Disease overview

Alterations

107

Molecular (A)

100

Clinical (B–E)

Direct drugs

104

Via biomarker

176

Natural agents

Natural products

Merged ranked

289

With trial/literature evidence

Sources: Open Targets, ClinicalTrials.gov, DGIdb, ChEMBL, OSMF Chronic Disease Review, PubMed MeSH, PubMed Literature, PubMed NP · Pipeline phase 7 · Updated 2026-07-05

Remission & chronicity

Spontaneous remission

Spontaneous recovery (without MOUD) in 20-30% of OUD patients over 10 years; but overdose mortality risk during active disorder is extreme (5-10 per 1000 person-years); relapse rate 90%+ in first year after discontinuing MOUD

Best-intervention remission

Buprenorphine maintenance: 50-70% retention in treatment at 1 year vs <20% for placebo; naltrexone extended-release (Vivitrol): comparable to buprenorphine when initiated; methadone: superior retention but restricted distribution; overdose mortality reduced 50-70% with any MOUD

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Very large — only 20% of people with OUD receive MOUD; massive unmet need

Primary barrier

access/policy

Barrier detail: US eliminated the DEA X-waiver requirement for buprenorphine prescribing in December 2022 (a major policy win) but prescribing rates have increased slowly; stigma remains; methadone access restricted to OTPs (clinics); harm reduction infrastructure (fentanyl test strips, naloxone) still insufficiently deployed; 80% of people with OUD receive no treatment

Last SoC change: 2023 — DEA X-waiver elimination fully implemented; 2022 federal legislation allowing take-home methadone expanded; 2021 FDA approved injectable buprenorphine (Sublocade) for once-monthly dosing; buprenorphine SL since 2002; methadone for OUD since 1964

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0005530 · MESH: D009293 · UMLS_CUI: C0027412

Alterations

107 total · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
ADCY1 adenylate cyclase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADGRV1 adhesion G protein-coupled receptor V1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADH1B alcohol dehydrogenase 1B (class I), beta polypeptide	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2A adrenoceptor alpha 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2B adrenoceptor alpha 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2C adrenoceptor alpha 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AGBL4 AGBL carboxypeptidase 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ALDH2 aldehyde dehydrogenase 2 family member	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ANKK1 ankyrin repeat and kinase domain containing 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ANKS1B ankyrin repeat and sterile alpha motif domain containing 1B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AUTS2 activator of transcription and developmental regulator AUTS2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BDNF brain derived neurotrophic factor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1A calcium voltage-gated channel subunit alpha1 A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1B calcium voltage-gated channel subunit alpha1 B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1C calcium voltage-gated channel subunit alpha1 C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1D calcium voltage-gated channel subunit alpha1 D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1E calcium voltage-gated channel subunit alpha1 E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1F calcium voltage-gated channel subunit alpha1 F	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1G calcium voltage-gated channel subunit alpha1 G	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1H calcium voltage-gated channel subunit alpha1 H	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1I calcium voltage-gated channel subunit alpha1 I	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1S calcium voltage-gated channel subunit alpha1 S	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D1 calcium voltage-gated channel auxiliary subunit alpha2delta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D2 calcium voltage-gated channel auxiliary subunit alpha2delta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D3 calcium voltage-gated channel auxiliary subunit alpha2delta 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D4 calcium voltage-gated channel auxiliary subunit alpha2delta 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB1 calcium voltage-gated channel auxiliary subunit beta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB2 calcium voltage-gated channel auxiliary subunit beta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB3 calcium voltage-gated channel auxiliary subunit beta 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB4 calcium voltage-gated channel auxiliary subunit beta 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG2 calcium voltage-gated channel auxiliary subunit gamma 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG3 calcium voltage-gated channel auxiliary subunit gamma 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG4 calcium voltage-gated channel auxiliary subunit gamma 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG5 calcium voltage-gated channel auxiliary subunit gamma 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG6 calcium voltage-gated channel auxiliary subunit gamma 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG7 calcium voltage-gated channel auxiliary subunit gamma 7	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG8 calcium voltage-gated channel auxiliary subunit gamma 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CCK cholecystokinin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CHRNA4 cholinergic receptor nicotinic alpha 4 subunit	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CHRNB2 cholinergic receptor nicotinic beta 2 subunit	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CNIH3 cornichon family AMPA receptor auxiliary protein 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CNKSR3 CNKSR family member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CNR1 cannabinoid receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
COMT catechol-O-methyltransferase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CTNNA2 catenin alpha 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Change in rates of methadone prescribing during hospitalization	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
DRD1 dopamine receptor D1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD2 dopamine receptor D2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD4 dopamine receptor D4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ELAVL4 ELAV like RNA binding protein 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ENO2 enolase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FAM13A family with sequence similarity 13 member A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB3 gamma-aminobutyric acid type A receptor subunit beta3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GARIN6 golgi associated RAB2 interactor family member 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GPRIN3 GPRIN family member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN1 glutamate ionotropic receptor NMDA type subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2A glutamate ionotropic receptor NMDA type subunit 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2B glutamate ionotropic receptor NMDA type subunit 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2C glutamate ionotropic receptor NMDA type subunit 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2D glutamate ionotropic receptor NMDA type subunit 2D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN3A glutamate ionotropic receptor NMDA type subunit 3A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN3B glutamate ionotropic receptor NMDA type subunit 3B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HP haptoglobin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1A 5-hydroxytryptamine receptor 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2A 5-hydroxytryptamine receptor 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2C 5-hydroxytryptamine receptor 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3B 5-hydroxytryptamine receptor 3B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IQGAP1 IQ motif containing GTPase activating protein 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAOA monoamine oxidase A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NOS1 nitric oxide synthase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NR3C1 nuclear receptor subfamily 3 group C member 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NTF3 neurotrophin 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NTF4 neurotrophin 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Numeric Pain Rating Scale (NPRS)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
OPRD1 opioid receptor delta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OPRK1 opioid receptor kappa 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OPRM1 opioid receptor mu 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OXTR oxytocin receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Opioid consumption	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
PDE10A phosphodiesterase 10A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE3A phosphodiesterase 3A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE4A phosphodiesterase 4A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE4B phosphodiesterase 4B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE4C phosphodiesterase 4C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE4D phosphodiesterase 4D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE5A phosphodiesterase 5A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDYN prodynorphin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PENK proenkephalin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PPARG peroxisome proliferator activated receptor gamma	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PRIM2 DNA primase subunit 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Postoperative pain score in NRS scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
RGMA repulsive guidance molecule BMP co-receptor a	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SIGMAR1 sigma non-opioid intracellular receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC18A2 solute carrier family 18 member A2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A1 solute carrier family 6 member 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A2 solute carrier family 6 member 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A3 solute carrier family 6 member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A4 solute carrier family 6 member 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SNCA synuclein alpha	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SV2A synaptic vesicle glycoprotein 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Stress-reactivity	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
TACR1 tachykinin receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TH tyrosine hydroxylase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TPH2 tryptophan hydroxylase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
cocaine use (self-report)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
opioid use (self-report)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, merged ranking, and clinical trial / literature evidence (top agents)

