WO2023230303A1 - Traitement de déclin cognitif lié à l'anesthésie et à la sédation - Google Patents
Traitement de déclin cognitif lié à l'anesthésie et à la sédation Download PDFInfo
- Publication number
- WO2023230303A1 WO2023230303A1 PCT/US2023/023649 US2023023649W WO2023230303A1 WO 2023230303 A1 WO2023230303 A1 WO 2023230303A1 US 2023023649 W US2023023649 W US 2023023649W WO 2023230303 A1 WO2023230303 A1 WO 2023230303A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- entheogen
- subject
- group
- psilocybin
- administration
- Prior art date
Links
- 206010002091 Anaesthesia Diseases 0.000 title claims abstract description 40
- 230000037005 anaesthesia Effects 0.000 title claims abstract description 40
- 206010039897 Sedation Diseases 0.000 title claims abstract description 25
- 230000036280 sedation Effects 0.000 title claims abstract description 25
- 208000010877 cognitive disease Diseases 0.000 title claims abstract description 14
- 230000006999 cognitive decline Effects 0.000 title claims abstract description 12
- 238000011282 treatment Methods 0.000 title description 19
- 238000001356 surgical procedure Methods 0.000 claims abstract description 19
- QKTAAWLCLHMUTJ-UHFFFAOYSA-N psilocybin Chemical compound C1C=CC(OP(O)(O)=O)=C2C(CCN(C)C)=CN=C21 QKTAAWLCLHMUTJ-UHFFFAOYSA-N 0.000 claims description 75
- QVDSEJDULKLHCG-UHFFFAOYSA-N Psilocybine Natural products C1=CC(OP(O)(O)=O)=C2C(CCN(C)C)=CNC2=C1 QVDSEJDULKLHCG-UHFFFAOYSA-N 0.000 claims description 74
- WTPBXXCVZZZXKR-UHFFFAOYSA-N baeocystin Chemical compound C1=CC(OP(O)(O)=O)=C2C(CCNC)=CNC2=C1 WTPBXXCVZZZXKR-UHFFFAOYSA-N 0.000 claims description 66
- IKQGYCWFBVEAKF-UHFFFAOYSA-N norbaeocystin Chemical compound C1=CC(OP(O)(O)=O)=C2C(CCN)=CNC2=C1 IKQGYCWFBVEAKF-UHFFFAOYSA-N 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 46
- 208000003443 Unconsciousness Diseases 0.000 claims description 45
- MTJOWJUQGYWRHT-UHFFFAOYSA-N 3-[2-(methylamino)ethyl]-1h-indol-4-ol Chemical compound C1=CC(O)=C2C(CCNC)=CNC2=C1 MTJOWJUQGYWRHT-UHFFFAOYSA-N 0.000 claims description 36
- 235000001674 Agaricus brunnescens Nutrition 0.000 claims description 36
- 230000001337 psychedelic effect Effects 0.000 claims description 33
- 206010012373 Depressed level of consciousness Diseases 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 26
- 239000000284 extract Substances 0.000 claims description 19
- 208000022540 Consciousness disease Diseases 0.000 claims description 15
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 claims description 15
- 229960004134 propofol Drugs 0.000 claims description 15
- ZSTKHSQDNIGFLM-UHFFFAOYSA-N 5-methoxy-N,N-dimethyltryptamine Chemical compound COC1=CC=C2NC=C(CCN(C)C)C2=C1 ZSTKHSQDNIGFLM-UHFFFAOYSA-N 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 claims description 11
- 239000003193 general anesthetic agent Substances 0.000 claims description 11
- 229960003299 ketamine Drugs 0.000 claims description 11
- -1 aurugeniscin Chemical compound 0.000 claims description 10
- 208000014674 injury Diseases 0.000 claims description 10
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 10
- 239000002671 adjuvant Substances 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 230000008733 trauma Effects 0.000 claims description 9
- 230000001149 cognitive effect Effects 0.000 claims description 7
- 239000003723 serotonin 1A agonist Substances 0.000 claims description 7
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims description 6
- 230000003444 anaesthetic effect Effects 0.000 claims description 6
- 229940049706 benzodiazepine Drugs 0.000 claims description 6
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 claims description 6
- DDLIGBOFAVUZHB-UHFFFAOYSA-N midazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F DDLIGBOFAVUZHB-UHFFFAOYSA-N 0.000 claims description 6
- 229960003793 midazolam Drugs 0.000 claims description 6
- 239000000932 sedative agent Substances 0.000 claims description 6
- 230000001624 sedative effect Effects 0.000 claims description 6
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 5
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 5
- 201000009916 Postpartum depression Diseases 0.000 claims description 5
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical group C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 claims description 5
- 229960002495 buspirone Drugs 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 208000012826 adjustment disease Diseases 0.000 claims description 4
- 230000003920 cognitive function Effects 0.000 claims description 4
- 208000015238 neurotic disease Diseases 0.000 claims description 4
- 238000011084 recovery Methods 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 claims description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 3
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 claims description 3
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 3
- NZXKDOXHBHYTKP-UHFFFAOYSA-N Metohexital Chemical compound CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O NZXKDOXHBHYTKP-UHFFFAOYSA-N 0.000 claims description 3
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 claims description 3
- 229960002896 clonidine Drugs 0.000 claims description 3
- 229960003537 desflurane Drugs 0.000 claims description 3
- DPYMFVXJLLWWEU-UHFFFAOYSA-N desflurane Chemical compound FC(F)OC(F)C(F)(F)F DPYMFVXJLLWWEU-UHFFFAOYSA-N 0.000 claims description 3
- 229960003957 dexamethasone Drugs 0.000 claims description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
- 229960004253 dexmedetomidine Drugs 0.000 claims description 3
- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 claims description 3
- 229960003529 diazepam Drugs 0.000 claims description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 3
- RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 claims description 3
