dependence describes physical adaptations including tolerance and withdrawal, which happen to the body due to repeatedly taking a drug (O’Brien and Volkow, 2006). 

Natural rewards including food and sex, and rewards such as drugs activate part of the brain known as the dopaminergic mesocorticolimbic pathway (review by Adinoff, 2004; review by Hayes et al., 2020). This pathway includes multiple brain structures (see Figure 2) with special roles in reward including the nucleus accumbens (NAc), the ventral tegmental area (VTA), the locus coeruleus (LC), and the prefrontal cortex (PFC), which, when activated, work together to create pleasurable feelings and reinforce the reward (Hayes et al., 2020). These brain structures relay chemical messages directly or indirectly to each other through neurotransmitters, such as dopamine. Pergolizzi et al.’s (2020) review states that this increased amount of dopamine in the NAc and other mesolimbic brain regions is important in activation of reward signals to the drug itself and associated environmental stimuli.

When this mesolimbic pathway is repeatedly activated, neuroadaptations may take place, making these regions less sensitive to activation (as mentioned in review by Wise & Koob, 2014). This translates to increased tolerance of the drug, meaning that higher doses of the drug are needed in order for the user to experience its original effectiveness (as mentioned in review by Pergolizzi et al., 2020). After tolerance is formed, and those neural changes have taken place, depending on the type of drug taken, abrupt abstinence of the drug may result in a set of uncomfortable bodily symptoms known as withdrawal (as mentioned in review by Wise & Koob, 2014). Diana et al’s (1993) study looked at electrophysiological recordings of rats in vivo undergoing ethanol withdrawal and found decreased activity in the mesocorticolimbic system which was reinstated after ethanol re-administration (Wise & Koob, 2014; Diana et al., 1993). Basically these experimenters administered ethanol (alcohol) to rats, which the rats overtime developed a tolerance for. When the rat was no longer given ethanol, they experienced withdrawal. During withdrawal, rats showed both behavioral symptoms and neural adaptations including decreased firing rate of neurons in the mesolimbic system (Diana et al., 1993). Re-administration of ethanol restored electrophysiological recordings (Diana et al., 1993). This data suggests that the ethanol withdrawn rat’s mesocorticolimbic system did not function with the same sensitivity as it did before having taken the drug due to neuroadaptations. Besides the within system adaptations, drug dependence may also facilitate between system circuitry changes, including what Roy Wise refers to as changes in the “anti-reward circuit” as well, responsible for negative reinforcement (Wise & Koob, 2014).

This might all sound very concerning, but it is useful to keep in mind that to have a dependence is not necessarily problematic, and it does not make the drug user an “addict”. Even drugs which are not seen as illicit can cause a user to have symptoms of dependence. For example drugs prescribed to treat depressive symptoms can lead to withdrawal symptoms when the patient stops taking the drug (as mentioned in review by Massabiki & Abi-Jaoude, 2020). Of participants who responded to a survey about their experiences with antidepressants, although 55% of people reported ‘withdrawal effects’ after stopping their antidepressant, 82.8% of participants expressed that these drugs had reduced their depression (Massabiki & Abi-Jaoude, 2020). This survey shows that yes, patient’s brains were adapting in response to these drugs, but also that these drugs were improving their depressive symptoms. If asked, these users would likely report that these brain changes were not necessarily problematic, but rather, helpful for their everyday functioning.

Figure 2: Brain regions associated with the mesolimbic reward pathway involved in drug use and development of dependence

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What is Addiction?

From a clinical perspective, addiction is typically associated with people diagnosed with severe substance use disorder, meaning greater than or equal to 6 symptoms of SUD (as stated in editorial commentary by Blum et al., 2022). Whether or not this person has biological symptoms of dependence, they show changes in behavior which are problematic. The person who is addicted may feel unable to stop engaging in the behavior even though they may be experiencing negative health, psychological, or social consequences (as mentioned in an editorial by West, 2001). A review article by Hayes et al. (2020), describes several theories about how addiction develops and is maintained, many of which involve dysfunction of the reward pathway and impairments in inhibitory control (Hayes et al., 2020). One theory, which puts together Wise and Koob’s theories of addiction (2014), states that addiction is maintained due to both positive and negative reinforcement of drug taking behavior contributing to a cycle of drug taking. In positive reinforcement, an appetitive stimulus is added (ex: feelings of pleasure) which may increase the likelihood that this behavior (drug taking) will be repeated. Wise and Koob agree that positive reinforcement may enhance the initial development and repetition of the drug taking behavior. In negative reinforcement, an aversive stimulus (ex: withdrawal symptoms) are removed when a target behavior (drug taking) is performed, which may further increase the likelihood that the behavior will be repeated. Figure 3 distinguishes negative and positive reinforcement from negative or positive punishment (Figure 3). According to Roy Wise, memory of the experience is also an important part of the maintenance of drug addiction (Wise & Koob, 2014). A person who has a dependence on heroin for example, might experience uncomfortable withdrawal symptoms if they stopped taking heroin all together. In order to alleviate or avoid those symptoms, they may feel motivated to continue taking heroin.