From opensourcemed.info/chronic-disease — Therapeutic potential of herbalism for opioid use disorder. Candidates for further study, not approved treatments.

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
BUPRENORPHINE	Small molecule	Approved	Strong	100	8 trials 107 Cochrane 88 Meta-analysis 723 Trial pubs 586 RCT View evidence Registry trials NCT04449744 — Evaluating Adaptive Dispenser Initiation Protocols for MySafeRx During Post-detox Buprenorphine Treatment- a Pilot Study (COMPLETED) NA NCT07631598 — Buprenorphine Implementation at Syringe Service Programs to Reduce Overdoses (NOT_YET_RECRUITING) NA NCT06999811 — Technology-Enhanced Therapy vs. Medication Monitoring for Buprenorphine Retention in Pregnant Persons (RECRUITING) NA NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03818399 — Virginia Opioid Overdose Treatment InitiatVE (TERMINATED) PHASE3 NCT05944133 — Health Insurance Instability and Mortality Among Patients Receiving Bup Tx for OUD (ACTIVE_NOT_RECRUITING) NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT03766893 — Medication Maintenance Therapy in Community Pharmacy Settings (COMPLETED) EARLY_PHASE1 Published literature Cochrane review Quantitative sensory testing of pain in persons with opioid use disorder on opioid agonist treatment: a scoping review (Pain medicine (Malden, Mass.), 2026) Cochrane review Buprenorphine-naloxone vs methadone for opioid use disorder: a systematic review and meta-analysis of randomized clinical trials (Journal of addictive diseases, 2026) Cochrane review Acute Pain Management in People With Opioid Use Disorder : A Systematic Review (Annals of internal medicine, 2025) Cochrane review Buprenorphine-naloxone versus buprenorphine for opioid use disorder during pregnancy: A systematic review and meta-analysis (Drug and alcohol dependence, 2025) Cochrane review Buprenorphine's Effect on the Human Immune System and Inflammation (Clinical and translational science, 2025) Meta-analysis Effectiveness and safety of therapies for patients with opioid use disorder: a systematic review and network meta-analysis (Journal of comparative effectiveness research, 2026) Meta-analysis Buprenorphine-based treatments outcomes in pregnant opioid-dependent women: A systematic review and meta-analysis (Addiction (Abingdon, England), 2026) Meta-analysis Oral and injectable opioid agonist treatments for people who use street opioids: a systematic literature review and network meta-analysis (BMC public health, 2025) Meta-analysis The association between mental disorders and treatment retention among people with opioid use disorder receiving opioid agonist treatment: A systematic review and meta-analysis (Drug and alcohol dependence, 2025) Systematic review Systematic review of real-world data associated with opioid scheduling and nonmedical use (Journal of opioid management, 2026) Systematic review Pharmacological treatment strategies to manage precipitated withdrawal following the administration of buprenorphine in opioid use disorder: A systematic review (Addiction (Abingdon, England), 2026) Systematic review Low-Dose Buprenorphine Initiation for Opioid Agonist Therapy in Patients with Opioid Use Disorder: A Dutch Consensus Paper (European addiction research, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
BUPRENORPHINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 10 Trial pubs 10 RCT View evidence Registry trials NCT04449744 — Evaluating Adaptive Dispenser Initiation Protocols for MySafeRx During Post-detox Buprenorphine Treatment- a Pilot Study (COMPLETED) NA NCT07631598 — Buprenorphine Implementation at Syringe Service Programs to Reduce Overdoses (NOT_YET_RECRUITING) NA NCT06999811 — Technology-Enhanced Therapy vs. Medication Monitoring for Buprenorphine Retention in Pregnant Persons (RECRUITING) NA NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03818399 — Virginia Opioid Overdose Treatment InitiatVE (TERMINATED) PHASE3 NCT05944133 — Health Insurance Instability and Mortality Among Patients Receiving Bup Tx for OUD (ACTIVE_NOT_RECRUITING) NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT03766893 — Medication Maintenance Therapy in Community Pharmacy Settings (COMPLETED) EARLY_PHASE1 Published literature Clinical trial publication Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial (JAMA internal medicine, 2018) Clinical trial publication Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial (JAMA psychiatry, 2017) Clinical trial publication Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial (JAMA psychiatry, 2017) Clinical trial publication Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial (JAMA, 2016) Clinical trial publication Primary care-based buprenorphine taper vs maintenance therapy for prescription opioid dependence: a randomized clinical trial (JAMA internal medicine, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMETHADYL ACETATE	Small molecule	Approved	Strong	100	1 trials 1 Cochrane 4 Trial pubs 4 RCT View evidence Registry trials NCT00158288 — The Efficacy of Methadyl Acetate (LAAM) and Contingency Management Procedures for Treating Dual Opioid and Cocaine Abuse - 1 (COMPLETED) PHASE2 Published literature Cochrane review The impact of chronic pain on opioid addiction treatment: a systematic review protocol (Systematic reviews, 2015) Clinical trial publication HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone (Journal of substance abuse treatment, 2006) Clinical trial publication A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence (The New England journal of medicine, 2000) Clinical trial publication Induction with levomethadyl acetate: safety and efficacy (Archives of general psychiatry, 1998) Clinical trial publication Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial (JAMA, 1997) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
METHADONE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Meta-analysis 21 Trial pubs 18 RCT View evidence Registry trials NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT05529927 — Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder (RECRUITING) PHASE2 NCT05924022 — Hyperbaric Oxygen Treatment (HBOT) During Methadone Tapering (COMPLETED) PHASE1 NCT06291090 — A Multi-site Intervention to Expand Hospital Based OUD Treatment Provision (COMPLETED) NA NCT05341219 — Light Needle for Opioid Use Disorder (UNKNOWN) NA NCT03065049 — Transforming Recovery Through Exercise and Community (COMPLETED) NA NCT01847729 — OPAL: "Opiates and PhArmacoLogy" (COMPLETED) Published literature Meta-analysis The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis (Addiction (Abingdon, England), 1998) Clinical trial publication Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared (Journal of substance abuse treatment, 2013) Clinical trial publication Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population (Archives of general psychiatry, 2006) Clinical trial publication Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study (Archives of general psychiatry, 2006) Clinical trial publication A randomized controlled trial of interim methadone maintenance (Archives of general psychiatry, 2006) Clinical trial publication Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone (Archives of general psychiatry, 1999) Randomized controlled trial Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance (Archives of general psychiatry, 2000) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLNALTREXONE BROMIDE	Small molecule	Approved	Strong	100	2 trials View evidence Registry trials NCT01368562 — Compassionate Use Study of Methylnaltrexone (COMPLETED) NA NCT01889290 — Methylnaltrexone Pharmacokinetics in Neurointensive Care Patients (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXEGOL OXALATE	Small molecule	Approved	Strong	100	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXONE HYDROCHLORIDE DIHYDRATE	Small molecule	Approved	Strong	100	2 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT02559973 — Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine at Three Different Molecular Weights in Treatment-Seeking Subjects With Opioid Use Disorder (COMPLETED) PHASE1 NCT07439549 — Symptom-Inhibited Naloxone Induction (SINI) for Buprenorphine Initiation: A Feasibility Trial (RECRUITING) PHASE4 Published literature Clinical trial publication A randomized, double-blind evaluation of buprenorphine taper duration in primary prescription opioid abusers (JAMA psychiatry, 2013) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NICOTINE	Small molecule	Approved	Strong	100	8 trials 3 Cochrane 3 Meta-analysis 35 Trial pubs 28 RCT View evidence Registry trials NCT02250664 — Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers (COMPLETED) PHASE1, PHASE2 NCT03745339 — Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder (RECRUITING) NCT04092101 — Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder (COMPLETED) PHASE2 NCT06277271 — E-cigarettes as a Harm Reduction Strategy (COMPLETED) NA NCT05290025 — Easy Access to Smoking Cessation for People Receiving Opioid Agonist Therapy Who Are Smoking Tobacco (ACTIVE_NOT_RECRUITING) NA NCT01386138 — Treating South African Pregnant Women for Methamphetamine (COMPLETED) NA NCT01395797 — Pioglitazone for Heroin and for Nicotine Dependence (TERMINATED) PHASE1, PHASE2 NCT06552741 — Screening, Evaluation and Assessment (SEA) Protocol at the