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The effects of Δ9-tetrahydrocannabinol on the dopamine system

Abstract

The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid–dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system. Acute THC administration causes increased dopamine release and neuron activity, whereas long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of THC.

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Figure 1: THC binds to CB1 receptors on glutamatergic and GABAergic neurons, disrupting normal endocannabinoid retrograde signalling from dopaminergic neurons135.
Figure 2: Summary of the acute effects of THC on dopaminergic function.
Figure 3: Cannabis use in humans is associated with reduced dopamine in the striatum. PET studies have shown lower striatal dopamine synthesis and release capacity in cannabis users.

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Acknowledgements

We thank V. M. Rajagopal and Nature for assistance with illustrations. This work was funded by a Medical Research Council (UK) Grant to O.D.H. (MC-A656-5QD30).

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M.A.P.B. and O.D.H. conceptualized this review. M.A.P.B. and A.H.A. systematically reviewed the literature. All the authors contributed intellectually.

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Correspondence to Oliver D. Howes.

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M.A.P.B. conducts research funded by the Medical Research Council (UK), the National Institute of Health Research (UK) and the British Medical Association. A.H.A. conducts research funded by the Medical Research Council (UK) and Kings College London. N.D.V. is Director of the National Institute on Drug Abuse (USA). O.D.H. conducts research funded by the Medical Research Council (UK), the National Institute of Health Research (UK) and the Maudsley Charity. O.D.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Astra-Zeneca, BMS, Eli Lilly, Jansenn, Lundbeck, Lyden-Delta, Servier, and Roche. Neither O.D.H. nor his family have been employed by or have holdings/a financial stake in any biomedical company.

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Nature thanks P. Fadda and R. Mechoulam for their contribution to the peer review of this work.

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Bloomfield, M., Ashok, A., Volkow, N. et al. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature 539, 369–377 (2016). https://doi.org/10.1038/nature20153

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