List of investigational hallucinogens and entactogens
This is a list of investigational hallucinogens and entactogens, or hallucinogens and entactogens that are currently under formal development for clinical use but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The list also includes non-hallucinogenic drugs related to hallucinogens, such as non-hallucinogenic serotonin 5-HT2A receptor agonists and non-hallucinogenic ketamine analogues. Cannabinoids, or cannabinoid receptor modulators, are not included in this list. Many of the indications are not for continuous medication therapy but rather are for medication-assisted psychotherapy or short-term use only.
This list was last comprehensively updated in October 2024. It is likely to become outdated with time.
Under development
[edit]Preregistration
[edit]- Midomafetamine (MDMA; "ecstasy") – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – post-traumatic stress disorder, alcoholism, social anxiety in autism – Multidisciplinary Association for Psychedelic Studies (MAPS), Lykos Therapeutics [1][2]
Phase 3
[edit]- CYB003 (CYB-003; deuterated psilocybin analogue; deuterated psilocin) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – major depressive disorder, alcoholism, psychiatric disorders – Cybin [3][4][5][6][7]
- Ketamine (HTX-100; NRX-100) – ionotropic glutamate NMDA receptor antagonist – suicidal ideation, mental disorders – NRx Pharmaceuticals [8]
- Psilocybin (COMP-360; COMP360) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders, anorexia nervosa, bipolar depression, major depressive disorder, post-traumatic stress disorder, somatoform disorders, pervasive child development disorders – COMPASS Pathways [9][10]
Phase 2
[edit]- Arketamine ((R)-ketamine; PCN-101) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders – ATAI Life Sciences [11]
- CYB004 (CYB-004; deuterated dimethyltryptamine; deuterated DMT; dDMT) – non-selective serotonin receptor agonist and psychedelic hallucinogen – Cybin [12]
- Dimethyltryptamine (DMT; BMND-01, BMND-02, BMND-03) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders, fibromyalgia, substance-related disorders – Biomind Labs [13]
- Esketamine (CLE-100) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Clexio Biosciences [14]
- GM-2505 – serotonin 5-HT2A and 5-HT2C receptor agonist, psychedelic hallucinogen, and serotonin releasing agent – major depressive disorder – Gilgamesh Pharmaceuticals [15]
- Ketamine (Ereska; IN ketamine; ketamine IN; intranasal ketamine; intranasal racemic ketamine; PMI-100, PMI-150, SLS-002, TUR-002) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – post-traumatic stress disorder, suicidal ideation, acute pain, cancer pain – Seelos Therapeutics [16]
- Ketamine (AWKN-001, AWKN-P-001) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – alcoholism, binge-eating disorder, gambling, impulse control disorders, obsessive–compulsive disorder – Awakn Life Sciences [17]
- Ketamine extended-release (R-107, R107) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Douglas Pharmaceuticals [18]
- Ketamine prolonged-release oral (KET-01) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders, neuropathic pain – Ketabon [19]
- Lysergic acid diethylamide (LSD; lysergide; MM-120) – non-selective serotonin receptor agonist and psychedelic hallucinogen – anxiety disorders, attention-deficit hyperactivity disorder, cluster headache, major depressive disorder, pain – MindMed [20] [21] [22]
- Lysergic acid diethylamide (LSD; lysergide; MB-22001) – non-selective serotonin receptor agonist and psychedelic hallucinogen – major depressive disorder – MindBio Therapeutics [23]
- Mebufotenin (5-MeO-DMT; BPL-002, BPL-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen – alcoholism, major depressive disorder – Beckley Psytech [24]
- Mebufotenin (5-MeO-DMT; BMND-05, BMND-08) – non-selective serotonin receptor agonist and psychedelic hallucinogen – Alzheimer's disease, pain – Biomind Labs [25]