NIDA IRP (RECRUITING) Published literature Cochrane review Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol (BMJ open, 2021) Cochrane review Screening, treatment initiation, and referral for substance use disorders (Addiction science & clinical practice, 2017) Cochrane review [Naltrexone in the treatment of addiction] (Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2003) Meta-analysis Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials (European journal of clinical pharmacology, 2023) Meta-analysis Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies (European psychiatry : the journal of the Association of European Psychiatrists, 2019) Meta-analysis BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysis (Pharmacogenomics, 2013) Systematic review Pharmacotherapy for pregnant women with addictions (American journal of obstetrics and gynecology, 2004) Clinical trial publication Assessing the impact of nicotinic partial agonists compared to NRT on opioid and cigarette use: A secondary analysis investigating treatment outcomes for co-occurring nicotine and opioid use (Journal of substance use and addiction treatment, 2026) Clinical trial publication Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy: A Randomized Clinical Trial (JAMA psychiatry, 2025) Clinical trial publication Exposure to Bupropion-SR vs. Placebo is associated with reductions in smoking among persons receiving methadone with no stated interest in smoking cessation (Addictive behaviors, 2025) Clinical trial publication FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study (Trials, 2022) Clinical trial publication Transcranial direct current stimulation of the frontal-parietal-temporal brain areas reduces cigarette consumption in abstinent heroin users (Journal of psychiatric research, 2022) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ACEBUTOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETALDEHYDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ADENOSINE MONOPHOSPHATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMISULPRIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APOMORPHINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ARIPIPRAZOLE LAUROXIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ASENAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL Repurposing	Small molecule	Approved	Strong	95	2 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BETHANIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CELIPROLOL Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CHLORPROMAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CISPLATIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CLOMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	7 trials 5 Trial pubs 2 RCT View evidence Registry trials NCT03174067 — Buprenorphine in the Emergency Department (COMPLETED) PHASE4 NCT06447194 — Effect of RECK in Posterior Spinal Fusion (WITHDRAWN) PHASE1, PHASE2 NCT05172739 — Opioid Free Anaesthesia-Analgesia Strategy on Surgical Stress and Immunomodulation in Elective VATS-Lobectomy for NSCLC (RECRUITING) PHASE4 NCT03388814 — Speeding Recovery From Pain and Opioid Use (WITHDRAWN) EARLY_PHASE1 NCT04600414 — Collaborating to Heal Addiction and Mental Health in Primary Care (COMPLETED) NA NCT03090152 — Minimal Opioid Use After Total Hip Replacement (THR) (COMPLETED) PHASE4 NCT06137924 — Intraoperative Autonomic Neural Blockade (UNKNOWN) PHASE3 Published literature Clinical trial publication Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial (Archives of general psychiatry, 2005) Clinical trial publication Clonidine in morphine withdrawal. Differential effects on signs and symptoms (Archives of general psychiatry, 1985) Clinical trial publication Clonidine in outpatient detoxification from methadone maintenance (Archives of general psychiatry, 1985) Clinical trial publication Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy (Archives of general psychiatry, 1982) Clinical trial publication Clonidine in opiate withdrawal: review and appraisal of clinical findings (Pharmacotherapy, 1981) CT.gov search · Cochrane · PubMed	DGIdb	—
CYCLOBENZAPRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEBRISOQUIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEHYDRATED ALCOHOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DISULFIRAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOCETAXEL ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOPAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
FOMEPIZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HALOPERIDOL DECANOATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
IMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDAPAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ISOPROTERENOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LEVONORDEFRIN Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
LITHIUM CATION Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	8 trials 2 Trial pubs 2 RCT View evidence Registry trials NCT05027919 — Assessing a Clinically-meaningful Opioid Withdrawal Phenotype (RECRUITING) PHASE2 NCT04360681 — Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (COMPLETED) PHASE2 NCT05053503 — Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (COMPLETED) NA NCT04325659 — An Innovative Intervention for OUD Treatment (COMPLETED) PHASE2, PHASE3 NCT04056182 — Lofexidine for Management of Opioid Withdrawal With XR-NTX Treatment (COMPLETED) PHASE2 NCT06711640 — A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (WITHDRAWN) PHASE1 NCT05712707 — Sublingual Dexmedetomidine for Treating Opioid Withdrawal (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT03718065 — Impact of Lofexidine on Stress, Craving and Opioid Use (COMPLETED) PHASE2 Published literature Clinical trial publication A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal (Drug and alcohol dependence, 2017) Clinical trial publication [Clinical observation on effect of modified banxia houpu decoction in treating patients with protracted heroin abstinence syndrome] (Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine, 2004) CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
LURASIDONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MECAMYLAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHAMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOXSALEN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MIANSERIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MILNACIPRAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
NALIDIXIC ACID Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NALTREXONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NITREFAZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NITROGLYCERIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	1 trials 12 Trial pubs 8 RCT View evidence Registry trials NCT03271151 — Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty (COMPLETED) PHASE4 Published literature Clinical trial publication Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial (The Journal of arthroplasty, 2022) Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and α1A-adrenoceptor gene variation (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013) Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylase (Biological psychiatry, 2013) Clinical trial publication Clonidine improved laboratory-measured decision-making performance in abstinent heroin addicts (PloS one, 2012) Clinical trial publication Venlafaxine for acute heroin detoxification: a double-blind, randomized, control trial (Journal of clinical psychopharmacology, 2008) CT.gov search · Cochrane · PubMed	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PERGOLIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYTOIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PINDOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PROPRANOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	1 Trial pubs View evidence Published literature Clinical trial publication Evaluation of propranolol in opiate dependence (Archives of general psychiatry, 1976) CT.gov search · Cochrane · PubMed	DGIdb	—
PROPYLHEXEDRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
QUETIAPINE FUMARATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RIFAMPIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAZOBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
USTEKINUMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
VALPROIC ACID Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing	Small molecule	Approved	Strong	95	3 trials 3 Trial pubs 2 RCT View evidence Registry trials NCT04181515 — Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use (WITHDRAWN) PHASE2 NCT03015246 — Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence (COMPLETED) PHASE1, PHASE2 NCT04231708 — Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder (NOT_YET_RECRUITING) PHASE2 Published literature Clinical trial publication Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals (Psychopharmacology, 2013) Clinical trial publication Clonidine and yohimbine in opioid-dependent humans responding under a naloxone novel-response discrimination procedure (Behavioural pharmacology, 2003) Clinical trial publication Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients (Biological psychiatry, 2002) CT.gov search · Cochrane · PubMed	DGIdb	—
