List of investigational post-traumatic stress disorder drugs

Short description: Investigational PTSD drugs

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.

This is a list of investigational post-traumatic stress disorder (PTSD) 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 It is likely to become outdated with time.

## Contents

* 1 Under development
* 1.1 Preregistration
* 1.2 Phase 3
* 1.3 Phase 2
* 1.4 Phase 1/2
* 1.5 Phase 1
* 1.6 Preclinical
* 2 Not under development
* 2.1 Development suspended
* 2.2 No development reported
* 2.3 Discontinued
* 3 Clinically used drugs
* 3.1 Approved drugs
* 3.1.1 Selective serotonin reuptake inhibitors (SSRIs)
* 3.2 Off-label drugs
* 4 See also
* 5 References
* 6 External links

## Under development

### Preregistration

* Brexpiprazole (Lu-AF41156; OPC-34712; Rexulti) – atypical antipsychotic (non-selective monoamine receptor modulator) [1][1]
* Midomafetamine (MDMA; Ecstasy) – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT2 receptor agonist, and entactogen [2][2]

### Phase 3

* Aripiprazole (Abilify; OPC-14597) – atypical antipsychotic (non-selective monoamine receptor modulator) [3]
* Cyclobenzaprine (KRL-102; TNX-102; Tonmya) – tricyclic antidepressant (monoamine reuptake inhibitor and monoamine receptor modulator) [4]

### Phase 2

* 7-Oxoprasterone (7-keto-DHEA; HBL-9001; HL-9001; At-Ease) – undefined mechanism of action (immunomodulator) [5] [6]
* Amdiglurax (ALTO-100; NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator) [7] [8]
* BI-1358894 – transient receptor potential cation channel TRPC4 and TRPC5 inhibitor [9]
* Cannabidiol (A-1002-N5S; CBD; Nantheia™) – cannabinoid, various actions [10]
* CORT-108297 (ADS-108297) – glucocorticoid receptor antagonist [11]
* Dronabinol (BX-1) – cannabinoid CB1 and CB2 receptor agonist [12]
* Iloperidone (Fanapt; Fanaptum; Fiapta; HP-873; ILO-522; VYV-683; Zomaril) – atypical antipsychotic (non-selective monoamine receptor modulator) [13]
* Ketamine intranasal (Ereska; PMI-100; PMI-150; SLS-002; TUR-002) – NMDA receptor antagonist and dissociative hallucinogen [14]
* Lithium cocrystal (AL-001; LiProSal; lithium salicylate/L-proline cocrystal) – undefined mechanism of action [15]
* Methylone (MDMC; TSND-201) – serotonin–norepinephrine–dopamine releasing agent and entactogen [3][4]
* Midomafetamine/citalopram (MDMA/citalopram) – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT2 receptor agonist, and entactogen followed by a selective serotonin reuptake inhibitor [4][5][6][7]
* Psilocybin (COMP-360; COMP360) – non-selective serotonin receptor agonist, serotonin 5-HT2A receptor agonist, and psychedelic hallucinogen [16]
* Psilocybin (MYCO-001, MYCO-003) – non-selective serotonin receptor agonist, serotonin 5-HT2A receptor agonist, and psychedelic hallucinogen [17][8]
* Soclenicant (BNC-210; IW-2143) – α7-nicotinic acetylcholine receptor antagonist [18]
* SRX-246 (API-246) – vasopressin V1A receptor antagonist [19]
* Xenon (NBTX-001) – NMDA receptor antagonist [20]

### Phase 1/2

* PT-00114 – corticotropin-releasing hormone (CRH) inhibitor [21]

### Phase 1

* Dexmedetomidine (BXCL-501; Igalmi; KalmPen) – α2-adrenergic receptor agonist [22]
* (R)-Midomafetamine ((R)-MDMA; EMP-01) – serotonin–norepinephrine releasing agent, weak serotonin 5-HT2 receptor agonist, and entactogen [23]
* Mirodenafil (AR-1001) – phosphodiesterase PDE5 inhibitor [24]

