Drug-induced stress responses and addiction risk and relapse

Abstract

A number of studies have assessed the effects of psychoactive drugs on stress biology, the neuroadaptations resulting from chronic drug use on stress biology, and their effects on addiction risk and relapse. This review mainly covers human research on the acute effects of different drugs of abuse (i.e., nicotine, cannabis, psychostimulants, alcohol, and opioids) on the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) responses. We review the literature on acute peripheral stress responses in naïve or light recreational users and binge/heavy or chronic drug users. We also discuss evidence of alterations in tonic levels, or tolerance, in the latter relative to the former and associated changes in the phasic stress responses. We discuss the impact of the stress system tolerance in heavy users on their response to drug- and stress-related cue responses and craving as compared to control subjects. A summary is provided of the effects of glucocorticoid responses and their adaptations on brain striatal and prefrontal cortices involved in the regulation of drug seeking and relapse risk. Finally, we summarize important considerations, including individual difference factors such as gender, co-occurring drug use, early trauma and adversity and drug use history and variation in methodologies, that may further influence the effects of these drugs on stress biology.

“Chasing the first high”: memory sampling in drug choice

“…Finally, does the impact of stress on memory retrieval change with the adapted cortisol response often observed in chronic drug users 156? • While many studies suggest that drug-related memories are strongly encoded and persistent [156][157][158][159], little is known about the precise ways in which drugs alter memory encoding. The prominence of surprising rewards in memory recall [114,116] may arise from event boundaries introduced at encoding that establish the surprising reward memories as the primary event in a new context [115], a feature known to promote resistance to extinction [160].…”

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study

“…Some studies about this topic have revealed that a deviation of cortisol secretion away from the homeostatic diurnal pattern in cocaine-dependent subjects was associated with reduced success at achieving early abstinence [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. This finding suggests a feed-forward cascade of effects of drugs on stress biology [ 58 ]. Hence, chronic drug users are more vulnerable to negative affect, driving a cycle of increased drug use and stress disruption that further drive greater compulsive drug motivation and relapse risk.…”

“…Concerning this, some studies have demonstrated the influence of parental history of substance abuse on the risk of early drug abuse in their offspring [ 63 , 64 ], and for instance, higher morning cortisol levels have been found among crack cocaine users with positive family history and lower treatment retention [ 44 ]. Indeed, activation of the HPA response may be an early dysregulation associated with excessive and early drug taking that ultimately sensitizes the extrahypothalamic CRH systems [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , ...…”

Participant stress in the COVID-19 era and beyond

“…In the United States, these challenges have been disproportionately faced by Black and Indigenous people and other people of colour, who are also systematically exposed to more stressful experiences 1 , 2 . Isolation and lack of social support can also trigger maladaptive coping behaviours such as increased substance use that can potentiate risk for COVID-19-related complications 3 and interact with stress pathways to alter brain circuitry and cognitive function 4 .…”