“Background: recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. the understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. however, recent studies in both healthy and clinical populations suggest a role for personality changes. aim: to test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (mdma) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2a-receptor binding). methods: in 10 psychedelic-preferring recreational users, 14 mdma-preferring users and 21 non-using controls, personality was assessed using the ‘big five‘ instrument revised neo personality inventory (neo-pi-r). frontal serotonin transporter and serotonin-2a-receptor binding potentials were quantified using [11c]dasb and [18f]altanserin positron emission tomography, respectively. results: of the five neo-pi-r traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both mdma-preferring users and controls. openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all mdma-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2a-receptor binding – was positively associated with openness to experience. conclusion: our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of “recreational” psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. a modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.”