- Mebufotenin (5-MeO-DMT; GH001, GH-001) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders – GH Research [26] [27] [28]
- Methylone (MDMC; TSND-201) – serotonin, norepinephrine, and dopamine releasing agent and entactogen – post-traumatic stress disorders – Transcend Therapeutics [29]
- Midomafetamine (MDMA; "ecstasy") – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – alcoholism – Awakn Life Sciences [30]
- MSP-1014 (psilocin prodrug) – non-selective serotonin receptor agonist and psychedelic hallucinogen – major depressive disorder – Mindset Pharma, Otsuka America Pharmaceutical [31][32]
- OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – non-hallucinogenic serotonin 5-HT2A receptor partial agonist, dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer") – bipolar depression, chronic fatigue syndrome, depressive disorders, stroke, subarachnoid hemorrhage, Parkinson's disease – Carlsson Research AB, Pfizer [33][34][35][36][37][38][39]
- Psilocybin (CYB-001; INT0052/2020) – non-selective serotonin receptor agonist and psychedelic hallucinogen – mental disorders, major depressive disorder, anxiety disorders – Cybin [40]
- Psilocybin (MYCO-001, MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen – post-traumatic stress disorder, anxiety disorders, depressive disorders, headache, substance-related disorders – Mydecine [41] [42]
- Psilocybin (PEX-010) – non-selective serotonin receptor agonist and psychedelic hallucinogen – adjustment disorders, alcoholism, depressive disorders, anxiety disorders – Filament Health [43]
- Psilocybin (PFN™; TRP-8802, TRP-8803, TRP-8804, TRYP-0082) – non-selective serotonin receptor agonist and psychedelic hallucinogen – binge-eating disorder, fibromyalgia, irritable bowel syndrome, cancer, complex regional pain syndrome, pain – Tryp Therapeutics [44]
- Psilocybin (SYNP-101; synthetic psilocybin) – alcoholism, obsessive–compulsive disorders, cluster headache, migraine – Ceruvia Lifesciences [45]
- RE-104 (FT-104; 4-HO-DiPT/iprocin prodrug) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – postnatal depression – Reunion Neuroscience [46]
- Xenon (NBTX-001) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – post-traumatic stress disorder, Alzheimer's disease, irritable bowel syndrome, Parkinson's disease, pervasive child development disorders, panic disorder – Nobilis Therapeutics [47]
- Zolunicant (18-methoxycoronaridine; 18-MC; MM-110) – α3β4 nicotinic acetylcholine receptor antagonist, other actions – leishmaniasis, opioid-related disorders, substance-related disorders – MindMed [48]
Phase 1/2
[edit]- Dimethyltryptamine (DMT; SPL-026) – non-selective serotonin receptor agonist and psychedelic hallucinogen – major depressive disorder – Small Pharma, Cybin [49]
- Ibogaine – various actions and hallucinogen – opioid-related disorders – ATAI Life Sciences/DemeRx [50]
- Psilocybin (PSY-0.1, PSY-0.2, PSY-0.3, PSY-0.4/0.5, PSY-0.6) – non-selective serotonin receptor agonist and psychedelic hallucinogen – substance-related disorders, neurological disorders, opioid-related disorders, psychiatric disorders, traumatic brain injury, cancer, anxiety disorders, bipolar disorders, depressive disorders, eating disorders, and additional unspecified conditions – Revive Therapeutics [51]
- Psilocybin infusion (ELE-101, ELE-Psilo, ELE-Psilo+) – non-selective serotonin receptor agonist and psychedelic hallucinogen – major depressive disorder – Eleusis, Beckley Psytech [52]
Phase 1
[edit]- (R)-Midomafetamine ((R)-MDMA; (R)-methylenedioxymetamfetamine; MM-402) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – pervasive child development disorders – MindMed [53]
- (R)-Midomafetamine ((R)-MDMA; R-MDMA; EMP-01) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – post-traumatic stress disorder, social phobia – EmpathBio [54][55]
- Dimethyltryptamine (DMT; VLS-01) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders – ATAI Life Sciences, Viridia Life Sciences [56] [57]