- 229960000394 droperidol Drugs 0.000 claims description 3
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 claims description 3
- 229960001690 etomidate Drugs 0.000 claims description 3
- 229960002428 fentanyl Drugs 0.000 claims description 3
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims description 3
- 229960003878 haloperidol Drugs 0.000 claims description 3
- 229960002725 isoflurane Drugs 0.000 claims description 3
- 229960004194 lidocaine Drugs 0.000 claims description 3
- 229960004391 lorazepam Drugs 0.000 claims description 3
- 229960002683 methohexital Drugs 0.000 claims description 3
- 239000003176 neuroleptic agent Substances 0.000 claims description 3
- 239000001272 nitrous oxide Substances 0.000 claims description 3
- 229960002078 sevoflurane Drugs 0.000 claims description 3
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 claims description 3
- 229960003279 thiopental Drugs 0.000 claims description 3
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 2
- 229940099433 NMDA receptor antagonist Drugs 0.000 claims description 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 2
- 229950000688 phenothiazine Drugs 0.000 claims description 2
- OIIPFLWAQQNCHA-UHFFFAOYSA-N aeruginascin Chemical compound C1=CC(OP(O)([O-])=O)=C2C(CC[N+](C)(C)C)=CNC2=C1 OIIPFLWAQQNCHA-UHFFFAOYSA-N 0.000 description 24
- 239000003814 drug Substances 0.000 description 22
- 229940079593 drug Drugs 0.000 description 21
- 239000003196 psychodysleptic agent Substances 0.000 description 16
- SPCIYGNTAMCTRO-UHFFFAOYSA-N Psilocine Natural products C1=CC(O)=C2C(CCN(C)C)=CNC2=C1 SPCIYGNTAMCTRO-UHFFFAOYSA-N 0.000 description 15
- ZBWSBXGHYDWMAK-UHFFFAOYSA-N psilocin Chemical compound C1=CC=C(O)[C]2C(CCN(C)C)=CN=C21 ZBWSBXGHYDWMAK-UHFFFAOYSA-N 0.000 description 15
- 238000004113 cell culture Methods 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 12
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 229950002454 lysergide Drugs 0.000 description 8
- 208000019901 Anxiety disease Diseases 0.000 description 7
- 241000252212 Danio rerio Species 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 7
- 230000035882 stress Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 230000036506 anxiety Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 208000028399 Critical Illness Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 206010012335 Dependence Diseases 0.000 description 4
- 241000233866 Fungi Species 0.000 description 4
- 208000019022 Mood disease Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 208000024714 major depressive disease Diseases 0.000 description 4
- 238000005399 mechanical ventilation Methods 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 3
- MIANLSMIRRRMJS-UHFFFAOYSA-N 5-meo-dmt Chemical compound [CH]1C(OC)=CC=C2N=CC(CCN(C)C)=C21 MIANLSMIRRRMJS-UHFFFAOYSA-N 0.000 description 3
- 208000007848 Alcoholism Diseases 0.000 description 3
- 239000002028 Biomass Substances 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 201000007930 alcohol dependence Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 230000003416 augmentation Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000002980 postoperative effect Effects 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000001671 psychotherapy Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- 206010010071 Coma Diseases 0.000 description 2
- 206010054089 Depressive symptom Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- DMULVCHRPCFFGV-UHFFFAOYSA-N N,N-dimethyltryptamine Chemical compound C1=CC=C2C(CCN(C)C)=CNC2=C1 DMULVCHRPCFFGV-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 208000026301 Postoperative Cognitive Complications Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 241001237914 Psilocybe Species 0.000 description 2
- 241000801619 Psilocybe fagicola Species 0.000 description 2
- 241001062351 Psilocybe liniformans Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 230000003400 hallucinatory effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000004630 mental health Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 238000002663 nebulization Methods 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002627 tracheal intubation Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 1
- 108091005479 5-HT2 receptors Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010001854 Altered state of consciousness Diseases 0.000 description 1
- 240000000662 Anethum graveolens Species 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000989645 Conocybe sp. Species 0.000 description 1
- 241000720822 Copelandia sp. Species 0.000 description 1
- 241001427779 Cortinarius mairei Species 0.000 description 1
- 241000757218 Cortinarius moseri Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 241000586648 Deprea orinocensis Species 0.000 description 1
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 101100297484 Escherichia coli (strain K12) phnD gene Proteins 0.000 description 1
- 101100463961 Escherichia coli (strain K12) phoH gene Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000051355 Galerina sp. Species 0.000 description 1
- 241000502286 Gerronema Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000989619 Gymnopilus sp. Species 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 241000013337 Hypholoma sp. Species 0.000 description 1
- 241000376404 Hyphopichia heimii Species 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- 241000509007 Inocybe sp. Species 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001067181 Lecanora impudens Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000989278 Mycena sp. Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000027626 Neurocognitive disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 241001290312 Ombrophila Species 0.000 description 1
- 241000051598 Panaeolus sp. Species 0.000 description 1
