title: Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.
abstract: BACKGROUND
  Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results.
  
  
  OBJECTIVE
  The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants.
  
  
  METHODS
  We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis.
  
  
  RESULTS
  THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions.
  
  
  CONCLUSIONS
  In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.
authors: Brain Center Rudolf Magnus, Department of Psychiatry, A01.126, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands, m.bossong@umcutrecht.nl.
authors: Matthijs G
authors: MG
authors: Bossong
authors: Mitul A
authors: MA
authors: Mehta
authors: Bart N M
authors: BN
authors: van Berckel
authors: Oliver D
authors: OD
authors: Howes
authors: René S
authors: RS
authors: Kahn
authors: Paul R A
authors: PR
authors: Stokes
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism*; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2; D020891:Raclopride; D013759:Dronabinol; D004298:Dopamine