“Drug addiction” has been always a controversial term to define. National Institute on Drug Abuse (NIDA) defines drug addiction as compulsive drug seeking despite negative consequences. However, “addiction” does not have a specific diagnosis in DSM-5: it only has the diagnostic criteria for substance use disorder, which includes withdrawal syndrome for the substance. NIDA’s use of the term “addiction” roughly corresponds to the DSM definition of substance disorder. Dr. Hart, a neuroscientist who learns about drugs, on the contrary, argues that undergoing opioid withdrawal does not make him meet the criteria for opioid addiction.

According to Wise and Koob (2014), the emergence of negative emotional states during drug withdrawal plays a critical role in motivating individuals to seek drugs. They assert that addiction involves a crucial element of negative reinforcement.

Should experiencing withdrawal symptoms be included as a criterion of drug addiction? Before answering this question, we need to figure out what is happening in our brain during the withdrawal symptoms and examine whether they make people become crave drugs more.

A study on chronic cocaine administration measured the mood states in mice with brain reward thresholds during cocaine injection and withdrawal (Stoker and Markou, 2011). Three groups of mice were treated with 90mg/kg/day cocaine, 180mg/kg/day cocaine, and saline for three days. Researchers treated the saline group as a baseline and found that the injection of cocaine lowered the brain reward thresholds while the withdrawal elevated the thresholds, which explained why continuous cocaine administration brings euphoria while its discontinuation leads to anhedonia. However, the elevation effect only lasted for 3 days for the two cocaine withdrawal groups, and the thresholds went back to the normal level on Day 5.

From this study, can we conclude that withdrawal symptoms make people crave drugs? It is possible because anhedonia followed by cocaine withdrawals might drive people to take the drug to resume the pleasant feelings, but the cravings caused by withdrawal symptoms should be temporary: the brain reward thresholds gradually go back to a normal level after undergoing withdrawal symptoms. Even after only a 3-day cocaine injection, the withdrawal symptoms that rats experienced lasted for more than the cocaine-administration time. Does a longer drug administration period relate to withdrawal symptoms that last for a longer time thus causing an increased addiction vulnerability? If people do not take the drug during the withdrawal period despite the strong cravings, will they be less likely to get an addiction to the drug? Future research is needed to further learn about the long-run impact of drug withdrawal on brain reward thresholds.

Another study examines the effect of cocaine withdrawal on reversal learning (Peter, et al. 2019). Researchers trained rats in the treatment and control group to self-administer cocaine and food pellets. After 8 days, both cohorts were tested on reversal learning tasks, which assessed their ability to learn from negative feedback and adjust their behavior accordingly. The results show a significant decrease in lose-shift as opposed to win-stay probability for the cocaine administration group during the withdrawal period, indicating an impaired reversal learning ability. This finding explains why some individuals continue drug consumption despite knowing the negative consequences it might cause. The impairment might be a result of reduced HTR2C expression during cocaine withdrawal, which is important for the learning of negative feedback.

Both studies reveal the possible biological changes in brains during cocaine withdrawals. The cocaine withdrawal state might exert a motivational drive for drug intake to alleviate depressive-like symptoms (Koob & Le Moal, 2001), but the symptoms should gradually mitigate, as well as the craving for drugs, due to the back-to-normal level brain reward thresholds (Stoker & Markou, 2011). Aside from increasing cravings, cocaine withdrawals might also induce impairment in reversal learning ability by reducing HTR2C expression (Peter, et al. 2019).

Drug withdrawal might make people more prone to drug addiction to some extent. How about behavioral addiction? There is less research on the withdrawals of addictive behaviors and how they influence brains, and some people do doubt the existence of withdrawal symptoms of behavioral addiction. A study on internet exposure examined the mood and psychological states of high-internet users and low-internet users and found that high-internet users showed a more significant decrease in mood than low-internet users (Romano, et al. 2013). Another study on pathological gambling showed that pathological gamblers self-reported physical symptoms, such as insomnia, headaches, loss of appetite, and diarrhea when attempting to stop gambling (Rosenthal and Lesieur, 1992). These findings indicate that withdrawal symptoms not only exist in substance addiction but also in behavioral addiction.

In conclusion, withdrawal symptoms experienced when stopping addictive substances might make people more prone to addiction if they cannot develop coping mechanisms to manage stress and negative emotions without turning to addictive behaviors or substances. If they could successfully build a repertoire of psychological strategies to draw upon, experiencing withdrawal symptoms do not necessarily mean that they meet the criteria for addiction.

References:

Wise, R. A., & Koob, G. F. (2013). The development and maintenance of drug addiction. Neuropsychopharmacology, 39(2), 254–262. https://doi.org/10.1038/npp.2013.261

Hart, C. L. (2022). Drug use for grown-ups: Chasing liberty in the land of fear. Penguin Books, imprint of Penguin Random House LLC.

Zhukovsky, P., Puaud, M., Jupp, B., Sala-Bayo, J., Alsiö, J., Xia, J., Searle, L., Morris, Z., Sabir, A., Giuliano, C., Everitt, B. J., Belin, D., Robbins, T. W., & Dalley, J. W. (2019). Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(13), 2163–2173. https://doi.org/10.1038/s41386-019-0381-0

Koob, G. F., & Le Moal, M. (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 24(2), 97–129. https://doi.org/10.1016/S0893-133X(00)00195-0

Stoker, A.K. and Markou, A. (2011) “Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J MICE,” Behavioural Brain Research, 223(1), pp. 176–181. Available at: https://doi.org/10.1016/j.bbr.2011.04.042.

Rosenthal, R. J., & Lesieur, H. R. (1992). Self-reported withdrawal symptoms and pathological gambling. The American Journal on Addictions, 1(2), 150–154. https://doi.org/10.1111/j.1521-0391.1992.tb00020.x

Romano, M., Osborne, L. A., Truzoli, R., & Reed, P. (2013). Differential psychological impact of internet exposure on internet addicts. PLoS ONE, 8(2). https://doi.org/10.1371/journal.pone.0055162