- Dimethyltryptamine (DMT; EBRX-101) – non-selective serotonin receptor agonist and psychedelic hallucinogen – smoking withdrawal, alcoholism – Entheon Biomedical [58] [59]
- DLX-001 (DLX-1; AAZ; AAZ-A-154) – non-hallucinogenic serotonin 5-HT2A receptor agonist – CNS disorders, major depressive disorder – Delix Therapeutics [60][61]
- Esketamine ((S)-ketamine; S-ketamine; AWKN-002) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – alcoholism – Awakn Life Sciences [62]
- Ketamine oral (Keticap) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – mood disorders – Neurocentrx Pharma [63]
- Ketanserin – serotonin 5-HT2A and α1-adrenergic receptor antagonist – hallucinogen antidote – MindMed [64][65]
- Lys-MDA – methylenedioxyamphetamine (MDA) prodrug (serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen) – unknown – MindMed, MiHKAL [66] [67]
- Lys-MDMA – midomafetamine (MDMA) prodrug (serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen) – unknown – MindMed, MiHKAL [66] [67]
- Mescaline (BMND-06, BMND-09) – non-selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – obesity, Parkinson's disease, inflammation – Biomind Labs [68] [69]
- Psilocybin (MLS-101) – non-selective serotonin receptor agonist and psychedelic hallucinogen – psychiatric disorders – MycoMedia Life Sciences [70]
Preclinical
[edit]- 2-Bromo-LSD (bromolysergide; BOL-148; NYPRG-101) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – cluster headache, migraine – Ceruvia Lifesciences [71][72]
- 2-Bromo-LSD (bromolysergide; BOL-148; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – cluster headache, major depressive disorder, neuropathic pain, post-traumatic stress disorders – Transcend Biodynamics, BetterLife Pharma [73][74][75]
- 2-Fluorodeschloroketamine (2-FDCK) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Clearmind Medicine [76]
- 3-Methylmethcathinone (3-MMC; metaphedrone) – serotonin, norepinephrine, and dopamine releasing agent and entactogen – dyskinesias – Clearmind Medicine [77]
- 5-Methoxy-2-aminoindane (5-MeO-AI; MEAI; CMND-100) – serotonin releasing agent and entactogen – alcoholism, cocaine use disorder, metabolic syndrome, obesity – Clearmind Medicine [78]
- 5-MeO-MiPT (MSD-001; "moxy") – non-selective serotonin receptor agonist and psychedelic hallucinogen – undefined indication – Mindstate Design Labs [79][80][81]
- AKO-001 – serotonin 5-HT2 receptor agonist – stroke – Akome Biotech [82]
- AKO-002 (psilocybin-based formulation) – non-selective serotonin receptor agonist and psychedelic hallucinogen – Alzheimer's disease – Akome Biotech [83]
- AKO-003 (ketamine-based psychedelic formulation) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Akome Biotech [84]
- AKO-004 – serotonin 5-HT2 receptor agonist and psychedelic hallucinogen – Parkinson's disease – Akome Biotech [85]
- BMB-201 (BMB-A39a prodrug) – non-hallucinogenic serotonin 5-HT2A and 5-HT2C receptor agonist and psychoplastogen – generalized anxiety disorder, pain – Bright Minds Biosciences [86] [87] [88] [89]
- BMB-202 – selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – depressive disorders, post-traumatic stress disorder – Bright Minds Biosciences [90] [91] [92] [87]
- Dimethyltryptamine (DMT) – non-selective serotonin receptor agonist and psychedelic hallucinogen – psychiatric disorders, social phobia – Psilera [93]
- EB-002 (EB-373; psilocin prodrug) – non-selective serotonin receptor agonist and psychedelic hallucinogen – anxiety disorders – Enveric Biosciences [94]
- EGX-A – serotonin 5-HT2A receptor agonist – depressive disorders – ATAI Life Sciences [95] [96] [97]
- EGX-B – serotonin 5-HT2A receptor agonist – depressive disorders – ATAI Life Sciences [98] [96] [97]
- ENX-105 – dopamine D2 and D3 receptor antagonist and non-hallucinogenic serotonin 5-HT1A and 5-HT2A receptor agonist – mood disorders, post-traumatic stress disorder – Engrail Therapeutics [99][100][101]