- 241000056921 Passiflora actinia Species 0.000 description 1
- 244000248753 Passiflora van volxemii Species 0.000 description 1
- 241001310183 Pectis portoricensis Species 0.000 description 1
- 241000614217 Pedicularis inconspicua Species 0.000 description 1
- 241000047410 Penelomax septentrionalis Species 0.000 description 1
- 241001468888 Penidiella columbiana Species 0.000 description 1
- 241000604700 Persea meridensis Species 0.000 description 1
- 241000893849 Pervillaea venenata Species 0.000 description 1
- 244000145345 Phaleria papuana Species 0.000 description 1
- 241000609654 Phallusia mammillata Species 0.000 description 1
- 241001321557 Phanerochaete brunneocystidiata Species 0.000 description 1
- 241000013412 Phrynobatrachus natalensis Species 0.000 description 1
- 241001538420 Phylloscopus laurae Species 0.000 description 1
- 240000000793 Pinus armandii Species 0.000 description 1
- 241000369911 Pinus herrerae Species 0.000 description 1
- 241001209059 Pinus jaliscana Species 0.000 description 1
- 241000954752 Platanus rzedowskii Species 0.000 description 1
- 241000219087 Platycarpum schultesii Species 0.000 description 1
- 241000156806 Plicaria anthracina Species 0.000 description 1
- 240000002904 Plumbago indica Species 0.000 description 1
- 241000989681 Pluteus sp. Species 0.000 description 1
- 241001300080 Plutonia Species 0.000 description 1
- 241000163460 Podocarpus brasiliensis Species 0.000 description 1
- 241000932193 Podocarpus subtropicalis Species 0.000 description 1
- 241000134465 Pogonomyrmex uruguayensis Species 0.000 description 1
- 241001348479 Polystachya ramulosa Species 0.000 description 1
- 241000619270 Potentilla pusilla Species 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 241000882353 Pseudostellaria sierrae Species 0.000 description 1
- 241001261678 Psilocybe argentipes Species 0.000 description 1
- 241001156627 Psilocybe australiana Species 0.000 description 1
- 241000332760 Psilocybe azurescens Species 0.000 description 1
- 241001373540 Psilocybe caeruleoannulata Species 0.000 description 1
- 241001061682 Psilocybe caerulescens Species 0.000 description 1
- 241001156628 Psilocybe caerulipes Species 0.000 description 1
- 241001062357 Psilocybe cubensis Species 0.000 description 1
- 241000332761 Psilocybe cyanescens Species 0.000 description 1
- 241001062358 Psilocybe fimetaria Species 0.000 description 1
- 241000801620 Psilocybe hispanica Species 0.000 description 1
- 241001486246 Psilocybe makarorae Species 0.000 description 1
- 241001061684 Psilocybe mexicana Species 0.000 description 1
- 241001156629 Psilocybe pelliculosa Species 0.000 description 1
- 241001156623 Psilocybe quebecensis Species 0.000 description 1
- 241000482374 Psilocybe samuiensis Species 0.000 description 1
- 241001062330 Psilocybe semilanceata Species 0.000 description 1
- 241001418126 Psilocybe serbica Species 0.000 description 1
- 241001072092 Psilocybe serbica var. bohemica Species 0.000 description 1
- 241001237913 Psilocybe silvatica Species 0.000 description 1
- 241000236307 Psilocybe strictipes Species 0.000 description 1
- 241001237928 Psilocybe stuntzii Species 0.000 description 1
- 241001261681 Psilocybe subaeruginascens Species 0.000 description 1
- 241001062322 Psilocybe subaeruginosa Species 0.000 description 1
- 241000263272 Psilocybe subcubensis Species 0.000 description 1
- 241001258934 Psilocybe tampanensis Species 0.000 description 1
- 241001373541 Psilocybe wrightii Species 0.000 description 1
- 241000801653 Psilocybe yungensis Species 0.000 description 1
- 241000801641 Psilocybe zapotecorum Species 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 244000039510 Psychotria rostrata Species 0.000 description 1
- 241001617921 Pultenaea ochreata Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241001047627 Rhyacornis fuliginosa Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 208000037842 advanced-stage tumor Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000011013 aquamarine Substances 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000036995 brain health Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000002802 cardiorespiratory effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000000442 dopamine 2 receptor blocking agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000002635 electroconvulsive therapy Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960004341 escitalopram Drugs 0.000 description 1
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000009808 hippocampal neurogenesis Effects 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001785 mirtazapine Drugs 0.000 description 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000005026 persistent vegetative state Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- UTDLAEPMVCFGRJ-UHFFFAOYSA-N plutonium dihydrate Chemical compound O.O.[Pu] UTDLAEPMVCFGRJ-UHFFFAOYSA-N 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 210000001176 projection neuron Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 101150068531 psiD gene Proteins 0.000 description 1
- 101150117145 psiH gene Proteins 0.000 description 1
- 101150049598 psiK gene Proteins 0.000 description 1
- 101150047831 psiM gene Proteins 0.000 description 1
- 230000004800 psychological effect Effects 0.000 description 1
- 230000001273 psychotogenic effect Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000002400 serotonin 2A antagonist Substances 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
Definitions
- the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
- Postoperative neurocognitive disorders is an overarching term that includes postoperative delirium, an acute state of confusion and inattention; and postoperative cognitive dysfunction (POCD), a prolonged state of cognitive impairment that predominantly affects higher-level cognitive skills and memory.
