P.363 Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Madsen MK1,2, Fisher PM1, Burmester D1,2, Dyssegaard A1, Stenbæk DS1, Kristiansen S1, Johansen SS4, Lehel S3, Linnet K4, Svarer C1, Erritzoe D5, Ozenne B6, Knudsen GM1,2

Introduction Results 5-HT R BP •Psilocybin is a psycheTelic anT promising novel 2A ND treatment for mental TisorTers Occmnx = 77% •Psychoactive effects via serotonin 2A receptor EC50 = 1.95 μg/L R2 = 0.92 (5-HT2AR) but brain occupancy not TescribeT 11 •[ C]Cimbi-36 is 5-HT2AR agonist PET raTiotracer •We evaluateT psilocybin-inTuceT brain 5-HT2AR occupancy (eq. 1) in eight healthy humans •We evaluateT occupancy association rith: •plasma psilocin (active metabolite) (eq. 2) •subjective intensity of experience Participants and Methods Pnst psych. Dose w.n. dose Menn Psilocin Menn Psilocin 5-HT R Occ 5-HT R Occ Pnrticipnnt Age Sex 2A 2A use (mg) (mg/kg) PET1 ( μ g/L) PET2 ( μ g/L) PET1 (%) PET2 (%) 1 33 F Psi: 2; LSD: 1 3 0.05 1.9

 !"# $% &#
  ' ()) (1)  !"# 
  (2)  Intmnx = 10.8 EC50 = 4.5 μg/L Intervention day R2 = 0.35

Self-reporteT subjective intensity associateT rith brain 5-HT2AR occupancy (left) anT plasma psilocin levels (right). Psilocin and intensity time courses Conclusion

•First report of psilocybin-inTuceT 5-HT2AR occupancy in living human brain •Plasma psilocin very gooT marker for brain occupancy •Subjective intensity correlateT rith brain occupancy anT plasma psilocin levels

•Consistent rith central role of 5-HT2AR in psilocybin-inTuceT psycheTelic experience

1Neurobiology Research Unit, Rigshospitalet; 2Faculty of Health anT MeTical Sciences, University of Copenhagen; 3PET anT Cyclotron [email protected] Unit, Rigshospitalet; 4Department of Forensic MeTicine, University of Copenhagen; 6Section of Biostatistics, University of Copenhagen, Denmark; 5PsycheTelic Research Group, Imperial College LonTon, UniteT KingTom np.nru.Tk