This is a list of investigational substance-related disorder drugs, or drugs that are currently under development for clinical use for the treatment of substance-related disorders but are not yet approved. Substance-related disorders include substance use disorders like alcoholism (alcohol use disorder), amphetamine use disorder, cocaine use disorder, nicotine use disorder, and opioid use disorder, among others. In addition, they include substance withdrawal syndromes like alcohol withdrawal and opioid withdrawal as well as substance overdoses like opioid overdose.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action – Indication [Reference]".
This list was last comprehensively updated in January 2026. It is likely to become outdated with time.
Under development Phase 3 Brenipatide (LY-3537031) – glucagon-like peptide-1 (GLP-1) receptor agonist, gastric inhibitory polypeptide (GIP) receptor agonist – alcoholism Brenipatide - Eli Lily and Company - AdisInsight Ketamine (AWKN-001; AWKN-P-001) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – alcoholism Ketamine - Awakn Life Sciences - AdisInsight Naloxone intranasal (FMXIN-001; NS-001; naloxone microspheres powder nasal spray) – μ-opioid receptor antagonist – opioid-related disorders Naloxone hydrochloride intranasal - Nasus Pharma - AdisInsight Ondansetron (AD-04) – serotonin 5-HT3 receptor antagonist – alcoholism Ondansetron - ADial Pharmaceuticals - AdisInsight Zolpidem (ALM-006; ALM006) – GABAA receptor positive allosteric modulator/nonbenzodiazepine – substance-related disorders ALM 006 - AdisInsight
Phase 2/3 Metyrapone/oxazepam (EMB-001C; EMB-001) – combination of metyrapone (11β-hydroxylase inhibitor and cortisol synthesis inhibitor) and oxazepam (benzodiazepine/GABAA receptor positive allosteric modulator) – smoking withdrawal Metyrapone/oxazepam - Embera - AdisInsight NFL-101 (tobacco leaf extract) – immunomodulator (smoking vaccine) – smoking withdrawal NFL 101 - AdisInsight
Phase 2 ASP-8062 – GABAB receptor positive allosteric modulator – alcoholism ASP 8062 - AdisInsight BP-1.3656B (BP-1.3656; BP1.3656B; BP13656) – histamine H3 receptor antagonist – alcoholism BP 1.3656B - AdisInsight BP-1.4979 (BP-1.4979; BP-14979; BP14979) – dopamine D3 receptor partial agonist – smoking withdrawal BP 14979 - AdisInsight Brenipatide (LY-3537031) – glucagon-like peptide-1 (GLP-1) receptor agonist, gastric inhibitory polypeptide (GIP) receptor agonist – smoking withdrawal Brenipatide - Eli Lily and Company - AdisInsight Buprenorphine sublingual ethanol-free (CHF-6563; CHF6563) – μ-opioid receptor agonist, δ-opioid receptor agonist, κ-opioid receptor antagonist, nociceptin receptor agonist – opioid-related disorders CHF 6563 - AdisInsight Buprenorphine/naloxone (naloxone/buprenorphine) – combination of buprenorphine (non-selective opioid receptor modulator) and naloxone (orally/sublingually inactive opioid receptor antagonist) – opioid-related disorders Buprenorphine/naloxone - Aoxing Pharmaceutical Company - AdisInsight Bupropion/dextromethorphan (bupropion/DXM; Auvelity; AXS-05) – combination of bupropion (norepinephrine–dopamine reuptake inhibitor (NDRI), nicotinic acetylcholine receptor antagonist, CYP2D6 inhibitor) and dextromethorphan (DXM) (NMDA receptor antagonist, serotonin reuptake inhibitor, sigma receptor agonist, other actions) – smoking withdrawal Bupropion/dextromethorphan - Axsome Therapeutics - AdisInsight Bupropion/naltrexone (Contrave; CX-101; Mysimba; naltrexone/bupropion; NB32) – combination of bupropion (norepinephrine–dopamine reuptake inhibitor (NDRI), nicotinic acetylcholine receptor antagonist) and naltrexone (opioid receptor antagonist) – smoking withdrawal Bupropion/naltrexone - Currax Pharmaceuticals - AdisInsight Cannabidiol (CBD; A-1002-N5S; Nantheia) – cannabinoid/various actions – opioid-related disorders, smoking