List of investigational post-traumatic stress disorder drugs

This is a list of investigational post-traumatic stress disorder drugs, or drugs that are currently under development for clinical use for the treatment of post-traumatic stress disorder (PTSD) but are not yet approved.

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 [Reference]".

This list was last comprehensively updated in September 2025. It is likely to become outdated with time.

Under development

Preregistration

Midomafetamine (MDMA; Ecstasy) – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT₂ receptor agonist, and entactogen ^[1]

Phase 3

Aripiprazole (Abilify; OPC-14597) – atypical antipsychotic (non-selective monoamine receptor modulator)
Cyclobenzaprine (KRL-102; TNX-102; Tonmya) – tricyclic antidepressant (monoamine reuptake inhibitor and monoamine receptor modulator)

Phase 2

7-Oxoprasterone (7-keto-DHEA; HBL-9001; HL-9001; At-Ease) – undefined mechanism of action (immunomodulator)
Amdiglurax (ALTO-100; NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator)
BI-1358894 – transient receptor potential cation channel TRPC4 and TRPC5 inhibitor
Cannabidiol (A-1002-N5S; CBD; Nantheia™) – cannabinoid, various actions
CORT-108297 (ADS-108297) – glucocorticoid receptor antagonist
Dronabinol (BX-1) – cannabinoid CB₁ and CB₂ receptor agonist
Iloperidone (Fanapt; Fanaptum; Fiapta; HP-873; ILO-522; VYV-683; Zomaril) – atypical antipsychotic (non-selective monoamine receptor modulator)
Ketamine intranasal (Ereska; PMI-100; PMI-150; SLS-002; TUR-002) – NMDA receptor antagonist and dissociative hallucinogen
Lithium cocrystal (AL-001; LiProSal; lithium salicylate/L-proline cocrystal) – undefined mechanism of action and mood stabilizer (improved formulation of lithium)
Methylone (MDMC; TSND-201) – serotonin–norepinephrine–dopamine releasing agent and entactogen ^[2]^[3]
Midomafetamine/citalopram (MDMA/citalopram) – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT₂ receptor agonist, and entactogen followed by a selective serotonin reuptake inhibitor ^[3]^[4]^[5]^[6]
Psilocybin (COMP-360; COMP360) – non-selective serotonin receptor agonist, serotonin 5-HT_2A receptor agonist, and psychedelic hallucinogen
Psilocybin (MYCO-001, MYCO-003) – non-selective serotonin receptor agonist, serotonin 5-HT_2A receptor agonist, and psychedelic hallucinogen ^[7]
Soclenicant (BNC-210; IW-2143) – α₇-nicotinic acetylcholine receptor antagonist
SRX-246 (API-246) – vasopressin V_1A receptor antagonist
Xenon (NBTX-001) – NMDA receptor antagonist

Phase 1/2

PT-00114 – corticotropin-releasing hormone (CRH) inhibitor

Phase 1

Dexmedetomidine (BXCL-501; Igalmi; KalmPen) – α₂-adrenergic receptor agonist
ENX-205 – dopamine D₂ and D₃ receptor antagonist and serotonin 5-HT_1A and 5-HT_2A receptor agonist
(R)-Midomafetamine ((R)-MDMA; EMP-01) – serotonin–norepinephrine releasing agent, weak serotonin 5-HT₂ receptor agonist, and entactogen
Mirodenafil (AR-1001) – phosphodiesterase PDE5 inhibitor

Preclinical

2-Bromo-LSD (bromolysergide; BOL-148; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT_2A receptor agonist and other actions ^[8]^[9]^[10]
ART-2612 (ART2612) – FABP5 inhibitor
BMB-202 – serotonin 5-HT_2A receptor agonist ^[11]^[12]
Cycloserine/lurasidone (NRX-101) – combination of cycloserine (NMDA receptor partial agonist) and lurasidone (atypical antipsychotic or non-selective monoamine receptor modulator)
Cyproheptadine/prazosin (KT-110; Periactine/Alpress) – combination of cyproheptadine (H₁ receptor antagonist, muscarinic acetylcholine receptor antagonist, serotonin receptor antagonist, other actions) and prazosin (α₁-adrenergic receptor antagonist)
GM-3009 (ibogaine analogue(s); GMX-3009) – various actions ^[13]
Leu-enkephalin (leucine enkephalin; Envelta; METDoloron; NES-100; NM-0127; NM-127; PES200) – δ-opioid receptor agonist
Metyrapone/oxazepam (EMB-001C; EMB-001) – combination of metyrapone (11β-hydroxylase inhibitor, antiglucocorticoid) and oxazepam (GABA_A receptor positive allosteric modulator, benzodiazepine)
Midomafetamine microneedle transdermal patch (MDMA; "ecstasy") – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT₂ receptor agonist, and entactogen ^[14]
NB-127 – undefined mechanism of action
NNI-351 – DYRK kinase inhibitor, nerve growth factor (NGF) stimulant
Non-racemic midomafetamine (non-racemic MDMA; AM-1002) – undefined mechanism of action (non-neurotoxic, non-racemic form of MDMA) ^[3]^[15]
Prabotulinumtoxin A (ABP-450; DWP-450; Evosyal; Jeuveau; Nabota; Nuceiva) – acetylcholine release inhibitor and neuromuscular blocking agent
Research programme: neurotransmitter modulators - Awakn Life Sciences (AWKN-SDN-14) – serotonin–norepinephrine–dopamine reuptake inhibitors
TN-001 – non-hallucinogenic serotonin 5-HT_2A receptor partial agonist and serotonin 5-HT_2B receptor antagonist and neuroplastogen ^[16]^[17]^[18]

