MDMA, cortisol, and heightened stress in recreational ecstasy users

Recreational use of MDMA (ecstasy) increases cortisol levels, a marker of stress, both immediately and over longer periods. In laboratory settings, acute use raises cortisol by 100-200%, while dance clubbers combining the drug with dancing experience an 800% increase. Abstinent users' three-month hair samples show cortisol levels 400% higher than controls. Chronic users exhibit heightened cortisol in stressful settings, deficits in complex cognitive tasks, and altered brain activation patterns suggesting increased mental effort. Mood deficits include more daily stress and higher depression in susceptible individuals. Changes in the hypothalamic-pituitary-adrenal (HPA) axis may explain these neuropsychobiological stress effects.

Study at a glance

Abstract

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.