DEXTROMETHORPHAN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DIACETYLMORPHINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
HYDROMORPHONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MEMANTINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHADONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MORPHINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYCODONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAMADOL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1005	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1059	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1714	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1788132	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107914	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL556578	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
DEXMEDETOMIDINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABAPENTIN	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
LOFEXIDINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
MINOCYCLINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MORPHINE SULFATE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXONE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
PALIPERIDONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DARAPLADIB Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
ATOMOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CLONIDINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CYCLOSERINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROAMPHETAMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DISULFIRAM	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
IBOGAINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
IBUDILAST	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
KETAMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEVETIRACETAM	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIOGLITAZONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
BUSPIRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1083659	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200689	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200694	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1234579	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1234886	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1256	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1373	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL15245	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL194378	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2219418	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL360328	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL370805	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL389621	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL5314358	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL549	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL64391	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL689	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL715	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL741	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL74415	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
DEXTROAMPHETAMINE SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NALDEMEDINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NORIBOGAINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
OMS405	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TIAGABINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VARENICLINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL:CHEMBL401844 Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	ChEMBL Open Targets
HEROIN Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
MIRIVADELGAT Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
NEMONAPRIDE Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
PRUNETIN Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ST034307 Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ALPRENOLOL Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
APREPITANT	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
ISRADIPINE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMETHADONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLPHENIDATE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALMEFENE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYTOCIN	Biologic	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
RISPERIDONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZIPRASIDONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1186579	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201132	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201149	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201152	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1718	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2311157	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL4084119	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL46	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL476413	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL4802157	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL5314589	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL596	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL846	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
DARUNAVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
FOSAMPRENAVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RIFABUTIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RIFAMPIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RILPIVIRINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TELAPREVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
Berberine OSMF review	Nutraceutical	Preclinical	Emerging	30	1 pubs View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Berberis vulgaris (Barberry) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Corydalis (Yan Hu Suo) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Fu-Yuan Pellet OSMF review	Herbal	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Ibogaine OSMF review	Psychedelic	Preclinical	Emerging	30	3 trials 2 Trial pubs 1 RCT View evidence Registry trials NCT04003948 — Preliminary Efficacy and Safety of Ibogaine in the Treatment of Methadone Detoxification (COMPLETED) PHASE2 NCT07226570 — Mapping Ibogaine Neural Dynamics in Opioid Use Disorder (RECRUITING) NCT05029401 — A Study of Oral Ibogaine in Opioid Withdrawal (COMPLETED) PHASE1, PHASE2 Published literature Systematic review The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies (Psychiatry research, 2025) Clinical trial publication Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients (Clinical pharmacology in drug development, 2016) Clinical trial publication Treatment of acute opioid withdrawal with ibogaine (The American journal on addictions, 1999) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Matricaria chamomilla (Chamomile) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Nigella sativa (Black seed) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Saffron (Crocin) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Sophora alopecuroides (Matrine) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Tai-Kang Ning OSMF review	Herbal	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
(+/-)NICOTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL2104769	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CHEMBL417675	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
ISONIAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHADYL ACETATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
RIFAPENTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
BUPRENORPHINE	Small molecule	Approved	Strong	100	8 trials 107 Cochrane 88 Meta-analysis 723 Trial pubs 586 RCT View evidence Registry trials NCT04449744 — Evaluating Adaptive Dispenser Initiation Protocols for MySafeRx During Post-detox Buprenorphine Treatment- a Pilot Study (COMPLETED) NA NCT07631598 — Buprenorphine Implementation at Syringe Service Programs to Reduce Overdoses (NOT_YET_RECRUITING) NA NCT06999811 — Technology-Enhanced Therapy vs. Medication Monitoring for Buprenorphine Retention in Pregnant Persons (RECRUITING) NA NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03818399 — Virginia Opioid Overdose Treatment InitiatVE (TERMINATED) PHASE3 NCT05944133 — Health Insurance Instability and Mortality Among Patients Receiving Bup Tx for OUD (ACTIVE_NOT_RECRUITING) NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT03766893 — Medication Maintenance Therapy in Community Pharmacy Settings (COMPLETED) EARLY_PHASE1 Published literature Cochrane review Quantitative sensory testing of pain in persons with opioid use disorder on opioid agonist treatment: a scoping review (Pain medicine (Malden, Mass.), 2026) Cochrane review Buprenorphine-naloxone vs methadone for opioid use disorder: a systematic review and meta-analysis of randomized clinical trials (Journal of addictive diseases, 2026) Cochrane review Acute Pain Management in People With Opioid Use Disorder : A Systematic Review (Annals of internal medicine, 2025) Cochrane review Buprenorphine-naloxone versus buprenorphine for opioid use disorder during pregnancy: A systematic review and meta-analysis (Drug and alcohol dependence, 2025) Cochrane review Buprenorphine's Effect on