Not under development

Development suspended

Osanetant (ACER-801; SR-142801; SR-142806) – neurokinin NK₃ receptor antagonist

No development reported

Bupropion (amfebutamone; Wellbutrin) – norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator
Elcubragistat (ABX-1431; Lu-AG06466) – monoacylglycerol lipase (MAGL) inhibitor
EX-597 (KDS-4103; ORG-231295; URB-597) – fatty acid amide hydrolase (FAAH) inhibitor
IMM-201 (DAR-901; SRL-172; heat-killed Mycobacterium vaccae strain NCTC-11659) – immunomodulator, immunostimulant, and vaccine
Ketamine sublingual (SLS-003; Wafermine) – NMDA receptor antagonist and dissociative hallucinogen
Lanicemine (ARL-15896; ARR-15896; BHV-5500; FPL-15896) – NMDA receptor antagonist
Research programme: allosteric modulators - Addex Therapeutics – various actions
Research programme: cannabis extract therapeutics - Cannabis Science
Research programme: cannabinoid-based therapeutics - Axim Biotechnologies (Cannabidiol/Gabapentin; Cannbleph™)
Research programme: CNS disorders therapeutics - Sage Therapeutics (SAGE 105; SGE-202; SGE-301; SGE-516) – GABA_A receptor modulators and NMDA receptor modulators
Research programme: psychedelic and empathogenic compounds subcutaneous - Bexson Biomedical – undefined mechanisms of action ^[19]
Research programme: serotonin 2A receptor agonists - Bright Minds Biosciences ^[20]
Research programme: tryptamine based therapeutics - PsyBio Therapeutics – serotonin 5-HT_2A receptor agonists ^[21]
Topiramate (Epitomax; KW-6485; KW-6485P; MCN 4853; RWJ 17021; Topamax; Topimax; Topina) – various actions

Discontinued

Acamprosate controlled-release (SNC-102) – various actions
ALTO-202 – NMDA receptor antagonist
Balovaptan (RG-7314; RO-5028442; RO-5285119) – vasopressin V₁ receptor antagonist
Brexpiprazole (Lu-AF41156; OPC-34712; Rexulti) – atypical antipsychotic (non-selective monoamine receptor modulator) ^[22]
Carvedilol (Coreg) – α₁-, β₁-, and β₂-adrenergic receptor antagonist and dual alpha/beta blocker
Crinecerfont (Crenessity; NBI-74788; SSR-125543) – corticotropin releasing factor receptor 1 (CRF₁R) antagonist
ENX-105 – dopamine D₂ and D₃ receptor agonist, dopamine D₄ receptor agonist, and serotonin 5-HT_1A and 5-HT_2A receptor agonist ^[23]^[24]
Fluoxetine (Prozac, Sarafem) – selective serotonin reuptake inhibitor
Ganaxolone (GNX; CCD-1042; Ztalmy) – GABA_A receptor positive allosteric modulator and neurosteroid
JZP-150 (PF-04457845; PF-4457845; PF-’845) – fatty acid amide hydrolase (FAAH) inhibitor
Nabiximols (tetrahydrocannabinol/cannabidiol; THC/CBD; GW-1000; JZP-378; Nabidiolex®/Tetranabinex®; Sativex) – cannabinoid receptor modulator, other actions
Naloxone/tianeptine (TNX-601) – combination of tianeptine (weak and atypical μ-opioid receptor agonist) and naloxone (orally inactive opioid receptor antagonist)
Nepicastat (APL-1401; SYN-117) – dopamine β-hydroxylase (DBH) inhibitor
NYX-783 – NMDA receptor modulator
Orvepitant (GW-823296, GW823296X) – neurokinin NK₁ receptor antagonist
Pomaglumetad methionil (DB103; LY-2140023; LY-2812223; LY-404039 prodrug) – metabotropic glutamate mGlu₂ and mGlu₃ receptor agonist (pomaglumetad prodrug)
PRAX-114 – GABA modulator
PRX-3140 (PRX-03140; NTC-942) – serotonin 5-HT₄ receptor agonist
Verucerfont (GSK-561679; NBI-77860) – corticotropin releasing factor receptor 1 (CRF₁R) antagonist

Clinically used drugs

Approved drugs

Selective serotonin reuptake inhibitors (SSRIs)

Paroxetine (Dropax, Paxil, Seroxat, Serestill) – selective serotonin reuptake inhibitor (SSRI)
Sertraline (Lustral, Zoloft) – selective serotonin reuptake inhibitor (SSRI)

Off-label drugs

Antipsychotics (non-selective monoamine receptor modulators) (e.g., olanzapine, quetiapine, risperidone)^[25]^[26]^[27]
Benzodiazepines (GABA_A receptor positive allosteric modulators) (e.g., alprazolam, clonazepam, diazepam, lorazepam)^[26]
Beta blockers (β-adrenergic receptor antagonists) (e.g., propranolol, sotalol)^[26]
Cannabinoids (cannabinoid receptor agonists) (e.g., cannabis, THC/dronabinol, nabilone)^[28]^[29]
Lamotrigine (sodium channel blocker, other actions)^[25]
Monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine)^[25]
NMDA receptor antagonists (dissociative hallucinogens) (e.g., ketamine, esketamine)^[30]^[31]
Other selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine)^[25]^[32]
Prazosin (α₁-adrenergic receptor antagonist)^[33]
Serotonin–norepinephrine reuptake inhibitors (SNRIs) (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine)^[32]
Topiramate (various actions)^[25]
Tricyclic antidepressants (TCAs) (e.g., imipramine, amitriptyline)^[34]