- Proposed potential mechanisms for postoperative neurocognitive decline are speculative but include neuroinflammation as a result of perioperative stress, vascular disorders, or the acceleration of neurocognitive decline in patients with a previously undiagnosed neurodegenerative disorder (Mahanna-GabrielliE, SchenningKJ, ErikssonLI, et al. State of the clinical science of perioperative brain health. Br J Anae sth. 2019;123(4):464-478).
- Entheogens are chemical substances, originating from fungi, plants and animals, that have been ingested for thousands of years for religious or spiritual purposes to produce an altered state of consciousness (Nichols DE: Psychedelics. Pharmacol Rev. 2016 Apr; 68(2): 264-355).
- entheogens such as psilocybin
- psilocybin for the treatment of mental health disorders (Geiger HA, Wurst MG et al: DARK Classics in chemical neuroscience. Psilocybin. ACS Chem. Neurosci.).
- Psilocybin is a naturally occurring psychedelic compound produced by over 200 mushrooms, that is being researched as treatment for a range of psychiatric disorders (Carhart- Harris RL and Goodwin GM. (2017) The therapeutic potential of psychedelic drugs: past, present and future. Neuropsychopharmacology). Five separate trials have reported improvements in depressive symptoms after psilocybin-assisted psychotherapy including in 'treatment-resistant depression' (Carhart-Harris R, Giribaldi B, Watts R et al Trial of Psilocybin versus Escital opram for Depression ⁇ Engl J Med.
- ketamine and psychedelics [including psilocybin, lysergic acid diethylamide (LSD), 5-MeO-DMT and N, N- dimethyltryptamine (DMT)] induce synaptic, structural, and functional changes, particularly in pyramidal neurons in the prefrontal cortex (David E. Olson: Biochemical Mechanisms Underlying Psychedelic- Induced Neuroplasticity Biochemistry 2022 61 (3), 127-136. DOI: 10.1021/acs.biochem.lc00812).
- the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
- the present invention provides methods of treating a subject comprising administering an entheogen or composition comprising an entheogen to a subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state.
- the present invention provides entheogens or entheogen compositions for use in treating a condition associated with being in an unconscious or semiconscious state.
- the unconscious or semiconscious state is caused by a modality selected from the group consisting of medically induced unconsciousness or semiconsciousness, trauma induced unconsciousness or semi-consciousness, illness induced unconsciousness or semi-consciousness, and condition induced unconsciousness or semiconsciousness.
- the medically induced unconsciousness or semiconsciousness is induced by administration of an agent selected from the group consisting of an anesthetic and a sedative.
- the anesthetic administered to the subject is selected from the group consisting of a general anesthetic agent delivered intravenously selected form the group consisting of propofol, etomidate, ketamine, methohexital and thiopental and a general anesthetic agent delivered via inhalation selected form the group consisting of sevoflurane, desflurane, and isoflurane.
- the general anesthetic agent is administered with a adjuvant.
- the adjuvant is selected from the group consisting of an opioid, a2-agonist, and NMDA receptor antagonist.
- the adjuvant is selected from the group consisting of fentanyl, lidocaine, midazolam, dexamethasone, and dexmedetomidine.
- the sedative administered to the subject is selected from the group consisting of a benzodiazepine, an a2- agonist, an opioid, ketamine and nitrous oxide.
- the benzodiazepine is selected from the group consisting of diazepam, midazolam and lorazepam.
- the neuroleptic agent is selected from the group consisting of haloperidol, droperidol, and phenothiazine.
- the a2-agonist is clonidine.
- administration of the entheogen inhibits, reduces or prevents cognitive decline related to anesthesia and/or sedation.
- administration of the entheogen increases the resilience of patients to the stresses of surgery and anesthesia including physical and psychological sequelae of anesthesia and/or sedation.
- administration of the entheogen improves cognitive recovery, and prevents or reduces reactive depression or prevents or reduces PTSD in subject following being in the unconscious or semi-conscious state.
- the subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state is subject to heart surgery or surgery for major trauma.
- the subject is in an intensive care unit.
- the subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state is subject to an obstetrical intervention.
- administration of the entheogen reduces or prevents post-natal depression.
- administration of the entheogen inhibits, reduces or prevents a condition in the subject selected from the group consisting of post-traumatic stress disorder, depression, obsessive-compulsive disorder, an addictive disorder, and schizophrenia.
- administration of the entheogen improves cognitive function or neuroplasticity in the subject.
- the entheogen is psilocybin. In some preferred embodiments, the entheogen composition comprises psilocybin. In some preferred embodiments, the entheogen composition is a combination psilocybin and one or more compounds selected from the group consisting of psilocybin, baeocystin, aurugeniscin, norpsilocin, and norbaeocystin.
- the entheogen composition is a mushroom extract composition comprising one or more compounds selected from the group consisting of psilocybin, baeocystin, aurugeniscin, norpsilocin, and norbaeocystin.
- the mushroom extract is free of psilocybin.
- the entheogen is 5-rnethoxy-N,N-dimethyltryptamine (5- MeO-DMT).
