Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users

Abstract

Aims: 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. Methods: The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. Results: Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. Conclusions: The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage.

MDMA: Neurohormonal, Neurocognitive, and Psychobiological Aspects of Recreational Ecstasy

“…This is consistent with the animal literature, where high ambient temperature and other metabolic stimulants boost the acute effects of MDMA, and cause greater serotonergic neurotoxicity [21,29]. These multiple influences have been integrated within a bioenergetic stress model for recreational MDMA [24,27]. According to this model, metabolic cellular activity is increased by MDMA and other CNS stimulants.…”

“…The putative role of oxytocin was debated by Gillian Broadbear in the previous paragraph. Here the energetic stress neurohormone cortisol was debated [27]. In a recent study of Ecstasy using dance clubbers, where MDMA was biochemically confirmed, an 800% increase in cortisol emerged.…”

“…This drug-induced activation is further enhanced by environmental co-stimulants; these may make the drug more rewarding, but which also increase cellular distress. Hence according to the bioenergetic stress model, the longer term neuropsychobiological consequences will reflect a complex amalgam of drug and non-drug factors [24,27].…”

Prospective Memory: The Influence of Ecstasy, Cannabis and Nicotine Use and the WWW

“…Given the high frequency of tobacco smokers who also use ecstasy and the finding here that suggests that the use of both substances may work additively to confer greater vulnerability, more work needs to be undertaken to explore the psychobiological effects of tobacco/ecstasy co-use. For instance, in one study Ecstasy users had significantly higher cortisol levels during tobacco abstinence, than an equivalent group of abstaining smokers who were not MDMA users [7,8]. The differences between the data from the bulletin board and non-bulletin board participants reported here are intriguing and clearly warrant further investigation, including a more in-depth exploration of user characteristics from different website addresses and the complex relationship between beliefs, performance and self reports of functioning.…”

Psychiatric Aspects Of MDMA (3,4-Methylenedioxymethamphetamine): The ‘Diathesis-Stress’ Explanatory Model

“…(MDMA) or 'Ecstasy', is a powerful sympathomimetic and metabolic stressor [1,2]. As with every other recreational stimulant, this methamphetamine derivative is associated with increased levels of psychiatric distress.…”