### Preclinical

* 2-Bromo-LSD (bromolysergide; BOL-148; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions [9][10][11]
* ART-2612 (ART2612) – FABP5 inhibitor [25]
* BMB-202 – serotonin 5-HT2A receptor agonist [26][12][13]
* Cycloserine/lurasidone (NRX-101) – combination of cycloserine (NMDA receptor partial agonist) and lurasidone (atypical antipsychotic or non-selective monoamine receptor modulator) [27]
* 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) [28]
* ENX-205 – dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist [29]
* GM-3009 (ibogaine analogue(s); GMX-3009) – various actions [14]
* Leu-enkephalin (leucine enkephalin; Envelta; METDoloron; NES-100; NM-0127; NM-127; PES200) – δ-opioid receptor agonist [30]
* Metyrapone/oxazepam (EMB-001C; EMB-001) – combination of metyrapone (11β-hydroxylase inhibitor, antiglucocorticoid) and oxazepam (GABAA receptor positive allosteric modulator, benzodiazepine)
* Midomafetamine microneedle transdermal patch (MDMA; "ecstasy") – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT2 receptor agonist, and entactogen [15]
* NB-127 – undefined mechanism of action [31]
* NNI-351 – DYRK kinase inhibitor, nerve growth factor (NGF) stimulant [32]
* Non-racemic midomafetamine (non-racemic MDMA; AM-1002) – undefined mechanism of action (non-neurotoxic, non-racemic form of MDMA) [4][16]
* Prabotulinumtoxin A (ABP-450; DWP-450; Evosyal; Jeuveau; Nabota; Nuceiva) – acetylcholine release inhibitor and neuromuscular blocking agent [33]
* Research programme: neurotransmitter modulators - Awakn Life Sciences (AWKN-SDN-14) – serotonin–norepinephrine–dopamine reuptake inhibitors [34]
* TN-001 – non-hallucinogenic serotonin 5-HT2A receptor partial agonist and serotonin 5-HT2B receptor antagonist and neuroplastogen [17][18][19]

## Not under development

### Development suspended

* Osanetant (ACER-801; SR-142801; SR-142806) – neurokinin NK3 receptor antagonist [35]

### No development reported

* Bupropion (amfebutamone; Wellbutrin) – norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator [36]
* Elcubragistat (ABX-1431; Lu-AG06466) – monoacylglycerol lipase (MAGL) inhibitor [37]
* EX-597 (KDS-4103; ORG-231295; URB-597) – fatty acid amide hydrolase (FAAH) inhibitor [38]
* IMM-201 (DAR-901; SRL-172; heat-killed Mycobacterium vaccae strain NCTC-11659) – immunomodulator, immunostimulant, and vaccine [39]
* Ketamine sublingual (SLS-003; Wafermine) – NMDA receptor antagonist and dissociative hallucinogen [40]
* Lanicemine (ARL-15896; ARR-15896; BHV-5500; FPL-15896) – NMDA receptor antagonist [41]
* Research programme: allosteric modulators - Addex Therapeutics – various actions [42]
* Research programme: cannabis extract therapeutics - Cannabis Science [43]
* Research programme: cannabinoid-based therapeutics - Axim Biotechnologies (Cannabidiol/Gabapentin; Cannbleph™) [44]
* Research programme: CNS disorders therapeutics - Sage Therapeutics (SAGE 105; SGE-202; SGE-301; SGE-516) – GABAA receptor modulators and NMDA receptor modulators [45]
* Research programme: psychedelic and empathogenic compounds subcutaneous - Bexson Biomedical – undefined mechanisms of action [20]
* Research programme: serotonin 2A receptor agonists - Bright Minds Biosciences [21]
* Research programme: tryptamine based therapeutics - PsyBio Therapeutics – serotonin 5-HT2A receptor agonists [22]
* Topiramate (Epitomax; KW-6485; KW-6485P; MCN 4853; RWJ 17021; Topamax; Topimax; Topina) – various actions [46]