- the entheogen composition comprises 5-methoxy- N,N-dimethyltryptamine (5 -MeO-DMT) .
- entheogen is provided in a psychedelic dose.
- the entheogen is provided in a sub-psychedelic dose.
- the entheogen is administered intravenously.
- the entheogen is co-administered with a 5-HT1 A agonist.
- 5-HT1A agonist is buspirone.
- a “patient,” “subject,” or “individual” are used interchangeably and refer to either a human or a non-human animal. These terms include mammals, such as humans, primates, livestock animals (including bovines, porcines, etc.), companion animals (e.g., canines, felines, etc.) and rodents (e.g., mice and rats).
- administering or "administration of a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art.
- a PBP can be administered, intravenously, arterially, intradermally, intra-muscularly, intraperitonealy, intravenously, subcutaneously, sublingually, orally (by ingestion), intranasally (by inhalation), intrapulmonary (by nebulization or instillation) intraspinally, intracerebrally, and transdermally (by absorption, e.g., through a skin duct).
- a compound or agent can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow or controlled release of the compound or agent.
- Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.
- the administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug.
- a physician who instructs a patient to self-administer a drug, or to have the drug administered by another and/or who provides a patient with a prescription for a drug is administering the drug to the patient.
- a “therapeutically effective amount” or a “therapeutically effective dose” of a drug or agent, such as the entheogen compositions described herein, is an amount of a drug or an agent that, when administered to a subject will have the intended therapeutic effect.
- the full therapeutic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses.
- a therapeutically effective amount may be administered in one or more administrations.
- the precise effective amount needed for a subject will depend upon, for example, the subject's size, health and age, the nature and extent of symptoms of the condition being treated. The skilled worker can readily determine the effective amount for a given situation by routine experimentation.
- a “prophylactically effective amount” or a “prophylactically effective dose” of a drug or agent, such as an entheogen composition is an amount of a drug or an agent that, when administered to a subject will have the intended prophylactic effect.
- the full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses.
- a prophylactically effective amount may be administered in one or more administrations.
- the precise effective amount needed for a subject will depend upon, for example, the subject's size, health and age, the nature and extent of symptoms of the condition being treated. The skilled worker can readily determine the effective amount for a given situation by routine experimentation.
- Treating” a condition or patient refers to taking steps to obtain beneficial or desired results, including clinical results.
- Beneficial or desired clinical results include, but are not limited to, alleviation, amelioration, or slowing the progression, of one or more symptoms associated with the disease or disorder being treated.
- treatment may be prophylactic.
- the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
- Entheogens are naturally occurring compounds with psychedelic properties that have historically been used for religious and spiritual ceremonies and also for medicinal purposes. In spite of legal barriers, there is rapidly increasing interest among clinicians and researchers in the use of natural or synthetic psychedelics for the treatment of psychiatric disorders.
- the present invention provides methods of using psilocybin and other fungal/plant/animal-derived entheogens in different formulations (including IV), dosages and schedules in semi-conscious and unconscious (including medically induced, trauma-induced, illness or condition-induced) states to prevent and treat a range of conditions including psychiatric conditions (including PTSD, depression and OCD and addictive disorders, schizophrenia etc.) and to specifically prevent and treat cognitive decline related to anesthesia and sedation or increase the resilience of patients to the stresses of surgery and anesthesia including physical and psychological sequelae of anesthesia and sedation.
- psychiatric conditions including PTSD, depression and OCD and addictive disorders, schizophrenia etc.
- Semiconscious and unconscious states may be induced by, anesthesia, sedation, drugs, trauma, vegetative states, hyperthermia, hypothermia, Electro-Convulsive-Therapy, major surgery, medically induced coma, drug induced coma, cardiac arrest, asphyxia, prematurity, psychiatric conditions, etc.
- an anesthetic agent administered to the subject is a general anesthetic agent delivered intravenously selected form the group consisting of propofol, etomidate, ketamine, methohexital and thiopental or a general anesthetic agent delivered via inhalation selected form the group consisting of sevoflurane, desflurane, and isoflurane.
- one or more adjuvants are administered with the general anesthetic agent. Suitable adjuvants include, but are not limited to, opioids, a2-agonists, NMD A receptor antagonists.
- the adjuvant is selected from the group consisting of opioid agents (e.g., morphine or fentanyl), lidocaine, midazolam, dexamethasone, and dexmedetomidine.
- a sedative administered to the subject is a benzodiazepine, a2-agonists (e.g., clonidine), opioid (neuroleptic agents (e.g., haloperidol, droperidol, phenothiazines), ketamine or nitrous oxide.
- a2-agonists e.g., clonidine
- opioid neuropeptide
- neutral agents e.g., haloperidol, droperidol, phenothiazines
- ketamine nitrous oxide
- the benzodiazepine is selected from the group consisting of diazepam, midazolam and lorazepam.
- the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens pre- or during anesthesia for example in patients being operated on for heart disease or major trauma with the specific purpose of improving cognitive recovery and preventing reactive depression or PTSD.
- the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens pre- or during obstetrical interventions such as Caesarian section in order to prevent post-natal depression.
- the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens to patients in a semi-conscious or unconscious state in critical care and ICU settings over various periods of time in order to improve cognitive and other outcomes and prevent depression and PTSD.
