A systematic review found that anhedonia in depression and amotivation in cannabis use involve similar brain regions (anterior cingulate, nucleus accumbens, medial prefrontal cortex) but no consistent biomarkers have been identified.
Neuroscience researchers, psychiatrists treating comorbid depression and cannabis use, neuroimaging researchers
What the researchers found
Across 46 articles, brain regions most frequently associated with anhedonia across neuroimaging studies were the anterior cingulate cortex, nucleus accumbens, and medial prefrontal cortex, which are the same regions implicated in cannabis-related reward processing deficits. However, no biochemical marker (including IL-6 and CRP) was consistently associated with anhedonia, and only 2 articles specifically examined amotivation in cannabis use. Study designs and anhedonia measures were highly heterogeneous.
Why it matters
The neurobiological overlap between depression-related anhedonia and cannabis-related amotivation could inform shared treatment approaches. Understanding these deficits in adolescents may be particularly important given the co-development of mood disorders and cannabis use during this period.
The numbers in context
46 articles included (44 on depression/anhedonia, 2 on cannabis/amotivation); key brain regions: anterior cingulate cortex, nucleus accumbens, medial prefrontal cortex; no consistent biochemical biomarkers found
How the study worked
Systematic review searching 8 electronic databases. Included original research on biological factors or behavioral tasks associated with anhedonia in depression (44 articles) or amotivation in cannabis use (2 articles). PROSPERO-registered.
What this study cannot tell us
Overwhelmingly focused on depression (44 studies) vs cannabis (only 2 studies). Heterogeneous study designs prevent quantitative synthesis. Most anhedonia measures were self-report. Small sample sizes in many included studies. Cannot determine if shared brain regions reflect shared pathology or coincidental overlap.
How to read the evidence
Moderate: systematic review with PROSPERO registration, but limited by extreme imbalance in literature (44 vs 2 studies) and heterogeneous methods.
When this study was published
2025 publication
The bigger picture
The "amotivational syndrome" long attributed to cannabis use and the anhedonia of depression may share common neurobiological roots in disrupted reward processing. Identifying shared mechanisms could unlock treatments that address both conditions simultaneously.
Questions still open
- Would treatments targeting reward processing deficits improve both depression and cannabis-related amotivation?
- Why has cannabis-related amotivation received so little rigorous biological investigation?
Read the original research
A Systematic Review: Investigating Biomarkers of Anhedonia and Amotivation in Depression and Cannabis Use.
JAACAP open, 3(3), 379-405
Citation
Hinckley, Jesse D; Conner, Bradley T; Mauch, Roseanne; Arkfeld, Patrice A; Bhatia, Devika; Smith, Emma E; Svoboda, Ellie; Singh, Manpreet K. (2025). A Systematic Review: Investigating Biomarkers of Anhedonia and Amotivation in Depression and Cannabis Use.. JAACAP open, 3(3), 379-405. https://doi.org/10.1016/j.jaacop.2024.08.005
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