### Discontinued

* Acamprosate controlled-release (SNC-102) – various actions [47]
* ALTO-202 – NMDA receptor antagonist [48]
* Balovaptan (RG-7314; RO-5028442; RO-5285119) – vasopressin V1 receptor antagonist [49]
* Carvedilol (Coreg) – α1-, β1-, and β2-adrenergic receptor antagonist and dual alpha/beta blocker [50]
* Crinecerfont (Crenessity; NBI-74788; SSR-125543) – corticotropin releasing factor receptor 1 (CRF1R) antagonist [51]
* ENX-105 – dopamine D2 and D3 receptor agonist, dopamine D4 receptor agonist, and serotonin 5-HT1A and 5-HT2A receptor agonist [52][23][24]
* Fluoxetine (Prozac, Sarafem) – selective serotonin reuptake inhibitor [53]
* Ganaxolone (GNX; CCD-1042; Ztalmy) – GABAA receptor positive allosteric modulator and neurosteroid [54]
* JZP-150 (PF-04457845; PF-4457845; PF-’845) – fatty acid amide hydrolase (FAAH) inhibitor [55]
* Nabiximols (tetrahydrocannabinol/cannabidiol; THC/CBD; GW-1000; JZP-378; Nabidiolex®/Tetranabinex®; Sativex) – cannabinoid receptor modulator, other actions [56]
* 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 [57]
* NYX-783 – NMDA receptor modulator [58]
* Orvepitant (GW-823296, GW823296X) – neurokinin NK1 receptor antagonist [59]
* Pomaglumetad methionil (DB103; LY-2140023; LY-2812223; LY-404039 prodrug) – metabotropic glutamate mGlu2 and mGlu3 receptor agonist (pomaglumetad prodrug) [60]
* PRAX-114 – GABA modulator [61]
* PRX-3140 (PRX-03140; NTC-942) – serotonin 5-HT4 receptor agonist [62]
* Verucerfont (GSK-561679; NBI-77860) – corticotropin releasing factor receptor 1 (CRF1R) antagonist [63]

## Clinically used drugs

### Approved drugs

#### Selective serotonin reuptake inhibitors (SSRIs)

* Paroxetine (Dropax, Paxil, Seroxat, Serestill) – selective serotonin reuptake inhibitor (SSRI) [64] [65]
* Sertraline (Lustral, Zoloft) – selective serotonin reuptake inhibitor (SSRI) [66]

### Off-label drugs

* Antipsychotics (non-selective monoamine receptor modulators) (e.g., olanzapine, quetiapine, risperidone)
* Benzodiazepines (GABAA receptor positive allosteric modulators) (e.g., alprazolam, clonazepam, diazepam, lorazepam)
* Beta blockers (β-adrenergic receptor antagonists) (e.g., propranolol, sotalol)
* Cannabinoids (cannabinoid receptor agonists) (e.g., cannabis, THC, nabilone)
* NMDA receptor antagonists (dissociative hallucinogens) (e.g., ketamine, esketamine)
* Other selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine)
* Prazosin (α1-adrenergic receptor antagonist)
* Serotonin–norepinephrine reuptake inhibitors (SNRIs) (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine)
* Topiramate (various actions)
* Tricyclic antidepressants (TCAs) (e.g., imipramine, amitriptyline)

## See also

* List of investigational drugs
* List of investigational generalized anxiety disorder drugs
* List of investigational panic disorder drugs
* List of investigational social anxiety disorder drugs
* List of investigational anxiety disorder drugs