withdrawal Cannabidiol - ANANDA Scientific - AdisInsight Cannabidiol (CBD; Epidiolex; Epidyolex; Epidiolexa; GW-42003; GWP-42003; GWP-42003-P; JZP-926) – cannabinoid/various actions – heroin-related disorders, opioid-related disorders Cannabidiol - GW Pharmaceuticals - AdisInsight Centanafadine (CTN-SR; EB-1020) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) – smoking withdrawal Centanafadine - Otsuka Pharmaceutical - AdisInsight Cocaine esterase (RBP-8000; TNX-1300) – enzyme replacement – cocaine-related disorders Cocaine esterase - Tonix Pharmaceuticals Holding Corp - AdisInsight Cyproheptadine/prazosin (KT-110; Periactine/Alpress) – combination of cyproheptadine (various actions) and prazosin (α1-adrenergic receptor antagonist) – alcoholism Cyproheptadine/Prazosin - Kinnov Therapeutics - AdisInsight Devextinetug (anti-methamphetamine chimeric monoclonal antibody; Ch-mAb7F9; IXT-m200; METH-mAb) – immunomodulator (monocloncal antibody against methamphetamine) – substance-related disorders Devextinetug - InterveXion Therapeutics - AdisInsight F-652 (IL-22 IgG2 Fusion Protein; IL-22 IgG2-Fc; rhIL-22 dimer) – interleukin, immunoglobulin Fc fragment, recombinant fusion protein, anti-inflammatory, hepatoprotectant – alcoholism and alcoholic hepatitis F 652 - AdisInsight Ibudilast (AV-411; Eyevinal; Ibinal; KC-404; Ketas; MN-166; Pinatos) – phosphodiesterase PDE4 inhibitor, toll-like receptor 4 (TLR4) antagonist – alcoholism, opioid-related disorders, substance-related disorders Ibudilast - MediciNova - AdisInsight Liraglutide (LATIN-T1D; NN-2211; NN-9211; NN-8022; NNC-90-1170; Saxenda; Victoza) – glucagon-like peptide-1 (GLP-1) receptor agonist – smoking withdrawal Liraglutide - Novo Nordisk - AdisInsight Lixosicone (AEF-0117; AEF0117) – biased cannabinoid CB1 receptor negative allosteric modulator (pregnenolone derivative) – substance-related disorders AEF 0117 - AdisInsight Mavoglurant (AFQ-056; STP-7) – metabotropic glutamate mGlu5 receptor antagonist – alcoholism Mavoglurant - STALICLA - AdisInsight Mazdutide (IBI-362; LY-3305677; OXM-3) – glucagon-like peptide-1 (GLP-1) receptor agonist, glucagon receptor agonist – alcoholism Mazdutide - Eli Lilly and Company - AdisInsight Mebufotenin benzoate (5-MeO-DMT; BPL-002; BPL-003) – non-selective serotonin receptor agonist, serotonin 5-HT1A and 5-HT2A receptor agonist, serotonergic psychedelic – alcoholism Mebufotenin benzoate- Atai Beckley - AdisInsight Metyrapone/oxazepam (EMB-001C; EMB-001) – combination of metyrapone (11β-hydroxylase inhibitor and cortisol synthesis inhibitor) and oxazepam (benzodiazepine/GABAA receptor positive allosteric modulator) – cocaine-related disorders Metyrapone/oxazepam - Embera - AdisInsight Midomafetamine (MDMA) – serotonin–norepinephrine–dopamine releasing agent (SNDRA), serotonin 5-HT2 receptor agonist, entactogen – alcoholism Methylenedioxymetamfetamine - MAPS Europe B.V. - AdisInsight Mifepristone (C-1073; Corlux; Corluxin; Korlym; Mifegyne; Mifeprex; RU-38486; RU-486) – glucocorticoid, progesterone, and androgen receptor antagonist – alcoholism Mifepristone - Corcept Therapeutics - AdisInsight Miricorilant (CORT-118335) – glucocorticoid and mineralocorticoid receptor antagonist – alcoholism Miricorilant - Corcept Therapeutics - AdisInsight Nadolol (INV-102; INV102) – non-selective beta blocker (β1- and β2 adrenergic receptor agonist) – smoking withdrawal Nadolol - Invion - AdisInsight Neboglamine (nebostinel; CR-2249; XY-2401) – ionotropic glutamate glycine-gated NMDA receptor agonist – cocaine-related disorders Neboglamine - AdisInsight NNC0194-0499 (NN-9500; NN-9499; NNC-0194-0499) – fibroblast growth factor (FGF) receptor agonist – substance-related disorders NNC0194 0499 - AdisInsight NS-2359 (GSK-372475) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) – cocaine-related disorders NS 2359 - AdisInsight