In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users
Vibe G. Frøkjær, David Erritzøe, Klaus K. Holst, Kathrine Skak Madsen, Patrick M. Fisher, Jacob Madsen, Claus Svarer, Gitte M. Knudsen
The International Journal of Neuropsychopharmacology February 14, 2014 DOI: 10.1017/s1461145714000066 via OpenAlex
Summary
Prefrontal serotonin transporter binding is positively associated with the cortisol awakening response, a measure of hypothalamic-pituitary-adrenal-axis output, in both MDMA users and non-users. MDMA users showed a significantly higher cortisol awakening response than non-users. The findings suggest that the inhibitory control on HPA-axis output is less efficient after recent MDMA use, likely through mechanisms beyond those compensated by reduced serotonin transporter levels.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 50 |
| Population | MDMA users and non-using healthy volunteers |
| Topics | MDMA Serotonin |
| Keywords | Serotonin transporter Psychiatry Clinical psychology Internal medicine |
| Citations | 19 |
| Key finding | Prefrontal serotonin transporter binding is positively associated with cortisol awakening response, and MDMA users show significantly higher cortisol awakening response than non-users. |
Abstract
Serotonergic signaling is considered critical for an appropriate adaptation to stress. We have previously observed that in healthy volunteers, prefrontal serotonin transporter (SERT) binding is positively associated with hypothalamic-pituitary-adrenal (HPA)-axis output in terms of the cortisol awakening response (CAR). Here, we tested (1) if such a correlation persists in a human model of chronic serotonin depletion, namely in 3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') users, and (2) if CAR differed between MDMA users (N = 18) and non-using healthy volunteers (N = 32). Participants underwent SERT brain imaging with [11C]DASB-PET, and performed home-sampling of CAR, defined as the area under curve with respect to cortisol increase from awakening level. When adjusting for age and group, CAR was positively coupled to prefrontal SERT binding (p = 0.006) and MDMA users showed significantly higher CAR than the control group (p = 0.0003). In conclusion, our data confirm the recently described positive association between prefrontal SERT binding and CAR, this time in a human model of serotonin deficiency. Also, we find that CAR was higher in MDMA users relative to non-users. We suggest that the inhibitory control on HPA-axis output is less efficient in the off-balance state established by recent MDMA use, most likely through mechanisms other than those that can be compensated by lowering SERT levels.