- GM-3009 (ibogaine analogue) – various actions – opioid-related disorders – Gilgamesh Pharmaceuticals [102]
- Ibogaine – various actions and hallucinogen – CNS disorders, neuropathic pain, traumatic brain injury – MINDCURE [103]
- Ibogaine derivatives - Terran Biosciences – various actions and potential hallucinogens – neurological disorders, psychiatric disorders – Terran Biosciences [104]
- ITI-1549 – non-hallucinogenic serotonin 5-HT2A receptor agonist and serotonin 5-HT2B receptor antagonist – psychiatric disorders – Intra-Cellular Therapies [105] [106][107]
- Ketamine depot (ALA-3000) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders – Alar Pharmaceuticals [108]
- Ketamine subcutaneous (BB-106) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – acute pain, mental disorders – Bexson Biomedical [109]
- Ketamine analogue (Ketamir, Ketamir-2) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders – MIRA Pharmaceuticals [110]
- Long-acting MDMA prodrug (long-acting midomafetamine prodrug) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – neurological disorders, psychiatric disorders – Terran Biosciences [111]
- LPH-5 – selective serotonin 5-HT2A receptor partial agonist and psychedelic hallucinogen – major depressive disorder – Lophora, Beckley Psytech [112][113][114]
- LPH-48 (shorter-acting LPH-5 analogue) – undefined mechanism of action and serotonergic hallucinogen – alcoholism – Lophora [115] [116] [117]
- Lucid-PSYCH (Lucid-201) – undefined mechanism of action and psychedelic hallucinogen – major depressive disorder – Lucid Psycheceuticals [118][119][120]
- Lysergic acid diethylamide (LSD; lysergide) – non-selective serotonin receptor agonist and psychedelic hallucinogen – neurological disorders, psychiatric disorders – Delix Therapeutics [121]
- MBDB – serotonin and norepinephrine releasing agent, weak serotonin 5-HT1 and 5-HT2 receptor ligand, and entactogen – autism – PharmAla Biotech [122][123][124][125]
- Mebufotenin (5-MeO-DMT; LSR-1019) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders, psychiatric disorders – Lusaris Therapeutics [126]
- Mescaline (JOUR-5700) – non-selective serotonin receptor agonist and psychedelic hallucinogen – alcoholism – Journey Colab [127]
- Midomafetamine microneedle transdermal patch (MDMA; "ecstasy") – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – anxiety disorders, depressive disorders, post-traumatic stress disorder, substance-related disorders – PharmaTher, Revive Therapeutics [128]
- MSP-4019 – undefined mechanism of action (5-MeO-DMT- and DMT-inspired drug) – neurological disorders, psychiatric disorders – Mindset Pharma, Otsuka America Pharmaceutical [129] [130]
- MSP-4020 – undefined mechanism of action (5-MeO-DMT- and DMT-inspired drug) – neurological disorders, psychiatric disorders – Mindset Pharma, Otsuka America Pharmaceutical [131] [130]
- MYCO-006 – undefined mechanism of action and short-acting MDMA-like entactogen – anxiety disorders – Mydecine [132] [133][134][135]
- MYCO-007 – undefined mechanism of action and short-acting MDMA-like entactogen – undefined indication – Mydecine [136][134][135]
- Norbaeocystin – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – mental disorders – PsyBio Therapeutics [137]
- PSIL-001 (DMT analogue) – non-hallucinogenic serotonin 5-HT1 receptor modulator – depressive disorders, mood disorders, neurodegenerative disorders, substance-related disorders – Psilera [138][139]
- PSIL-002 (DMT analogue) – non-hallucinogenic serotonin 5-HT1 receptor modulator – depressive disorders, mood disorders, neurodegenerative disorders, substance-related disorders – Psilera [140][139][141]
- Psilacetin (O-acetylpsilocin; 4-AcO-DMT) – non-selective serotonin receptor agonist and psychedelic hallucinogen – substance-related disorders – Psilera [142]
- Psilocin (PLZ-1015) – non-selective serotonin receptor agonist and psychedelic hallucinogen – pervasive child development disorders – Pilz Bioscience [143]