- administration e.g., intravenous administration
- psilocybin or other entheogens to patients in a semi-conscious or unconscious state in critical care and ICU settings over various periods of time in order to improve cognitive and other outcomes and prevent depression and PTSD.
- the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens to these patients in a semi-conscious or unconscious state to improve outcome in terms of cognitive function (improving neuroplasticity) and the prevention of depression, OCD and other negative psychological outcomes.
- administration e.g., intravenous administration
- psilocybin or other entheogens to these patients in a semi-conscious or unconscious state to improve outcome in terms of cognitive function (improving neuroplasticity) and the prevention of depression, OCD and other negative psychological outcomes.
- the present invention is not limited to any particular mechanism of action. Indeed, a mechanism of action is not necessary to practice the present invention. Nevertheless, it is contemplated that psilocybin or other entheogens play a prophylactic ( or therapeutic) role in the management of unconscious or semi-conscious patents in a similar manner to antacids (prevention of gastric damage) and antibiotics (prevention of infection) and anti -coagulants (prevention of hemorrhagic disorders) are generally used in operating rooms and critical care settings as preventive modalities.
- the psilocybin and entheogens are administered as prophylaxis against cognitive decline and negative psychological outcomes such as depression and PTSD associated with the underlying condition that required anesthesia or sedation and/or caused an unconscious or semi-conscious state.
- Preferred entheogens for use in the present invention include those derived from mushrooms, including psilocybin, alone or in combination with one or more of baeocystin, aurugeniscin, norpsilocin, norbaeocystin, as well as 5-methoxy-N,N-dimethyltryptamine (5- MeO-DMT).
- the entheogen compositions may be prepared by a variety of methods including, but not limited to, chemical synthesis, extraction and/or purification from plants or fungi, and extraction and/or purification from mushroom cell cultures.
- the entheogen compositions comprise psilocybin.
- the entheogen compositions comprise psilocybin and additionally one or more compounds selected from the group consisting of baeocystin, aeruginascin, norpsilocin, norbaeocystin, and combinations thereof.
- the entheogen composition comprises one or more compounds selected from the group consisting of baeocystin, aeruginascin, norpsilocin, norbaeocystin, and combinations thereof and is essentially free of psilocybin.
- Exemplary entheogen compositions are provided below.
- the compounds listed may, for example, be chemically synthesized (see, e.g., Sherwood et al., (2020) Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin; J. Nat. Prod. 83(2) 461-67, incorporated herein by reference in its entirety), may be provided in an extract from mushrooms or from mushroom cell cultures as described in detail below, or be isolated from mushrooms or mushroom cell cultures as described in detail below.
- he listed composition comprises the listed compounds.
- the listed compositions consist essentially of the listed compounds.
- the listed compositions consist of the listed compounds.
- composition Compounds in composition
- baeocystin 15 baeocystin, aeruginascin, norpsilocin, norbaeocystin
- baeocystin 16 baeocystin 17. baeocystin, aeruginascin
- Biotechnology -based production of entheogens offers a promising route to ensure a cost- effective, cGMP, robust supply for clinical development.
- Naturally derived psychedelic compounds may offer significant therapeutic advantages over synthetic molecules because of entourage effects. These reflect the action of additional components that may act synergistically or additively with the principal molecule or have pharmacokinetic effects.
- additional components may act synergistically or additively with the principal molecule or have pharmacokinetic effects.
- psilocybin which is derived from multiple mushroom species that contain a wealth of additional active components.
- Anecdotal and clinical reports as well as preclinical studies suggest a discernible difference between the effects of chemically synthesized psilocybin and those of psychedelic mushrooms and also differences among the effects of different mushroom strains.
- the entheogen compounds utilized in the present invention are derived from cell culture and in particular on mushroom cell cultured, psychoactive compound-containing mushroom compositions.
- the term "mushroom culture compositions” refers to compositions comprising a mushroom cell culture and products derived therefrom specifically including 1) fractions, such as aqueous fractions, prepared from the mushroom cell culture that contain one or more psychoactive compounds, 2) extracts, such as aqueous solvent extracts or organic solvent extracts, prepared from the mushroom cell culture that comprise one or more psychoactive compounds, and 3) purified preparations of one or more psychoactive compounds prepared from a mushroom cell culture by methods including one or more of solvent extraction, concentration by solvent removal, chromatography and other methods of extraction, purification and fractionation.
- neuroactive compounds refers to chemical substances that change a person's mental state by affecting the way the brain and nervous system work, and specifically, includes, but is not limited to psilocybin, baeocystin, aurugeniscin, norpsilocin, norbaeocystin, and combinations thereof.
- the effective dosage of the mushroom cell culture compositions is a sub-psychedelic dose.
- a "sub-psychedelic dose” as used herein is a sub-hallucinogenic doses of a psychedelic substance such as a psilocybin.
- Sub-psychedelic dosing can be achieved via several schedules: 1) sub-chronic, sub-psychedelic doses of psilocybin given over several days with or without other components of mushroom cell culture extract, 2) a sustained release preparation of psilocybin with or without other components of the mushroom cell culture extract which will allow the full psychedelic dose to be administered over 24 hours and thus avoid acute psychotogenic effects; 3) a psychedelic dose of psilocybin with or without other components of mushroom cell culture spectrum extract in conjunction with a 5-HT2A receptor antagonist, that blocks psilocybin- induced psychedelic effects.