OMS-405 (OMS405) – PPARγ agonist – opioid-related disorders, smoking withdrawal OMS 405 - AdisInsight Pemvidutide (ALT-801- Altimmune; SP-1373; VPD-107) – glucagon-like peptide-1 (GLP-1) receptor agonists, glucagon receptor agonist – alcoholism Pemvidutide - Altimmune - AdisInsight Psilocybin (SYNP-101; synthetic psilocybin) – non-selective serotonin receptor agonist, serotonin 5-HT2A receptor agonist, and serotonergic psychedelic – alcoholism SYNP 101 - AdisInsight Selonabant (ANEB-001; V-24343) – cannabinoid CB1 receptor antagonist – substance-related disorders Selonabant - Anebulo Pharmaceuticals - AdisInsight Sunobinop (IMB-115; IT-1315; RSC117957; S-117957; V-117957) – nociceptin receptor agonist – alcoholism Sunobinop - Imbrium Therapeutics/Shionogi - AdisInsight TA-CD (TA-CD; TA-CD09) – immunostimulant (cocaine vaccine) – cocaine-related disorders Cocaine abuse vaccine TA-CD - AdisInsight Zabaglurant (Heptares 25; HTL-0014242; HTL14242; TMP-301) – metabotropic glutamate mGlu5 receptor negative allosteric modulator – alcoholism TMP 301 - AdisInsight Zolunicant (18-methoxycoronaridine; 18-MC; MM-110) – α3β4 nicotinic acetylcholine receptor antagonist – opioid-related disorders Zolunicant - Mindmed - AdisInsight
Phase 1/2 Dexmedetomidine (BXCL-501; Igalmi; KalmPen) – α2-adrenergic receptor agonist – opioid-related disorders Dexmedetomidine - BioXcel Therapeutics - AdisInsight Ibogaine (DMX-1002; IBX-210) – various actions/unknown mechanism of action and oneirogen/hallucinogen – opioid-related disorders Ibogaine - Atai Beckley/DemeRx - AdisInsight 5-Methoxy-2-aminoindane (MEAI; 5-MeO-AI; CMND-100) – serotonin–norepinephrine releasing agent – alcoholism 5-Methoxy 2-aminoindane - Clearmind Medicine - AdisInsight PT-00114 (PT100114; TCAP-1) – corticotropin-releasing hormone (CRH) inhibitor – opioid-related disorders PT 00114 - AdisInsight
Phase 1 AZD-4041 – orexin OX1 receptor antagonist – opioid-related disorders AZD 4041 - AdisInsight BI-1356225 – ghrelin O-acyltransferase (GOAT) inhibitor – opioid-related disorders BI 1356225 - AdisInsight Cebranopadol (GRT-6005; PRK-101; TRN-228) – μ-opioid receptor agonist, nociceptin receptor agonist – substance-related disorders Cebranopadol - Tris Pharma - AdisInsight CSX-1004 – monoclonal antibody against fentanyl – opioid-related disorders Dimethyltryptamine/harmine (DMT/harmine; RE-01) – combination of dimethyltryptamine (DMT) (serotonin 5-HT2A receptor agonist and serotonergic psychedelic) and harmine (monoamine oxidase inhibitor (MAOI) and other actions) – cocaine-related disorders Dimethyltryptamin/harmine - Reconnect Labs - AdisInsight DPI-125 (MCP-201) – μ-opioid receptor agonist, δ-opioid receptor agonist, κ-opioid receptor agonist – opioid-related disorders DPI 125 - AdisInsight Ibuprofen/ketotifen (SJP-005) – combination of ibuprofen (cyclooxygenase (COX) inhibitor/NSAID) and ketotifen (histamine H1 receptor antagonist, other actions) – opioid-related disorders Ibuprofen/ketotifen - Sen-Jam Pharmaceutical - AdisInsight Icalcaprant (ABBV-1354; CVL-354) – κ-opioid receptor antagonist – opioid-related disorders Icalcaprant - Cerevel Therapeutics - AdisInsight KNX-100 (SOC-1) – oxytocin-like drug / indirect oxytocin receptor modulator – opioid-related disorders, substance-related disorders KNX 100 - AdisInsightDelving into the Latest Updates on KNX-100 with Synapse Mavoglurant (AFQ-056; STP-7) – metabotropic glutamate mGlu5 receptor antagonist – cocaine-related disorders Mavoglurant - STALICLA - AdisInsight MEB-1170 – μ-opioid receptor biased agonist – opioid-related disorders MEB 1170 - AdisInsight Mebufotenin (5-MeO-DMT) – non-selective serotonin receptor agonist, serotonin 5-HT1A and 5-HT2A receptor agonist, and serotonergic psychedelic – substance use disorders MST-01 – undefined mechanism of action – smoking withdrawal MST 01 - AdisInsight