- PSYLO-1001 (Psylo-1001; PSYLO-100X) – non-hallucinogenic serotonin 5-HT2A and 5-HT6 receptor modulator – mental disorders – Psylo [144]
- PSYLO-3001 (Psylo-3001) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders, generalized anxiety disorder, social phobia – Psylo [145]
- PSYLO-4001 (Psylo-4001) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – depressive disorders, major depressive disorder – Psylo [146][147]
- Research programme: hydroxynorketamine derivatives - Spirify Pharma – amino acid modulators and serine protease modulators – depressive disorders, pain – Spirify Pharma [148]
- Research programme: Ibogaine analogues - Gilgamesh Pharmaceuticals (GM-300X) – various actions – opioid-related disorders – Gilgamesh Pharmaceuticals [149]
- Research programme: mental disorder therapeutics - Cybin (Deuterated DMT series - Cybin) – serotonin receptor modulators and psychedelic hallucinogens – mental disorders – Small Pharma, Cybin [150]
- Research programme: micro-dose serotonergics - Gilgamesh Pharmaceuticals – serotonin receptor agonists – attention-deficit hyperactivity disorder, major depressive disorder – Gilgamesh Pharmaceuticals [151]
- Research programme: non-hallucinogenic psychedelic therapeutics - Intra-Cellular Therapies (ITI-1500) – undefined mechanism of action – psychiatric disorders – Intra-Cellular Therapies [152]
- Research programme: psilocin derivatives - Enveric Biosciences – serotonin 5-HT2A receptor agonists and potential psychedelic hallucinogens – mental disorders – Enveric Biosciences [153]
- Research programme: psilocin prodrugs and derivatives - Terran Biosciences – serotonin 5-HT2A receptor agonists and psychedelic hallucinogens – neurological disorders, psychiatric disorders – Terran Biosciences [154]
- Research programme: psychedelic and empathogenic compounds - Terran Biosciences – serotonin receptor modulators – neurological disorders, psychiatric disorders – Terran Biosciences [155]
- Research programme: psychedelic-based neurological therapeutics - Psilera – undefined mechanism and psychedelic hallucinogens – alcoholism, anxiety disorders, depressive disorders, neurodegenerative disorders – Psilera [156]
- Research programme: psychedelic-based therapeutics - Clearmind Medicine/SciSparc – undefined mechanism of action – metabolic disorders, obesity, psychiatric disorders – Clearmind Medicine, SciSparc [157]
- Research programme: psychedelic microneedle patch - PharmaTher – undefined mechanism of action – neurological disorders, neuromuscular disorders, pain, psychiatric disorders – PharmaTher [158]
- Research programme: psychoplastogen therapeutics - Collaborations Pharmaceuticals – undefined mechanism of action – opioid-related disorders – Collaborations Pharmaceuticals [159]
- Research programme: serotonin 2A receptor agonists - Bright Minds Biosciences – serotonin 5-HT2A receptor agonists – major depressive disorder, post-traumatic stress disorder – Bright Minds Biosciences [160]
- Research programme: serotonin 2A/C receptor agonists - Bright Minds Biosciences – serotonin 5-HT2A and 5-HT2C receptor agonists – pain – Bright Minds Biosciences [161]
- Research programme: small tryptamine derivatives - Marvel Biosciences (non-hallucinogenic neuroplasticity program - Marvel Biosciences) – adenosine A2A receptor antagonists – depressive disorders – Marvel Biosciences [162]
- Research programme: SPL 029 series - Cybin (Oral DMT series - Cybin; SPL029) – non-selective serotonin receptor agonist and psychedelic hallucinogen – mental disorders – Small Pharma, Cybin [163]
- Serotonin 5-HT2 receptor agonists - Cybin – serotonin 5-HT2 receptor agonists (phenethylamines) – neurological disorders, psychiatric disorders – Cybin [164]
- Triptax – undefined mechanism of action – depressive disorders – Biomind Labs [165]
Research
[edit]- Baeocystin (PLZ-1019) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – pervasive developmental disorders in children – Pilz Bioscience [166][167]