## References

1. ↑ Kansteiner, Fraiser (22 September 2025). "FDA turns down Lundbeck, Otsuka's Rexulti in PTSD on lack of efficacy data". https://www.fiercepharma.com/pharma/heels-adcomm-scrutiny-fda-turns-down-lundbeck-otsukas-rexulti-ptsd.
2. ↑ "MDMA and MDMA-Assisted Therapy". Am J Psychiatry 182 (1): 79–103. January 2025. doi:10.1176/appi.ajp.20230681. PMID 39741438.
3. ↑ "Methylone - Transcend Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800072616.
4. ↑ 4.0 4.1 4.2 Michael Haichin (2024). "Psychedelics Drug Development Tracker". https://psychedelicalpha.com/data/psychedelic-drug-development-tracker.
5. ↑ "Tactogen Inc – Pipeline". 8 February 2021. https://tactogen.com/pipeline/.
6. ↑ Goodwin, Kate (30 September 2024). "MDMA Drug Developers Reprioritize Following Lykos Rejection in PTSD". https://www.biospace.com/drug-development/mdma-drug-developers-reprioritize-following-lykos-rejection-in-ptsd. "The company also hopes to improve tolerability with its program combining MDMA with citalopram, a selective serotonin reuptake inhibitor (SSRI) used to treat depression, for PTSD. Baggott anticipates beginning Phase II trials with the combo in 2025. [...] "The fact that Lykos didn't get their NDA approved on this cycle means that we are seriously considering prioritizing our novel compounds and waiting to move forward with our MDMA product," Baggott said. Tactogen's pipeline includes a number of preclinical molecules that Baggott said he believes will be superior to MDMA."
7. ↑ Hillier, David (15 June 2023). "Why Psychedelics Work Differently for People on Antidepressants". https://www.vice.com/en/article/psychedelics-and-antidepressants/. ""There are several studies that gave MDMA and an SSRI to healthy volunteers and compared the effects to MDMA alone. These studies show that even a single dose of an SSRI can reduce the psychological effects of MDMA by as much as 80 percent," says Matt Baggott, an MDMA research heavyweight and CEO of Tactogen, which develops MDMA-like compounds for medicinal use. [...] Interestingly, Baggott tells VICE that taking an SSRI after a MDMA roll "probably works" in alleviating a comedown. He points to animal studies that suggest SSRIs given shortly after MDMA may protect the brain from the negative effects of this overstimulation. He also ran a small, unpublished study with people who typically recorded a comedown post-MDMA, and did not normally take SSRIs. "When I gave them MDMA in a laboratory setting, they performed worse at a demanding cognitive task at both five and 26 hours after MDMA." In a separate session he gave them MDMA, followed three hours later by the SSRI citalopram. He says that this "prevented MDMA-induced performance difficulties without noticeably changing the main emotional effects of MDMA. This supports the idea that SSRIs can reduce the undesirable after-effects of MDMA.""
8. ↑ Ponieman, Natan. "Mydecine Unveils Four Psychedelic Drug Candidates - Mydecine Innovations Gr (OTC:MYCOF)". https://www.benzinga.com/markets/cannabis/21/04/20528665/mydecine-unveils-four-psychedelic-drug-candidates.
9. ↑ "BETR 001 - AdisInsight". https://adisinsight.springer.com/drugs/800061475.
10. ↑ "Delving into the Latest Updates on Bromolysergide with Synapse". https://synapse.patsnap.com/drug/3bcabbea8776452d8fcd680529dec52c.
11. ↑ "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep 42 (3). March 2023. doi:10.1016/j.celrep.2023.112203. PMID 36884348.
12. ↑ "Delving into the Latest Updates on BMB-202 with Synapse". https://synapse.patsnap.com/drug/f07b966d871a4b049536fd56f69aa280.
13. ↑ Biosciences, Bright Minds (April 19, 2023). "Bright Minds Biosciences Receives a Favorable Written Opinion from the International Searching Authority for BMB-202". GlobeNewswire News Room (Press release).
14. ↑ "GM 3009 - AdisInsight". https://adisinsight.springer.com/drugs/800077750.
15. ↑ "3,4-Methylenedioxymethamphetamine microneedle patch - PharmaTher/Revive Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800072394.
16. ↑ https://arcadiamedicine.com/ [bare URL]
17. ↑ "Delving into the Latest Updates on TN-001 with Synapse". 8 May 2025. https://synapse.patsnap.com/drug/659e9ca653394473a79c39efd4d6c046.
18. ↑ "Transneural Therapeutics". 7 May 2025. https://www.thepharmaletter.com/transneural-therapeutics.
19. ↑ Kuntz, Leah (23 April 2025). "Transneural Therapeutics: A New Company to Develop Novel Neuroplastogens". https://www.psychiatrictimes.com/view/transneural-therapeutics-a-new-company-to-develop-novel-neuroplastogens.
20. ↑ "Research programme: psychedelic and empathogenic compounds subcutaneous - Bexson Biomedical - AdisInsight". https://adisinsight.springer.com/drugs/800064980.
21. ↑ "Research programme: serotonin 2A receptor agonists - Bright Minds Biosciences - AdisInsight". https://adisinsight.springer.com/drugs/800062271.
22. ↑ "Research programme: tryptamine based therapeutics - PsyBio Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800058825.
23. ↑ "Engrail closes $157M series B, fueled by investors' renewed interest in neuropsychiatry". Fierce Biotech. 19 March 2024. https://www.fiercebiotech.com/biotech/engrail-closes-157-million-series-b-fueling-neuroscience-resurgence.
24. ↑ "Corporate Summary". Engrail Therapeutics, Inc.. 2024. https://www.engrail.com/wp-content/uploads/2024/03/Engrail-Therapeutics-Non-Confidential-Corporate-Summary-1Q24.pdf#page=19.