- the biomass used to prepare a mushroom extract useful in the compositions of the present invention is any fungi (including hybrids) of part thereof (e.g., mycelia, primordia, fruiting bodies, etc.) containing the psilocybin biosynthetic gene cluster (psiD, psiH, psiK, psiM) or other mushrooms, fungi, lichens, etc. producing psilocybin or psilocybin analogs or related tryptamines.
- the biomass is mycelial biomass.
- Exemplary mushroom species include, but are not limited to, Conocybe sp., Copelandia sp., Galerina sp., Gerronema sp., Gymnopilus sp., Hypholoma sp., Inocybe sp., Mycena sp., Panaeolina sp., Panaeolus sp., Pluteus sp., andPsilocybe sp.
- Exemplary Psilocybes include, but are not limited to, P. acutipilea, P. angustipleurocystidiata, P. antioquensis, P. aquamarine, P. argentipes, P.
- cordispora P. cubensis, P. cyanescens, P. cyanofibrillosa, P. dumontii, P. eucalypta, P. fagicola, P. fagicola mesocystidiata, P. farinacea, P. fimetaria, P. fuliginosa, P. furtadoana, P. galindoi, P. goniospora, P. graveolens, P. guatapensis, P. guilartsis, P. heimii, P. heliconiae, P. herrerae, P. hispanica, P. hoogshagenii hoogshagenii, P.
- pericystis P. pintonii, P. pleurocystidiosa, P. plutonia, P. portoricensis, P. pseudoaztecorum, P. puberula, P. quebecensis, P. ramulosa, P. rostrata, P. rzedowskii, P. samuiensis, P. sanctorum, P. schultesii, P. semilanceata, P. septentrionalis, P. serbica, P. sierrae, P. sylvatica, P. singerii, P. strictipes, P. stuntzii, P. subacutipilea, P.
- the entheogen may be further formulated with one or more pharmaceutically acceptable carriers or delivery vehicles.
- pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, drugs, drug stabilizers, gels, binders, excipients, disintegration agents, lubricants, sweetening agents, flavoring agents, dyes, such like materials and combinations thereof, as would be known to one of ordinary skill in the art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329, incorporated herein by reference). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the pharmaceutical compositions
- the entheogens of the present invention may be formulated with different types of carriers depending on whether it is to be administered in solid, liquid or aerosol form, and whether it need to be sterile for such routes of administration as injection.
- the cell extracts of the present invention can be administered intravenously, intradermally, transdermally, intrathecally, intraarterially, intraperitoneally, intranasally, intravaginally, intrarectally, topically, intramuscularly, subcutaneously, mucosally, orally, topically, locally, inhalation and nebulization (e.g., aerosol inhalation), injection, infusion, continuous infusion, localized perfusion bathing target cells directly, via a catheter, via a lavage, in cremes, in lipid compositions (e.g., liposomes), or by other method or any combination of the forgoing as would be known to one of ordinary skill in the art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990,
- entheogens of the present invention will be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective.
- the formulations are easily administered in a variety of dosage forms such as formulated for parenteral administrations such as injectable solutions, or aerosols for delivery to the lungs, or formulated for alimentary administrations such as drug release capsules and the like.
- the entheogens of the present invention suitable for administration is provided in a physiologically acceptable carrier with or without an inert diluent.
- the carrier should be assimilable and includes liquid, semi-solid, i.e., pastes, or solid carriers. Except insofar as any conventional media, agent, diluent or carrier is detrimental to the recipient or to the therapeutic effectiveness of the composition contained therein, its use in administrable composition for use in practicing the methods of the present invention is appropriate.
- carriers or diluents include fats, oils, water, saline solutions, lipids, liposomes, resins, binders, fillers and the like, or combinations thereof.
- composition may also comprise various antioxidants to retard oxidation of one or more component. Additionally, the prevention of the action of microorganisms can be brought about by preservatives such as various antibacterial and antifungal agents, including but not limited to parabens (e.g., methylparabens, propylparabens), chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof.
- parabens e.g., methylparabens, propylparabens
- chlorobutanol phenol
- sorbic acid thimerosal or combinations thereof.
- the entheogens are combined with the carrier in any convenient and practical manner, i.e., by solution, suspension, emulsification, admixture, encapsulation, absorption and the like. Such procedures are routine for those skilled in the art.
- Stabilizing agents can be also added in the mixing process in order to protect the composition from loss of therapeutic activity, i.e., denaturation in the stomach.
- stabilizers for use in the composition include buffers, amino acids such as glycine and lysine, carbohydrates such as dextrose, mannose, galactose, fructose, lactose, sucrose, maltose, sorbitol, mannitol, etc.
- the actual dosage amount of the entheogen of the present invention administered to an animal patient can be determined by physical and physiological factors such as body weight, severity of condition, the type of disease being treated, previous or concurrent therapeutic interventions, idiopathy of the patient and on the route of administration: Depending upon the dosage and the route of administration, the number of administrations of a preferred dosage and/or an effective amount may vary according to the response of the subject. The practitioner responsible for administration will, in any event, determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual subject.
- zebrafish (Danio rerio , Drugs: Propofol is a short-acting hypnotic drug that produces a rapid anesthesia induction with short duration being rapidly metabolized and without cumulative effects, being also capable of causing cardiorespiratory depression.