- CYB005 (CYB-005; deuterated phenethylamine derivative) – undefined mechanism of action ("non-hallucinogenic doses") – psychiatric disorders – Cybin [168] [169] [170]
- Ibogaine – various actions – anorexia nervosa, neurological disorders, substance-related disorders – Biomind Labs [171]
- LSR-3000 – undefined mechanism of action (tryptamine serotonergic neuroplastogen) – neurological disorders – Lusaris Therapeutics [172]
- Lysergic acid diethylamide (LSD; lysergide; LSD-CUREfilm) – non-selective serotonin receptor agonist and psychedelic hallucinogen – mental disorders – CURE Pharmaceutical [173]
- Mebufotenin (5-MeO-DMT; LSR-2000) – non-selective serotonin receptor agonist and psychedelic hallucinogen – alcoholism, major depressive disorder – Lusaris Therapeutics [174]
- Mescaline (BMND-04) – non-selective serotonin receptor agonist and psychedelic hallucinogen – eating disorders, neurological disorders – Biomind Labs [175]
- Midomafetamine (MDMA; "ecstasy"; MDMA-CUREfilm) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – mental disorders – CURE Pharmaceutical [176]
- MYCO-002 – undefined mechanism of action and MDMA-like entactogen – mental disorders – Mydecine [177] [178] [179]
- MYCO-004 (patch-delivered tryptamine compound) – undefined mechanism of action and psychedelic hallucinogen – smoking withdrawal, substance-related disorders – Mydecine [180] [181][179]
- MYCO-005 (psilocin analogue) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – anxiety disorders, depressive disorders – Mydecine [182][183]
- N-Methyltryptamine (NMT; monomethyltryptamine) – undefined mechanism of action and psychedelic hallucinogen – unspecified – Core One Labs [184]
- Noribogaine derived therapeutic – various actions – opioid-related disorders – Mindmed, Nextage Therapeutics [185]
- Norpsilocin (PLZ-1017) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – pervasive developmental disorders in children – Pilz Bioscience [186][167]
- Psilocybin – non-selective serotonin receptor agonist and psychedelic hallucinogen – cancer – Dominari Holdings [187]
- PSYLO-5001 (Psylo-5001) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen – mental disorders – Psylo [188]
- Research programme: 3,4-Methylenedioxymetamfetamine derivatives - Enveric Biosciences – serotonin, norepinephrine, and/or dopamine releasing agents and entactogens – mental disorders, neurological disorders, psychotic disorders – MagicMed Industries, Enveric Biosciences [189]
- Research programme: Ibogaine derivatives - MindMed/Nextage Therapeutics – various actions and potential hallucinogens – opioid-related disorders – Mindmed, Nextage Therapeutics [190]
- Research programme: lysergic acid diethylamide derivatives - Enveric Biosciences – serotonin 5-HT2A receptor agonists – mental disorders, neurological disorders, psychotic disorders – MagicMed Industries, Enveric Biosciences [191]
- Research programme: mescaline derivatives - Enveric Biosciences – serotonin 5-HT2 receptor agonists – mental disorders, neurological disorders – MagicMed Industries, Enveric Biosciences [192]
- Research programme: non-hallucinogenic psychedelic therapeutics - Sintalica Bioscience/University of Messina – undefined mechanism of action and non-hallucinogenic tryptamine serotonergic agents – Sintalica Bioscience, University of Messina [193]
- Research programme: psychiatric disorder therapies (neuroplastogens) - AbbVie/Gilgamesh Pharmaceuticals – undefined mechanism of action – psychiatric disorders – AbbVie, Gilgamesh Pharmaceuticals [194]
- Research programme: non-hallucinogenic psychiatric therapies - Daiichi Sankyo/Psylo – undefined mechanism of action – mental disorders – Daiichi Sankyo, Psylo [195]
- Research programme: non-tryptamine psychedelic small molecules - Otsuka America Pharmaceutical – serotonin receptor modulators – neurological disorders, psychiatric disorders – Mindset Pharma, Otsuka America Pharmaceutical [196]