## External links

* AdisInsight - Springer

* v
* t
* e

Anxiolytics (N05B)

5-HT1AR agonists|

* Buspirone
* Gepirone†
* Tandospirone

GABAAR PAMs|

* Benzodiazepines: Adinazolam
* Alprazolam
* Bromazepam
* Camazepam
* Chlordiazepoxide
* Clobazam
* Clonazepam
* Clorazepate
* Clotiazepam
* Cloxazolam
* Diazepam#
* Ethyl loflazepate
* Etizolam
* Fludiazepam
* Halazepam
* Ketazolam
* Lorazepam#
* Medazepam
* Nordazepam
* Oxazepam
* Pinazepam
* Prazepam; Others: Alpidem‡
* Barbiturates (e.g., phenobarbital)
* Carbamates (e.g., meprobamate)
* Chlormezanone‡
* Ethanol (alcohol)
* Etifoxine
* Imepitoin; Herbs:
* Kava
* Skullcap
* Valerian

Gabapentinoids
(α2δ VDCC blockers)|

* Gabapentin
* Gabapentin enacarbil
* Phenibut
* Pregabalin

Antidepressants|

* SSRIs (e.g., escitalopram)
* SNRIs (e.g., duloxetine)
* SARIs (e.g., trazodone)
* TCAs (e.g., clomipramine#)
* TeCAs (e.g., mirtazapine)
* MAOIs (e.g., phenelzine); Others: Agomelatine
* Bupropion
* Tianeptine
* Vilazodone
* Vortioxetine

Sympatholytics
(Antiadrenergics)|

* Alpha-1 blockers (e.g., prazosin)
* Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine)
* Beta blockers (e.g., propranolol)

Others|

* Benzoctamine
* Cannabidiol
* Cycloserine
* Fabomotizole
* Hydroxyzine
* Kanna
* Lavender
* Lorpiprazole
* Mebicar
* Mepiprazole
* Nicotine
* Opipramol
* Oxaflozane‡
* Phenaglycodol
* Phenibut
* Picamilon
* Selank
* Tiagabine
* Tofisopam
* Validolum

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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*[5-HT1AR]: 5-HT1A receptor
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[α2δ]: alpha2delta subunit
*[VDCC]: voltage-dependent calcium channel
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin-norepinephrine reuptake inhibitors
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[TeCAs]: Tetracyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors