A picture is beginning to emerge on the relationship between substance use disorders (SUDs), such as alcoholism, opioid addiction, and THC addiction, and behavioral disorders, such as eating disorders, compulsive gambling, and pornography addiction.

In theory, SUDs are built on the “pull” of the substance, the hedonistic desire to experience the mind-altering effect of intoxication. Also, theoretically, behavioral disorders are “push” compulsions resulting from trauma or chronic stress.

New research shows that the people who have the most trouble with SUDs are not those attracted to substances for hedonistic reasons, but those who use substances specifically to self-medicate for trauma or chronic stress.

The difference is displacement. The use of substances or behaviors to displace stressful energy often results in those substances or behaviors becoming addictive. The use of substances or behaviors without the underlying stressful motivations does not appear to lead to dependency, where abstinence causes withdrawal.

We can thank the Yale Stress Center at the Yale School of Medicine in New Haven, Connecticut, for a recent review in The Journal of Clinical Investigation summarizing the scientific literature on the relationship between stress and SUDs.

Dr. Rajita Sinha, Director of the Yale Stress Center and author of the review, refers to SUDs as “drug misuse as a coping mechanism to reduce stress.” She identifies several sources for the stressful impetus to indulge:

• stress
• anxiety
• tension
• withdrawal
• self-medication

All of these posit some source of stressful energy as the motivation for indulgence, with withdrawal being the stress resulting from abstinence. Without the stress, do you get addiction? Dr. Sinha hints at the answer, saying this model explains “stress-related sensitization of drug salience, which promotes increases in craving and drug use escalation.”

If I’m reading that correctly, she’s saying the use of substances and behaviors to displace stress is what drives the need to increase dosage and or frequency — the tailspin into addiction. If there’s no stress, there’s no escalation?

The first third of Dr. Singha’s review explains the physiological responses to stress. The investigation involves neurotransmitters, cortisol, dopamine, “the hypothalamic-pituitary-adrenal (HPA) axis,” and research on the immune system, the autonomic system, the endocrine system, and genomics. “This multilevel acute stress response,” Dr. Singha writes, “is dysregulated in those with chronic adversity, with a blunting of the physiologic and dopaminergic activation in response to acute stress and greater subjective distress.”

The second part of the review looks at stresses associated with the risk of SUD and the likelihood of relapse or failed treatment. Dr. Singha is not subtle about the causes for dysregulated stress responses:

Notably, traumatic and repeated or chronic adverse life events during early life or in adolescence may result in dysregulation of the multilevel stress responses.

She concludes that “the wealth of evidence clearly links sustained disruption of the adaptive stress responses with specific associations to risk of future substance use and misuse and related psychiatric and medical comorbidities.” In fact, a recent survey found that more than half of the people in the United States undergoing treatment for SUDs report being the victims of childhood sexual abuse.

Now we are really getting somewhere. There is a certain kind of stress, more acute and of longer duration than ordinary stress, that is behind more than half of the cases of addiction being treated in the U.S. Ordinary stress can be displaced with ordinary means, such as deep breathing and physical exercise that are not harmful, but extraordinary stress looks for any substance or behavior that will soften the blow. When these substances or behaviors are used for coping, stress soothing, support, and avoidance, they erode the reward response, leading to tolerance and addiction.

The disruptions to the stress response system caused by acute trauma or chronic stress predispose people to SUDs, suggests Dr. Singha. Reductions in the volume of gray matter in the prefrontal cortex and over-stimulation of the HPA axis “promote drug motivation, craving, and escalated drug intake,” writes Dr. Singha.

The third portion of her review asks if there is anything we know of that will repair the reward response, reduce drug intake, and improve treatment outcomes. In addressing the “multilevel stress disruptions in SUD,” Dr. Singha says it’s important to target the “stress pathophysiology of addiction.” She describes a precision medicine approach similar to the treatment of cancer to “identify prognostic markers” for relapse in order to tailor an intervention for SUD.

Dr. Singha then lists some promising treatments:

• Mifepristone – “was useful in decreasing alcohol intake in individuals with alcohol dependence”
• Prazosin – “reduced stress-induced alcohol craving and negative emotions”
• Doxazosin– “reduced cocaine use and improved abstinence outcomes in treatment-seeking individuals with cocaine use disorder”

Dr. Singha describes other promising work with neuroactive steroids, but never mentions GLP-1 drugs and their relationship to stress-based addiction. She courageously ends with the statement that “broad-based interventions are needed that can reverse and rescue the stress disruptions in addiction risk.” To cure the addiction, don’t target the substance; target the stress.

Written by Steve O’Keefe. First published May 26, 2026.

Sources:

“Stress and substance use disorders: risk, relapse, and treatment outcomes,” The Journal of Clinical Investigation, August 15, 2024.

“Theory-Based Processes that Promote the Remission of Substance Use Disorders,” Clinical Psychology Review, December 30, 2006.

“The Connection Between Stress and Addiction,” Riverside Recovery, February 17, 2026.

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