Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis.
BACKGROUND
Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms.


OBJECTIVE
To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning.


METHODS
Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design.


METHODS
University research center.


METHODS
Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime.


METHODS
Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation.


RESULTS
Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect.


CONCLUSIONS
The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.
Section of Neuroimaging, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, Box P067, De Crespigny Park, London SE5 8AF, England. s.bhattacharyya@iop.kcl.ac.uk
Sagnik
S
Bhattacharyya
Paolo
P
Fusar-Poli
Stefan
S
Borgwardt
Rocio
R
Martin-Santos
Chiara
C
Nosarti
Colin
C
O'Carroll
Paul
P
Allen
Marc L
ML
Seal
Paul C
PC
Fletcher
José A
JA
Crippa
Vincent
V
Giampietro
Andrea
A
Mechelli
Zerrin
Z
Atakan
Philip
P
McGuire
D000284:Administration, Oral; D000328:Adult; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D002185:Cannabidiol / Q000493:pharmacokinetics / Q000494:pharmacology; D002188:Cannabis; D003342:Corpus Striatum / Q000187:drug effects*; D004311:Double-Blind Method; D013759:Dronabinol / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D010100:Oxygen / Q000097:blood*; D010153:Paired-Associate Learning / Q000187:drug effects*; D020534:Parahippocampal Gyrus / Q000187:drug effects; D011605:Psychoses, Substance-Induced / Q000503:physiopathology*; D013702:Temporal Lobe / Q000187:drug effects*
D002185:Cannabidiol; D013759:Dronabinol; D010100:Oxygen