In addition to positive and negative reinforcement, some researchers including Siegel et al., emphasize the power of drug-associated environmental cues, which can contributing to a cycle of addiction (Siegel et al., 1982). When a person takes heroin for example, they do so surrounded by different environmental cues. If the person takes heroin in one surrounding repeatedly, their brain may unwittingly create associations between the environment and the drug’s effects, attaching formerly neutral stimuli including a familiar location or object, or a ritual surrounding the drug taking, to increased tolerance of the drug’s effects (Siegel et al., 1982). There is evidence that drug associated environmental cues affect survival in heroin treated rats. Siegel et. al., (1982) administered heroin to rats in their familiar home cage every other day in increasing amounts. Then on the testing day, they gave rats a high dose of heroin either in their familiar home cage, or an unfamiliar environment. They found that rats who were given this more potent final dose of heroin in a familiar environment were significantly more likely to survive compared to rats given this high dose in an unfamiliar environment, which shows that environmental cues influence the effect of the drug (Siegel et al, 1982). All of which may feed into a cycle of drug taking, attempts at discontinuation, relapse, etc. But addiction is not merely motivated by symptoms of dependence. There are many other theories of addiction, some of which might be more fitting to address other facets including psychological or social factors which may influence addiction.

Figure 3: This graphic depicts positive and negative reinforcement alongside positive and negative punishment. Together, Wise and Koob’s (2014) theories of addiction propose that addiction is maintained through factors including positive and negative reinforcement of the behavior of drug taking, lending to a cycle of addiction.

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Conclusion

Figure 4: A chart created to attempt to distinguish between the terms “addiction”, “SUD”, and “dependence”

In brief, dependence includes the physical, neurobiological changes which can result from repeatedly taking a substance– illicit, or non-illicit. Substance use disorder is a diagnosis with a spectrum ranging from mild, to moderate, to severe. It includes both behavioral and biological criteria. Severe SUD is often labeled as addiction.

So as you can see, these terms are distinct but may overlap. Dependence is not necessarily addiction, although addiction might include dependence. Addiction is substance use disorder, but Substance use disorder is not necessarily addiction unless it is severe. 

These labels are important to distinguish, because they carry different connotations for the patient. The label of “addict” carries intense stigma. A quick google search can exemplify the negative stereotypes surrounding these terms (Figure 5). Most people don’t want to see themselves as an addict. They may not want others to see them as an addict, especially if that label is false, or if they feel that it no longer applies to them. There are some people who have experienced addiction who continue to embrace the label as a reminder to stay vigilant against temptation, but for others, this term encompasses feelings of powerlessness over a substance. The battle between defining these three labels in the research and public sphere rages on. But what is important is that these labels are different. A person can seek help at any stage of a SUD if that help is relevant for them.

Figure 5: Google search for the terms “addict”, “substance abuser”, and “drug dependence”

Works cited

Adinoff, B. (2004). Neurobiologic Processes in Drug Reward and Addiction. Harvard Review of Psychiatry, 12(6), 305–320. https://doi.org/10.1080/10673220490910844

Blum, K., Elman, I., Dennen, C. A., McLaughlin, T., Thanos, P. K., Baron, D., Gold, M. S., & Badgaiyan, R. D. (2022). “Preaddiction” construct and reward deficiency syndrome: genetic link via dopaminergic dysregulation. Annals of Translational Medicine, 10(21), 1181–1181. https://doi.org/10.21037/atm-2022-32

Diana, M., Pistis, M., Carboni, S., Gessa, G. L., & Rossetti, Z. L. (1993). Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proceedings of the National Academy of Sciences, 90(17), 7966–7969. https://doi.org/10.1073/pnas.90.17.7966

Hayes, A., Herlinger, K., Paterson, L., & Lingford-Hughes, A. (2020). The neurobiology of substance use and addiction: evidence from neuroimaging and relevance to treatment. BJPsych Advances, 26(6), 367–378. https://doi.org/10.1192/bja.2020.68

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McLellan, A. T., Koob, G. F., & Volkow, N. D. (2022). Preaddiction—A Missing Concept for Treating Substance Use Disorders. JAMA Psychiatry, 79(8), 749. https://doi.org/10.1001/jamapsychiatry.2022.1652

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O’Brien, C. P., Volkow, N., & Li, T.-K. (2006). What’s in a Word? Addiction Versus Dependence in DSM-V. American Journal of Psychiatry, 163(5), 764–765. https://doi.org/10.1176/ajp.2006.163.5.764

Pergolizzi, J. V., Raffa, R. B., & Rosenblatt, M. H. (2020). Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management. Journal of Clinical Pharmacy and Therapeutics, 45(5), 892–903. https://doi.org/10.1111/jcpt.13114

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