Stress and Drug Abuse: A Structural and Genetic Link

SUBSTANCE USE DISORDERS

It is commonly believed-and well supported by evidence and anecdotal reports-that substances and substance abuse are a strategy for coping and mediating the feelings that result from both recent and remote stress. Due to their cellular and biochemical features, the structural changes associated with stress may increase an individual’s post-stress susceptibility to substance abuse.

Stress impacts the brain causing anatomical changes at the cellular level. While not visible with imaging studies, other investigational modalities, such as biochemical testing and microscopic examination, can verify the presence of post-stress brain tissue alterations.

There are similarities between some of the cellular changes associated with stress and those cellular changes that result from drug abuse. Several common features include neural plasticity and microglial changes. Researchers have suggested that these overlapping features could be clues to a causative association between exposure to stress and a predisposition to drug abuse.

Of course, many people who experience severe stress do not use or abuse drugs, and extremely difficult experiences are not always a part of the life history of those who abuse drugs. So, while there is a relationship between stress and subsequent drug abuse, other variables (eg, genetic predisposition) are involved.

Neuronal plasticity and microglial cells

McGrath and Briand,¹ researchers at Temple University, have examined synaptic plasticity, which is believed to be altered in association with both stress and substance abuse. The authors suggest that increased microglial alterations result from substance abuse and stress, both of which could cause the observed changes in synaptic plasticity.

This possible causative link is relevant in the study of the impact of stress on the predisposition to drug abuse for a number of reasons. Clinicians treating stress and substance use disorder (SUD) must take into consideration the fact that patients may have experienced cellular changes in brain tissue. If altered glial activity can be targeted in the treatment of stress or in the treatment or prevention of an SUD, it may prevent or correct alterations in synaptic plasticity.

Nevertheless, patients who experience stress-related neurobehavioral effects (including drug abuse) may benefit from a variety of therapeutic approaches. These include non-pharmacological therapies, such as counseling and mindfulness. In fact, if stress can induce cellular changes (eg, altered synaptic plasticity, microglial activation) in the brain, interventions like behavioral modification may also induce positive structural changes at a cellular level.

A genetic link

Genetic predisposition is one of the factors that links stress with subsequent drug abuse. Genes may shed some light on the question of whether stress undeniably and consistently induces cellular changes in the brain, which currently remains unanswered. The same gene variations that mediate how strongly a person feels stress in response to life events may also be linked with a patient’s ability to abstain from drugs after a period of substance abuse.

Specific genetic changes are linked both to stress responses and an ability to abstain from addictive substances. A multi-center research study examined over 1000 participants who were recovering from heroin addiction.² Participants who had specific genetic variations were better able to avoid relapse than participants who did not have this variation. Interestingly, the gene variations identified-CRHBP rs1500, NPY1R/NPY5R rs4234955, and NR3C1 rs10482672-are associated with variations in individual stress response. The researchers suggested that these results could point to a possible link between abnormal stress regulation and a vulnerability to relapse.

In another study, Peles and colleagues³ examined the effects of gene variations in OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP on cocaine use. Findings revealed that “reduction in cocaine abuse may be mediated by a genetic effect in a stress-related gene.” These results suggest that the effects of the stress genes on drug use are correlated with several drugs, not only with one drug of abuse.

The bottom line

It appears that stress can increase predisposition to SUD through changes in neuronal activity that occur at the cellular level. Genetic factors that increase susceptibility to drug abuse also appear to increase the chances of being highly impacted by stress.

It is possible that patients who have these genetic variations could also be more susceptible to the cellular changes associated with stress and SUDs, but a definitive link with a genetic predisposition to the noted structural changes has not been established.

Take home points

• Stress can change the microstructure of the brain in a way that predisposes a person to drug abuse.

• There are individual differences in stress response, and these differences are sometimes linked to an individual’s ability to abstain from addictive substances.

• Treatment approaches to reduce the effects of anatomical changes in the brain can include behavioral approaches and non-pharmacological interventions (eg, counseling).

Dr Moawad is Adjunct Professor at John Carroll University, and Instructor, Case Western Reserve University in Cleveland, OH. She is the Editor in Chief Emeritus of Neurology Times (2017-2019).