The Translation Gap: From Rodent Circuits to Human Disease

This section is represented as a source-backed SciDEX wiki artifact. The full source remains in the original computational-review repository.

Source: https://github.com/AllenNeuralDynamics/ComputationalReviewAddiction/blob/43d33061a22aa4fed3f7dc71fabbfa48ab1d6f48/content/08_species_translation.md

Citation anchors captured: 107

Citation contexts

^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience’s record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference} demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference} This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3 This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7 This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0 demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2....
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4....
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6....
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8....
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0....
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 Several structural factors help explain the systematic attrition ({numref}fig-sec8-translation-pipeline). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2....
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3 (A) Candidate gene odds ratios reported in small-sample studies compared to the typical effect size range observed in genome-wide association studies. The shaded region indicates the range of individual variant ORs detected at genome-wide significance. (B) Approximate attrition of pharmacological compounds across the translational pipeline for cocaine use disorder, illustrating near-total loss from preclinical scree...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4 (A) Candidate gene odds ratios reported in small-sample studies compared to the typical effect size range observed in genome-wide association studies. The shaded region indicates the range of individual variant ORs detected at genome-wide significance. (B) Approximate attrition of pharmacological compounds across the translational pipeline for cocaine use disorder, illustrating near-total loss from preclinical scree...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6 Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7 Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8 Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0 The foundational observation, reported by ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1, was that individually housed cynomolgus monkeys showed no initial differences in D2 receptor availability, but after formation of social hierarchies, dominant monkeys developed higher D2 receptor levels and were less vulnerable to cocaine reinforcement. ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2 extended this finding, demonstrating that dominant monkeys had higher D2 receptor levels and were...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3 The foundational observation, reported by ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4, was that individually housed cynomolgus monkeys showed no initial differences in D2 receptor availability, but after formation of social hierarchies, dominant monkeys developed higher D2 receptor levels and were less vulnerable to cocaine reinforcement. ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 extended this finding, demonstrating that dominant monkeys had higher D2 receptor levels and were...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6 The foundational observation, reported by ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7, was that individually housed cynomolgus monkeys showed no initial differences in D2 receptor availability, but after formation of social hierarchies, dominant monkeys developed higher D2 receptor levels and were less vulnerable to cocaine reinforcement. ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8 extended this finding, demonstrating that dominant monkeys had higher D2 receptor levels and were...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 The foundational observation, reported by ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0, was that individually housed cynomolgus monkeys showed no initial differences in D2 receptor availability, but after formation of social hierarchies, dominant monkeys developed higher D2 receptor levels and were less vulnerable to cocaine reinforcement. ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 extended this finding, demonstrating that dominant monkeys had higher D2 receptor levels and were...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4, and exposure during treatment can counte...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7, and exposure during treatment can counte...
^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{1Citationpaper:paper-419ce7456ebfThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0, and exposure during treatment can counte...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3, and exposure during treatment can counte...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6, and exposure during treatment can counte...
^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{3Citationpaper:paper-c3b758fa4c59The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9, and exposure during treatment can counte...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2, and exposure during treatment can counte...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3 Social status and D2 receptors: cause or consequence? The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5, and exposure during treatment can counte...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7, alpha-2 agonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8, and combined approaches ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 — have generally produced modest effects that are difficult to sustain. ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}0 reported that alpha-2 receptor agonists produced only small decrea...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}1 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}2, alpha-2 agonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}3, and combined approaches ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}4 — have generally produced modest effects that are difficult to sustain. ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}5 reported that alpha-2 receptor agonists produced only small decrea...
^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}6 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}7, alpha-2 agonists ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}8, and combined approaches ^{4Citationpaper:paper-f76f47e3d3c8The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}9 — have generally produced modest effects that are difficult to sustain. ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}0 reported that alpha-2 receptor agonists produced only small decrea...
^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}1 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}2, alpha-2 agonists ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}3, and combined approaches ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}4 — have generally produced modest effects that are difficult to sustain. ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}5 reported that alpha-2 receptor agonists produced only small decrea...
^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}6 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}7, alpha-2 agonists ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}8, and combined approaches ^{5Citationpaper:paper-163c3e962aa8This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...content/08_species_translation.md:line 11Open reference}9 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}00 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}01 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}02, alpha-2 agonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}03, and combined approaches ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}04 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}05 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}06 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}07, alpha-2 agonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}08, and combined approaches ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}09 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}10 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}11 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}12, alpha-2 agonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}13, and combined approaches ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}14 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}15 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}16 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}17, alpha-2 agonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}18, and combined approaches ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}19 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}20 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}21 The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}22, alpha-2 agonists ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}23, and combined approaches ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}24 — have generally produced modest effects that are difficult to sustain. ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}25 reported that alpha-2 receptor agonists produced only small decrea...
^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}26 Functional neuroimaging has produced robust group-level differences between substance users and controls across multiple paradigms and brain regions, yet the translation of these findings into individually predictive biomarkers remains elusive ^{2Citationpaper:paper-751642f6a86dThe most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...content/08_species_translation.md:line 9Open reference}27. PET studies have consistently demonstrated reduced D2 receptor availability in individuals with stimulant, alcohol, and o...
... 57 additional anchors in refs_json

References

[Czoty2016] paper:paper-419ce7456ebf “The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...”
[Nieto2025] paper:paper-751642f6a86d “The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...”
[Roberts2026] paper:paper-c3b758fa4c59 “The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...”
[Costa2026] paper:paper-f76f47e3d3c8 “The most direct test of mechanistic understanding is whether it enables therapeutic intervention. By this criterion, addiction neuroscience's record is sobering. Despite decades of preclinical research identifying molecular targets across dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems, the pipeline from bench to bedside has yielded remarkably few FDA-approved medications — and none for cocaine u...”
[Rodrigues2022] paper:paper-163c3e962aa8 “This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...”
[Zurrer2025] paper:paper-e6dc2de020f7 “This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...”
[Zannas2016] paper:paper-3e4ba155ac18 “This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...”
[Mantsch2022] paper:paper-27bb5f98af7d “This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...”
[Black2025] paper:paper-e7e8ad2f870a “This is not simply a statistical problem of insufficient power or a matter of time. Recent meta-analytic work highlights the pattern across drug classes: [Costa2026] demonstrated that cannabinoid CB-1R inverse agonists (SMD = −1.21) and CBD (SMD = −0.70) reduced alcohol intake in preclinical models, while CB-1R agonists increased consumption (SMD = +0.66) — robust preclinical signals that have not yielded approved t...”
[Webster2014] paper:paper-eabc66d6f001 “Several structural factors help explain the systematic attrition ({numref}`fig-sec8-translation-pipeline`). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders [Czoty2016, Mantsch2022, Webster2014]....”
[Gould2014] paper:paper-02fc0e23ff8e “Several structural factors help explain the systematic attrition ({numref}`fig-sec8-translation-pipeline`). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders [Czoty2016, Mantsch2022, Webster2014]....”
[Kalueff2016] paper:paper-9bc0eb775064 “Several structural factors help explain the systematic attrition ({numref}`fig-sec8-translation-pipeline`). Rodent SA typically employs fixed-ratio schedules with single-drug access in experimentally naive, singly housed male animals — conditions that poorly approximate the polydrug use, social context, and psychiatric comorbidity characteristic of human substance use disorders [Czoty2016, Mantsch2022, Webster2014]....”
[Annis2025] paper:paper-127ac8ea610d “(A) Candidate gene odds ratios reported in small-sample studies compared to the typical effect size range observed in genome-wide association studies. The shaded region indicates the range of individual variant ORs detected at genome-wide significance. (B) Approximate attrition of pharmacological compounds across the translational pipeline for cocaine use disorder, illustrating near-total loss from preclinical scree...”
[Morgan2000] paper:paper-dcac47917f69 “Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...”
[Czoty2004] paper:paper-bf75292b651b “Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...”
[Nader2008] paper:paper-73629e3832e1 “Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...”
[Czoty2010] paper:paper-98f6a1474183 “Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...”
[Nader2012] paper:paper-516d76717857 “Nonhuman primate research occupies a critical intermediate position in the translational chain, offering closer neuroanatomical and behavioral homology to humans than rodent models while permitting experimental manipulations impossible in human studies. The most extensively studied NHP model in addiction neuroscience involves social-hierarchy manipulations in cynomolgus macaques, where the relationship between socia...”
