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Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.
Psychopharmacology (Berl). 2015 Aug; 232(15):2723-9.P

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 [(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+Show Affiliations

Brain Center Rudolf Magnus, Department of Psychiatry, A01.126, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands, m.bossong@umcutrecht.nl.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25801289

Citation

Bossong, Matthijs G., et al. "Further Human Evidence for Striatal Dopamine Release Induced By Administration of ∆9-tetrahydrocannabinol (THC): Selectivity to Limbic Striatum." Psychopharmacology, vol. 232, no. 15, 2015, pp. 2723-9.
Bossong MG, Mehta MA, van Berckel BN, et al. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum. Psychopharmacology (Berl). 2015;232(15):2723-9.
Bossong, M. G., Mehta, M. A., van Berckel, B. N., Howes, O. D., Kahn, R. S., & Stokes, P. R. (2015). Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum. Psychopharmacology, 232(15), 2723-9. https://doi.org/10.1007/s00213-015-3915-0
Bossong MG, et al. Further Human Evidence for Striatal Dopamine Release Induced By Administration of ∆9-tetrahydrocannabinol (THC): Selectivity to Limbic Striatum. Psychopharmacology (Berl). 2015;232(15):2723-9. PubMed PMID: 25801289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum. AU - Bossong,Matthijs G, AU - Mehta,Mitul A, AU - van Berckel,Bart N M, AU - Howes,Oliver D, AU - Kahn,René S, AU - Stokes,Paul R A, Y1 - 2015/03/25/ PY - 2014/08/06/received PY - 2015/02/23/accepted PY - 2015/3/25/entrez PY - 2015/3/25/pubmed PY - 2016/2/26/medline SP - 2723 EP - 9 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 232 IS - 15 N2 - 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 [(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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/25801289/Further_human_evidence_for_striatal_dopamine_release_induced_by_administration_of_∆9_tetrahydrocannabinol__THC_:_selectivity_to_limbic_striatum_ L2 - https://dx.doi.org/10.1007/s00213-015-3915-0 DB - PRIME DP - Unbound Medicine ER -