- Research programme: psychedelic and empathogenic therapeutics - COMPASS Pathways – undefined mechanism of action – mental disorders – COMPASS Pathways, MiHKAL [197]
- Research programme: psychedelic and empathogenic compounds subcutaneous - Bexson Biomedical – undefined mechanism of action – depressive disorders, mental disorders, pain, post-traumatic stress disorder, substance-related disorders – Bexson Biomedical [198]
- Research programme: psychedelic therapeutics - COMPASS Discovery Center – serotonin 5-HT2A receptor modulators – mental disorders – COMPASS Discovery Center, COMPASS Pathways [199]
- Research programme: tryptamine analog therapeutics - Diamond Therapeutics – serotonin receptor modulators – Diamond Therapeutics [200]
Phase unknown
[edit]- Ketamine intravenous/oral (Braxia) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders – Braxia Scientific [201]
- Psilocybin (REL-P11) – non-selective serotonin receptor agonist and psychedelic hallucinogen – neurodegenerative disorders, metabolic disorders, psychiatric disorders – Arbormentis, Relmada Therapeutics [202]
Not under development
[edit]Development suspended
[edit]- Esketamine ((S)-ketamine; AM-101; esketamine otic gel; Keyzilen) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – tinnitus – Altamira Therapeutics [203]
No development reported
[edit]- Arketamine ((R)-ketamine; HR-071603; (R)-ketamine nasal spray) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – depressive disorders – Jiangsu Hengrui Medicine [204]
- Esketamine ((S)-ketamine; esketamine DPI; Falkieri; PG061) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – bipolar depression, depressive disorders – Celon Pharma [205]
- Esketamine ((S)-ketamine; IPX-237, IPX237-C0001, IPX237-C0002, IPX237-L0001) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – unspecified – IMPAX Laboratories, Amneal Laboratories [206]
- Hydroxynorketamine ((2R,6R)-hydroxynorketamine; 6-HNK; SPL-801-B) – unknown mechanism of action (non-hallucinogenic ketamine derivative and metabolite) – depressive disorders – Small Pharma, Cybin [207]
- Ketamine (ELE-Ket+) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Beckley Psytech [208]
- Ketamine intranasal – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – cluster headaches – CCH Pharmaceuticals [209]
- Ketamine sublingual (ketamine wafer; SLS-003; Wafermine) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – acute pain, dental pain, pain, depressive disorders – iX Biopharma [210]
- Ketamine transdermal patch (SHX-001) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Shenox Pharmaceuticals [211]
- Midomafetamine (MDMA; "ecstasy") – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – mood disorders, substance-related disorders – MindMed [212]
- Psilocybin (biosynthetic psilocybin; PB-1818) – non-selective serotonin receptor agonist and psychedelic hallucinogen – depressive disorders – PsyBio Therapeutics [213]
- Psilocybin (low-dose psilocybin; BPL-PSILO) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache – Beckley Psytech [214]
- Research programme: ketamine derivatives - Shenox Pharmaceuticals (SHX-004; SHX-004/005/006/007/011; SHX-005; SHX-006; SHX-007; SHX-011) – ionotropic glutamate NMDA receptor antagonists and dissociative hallucinogens – major depressive disorder, neuropathic pain – Shenox Pharmaceuticals [215]
- Research programme: serotonin psychedelics - Mydecine Innovations Group – serotonin modulators and psychedelic hallucinogens – mental disorders – Mydecine [216]
- Research programme: tryptamine based therapeutics - PsyBio Therapeutics – serotonin 5-HT2A receptor agonists – anxiety disorders, depressive disorders, post-traumatic stress disorder, substance-related disorders – PsyBio Therapeutics [217]
- XW-10508 (oral esketamine conjugate prodrug) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder, pain – XWPharma [218]
Development discontinued
