{
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{
"n": null,
"doi": "10.1038/s41398-026-03954-2",
"value": "0.9%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Huang2026a",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "Louis, MO, United States) and cocaine hydrochloride were dissolved in 0.9% saline.",
"experimental_conditions": "NAC significantly reduced cocaine-seeking behavior on the first day of extinction but not in subsequ"
},
{
"n": null,
"doi": "10.3390/ijms27010385",
"value": "50%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Cancela2025",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "Between 50% and 65% of individuals with post-traumatic stress disorder (PTSD) also suffer from SUDs, with a prevalence three to five times higher than in the general population [ 7 , 8 ].",
"experimental_conditions": "Finally, the review discusses preclinical evidence supporting the therapeutic potential of repurpose"
},
{
"n": null,
"doi": "10.7554/elife.100085",
"value": "25%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Oriol2025",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "Glutamate neurons are also prevalent in VTA and overlap with other populations such that ~25% of VTA glutamate neurons co-express a DA marker and ~25% express a GABA marker ( Conrad et al., 2024 ; Ma et al., 2023 ; Phillips et al., 2022 ).",
"experimental_conditions": "Challenging previous assumptions, we found that VTA neurons genetically defined by expression of par"
},
{
"n": 3,
"doi": "10.1016/j.biopsych.2025.05.027",
"value": null,
"method": "various",
"metric": "primary mechanism",
"cite_key": "Wittenberg2026",
"n_analyzed": 3,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "mice",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": null,
"experimental_conditions": "Finally, VTA GABA neurons were chemogenetically inhibited during morphine CPP.<h4>Results</h4>In adu"
},
{
"n": null,
"doi": "10.1016/j.addicn.2025.100230",
"value": "85%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Tyler2025",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "For Pavlovian drug discrimination (Experiment 1) and alcohol metabolism (Experiment 2), rats were fed daily to maintain 85 % of free-feeding weight.",
"experimental_conditions": "TMT exposure produced a leftward shift in the alcohol dose-response curve, indicating increased inte"
},
{
"n": 2,
"doi": "10.1016/j.alcohol.2009.09.027",
"value": "30%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Bell2009",
"n_analyzed": 2,
"text_access": "abstract_only",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "Adult male HAD-2 rats were given access to ethanol (15 and 30%, with ad libitum access to water and food) 22 h/day for 12 weeks, beginning at 60 days of age, after which cytisine (0.0, 0.5, and 1.5 mg/kg) was tested for 3 consecutive days.",
"experimental_conditions": "These findings provide further evidence that activity at the nAChR influences ethanol intake and is "
},
{
"n": null,
"doi": "10.3389/fnins.2025.1670883",
"value": null,
"method": "various",
"metric": "primary mechanism",
"cite_key": "Jiang2025",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": null,
"experimental_conditions": "Understanding the relationship between nicotine addiction and nAChR subtypes is crucial for fully un"
},
{
"n": null,
"doi": "10.3389/fradm.2026.1737529",
"value": "24.6%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Sullivan2026",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "1 Introduction Cannabis is one of the most commonly used substances in the United States with approximately 24.6% of adolescents (grades 8, 10, 12) and 42.0% of young adults (aged 19–28) reporting past year use ( 1 , 2 ).",
"experimental_conditions": "<h4>Introduction</h4>Regular cannabis use is associated with attenuated neural reward signaling, pri"
},
{
"n": null,
"doi": "10.3390/plants15030473",
"value": "20%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Erukainure2026",
"n_analyzed": null,
"text_access": "fulltext",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "rats",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "An average joint contains about 0.5 to 1 g of cannabis (20% to 70% THC), with 5–24% of THC being absorbed by the body [ 2 ].",
"experimental_conditions": "However, emerging evidence indicates that chronic or excessive exposure to these phytocannabinoids m"
},
{
"n": null,
"doi": "10.1002/npr2.70033",
"value": "81.5%",
"method": "various",
"metric": "primary mechanism",
"cite_key": "Masataka2025",
"n_analyzed": null,
"text_access": "abstract_only",
"n_definition": "varies by study",
"scope_region": "mesolimbic circuit",
"study_system": "human",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed subjects",
"value_source_sentence": "A Sankey diagram visualized substance use progression, and odds ratios were calculated to assess the likelihood of using other substances following cannabis use.<h4>Results</h4>Of all respondents, 81.5% were male, with the largest age group being 20-24.",
"experimental_conditions": "Odds for subsequent use of alcohol, tobacco, methamphetamine, and other illicit drugs after cannabis"
}
],
"comparison_id": "fig_sec5_mechanism_by_drug_class",
"comparison_type": "mechanistic_comparison",
"homogeneity_check": {
"caveats": [
"Different drugs studied with different methodologies across different labs",
"Doses and routes of administration vary by study",
"Some mechanisms are better characterized than others (cocaine >> cannabis)"
],
"comparable": true,
"n_definition": "varies by study design",
"scope_region": "mesolimbic and related circuits",
"taxonomic_level": "drug class",
"scope_population": "drug-exposed animals or humans"
},
"suggested_plot_type": "comparison_table_or_heatmap"
}