the Human Immune System and Inflammation (Clinical and translational science, 2025) Meta-analysis Effectiveness and safety of therapies for patients with opioid use disorder: a systematic review and network meta-analysis (Journal of comparative effectiveness research, 2026) Meta-analysis Buprenorphine-based treatments outcomes in pregnant opioid-dependent women: A systematic review and meta-analysis (Addiction (Abingdon, England), 2026) Meta-analysis Oral and injectable opioid agonist treatments for people who use street opioids: a systematic literature review and network meta-analysis (BMC public health, 2025) Meta-analysis The association between mental disorders and treatment retention among people with opioid use disorder receiving opioid agonist treatment: A systematic review and meta-analysis (Drug and alcohol dependence, 2025) Systematic review Systematic review of real-world data associated with opioid scheduling and nonmedical use (Journal of opioid management, 2026) Systematic review Pharmacological treatment strategies to manage precipitated withdrawal following the administration of buprenorphine in opioid use disorder: A systematic review (Addiction (Abingdon, England), 2026) Systematic review Low-Dose Buprenorphine Initiation for Opioid Agonist Therapy in Patients with Opioid Use Disorder: A Dutch Consensus Paper (European addiction research, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
BUPRENORPHINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 10 Trial pubs 10 RCT View evidence Registry trials NCT04449744 — Evaluating Adaptive Dispenser Initiation Protocols for MySafeRx During Post-detox Buprenorphine Treatment- a Pilot Study (COMPLETED) NA NCT07631598 — Buprenorphine Implementation at Syringe Service Programs to Reduce Overdoses (NOT_YET_RECRUITING) NA NCT06999811 — Technology-Enhanced Therapy vs. Medication Monitoring for Buprenorphine Retention in Pregnant Persons (RECRUITING) NA NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03818399 — Virginia Opioid Overdose Treatment InitiatVE (TERMINATED) PHASE3 NCT05944133 — Health Insurance Instability and Mortality Among Patients Receiving Bup Tx for OUD (ACTIVE_NOT_RECRUITING) NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT03766893 — Medication Maintenance Therapy in Community Pharmacy Settings (COMPLETED) EARLY_PHASE1 Published literature Clinical trial publication Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial (JAMA internal medicine, 2018) Clinical trial publication Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial (JAMA psychiatry, 2017) Clinical trial publication Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial (JAMA psychiatry, 2017) Clinical trial publication Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial (JAMA, 2016) Clinical trial publication Primary care-based buprenorphine taper vs maintenance therapy for prescription opioid dependence: a randomized clinical trial (JAMA internal medicine, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMETHADYL ACETATE	Small molecule	Approved	Strong	100	1 trials 1 Cochrane 4 Trial pubs 4 RCT View evidence Registry trials NCT00158288 — The Efficacy of Methadyl Acetate (LAAM) and Contingency Management Procedures for Treating Dual Opioid and Cocaine Abuse - 1 (COMPLETED) PHASE2 Published literature Cochrane review The impact of chronic pain on opioid addiction treatment: a systematic review protocol (Systematic reviews, 2015) Clinical trial publication HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone (Journal of substance abuse treatment, 2006) Clinical trial publication A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence (The New England journal of medicine, 2000) Clinical trial publication Induction with levomethadyl acetate: safety and efficacy (Archives of general psychiatry, 1998) Clinical trial publication Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial (JAMA, 1997) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
METHADONE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Meta-analysis 21 Trial pubs 18 RCT View evidence Registry trials NCT05534815 — Long-Term Treatment of Opioid Use Disorder (RECRUITING) NA NCT03976258 — Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV (COMPLETED) NCT05529927 — Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder (RECRUITING) PHASE2 NCT05924022 — Hyperbaric Oxygen Treatment (HBOT) During Methadone Tapering (COMPLETED) PHASE1 NCT06291090 — A Multi-site Intervention to Expand Hospital Based OUD Treatment Provision (COMPLETED) NA NCT05341219 — Light Needle for Opioid Use Disorder (UNKNOWN) NA NCT03065049 — Transforming Recovery Through Exercise and Community (COMPLETED) NA NCT01847729 — OPAL: "Opiates and PhArmacoLogy" (COMPLETED) Published literature Meta-analysis The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis (Addiction (Abingdon, England), 1998) Clinical trial publication Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared (Journal of substance abuse treatment, 2013) Clinical trial publication Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population (Archives of general psychiatry, 2006) Clinical trial publication Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study (Archives of general psychiatry, 2006) Clinical trial publication A randomized controlled trial of interim methadone maintenance (Archives of general psychiatry, 2006) Clinical trial publication Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone (Archives of general psychiatry, 1999) Randomized controlled trial Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance (Archives of general psychiatry, 2000) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLNALTREXONE BROMIDE	Small molecule	Approved	Strong	100	2 trials View evidence Registry trials NCT01368562 — Compassionate Use Study of Methylnaltrexone (COMPLETED) NA NCT01889290 — Methylnaltrexone Pharmacokinetics in Neurointensive Care Patients (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXEGOL OXALATE	Small molecule	Approved	Strong	100	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXONE HYDROCHLORIDE DIHYDRATE	Small molecule	Approved	Strong	100	2 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT02559973 — Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine at Three Different Molecular Weights in Treatment-Seeking Subjects With Opioid Use Disorder (COMPLETED) PHASE1 NCT07439549 — Symptom-Inhibited Naloxone Induction (SINI) for Buprenorphine Initiation: A Feasibility Trial (RECRUITING) PHASE4 Published literature Clinical trial publication A randomized, double-blind evaluation of buprenorphine taper duration in primary prescription opioid abusers (JAMA psychiatry, 2013) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROMETHORPHAN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DIACETYLMORPHINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
HYDROMORPHONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MEMANTINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHADONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MORPHINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYCODONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAMADOL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1005	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1059	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1714	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1788132	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107914	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL556578	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
DEXMEDETOMIDINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABAPENTIN	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
LOFEXIDINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
MINOCYCLINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MORPHINE SULFATE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALOXONE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
PALIPERIDONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ATOMOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CLONIDINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CYCLOSERINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROAMPHETAMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DISULFIRAM	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
IBOGAINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
IBUDILAST	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
KETAMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEVETIRACETAM	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIOGLITAZONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
BUSPIRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1083659	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200689	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200694	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1234579	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1234886	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1256	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1373	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL15245	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL194378	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2219418	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL360328	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL370805	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL389621	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL5314358	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL549	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL64391	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL689	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL715	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL741	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL74415	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
