Sci Rep
October 13, 2017
Robin L Carhart-Harris, Leor Roseman, Mark Bolstridge et al.
590 citations
In patients with treatment-resistant depression, a single dose of psilocybin combined with psychological support reduced depressive symptoms and altered brain activity and connectivity. Functional MRI scans before and after treatment showed decreased blood flow in the temporal cortex, including the amygdala, and increased resting-state functional connectivity within the default-mode network. Reduced amygdala blood flow correlated with fewer depressive symptoms. Changes in connectivity between the ventromedial prefrontal cortex and inferior lateral parietal cortex, as well as between the parahippocampus and prefrontal cortex, predicted treatment response at five weeks. These brain changes differ from the drug's acute effects and suggest a 'reset' of neural circuits.
J Psychopharmacol
June 15, 2020
Anna Borissova, Bart Ferguson, Matthew B Wall et al.
37 citations
MDMA did not increase prosocial behavior in a controlled laboratory setting, despite raising blood levels of the drug and self-reported feelings of closeness and euphoria. In a double-blind, placebo-controlled experiment with 20 healthy volunteers, MDMA (100 mg) failed to significantly change task-based measures of empathy, trust, or cooperative behavior compared to placebo. Bayesian analyses supported the conclusion that MDMA and placebo had equivalent effects on empathy and cooperation. The drug also did not alter mood three days after administration. These findings suggest that the acute prosocial effects of MDMA observed in naturalistic or therapeutic contexts may not replicate under controlled experimental conditions.
J Psychopharmacol
December 13, 2021
Ben Sessa, Jacob S Aday, Steve O’Brien et al.
18 citations
An open-label study of 14 participants found that mood remained positive during the week after receiving MDMA in a clinical setting, contrary to the 'Blue Monday' crash reported by recreational users. Self-reported sleep quality improved at 3- and 6-month follow-ups compared to baseline. No participants used or desired to use illicit MDMA, and anecdotal reports were favorable. The findings suggest that negative after-effects previously associated with MDMA may stem from confounds such as illicit drug sourcing and recreational settings, rather than the drug itself.
medRxiv Preprint Server
December 7, 2020
Vasileia Kotoula, Argyris Stringaris, Nuria Mackes et al.
9 citations
preprint
Ketamine, an antidepressant, can alter activity in brain reward areas within two hours of a single infusion, even in people who are not currently depressed. In a study of 37 remitted depression patients, ketamine increased brain responses in the nucleus accumbens and putamen during anticipation and receipt of small rewards, and the level of a ketamine metabolite (2R,6R)-HNK correlated with activation in the ventral tegmental area. These changes occurred without any changes in mood symptoms, suggesting ketamine may improve anhedonia by directly modulating how the brain processes reward feedback.
Drug and alcohol dependence
September 12, 2025
Matthijs Blankers, Ruben Van Beek, Desirée Spronk et al.
1 citation
In the three days after using ecstasy/MDMA, young adults who regularly use the drug report a small but significant drop in mental well-being, even after accounting for other substance use, sleep, and baseline depression or anxiety. Cocaine co-use and poor sleep further worsened the effect. No similar drop was seen after use of other common substances. The findings suggest the post-acute mood decline is specifically linked to ecstasy/MDMA, not just party or lifestyle factors.