title: Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.
abstract: BACKGROUND
  Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms. Method In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.
  
  
  RESULTS
  The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.
  
  
  CONCLUSIONS
  In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.
authors.affiliation: Section of Neuroimaging, Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. Zerrin.Atakan@kcl.ac.uk
authors.forename: Z
authors.initials: Z
authors.lastname: Atakan
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: P
authors.initials: P
authors.lastname: Allen
authors.forename: R
authors.initials: R
authors.lastname: Martín-Santos
authors.forename: J A
authors.initials: JA
authors.lastname: Crippa
authors.forename: S J
authors.initials: SJ
authors.lastname: Borgwardt
authors.forename: P
authors.initials: P
authors.lastname: Fusar-Poli
authors.forename: M
authors.initials: M
authors.lastname: Seal
authors.forename: H
authors.initials: H
authors.lastname: Sallis
authors.forename: D
authors.initials: D
authors.lastname: Stahl
authors.forename: A W
authors.initials: AW
authors.lastname: Zuardi
authors.forename: K
authors.initials: K
authors.lastname: Rubia
authors.forename: P
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002531:Cerebellum / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D013759:Dronabinol / Q000494:pharmacology*; D059907:Functional Neuroimaging; D006213:Hallucinogens / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020534:Parahippocampal Gyrus / Q000187:drug effects / Q000503:physiopathology; D011605:Psychoses, Substance-Induced / Q000209:etiology* / Q000503:physiopathology; D013702:Temporal Lobe / Q000187:drug effects / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D013759:Dronabinol