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Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum

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Abstract

Rationale

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.

Objectives

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 [11C]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 [11C]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.

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Abbreviations

BPND :

Non-displaceable binding potential

DVR:

Distribution volume ratio

PET:

Positron emission tomography

ROI:

Region of interest

SPECT:

Single-photon emission computed tomography

THC:

∆9-Tetrahydrocannabinol

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Acknowledgments

Dr. Matthijs Bossong was supported by a Rubicon grant from the Netherlands Organisation for Scientific Research. We would like to thank Dr. Ronald Boellaard and Dr. Lineke Zuurman for their help with data acquisition and analysis.

Conflict of interest

The authors declare no financial conflict of interest. The authors have full control of all primary data, and they agree to allow the journal to review their data if requested.

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Authors and Affiliations

  1. Brain Center Rudolf Magnus, Department of Psychiatry, A01.126, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Matthijs G. Bossong, Bart N. M. van Berckel & René S. Kahn

  2. Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK

    Matthijs G. Bossong & Oliver D. Howes

  3. Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, London, UK

    Mitul A. Mehta

  4. Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands

    Bart N. M. van Berckel

  5. Psychiatry Group, MRC Clinical Sciences Centre, Imperial College London, London, UK

    Oliver D. Howes & Paul R. A. Stokes

  6. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, King’s College London, London, UK

    Paul R. A. Stokes

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  1. Matthijs G. Bossong
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  2. Mitul A. Mehta
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  3. Bart N. M. van Berckel
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  6. Paul R. A. Stokes
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Corresponding author

Correspondence to Matthijs G. Bossong.

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Bossong, M.G., Mehta, M.A., van Berckel, B.N.M. et al. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum. Psychopharmacology 232, 2723–2729 (2015). https://doi.org/10.1007/s00213-015-3915-0

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