- FSME is “full spectrum” psychedelic mushroom extract - a purified, methanol extract of Psilocybe mushroom with precise quantitation of psilocybin and psilocin and tryptamines of the psilocybin biosynthetic chain (baeocystin, norbaeocystin, aerugenascin norpsilocin).
- Treatment groups, dosing, experimental design Four groups: Control (tank water); propofol only; propofol plus FSME; FSME only. Dosing: FSME - 5mg/L; Propofol - 1.25mg/L.
- mice Behavioral phenotyping is undertaken including the open field arena, novel object, social interaction, light-dark preference and other behavioral phenotyping tests. Other possible tests that may be conducted include brain metabolomics, brain synaptic proteins and microbiome metagenomics may be included. These experiments will subsequently be conducted in disease models for psychiatric and neurological disorders.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne l'utilisation d'enthéogènes pour réduire ou améliorer le déclin cognitif lié à l'anesthésie ou à la sédation ou augmenter la résilience des patients aux stress de chirurgie comprenant les séquelles physiques et psychologiques de l'anesthésie et de la sédation et des affections sous-jacentes nécessitant une anesthésie ou une sédation.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202263346647P | 2022-05-27 | 2022-05-27 | |
US63/346,647 | 2022-05-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2023230303A1 true WO2023230303A1 (fr) | 2023-11-30 |
Family
ID=88919934
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2023/023649 WO2023230303A1 (fr) | 2022-05-27 | 2023-05-26 | Traitement de déclin cognitif lié à l'anesthésie et à la sédation |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2023230303A1 (fr) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019226599A1 (fr) * | 2018-05-22 | 2019-11-28 | Alkalidx, Inc. | Diagnostics et traitements de sujets insensibles à un anesthésique |
WO2022082058A1 (fr) * | 2020-10-16 | 2022-04-21 | Eleusis Therapeutics Us, Inc. | Méthode de traitement par alcaloïdes tryptamines |
-
2023
- 2023-05-26 WO PCT/US2023/023649 patent/WO2023230303A1/fr unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019226599A1 (fr) * | 2018-05-22 | 2019-11-28 | Alkalidx, Inc. | Diagnostics et traitements de sujets insensibles à un anesthésique |
WO2022082058A1 (fr) * | 2020-10-16 | 2022-04-21 | Eleusis Therapeutics Us, Inc. | Méthode de traitement par alcaloïdes tryptamines |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Hazekamp et al. | Review on clinical studies with cannabis and cannabinoids 2005-2009 | |
EP1001760B1 (fr) | Composition permettant de controler les problemes d'humeur chez des individus sains | |
Mínguez Serra et al. | Pharmacological treatment of burning mouth syndrome: A review and update | |
US20100016418A1 (en) | Cannabinoids for use in the treatment of neuropathic pain | |
WO2014031975A1 (fr) | Composition anxiolytique, formulation et procédé d'utilisation | |
Ye et al. | Ketamine metabolite (2R, 6R)-hydroxynorketamine enhances aggression via periaqueductal gray glutamatergic transmission | |
JP2000514420A (ja) | 末梢または中枢神経障害およびサイトカイン過剰産生の治療のためのk―252a誘導体の使用 | |
Dominguini et al. | The effects of anaesthetics and sedatives on brain inflammation | |
WO2021178579A1 (fr) | Traitement au cannabis de l'insomnie, de la douleur et d'affections cutanées | |
US6835728B2 (en) | Drug combination for the treatment of depression and related disorders comprising mirtazapine | |
JP2023521064A (ja) | 疼痛調節因子を含む幹細胞由来エクソソーム及びその用途 | |
US20180015054A1 (en) | Method of Maintaining the Anti-Depressant Effect of Ketamine With Lithium | |
JP2019537628A (ja) | 併用療法 | |
WO2023230303A1 (fr) | Traitement de déclin cognitif lié à l'anesthésie et à la sédation | |
AU2013264943B2 (en) | Combination comprising parthenolide for use in the treatment of Alzheimer's Disease and other neurodegenerative disorders | |
Ashton | Emerging treatment options for spasticity in multiple sclerosis–clinical utility of cannabinoids | |
WO2011084025A2 (fr) | Extrait d'hexane | |
Akyuz et al. | An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission | |
Krames et al. | Future trends in the development of local drug delivery systems: intraspinal, intracerebral, and intraparenchymal therapies | |
US11364218B2 (en) | Method of treating or preventing mood disorders, mental disorders, and/or chronic fatigue syndrome | |
Liester et al. | Ketamine: Review and Hypothesis for Potential Use in Spinal Cord Injury | |
CN116459323B (zh) | 一种用于嗅觉障碍的精油组合物及其应用 | |
WO2011041920A2 (fr) | Composition nutraceutique à base d'extrait de shilajit, d'acide folique, de vitamine b12 et de vitamine b6 et son utilisation pour prévenir et/ou traiter des maladies neurodégénératives et/ou la détérioration cognitive associée au vieillissement cérébral | |
Amanpour et al. | Evaluation of the effect of Rosmarinic acid on depression by forced swimming and tail suspension tests in mice model compared to citalopram | |
Canavero et al. | Cannabinoids |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 23812610 Country of ref document: EP Kind code of ref document: A1 |