[edit]- Ketamine (Ketals) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – amyotrophic lateral sclerosis, anaesthesia, drug-induced dyskinesia, Rett syndrome – PharmaTher [219]
- Ketamine intranasal – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – autistic disorder – Roivant Sciences [220]
- Research programme: ketamine deuterated - Teva Pharmaceutical Industries – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – pain – Teva Pharmaceutical Industries [221]
- Salvinorin A (INT0054/2020; RLS-01) – κ-opioid receptor agonist – depressive disorders, unspecified – Revixia Life Sciences IntelGenx Corp [222]
20th century (1940s–1980s)
[edit]- (R)-Ariadne (BL-3912A; Dimoxamine) – non-hallucinogenic serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist – depression – Bristol-Myers Company [223][224][225][226]
- Dimethoxybromoamphetamine (DOB; brolamfetamine) – serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist and psychedelic hallucinogen – unknown – unknown [227][228]
- Lysergic acid diethylamide (LSD; LSD-25; lysergide; Delysid) – non-selective serotonin receptor agonist and psychedelic hallucinogen – various uses – Sandoz [229]
- Methylenedioxyamphetamine (MDA; tenamfetamine) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist, entactogen, and weak psychedelic hallucinogen – unknown – unknown [227]
- Psilocybin (Indocybin) – non-selective serotonin receptor agonist and psychedelic hallucinogen – various uses – Sandoz [230]
Formal development never or not yet started
[edit]- Nitrous oxide (N2O; "laughing gas") – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – being studied for depression but doesn't seem to be being formally developed towards approval[231][232][233][234]
Clinically used drugs
[edit]Approved drugs
[edit]- Bupropion/dextromethorphan (DXM/BUP; Auvelity) – sigma σ1 receptor agonist, serotonin reuptake inhibitor, norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, ionotropic glutamate NMDA receptor antagonist, other actions, CYP2D6 inhibitor, and dissociative hallucinogen combination – major depressive disorder – Axsome Therapeutics [235]
- Esketamine ((S)-ketamine; Spravato) – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder – Johnson & Johnson [236]
Off-label drugs
[edit]- Ketamine – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – major depressive disorder, other depressive disorders, and other conditions [237]
Discontinued drugs
[edit]- Tabernanthe spp. extracts (containing ibogaine) (Lambarène, Iperton) – various actions and stimulant – fatigue, asthenia, depression, illness recovery [238][239]
See also
[edit]- Psychedelic treatments for trauma-related disorders
- List of investigational drugs
- Ketamine-assisted psychotherapy
References
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Regardless, a more parsimonious explanation is that certain 5-HT2 receptor-activating compounds, such as DOI and psilocin, cause specific conformations of 5-HT2 receptors that lead to LSD-like psychedelic effects.[94,232] Moreover, although the 5-HT2 agonists mCPP, lorcaserin, and quipazine, are often considered 'non-hallucinogenic', they actually do produce perceptual, cognitive, and emotional changes that may be considered 'hallucinogenic'.[15,233,234] These effects, however, are generally not considered LSD-like. Finally, it is noteworthy that novel, partial 5-HT2A/D2 receptor agonists also attenuate the DOI-elicited HTR.[235,236]
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Author Disclosure Statement: H.K. is Vice President of Research at PharmAla Biotech and is listed as an inventor on patents related to the research in this review article. H.E.S. receives salary supported from a contract between PharmAla Biotech and UAMS. W.E.F. receives research funds and salary support from a contract between PharmAla Biotech and UAMS. The other authors have no conflicts to disclose.
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