Therapeutic Implications: What Circuit Knowledge Has and Has Not Delivered
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1CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
9CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in{ref}sec-dopamine-dynamicsor{ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo 2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1. Nalmefene, an opioid receptor modulator, showed pharm... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo 2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3. Nalmefene, an opioid receptor modulator, showed pharm... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo 2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5. Nalmefene, an opioid receptor modulator, showed pharm... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6 For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo 2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7. Nalmefene, an opioid receptor modulator, showed pharm... -
2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 2CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9. Peter et al. (2026) described efficacy mediated by changes... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1. Peter et al. (2026) described efficacy mediated by changes... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3. Peter et al. (2026) described efficacy mediated by changes... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5. Peter et al. (2026) described efficacy mediated by changes... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7. Peter et al. (2026) described efficacy mediated by changes... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9. Peter et al. (2026) described efficacy mediated by changes... -
4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1. Peter et al. (2026) described efficacy mediated by changes... -
4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3. Peter et al. (2026) described efficacy mediated by changes... -
4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 4CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
5CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3, while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care 3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5 Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating{ref}sec-dopamine-dynamicsknowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6 Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating{ref}sec-dopamine-dynamicsknowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7 Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating{ref}sec-dopamine-dynamicsknowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8 Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating{ref}sec-dopamine-dynamicsknowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par... -
3CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9 Forest plot of neuromodulation effect sizes for substance use disorders. Each row represents a study or meta-analytic estimate, separated by stimulation modality (TMS, tES, dTMS). The pooled TMS effect from 116 sham-controlled RCTs is medium (g ≈ 0.4–0.5) with substantial heterogeneity. Studies vary in stimulation target (dlPFC, OFC, network-guided), protocol parameters (frequency, session count), substance type (ni... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 Forest plot of neuromodulation effect sizes for substance use disorders. Each row represents a study or meta-analytic estimate, separated by stimulation modality (TMS, tES, dTMS). The pooled TMS effect from 116 sham-controlled RCTs is medium (g ≈ 0.4–0.5) with substantial heterogeneity. Studies vary in stimulation target (dlPFC, OFC, network-guided), protocol parameters (frequency, session count), substance type (ni... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1 Forest plot of neuromodulation effect sizes for substance use disorders. Each row represents a study or meta-analytic estimate, separated by stimulation modality (TMS, tES, dTMS). The pooled TMS effect from 116 sham-controlled RCTs is medium (g ≈ 0.4–0.5) with substantial heterogeneity. Studies vary in stimulation target (dlPFC, OFC, network-guided), protocol parameters (frequency, session count), substance type (ni... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 The heterogeneity is as informative as the pooled estimate ({numref}fig-sec11-tms-effect-sizes). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies 6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3, while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 The heterogeneity is as informative as the pooled estimate ({numref}fig-sec11-tms-effect-sizes). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies 6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5, while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6 The heterogeneity is as informative as the pooled estimate ({numref}fig-sec11-tms-effect-sizes). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies 6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7, while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen... -
6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8 The heterogeneity is as informative as the pooled estimate ({numref}fig-sec11-tms-effect-sizes). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies 6CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9, while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 The heterogeneity is as informative as the pooled estimate ({numref}fig-sec11-tms-effect-sizes). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies 7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1, while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2 TMS for addiction: robust meta-analytic effects vs. null individual trials. The pooled meta-analytic effect from Soleimani et al. (2025) is statistically significant (g = 0.52 craving), but individual sham-controlled trials show markedly variable results. Guldas et al. (2025) found no significant effects for OUD (n=21), while Del Mauro et al. (2025) reported large effects for dTMS in cocaine use disorder. Protoc... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3 TMS for addiction: robust meta-analytic effects vs. null individual trials. The pooled meta-analytic effect from Soleimani et al. (2025) is statistically significant (g = 0.52 craving), but individual sham-controlled trials show markedly variable results. Guldas et al. (2025) found no significant effects for OUD (n=21), while Del Mauro et al. (2025) reported large effects for dTMS in cocaine use disorder. Protoc... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 TMS for addiction: robust meta-analytic effects vs. null individual trials. The pooled meta-analytic effect from Soleimani et al. (2025) is statistically significant (g = 0.52 craving), but individual sham-controlled trials show markedly variable results. Guldas et al. (2025) found no significant effects for OUD (n=21), while Del Mauro et al. (2025) reported large effects for dTMS in cocaine use disorder. Protoc... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5 Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers 7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) 7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7. Petersen et al. (2025) identified the superior front... -
7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8 Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers 7CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0. Petersen et al. (2025) identified the superior front... -
8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1 Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference2. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference3. Petersen et al. (2025) identified the superior front... -
8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference4 Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference5. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference6. Petersen et al. (2025) identified the superior front... -
8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference7 Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference8. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) 8CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference9. Petersen et al. (2025) identified the superior front... -
9CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}
sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference0 Emerging modalities extend beyond conventional TMS. Arulpragasam et al. (2026) described low-intensity focused ultrasound (FUS) as a promising non-invasive neuromodulation technique with the potential to deliver reversible and focal deep brain stimulation, noting that its spatial precision exceeds TMS, tES, and DBS 9CitationThe pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}sec-dopamine-dynamicsor {ref}sec-drug-specific. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...content/11_therapeutic_implications.md:line 8Open reference1. Tang et al. (2025) investigated theta burst stimulation (TBS) to the dlPFC for OUD... -
... 85 additional anchors in refs_json
References
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- [Townsend2020] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [PereiradaSilva2025] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Shulman2025] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Balise2024] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Winhusen2026] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Goutham2026] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Hayes2026] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [Shin2025] “The pharmacological treatments with the strongest clinical evidence base for substance use disorders (SUDs) were discovered through serendipity or clinical observation, not through rational design targeting the circuit mechanisms detailed in {ref}`sec-dopamine-dynamics` or {ref}`sec-drug-specific`. Methadone and buprenorphine, the most effective medications for opioid use disorder (OUD), are mu-opioid receptor agoni...”
