Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.
Level 4 - case-series / case-control
Systematic review and meta-analysis of case-control imaging studies
PubMed 28297025 · doi:10.1001/jamapsychiatry.2017.0135
What was done
A systematic review and meta-analysis of PubMed, EMBASE, and PsycINFO (up to May 14, 2016) synthesized in vivo PET and SPECT imaging studies comparing striatal dopaminergic markers between stimulant users (cocaine, amphetamine, or methamphetamine) and healthy controls. Measured parameters included dopamine release (change in D2/D3 availability following a stimulant challenge), dopamine transporter (DAT) availability, receptor availability (D1, D2/D3), dopamine synthesis capacity, and vesicular monoamine transporter availability.
What was found
Across 31 case-control studies comprising 519 stimulant users and 512 healthy controls (abstinence mostly 5 days to 3 weeks), stimulant users showed significant reductions in: - Dopamine release: effect size = -0.84 (95% CI, -1.08 to -0.60; P < .001) for combined stimulants, and -0.87 (95% CI, -1.15 to -0.60; P < .001) for cocaine. - Dopamine transporter availability: effect size = -0.91 (95% CI, -1.50 to -0.32; P < .01) for combined stimulants, and -1.47 (95% CI, -1.83 to -1.10; P < .001) for amphetamine/methamphetamine. - D2/D3 receptor availability: effect size = -0.76 (95% CI, -0.92 to -0.60; P < .001) for combined stimulants, -0.73 (95% CI, -0.94 to -0.53; P < .001) for cocaine, and -0.81 (95% CI, -1.12 to -0.49; P < .001) for amphetamine/methamphetamine. No consistent alterations were found for vesicular monoamine transporter, dopamine synthesis, or D1 receptors.
Why it matters
This confirms widespread downregulation across both presynaptic (release, DAT) and postsynaptic (D2/D3 receptors) striatal dopamine systems in stimulant addiction, clarifying target mechanisms for pharmacotherapy.
Limits
All included studies were cross-sectional case-control designs, precluding causal inference regarding whether dopaminergic deficits precede or result from stimulant use. Most participants had short abstinence periods (5 days to 3 weeks), so persistence with long-term recovery remains unclear. Studies on D1 receptors, dopamine synthesis, and vesicular monoamine transporters were few and inconclusive.
Cited by
- supports Brain scans of individuals addicted to cocaine, methamphetamine, alcohol, or heroin show persistent dopamine transmission deficits two weeks after cessation of use.
- supports Brain imaging studies show that individuals stopping an addictive substance remain in a dopamine deficit state at two weeks of abstinence.