DEXTROAMPHETAMINE SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NALDEMEDINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NORIBOGAINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
OMS405	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TIAGABINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VARENICLINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
APREPITANT	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
ISRADIPINE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMETHADONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLPHENIDATE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALMEFENE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYTOCIN	Biologic	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
RISPERIDONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZIPRASIDONE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1186579	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201132	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201149	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1201152	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1718	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2311157	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL4084119	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL46	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL476413	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL4802157	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL5314589	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL596	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL846	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
DARUNAVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
FOSAMPRENAVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RIFABUTIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RIFAMPIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
RILPIVIRINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TELAPREVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
(+/-)NICOTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL2104769	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CHEMBL417675	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
ISONIAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHADYL ACETATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NICOTINE	Small molecule	Preclinical	Emerging	15	8 trials 3 Cochrane 3 Meta-analysis 35 Trial pubs 28 RCT View evidence Registry trials NCT02250664 — Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers (COMPLETED) PHASE1, PHASE2 NCT03745339 — Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder (RECRUITING) NCT04092101 — Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder (COMPLETED) PHASE2 NCT06277271 — E-cigarettes as a Harm Reduction Strategy (COMPLETED) NA NCT05290025 — Easy Access to Smoking Cessation for People Receiving Opioid Agonist Therapy Who Are Smoking Tobacco (ACTIVE_NOT_RECRUITING) NA NCT01386138 — Treating South African Pregnant Women for Methamphetamine (COMPLETED) NA NCT01395797 — Pioglitazone for Heroin and for Nicotine Dependence (TERMINATED) PHASE1, PHASE2 NCT06552741 — Screening, Evaluation and Assessment (SEA) Protocol at the NIDA IRP (RECRUITING) Published literature Cochrane review Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol (BMJ open, 2021) Cochrane review Screening, treatment initiation, and referral for substance use disorders (Addiction science & clinical practice, 2017) Cochrane review [Naltrexone in the treatment of addiction] (Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2003) Meta-analysis Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials (European journal of clinical pharmacology, 2023) Meta-analysis Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies (European psychiatry : the journal of the Association of European Psychiatrists, 2019) Meta-analysis BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysis (Pharmacogenomics, 2013) Systematic review Pharmacotherapy for pregnant women with addictions (American journal of obstetrics and gynecology, 2004) Clinical trial publication Assessing the impact of nicotinic partial agonists compared to NRT on opioid and cigarette use: A secondary analysis investigating treatment outcomes for co-occurring nicotine and opioid use (Journal of substance use and addiction treatment, 2026) Clinical trial publication Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy: A Randomized Clinical Trial (JAMA psychiatry, 2025) Clinical trial publication Exposure to Bupropion-SR vs. Placebo is associated with reductions in smoking among persons receiving methadone with no stated interest in smoking cessation (Addictive behaviors, 2025) Clinical trial publication FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study (Trials, 2022) Clinical trial publication Transcranial direct current stimulation of the frontal-parietal-temporal brain areas reduces cigarette consumption in abstinent heroin users (Journal of psychiatric research, 2022) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
RIFAPENTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACEBUTOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETALDEHYDE Repurposing via ALDH2	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ADENOSINE MONOPHOSPHATE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	DGIdb	—
AMISULPRIDE Repurposing via ANKS1B	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APOMORPHINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ARIPIPRAZOLE LAUROXIL Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
ASENAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	2 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BETHANIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CELIPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CHLORPROMAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CISPLATIN Repurposing via ALDH2	Small molecule	Approved	Strong	95	—	DGIdb	—
CLOMIPRAMINE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	7 trials 5 Trial pubs 2 RCT View evidence Registry trials NCT03174067 — Buprenorphine in the Emergency Department (COMPLETED) PHASE4 NCT06447194 — Effect of RECK in Posterior Spinal Fusion (WITHDRAWN) PHASE1, PHASE2 NCT05172739 — Opioid Free Anaesthesia-Analgesia Strategy on Surgical Stress and Immunomodulation in Elective VATS-Lobectomy for NSCLC (RECRUITING) PHASE4 NCT03388814 — Speeding Recovery From Pain and Opioid Use (WITHDRAWN) EARLY_PHASE1 NCT04600414 — Collaborating to Heal Addiction and Mental Health in Primary Care (COMPLETED) NA NCT03090152 — Minimal Opioid Use After Total Hip Replacement (THR) (COMPLETED) PHASE4 NCT06137924 — Intraoperative Autonomic Neural Blockade (UNKNOWN) PHASE3 Published literature Clinical trial publication Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial (Archives of general psychiatry, 2005) Clinical trial publication Clonidine in morphine withdrawal. Differential effects on signs and symptoms (Archives of general psychiatry, 1985) Clinical trial publication Clonidine in outpatient detoxification from methadone maintenance (Archives of general psychiatry, 1985) Clinical trial publication Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy (Archives of general psychiatry, 1982) Clinical trial publication Clonidine in opiate withdrawal: review and appraisal of clinical findings (Pharmacotherapy, 1981) CT.gov search · Cochrane · PubMed	DGIdb	—
CYCLOBENZAPRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEBRISOQUIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEHYDRATED ALCOHOL Repurposing via ALDH2	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DISULFIRAM Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
DOCETAXEL ANHYDROUS Repurposing via ALDH2	Small molecule	Approved	Strong	95	—	DGIdb	—
DOPAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
FOMEPIZOLE Repurposing via ADH1B	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
HALOPERIDOL DECANOATE Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
IMIPRAMINE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDAPAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ISOPROTERENOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LEVONORDEFRIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