- [CheibubDavidMarin2026] “For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo [CheibubDavidMarin2026]. Nalmefene, an opioid receptor modulator, showed pharm...”
- [Hashimoto2025] “For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo [CheibubDavidMarin2026]. Nalmefene, an opioid receptor modulator, showed pharm...”
- [LeFoll2026] “For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo [CheibubDavidMarin2026]. Nalmefene, an opioid receptor modulator, showed pharm...”
- [Ahmed2026] “For alcohol use disorder (AUD), the pharmacotherapy landscape reveals a similar pattern. Cheibub David Marin et al. (2026) conducted a systematic review of short-term pharmacological treatments for alcohol craving, finding that 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo [CheibubDavidMarin2026]. Nalmefene, an opioid receptor modulator, showed pharm...”
- [Volker2026] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Peter2026] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Essmat2025] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Chen2026c] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Alorfi2025] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Berube2026] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Zeabowski2025b] “The emerging interest in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for addiction represents a particularly instructive case. Originally developed for type 2 diabetes, these agents showed unexpected effects on addictive behaviors, drawing attention to metabolic–reward circuit interactions [Volker2026, Peter2026, Essmat2025, Chen2026c, Alorfi2025]. Peter et al. (2026) described efficacy mediated by changes...”
- [Rigotti2026] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [Gilman2025] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [LafayChebassier2026] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [So2025] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [Kawasaki2026] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [Witkiewitz2025] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [Campbell2025] “For smoking cessation, the evidence base is broad but again dominated by empirically discovered interventions. Rigotti and Benowitz (2026) reviewed the efficacy and safety landscape for US adults [Rigotti2026], while Gilman et al. (2025) demonstrated nicotine vaping cessation in an RCT (n=261) with enhanced usual care [Gilman2025]. Lafay-Chebassier et al. (2026) reported results from a Phase II trial of NFL-101, a n...”
- [Soleimani2025] “Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating {ref}`sec-dopamine-dynamics` knowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par...”
- [Orru2024] “Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating {ref}`sec-dopamine-dynamics` knowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par...”
- [Oesterle2025] “Transcranial magnetic stimulation (TMS) represents the most extensively studied circuit-based therapeutic intervention for addiction, and its evidence base illustrates both the promise and limitations of translating {ref}`sec-dopamine-dynamics` knowledge into clinical tools. Soleimani et al. (2025) conducted the largest meta-analysis to date, encompassing 116 sham-controlled RCTs with 5,106 active and 4,914 sham par...”
- [DelMauro2025] “Forest plot of neuromodulation effect sizes for substance use disorders. Each row represents a study or meta-analytic estimate, separated by stimulation modality (TMS, tES, dTMS). The pooled TMS effect from 116 sham-controlled RCTs is medium (g ≈ 0.4–0.5) with substantial heterogeneity. Studies vary in stimulation target (dlPFC, OFC, network-guided), protocol parameters (frequency, session count), substance type (ni...”
- [Guldas2025] “Forest plot of neuromodulation effect sizes for substance use disorders. Each row represents a study or meta-analytic estimate, separated by stimulation modality (TMS, tES, dTMS). The pooled TMS effect from 116 sham-controlled RCTs is medium (g ≈ 0.4–0.5) with substantial heterogeneity. Studies vary in stimulation target (dlPFC, OFC, network-guided), protocol parameters (frequency, session count), substance type (ni...”
- [Atoui2025] “The heterogeneity is as informative as the pooled estimate ({numref}`fig-sec11-tms-effect-sizes`). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies [DelMauro2025], while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen...”
- [Kinney2025] “The heterogeneity is as informative as the pooled estimate ({numref}`fig-sec11-tms-effect-sizes`). Del Mauro et al. (2025) found large effects for deep TMS (dTMS) targeting craving in a small number of studies [DelMauro2025], while Guldas et al. (2025) reported that wide-volume TMS using a double-cone coil applied to the left dorsolateral prefrontal cortex (dlPFC) did not produce statistically significant improvemen...”
- [Chen2025c] “Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers [Chen2025c]. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) [Li2026]. Petersen et al. (2025) identified the superior front...”
- [Li2026] “Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers [Chen2025c]. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) [Li2026]. Petersen et al. (2025) identified the superior front...”
- [Petersen2025] “Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers [Chen2025c]. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) [Li2026]. Petersen et al. (2025) identified the superior front...”
- [DeRossi2026] “Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers [Chen2025c]. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) [Li2026]. Petersen et al. (2025) identified the superior front...”
- [Wang2026b] “Target selection remains contested. Chen et al. (2025) reported that rTMS over the left dlPFC reduced nicotine craving, potentially through modulation of right NAc fibers [Chen2025c]. Li et al. (2026) investigated whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity, reporting significant effects (n=46) [Li2026]. Petersen et al. (2025) identified the superior front...”
- [Arulpragasam2026] “Emerging modalities extend beyond conventional TMS. Arulpragasam et al. (2026) described low-intensity focused ultrasound (FUS) as a promising non-invasive neuromodulation technique with the potential to deliver reversible and focal deep brain stimulation, noting that its spatial precision exceeds TMS, tES, and DBS [Arulpragasam2026]. Tang et al. (2025) investigated theta burst stimulation (TBS) to the dlPFC for OUD...”
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