[Czoty2013] paper:paper-b3639fe812ab “**Social status and D2 receptors: cause or consequence?** The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies [Morgan2000, Czoty2004, Czoty2010]. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability [Nader2012, Czoty2013], and exposure during treatment can counte...”
[Johnson2023] paper:paper-36cf13fa60e1 “**Social status and D2 receptors: cause or consequence?** The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies [Morgan2000, Czoty2004, Czoty2010]. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability [Nader2012, Czoty2013], and exposure during treatment can counte...”
[Johnson2025] paper:paper-8cb39cb78b62 “**Social status and D2 receptors: cause or consequence?** The canonical narrative — that social subordination reduces D2 receptors, which increases cocaine vulnerability — rests on strong correlational evidence from NHP studies [Morgan2000, Czoty2004, Czoty2010]. However, the causal direction remains contested. Cocaine SA itself reduces D2 availability [Nader2012, Czoty2013], and exposure during treatment can counte...”
[Czoty2015] paper:paper-36a9fbdf2e1a “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Czoty2020] paper:paper-bf9ce37d446e “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Czoty2017] paper:paper-8c7e62b966cd “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Czoty2021] paper:paper-d9e47b6242e9 “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Czoty2012] paper:paper-941e37bcd15c “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Yamaguchi2017] paper:paper-2179a9cede70 “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[GalboThomma2025] paper:paper-16aa6b22f730 “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Bajo2026] paper:paper-f214b8eb08b1 “The NHP pharmacotherapy literature also reveals the translation gap in microcosm. Systematic efforts to reduce cocaine choice using dopaminergic agents — including D3 antagonists [Czoty2015], alpha-2 agonists [Czoty2020], and combined approaches [Czoty2017, Czoty2021] — have generally produced modest effects that are difficult to sustain. [Czoty2020] reported that alpha-2 receptor agonists produced only small decrea...”
[Nader2014] paper:paper-1b727c7d5647 “Functional neuroimaging has produced robust group-level differences between substance users and controls across multiple paradigms and brain regions, yet the translation of these findings into individually predictive biomarkers remains elusive [Nader2014, MahdaviDoost2025, Brand2014, Volkow2006]. PET studies have consistently demonstrated reduced D2 receptor availability in individuals with stimulant, alcohol, and o...”
[MahdaviDoost2025] paper:paper-6b3206d4b704 “Functional neuroimaging has produced robust group-level differences between substance users and controls across multiple paradigms and brain regions, yet the translation of these findings into individually predictive biomarkers remains elusive [Nader2014, MahdaviDoost2025, Brand2014, Volkow2006]. PET studies have consistently demonstrated reduced D2 receptor availability in individuals with stimulant, alcohol, and o...”
[Brand2014] paper:paper-7dd579645da8 “Functional neuroimaging has produced robust group-level differences between substance users and controls across multiple paradigms and brain regions, yet the translation of these findings into individually predictive biomarkers remains elusive [Nader2014, MahdaviDoost2025, Brand2014, Volkow2006]. PET studies have consistently demonstrated reduced D2 receptor availability in individuals with stimulant, alcohol, and o...”
[Volkow2006] paper:paper-244a5ee39ed8 “Functional neuroimaging has produced robust group-level differences between substance users and controls across multiple paradigms and brain regions, yet the translation of these findings into individually predictive biomarkers remains elusive [Nader2014, MahdaviDoost2025, Brand2014, Volkow2006]. PET studies have consistently demonstrated reduced D2 receptor availability in individuals with stimulant, alcohol, and o...”

Sister wikis (recently updated · no domain on this page)

Recent activity here

No recent events touching this page.