LITHIUM CATION Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	8 trials 2 Trial pubs 2 RCT View evidence Registry trials NCT05027919 — Assessing a Clinically-meaningful Opioid Withdrawal Phenotype (RECRUITING) PHASE2 NCT04360681 — Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (COMPLETED) PHASE2 NCT05053503 — Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (COMPLETED) NA NCT04325659 — An Innovative Intervention for OUD Treatment (COMPLETED) PHASE2, PHASE3 NCT04056182 — Lofexidine for Management of Opioid Withdrawal With XR-NTX Treatment (COMPLETED) PHASE2 NCT06711640 — A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (WITHDRAWN) PHASE1 NCT05712707 — Sublingual Dexmedetomidine for Treating Opioid Withdrawal (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT03718065 — Impact of Lofexidine on Stress, Craving and Opioid Use (COMPLETED) PHASE2 Published literature Clinical trial publication A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal (Drug and alcohol dependence, 2017) Clinical trial publication [Clinical observation on effect of modified banxia houpu decoction in treating patients with protracted heroin abstinence syndrome] (Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine, 2004) CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
LURASIDONE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MECAMYLAMINE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHAMPHETAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOXSALEN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MIANSERIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MILNACIPRAN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
NALIDIXIC ACID Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NALTREXONE Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NICOTINE Repurposing via ADCY1	Small molecule	Approved	Strong	95	8 trials 3 Cochrane 3 Meta-analysis 35 Trial pubs 28 RCT View evidence Registry trials NCT02250664 — Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers (COMPLETED) PHASE1, PHASE2 NCT03745339 — Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder (RECRUITING) NCT04092101 — Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder (COMPLETED) PHASE2 NCT06277271 — E-cigarettes as a Harm Reduction Strategy (COMPLETED) NA NCT05290025 — Easy Access to Smoking Cessation for People Receiving Opioid Agonist Therapy Who Are Smoking Tobacco (ACTIVE_NOT_RECRUITING) NA NCT01386138 — Treating South African Pregnant Women for Methamphetamine (COMPLETED) NA NCT01395797 — Pioglitazone for Heroin and for Nicotine Dependence (TERMINATED) PHASE1, PHASE2 NCT06552741 — Screening, Evaluation and Assessment (SEA) Protocol at the NIDA IRP (RECRUITING) Published literature Cochrane review Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol (BMJ open, 2021) Cochrane review Screening, treatment initiation, and referral for substance use disorders (Addiction science & clinical practice, 2017) Cochrane review [Naltrexone in the treatment of addiction] (Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2003) Meta-analysis Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trials (European journal of clinical pharmacology, 2023) Meta-analysis Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies (European psychiatry : the journal of the Association of European Psychiatrists, 2019) Meta-analysis BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysis (Pharmacogenomics, 2013) Systematic review Pharmacotherapy for pregnant women with addictions (American journal of obstetrics and gynecology, 2004) Clinical trial publication Assessing the impact of nicotinic partial agonists compared to NRT on opioid and cigarette use: A secondary analysis investigating treatment outcomes for co-occurring nicotine and opioid use (Journal of substance use and addiction treatment, 2026) Clinical trial publication Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy: A Randomized Clinical Trial (JAMA psychiatry, 2025) Clinical trial publication Exposure to Bupropion-SR vs. Placebo is associated with reductions in smoking among persons receiving methadone with no stated interest in smoking cessation (Addictive behaviors, 2025) Clinical trial publication FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study (Trials, 2022) Clinical trial publication Transcranial direct current stimulation of the frontal-parietal-temporal brain areas reduces cigarette consumption in abstinent heroin users (Journal of psychiatric research, 2022) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
NITREFAZOLE Repurposing via ADH1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NITROGLYCERIN Repurposing via ALDH2	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	1 trials 12 Trial pubs 8 RCT View evidence Registry trials NCT03271151 — Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty (COMPLETED) PHASE4 Published literature Clinical trial publication Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial (The Journal of arthroplasty, 2022) Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and α1A-adrenoceptor gene variation (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013) Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylase (Biological psychiatry, 2013) Clinical trial publication Clonidine improved laboratory-measured decision-making performance in abstinent heroin addicts (PloS one, 2012) Clinical trial publication Venlafaxine for acute heroin detoxification: a double-blind, randomized, control trial (Journal of clinical psychopharmacology, 2008) CT.gov search · Cochrane · PubMed	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORFLOXACIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PERGOLIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYTOIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PINDOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PROPRANOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	1 Trial pubs View evidence Published literature Clinical trial publication Evaluation of propranolol in opiate dependence (Archives of general psychiatry, 1976) CT.gov search · Cochrane · PubMed	DGIdb	—
PROPYLHEXEDRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
QUETIAPINE FUMARATE Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
RIFAMPIN Repurposing via AGBL4	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAZOBACTAM Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing via ADCY1	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
USTEKINUMAB Repurposing via AGBL4	Small molecule	Approved	Strong	95	—	DGIdb	—
VALPROIC ACID Repurposing via ANKK1	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	3 trials 3 Trial pubs 2 RCT View evidence Registry trials NCT04181515 — Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use (WITHDRAWN) PHASE2 NCT03015246 — Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence (COMPLETED) PHASE1, PHASE2 NCT04231708 — Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder (NOT_YET_RECRUITING) PHASE2 Published literature Clinical trial publication Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals (Psychopharmacology, 2013) Clinical trial publication Clonidine and yohimbine in opioid-dependent humans responding under a naloxone novel-response discrimination procedure (Behavioural pharmacology, 2003) Clinical trial publication Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients (Biological psychiatry, 2002) CT.gov search · Cochrane · PubMed	DGIdb	—
DARAPLADIB Repurposing via ADCY1	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing via ADCY1	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
CHEMBL:CHEMBL401844 Repurposing via ADCY1	Small molecule	Phase II	Emerging	50	—	DGIdb	ChEMBL Open Targets
HEROIN Repurposing via ANKS1B	Small molecule	Phase II	Emerging	50	—	DGIdb	—
MIRIVADELGAT Repurposing via ALDH2	Small molecule	Phase II	Emerging	50	—	DGIdb	—
NEMONAPRIDE Repurposing via ANKK1	Small molecule	Phase II	Emerging	50	—	DGIdb	—
PRUNETIN Repurposing via ALDH2	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ST034307 Repurposing via ADCY1	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ALPRENOLOL Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing via ADCY1	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Berberine OSMF review	Nutraceutical	Preclinical	Emerging	30	1 pubs View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Berberis vulgaris (Barberry) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Corydalis (Yan Hu Suo) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Fu-Yuan Pellet OSMF review	Herbal	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Ibogaine OSMF review	Psychedelic	Preclinical	Emerging	30	3 trials 2 Trial pubs 1 RCT View evidence Registry trials NCT04003948 — Preliminary Efficacy and Safety of Ibogaine in the Treatment of Methadone Detoxification (COMPLETED) PHASE2 NCT07226570 — Mapping Ibogaine Neural Dynamics in Opioid Use Disorder (RECRUITING) NCT05029401 — A Study of Oral Ibogaine in Opioid Withdrawal (COMPLETED) PHASE1, PHASE2 Published literature Systematic review The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies (Psychiatry research, 2025) Clinical trial publication Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients (Clinical pharmacology in drug development, 2016) Clinical trial publication Treatment of acute opioid withdrawal with ibogaine (The American journal on addictions, 1999) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Matricaria chamomilla (Chamomile) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Nigella sativa (Black seed) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Saffron (Crocin) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Sophora alopecuroides (Matrine) OSMF review	Herbal	Preclinical	Emerging	30	No indexed hits View evidence CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Tai-Kang Ning OSMF review	Herbal	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation

Natural Products

40 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked)

Reference lookups: GreenMedInfo · Examine.com

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Passionflower Natural product A systematic review of integrative medicine for opioid withdrawal	Botanical	Preclinical	Moderate	17	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Melatonin Natural product Melatonin as an Integrative Adjunct in Multimodal Analgesia: Linking Ci… Evaluating remyelination compounds for new applications in opioid use d… Integrating Drug Target Information in Deep Learning Models to Predict…	Nutraceutical	Preclinical	Emerging	7	3 trials View evidence Registry trials NCT06487533 — Sensing Physiological Symptoms of Opioid Withdrawal and Cravings in Patients With Opioid Use Disorder (RECRUITING) NCT06104280 — Medications for Opioid Use Disorder Photosensitive Retinal Ganglion Cell Function, Sleep, and Circadian Rhythms: Implications for Treatment (RECRUITING) NCT04247646 — SLeep and OPioid UsE in Patients Undergoing Total Knee Arthroplasty (ACTIVE_NOT_RECRUITING) NA CT.gov search · Cochrane · PubMed	ClinicalTrials.gov	PubChem
Terazosin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Yohimbine Natural product Acute glucagon-like peptide-1 receptor agonist, semaglutide, attenuates… Oxytocin attenuates yohimbine-induced responding for oral oxycodone und… Oxytocin Reduces Noradrenergic-Induced Opioid-Like Withdrawal Symptoms…	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Indoramin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Phentolamine Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Prazosin Natural product Re-Purposing FDA-Approved Drugs for Opioid Use Disorder Prenatal Morphine Exposure Increases Cardiovascular Disease Risk and Pr…	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Tamsulosin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Clonidine Natural product Beneficial effects of the rapid vs. standard procedure for injection na… Pharmacological treatment strategies to manage precipitated withdrawal… Thresholds for adjunctive medication usage and probability of initiatin…	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Apraclonidine Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Doxazosin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Mianserin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Akuammigine Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Rauwolscine Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Corynantheine Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Oxymetazoline Natural product Should Excess Topical Decongestant Use Raise a Red Flag? Rhinitis Medic…	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Colforsin Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Nb-001 Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
N-Heptylformamide Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
N-Cyclohexylformamide Natural product	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL PubChem ChEMBL
Atipamezole Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Vancomycin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Desglymidodrine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Phenylpropanolamine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Dexniguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Niguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Daidzin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Daidzein Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
4'-hydroxychalcone Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Prunetin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Doramapimod Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Staurosporine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Lestaurtinib Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Ruxolitinib Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Fedratinib Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Axitinib Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Nifedipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Nitrendipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Verapamil Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(1R)-5-hydroxy-1,5-dimethyl-hexyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylene-cyclohexane-1,3-diol Natural product	Food compound	Preclinical	Emerging	0	—	ClinicalTrials.gov	PubChem

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.

Disease overview

Remission & chronicity

Alterations

Therapeutics

Natural Products

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