Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum

Neuropsychopharmacology. 2009 Feb;34(3):759-66. doi: 10.1038/npp.2008.138. Epub 2008 Aug 27.

Abstract

The influence of cannabis on mental health receives growing scientific and political attention. An increasing demand for treatment of cannabis dependence has refueled the discussion about the addictive potential of cannabis. A key feature of all addictive drugs is the ability to increase synaptic dopamine levels in the striatum, a mechanism involved in their rewarding and motivating effects. However, it is currently unknown if cannabis can stimulate striatal dopamine neurotransmission in humans. Here we show that Delta 9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum. Using the dopamine D(2)/D(3) receptor tracer [(11)C]raclopride and positron emission tomography in seven healthy subjects, we demonstrate that THC inhalation reduces [(11)C]raclopride binding in the ventral striatum and the precommissural dorsal putamen but not in other striatal subregions. This is consistent with an increase in dopamine levels in these regions. These results suggest that THC shares a potentially addictive property with other drugs of abuse. Further, it implies that the endogenous cannabinoid system is involved in regulating striatal dopamine release. This allows new directions in research on the effects of THC in neuropsychiatric disorders, such as schizophrenia.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Cannabinoid Receptor Modulators / physiology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Cross-Over Studies
  • Dopamine / metabolism*
  • Double-Blind Method
  • Dronabinol / analogs & derivatives
  • Dronabinol / blood
  • Dronabinol / pharmacology*
  • Heart Rate / drug effects
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Placebos
  • Positron-Emission Tomography
  • Psychiatric Status Rating Scales
  • Raclopride / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism

Substances

  • Cannabinoid Receptor Modulators
  • Placebos
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • 11-hydroxy-delta(9)-tetrahydrocannabinol
  • Raclopride
  • 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
  • Dronabinol
  • Dopamine