IP Library › Granted Patent US 12,454,516
Granted Patent B2
US 12,454,516 · App. 18/426,035 · Granted Oct 28, 2025

Nitric oxide releasing prodrugs of MDA and MDMA

Inventors: Robert B. Perni (Marlborough, MA); Glenn Short (Scituate, MA); Tanweer A. Khan (Bridgewater, NJ)
Assignee: EmpathBio, Inc.
C07D317/58C07D307/79C07D319/18
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,454,516
App. No.
18/426,035
Granted
Oct 28, 2025
Kind
B2
Abstract

Provided herein are compounds of Formula (I), Formula (II), and Formula (III) or pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and A are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I), Formula (II), or Formula (III) and methods of using a compound of Formula (I), Formula (II), or Formula (II), e.g., in the treatment of a mental health disease or disorder.

Claims (97)

1. A method of treating social anxiety in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein,

R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 or —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 ;

R 2 is H, C 1 -C 4 alkyl, or CF 3 ;

R 3 and R 4 are independently H or F;

R 5 and R 6 are independently H, C 1 -C 6 alkyl, or CF 3 ;

R 7 is H or CH 3 ;

R 8 is H, C 1 -C 6 alkyl, or CF 3 ;

R 9 and R 9 ′ are independently H, halogen, or C 1 -C 6 alkyl;

X and Y are independently H, F, Cl, Br, or OR 8 ,

n is an integer from 1 to 9; and

m is an integer from 1 to 9.

2. The method of claim 1 , wherein R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 .

3. The method of claim 1 , wherein R 1 is —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 .

4. The method of claim 1 , wherein R 1 is —(C═O) (CH 2 ) m —CH(NH 2 )CH 2 ONO 2 .

5. The method of claim 1 , wherein R 2 is C 1 -C 4 alkyl.

6. The method of claim 1 , wherein R 2 is methyl.

7. The method of claim 1 , wherein R 2 is CF 3 .

8. The method of claim 1 , wherein R 3 and R 4 are H.

9. The method of claim 1 , wherein R 3 and R 4 are F.

10. The method of claim 1 , wherein R 5 and R 6 are H.

11. The method of claim 1 , wherein R 5 and Re are C 1 -C 6 alkyl.

12. The method of claim 1 , wherein R 5 and R 6 are CF 3 .

13. The method of claim 1 , wherein R 7 is H.

14. The method of claim 1 , wherein R 7 is CH 3 .

15. The method of claim 1 , wherein X and Y are H.

16. The method of claim 1 , wherein X and Y are F.

17. The method of claim 1 , wherein m is 2.

18. The method of claim 1 , wherein n is 3.

19. The method of claim 1 , wherein n is 4.

20. The method of claim 1 , wherein the compound has the formula:

or a pharmaceutically acceptable salt thereof.

21. A method of treating social anxiety in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (II):

or a pharmaceutically acceptable salt thereof; wherein,

R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 or —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 ;

R 2 is H, C 1 -C 4 alkyl or CF 3 ;

R 3 and R 4 are independently H or F;

R 5 and R 6 are independently H, C 1 -C 6 alkyl, or CF 3 ;

R 7 is H or CH 3 ;

R 8 is H, C 1 -C 6 alkyl, or CF;

R 9 and R 9 ′ are independently H, halogen, or C 1 -C 6 alkyl;

X and Y are independently H, F, Cl, Br, or OR 8 ,

n is an integer from 1 to 9; and

m is an integer from 1 to 9.

22. The method of claim 21 , wherein R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 .

23. The method of claim 21 , wherein R 1 is —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 .

24. The method of claim 21 , wherein R 1 is —(C═O) (CH 2 ) n —ONO 2 .

25. The method of claim 21 , wherein R 1 is —(C═O) (CH 2 ) m —CH(NH 2 )CH 2 ONO 2 .

26. The method of claim 21 , wherein R 2 is C 1 -C 4 alkyl.

27. The method of claim 21 , wherein R 2 is methyl.

28. The method of claim 21 , wherein R 2 is CF 3 .

29. The method of claim 21 , wherein R 3 and R 4 are H.

30. The method of claim 21 , wherein R 3 and R 4 are F.

31. The method of claim 21 , wherein R 5 and R 6 are H.

32. The method of claim 21 , wherein R 5 and R 6 are C 1 -C 6 alkyl.

33. The method of claim 21 , wherein R 5 and R 6 are CF 3 .

34. The method of claim 21 , wherein R 7 is H.

35. The method of claim 21 , wherein R 7 is CH 3 .

36. The method of claim 21 , wherein X and Y are H.

37. The method of claim 21 , wherein X and Y are F.

38. The method of claim 21 , wherein m is 2.

39. The method of claim 21 , wherein n is 3.

40. The method of claim 21 , wherein n is 4.

41. A method of treating social anxiety in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (III):

or a pharmaceutically acceptable salt thereof; wherein,

A is

R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 or —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 ,

R 2 is H, C 1 -C 4 alkyl or CF 3 ;

R 3 and R 4 are independently H or F;

R 7 is H or CH 3 ;

R 8 is H, C 1 -C 6 alkyl, or CF 3 ;

R 9 and R 9 ′ are independently H, halogen, or C 1 -C 6 alkyl;

X and Y are independently H, F, Cl, Br, or OR 8 ;

n is an integer from 1 to 9; and

m is an integer from 1 to 9.

42. The method of claim 41 , wherein R 1 is —(C═O)(CR 9 R 9 ′) n —ONO 2 .

43. The method of claim 41 , wherein R 1 is —(C═O)(CR 9 R 9 ′) m —CH(NH 2 )CH 2 ONO 2 .

44. The method of claim 41 , wherein R 1 is —(C═O) (CH 2 ) n —ONO 2 .

45. The method of claim 41 , wherein R 1 is —(C═O) (CH 2 ) m —CH(NH 2 )CH 2 ONO 2 .

46. The method of claim 41 , wherein R 2 is C 1 -C 4 alkyl.

47. The method of claim 41 , wherein R 2 is methyl.

48. The method of claim 41 , wherein R 2 is CF 3 .

49. The method of claim 41 , wherein R 3 and R 4 are H.

50. The method of claim 41 , wherein R 3 and R 4 are F.

51. The method of claim 41 , wherein R 7 is H.

52. The method of claim 41 , wherein R 7 is CH 3 .

53. The method of claim 41 , wherein X and Y are H.

54. The method of claim 41 , wherein X and Y are F.

55. The method of claim 41 , wherein m is 2.

56. The method of claim 41 , wherein n is 3.

57. The method of claim 41 , wherein n is 4.

58. The method of claim 41 , wherein A is

59. The method of claim 41 , wherein A is

60. The method of claim 41 , wherein A is

61. A method of treating social anxiety in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having the formula:

or a pharmaceutically acceptable salt thereof.

62. The method of claim 1 , wherein the compound is administered to the subject in a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2024
From: PERNI, ROBERT B.
To: JMD PHARMA CREATIVITY, LLC
Reel/Frame 069226/0612 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2024
From: JMD PHARMA CREATIVITY, LLC
To: ATAI LIFE SCIENCES US, INC.
Reel/Frame 069226/0712 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2024
From: ATAI LIFE SCIENCES US, INC.
To: ATAI LIFE SCIENCES AG
Reel/Frame 069226/0806 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2024
From: SHORT, GLENN; KHAN, TANWEER A.
To: ATAI LIFE SCIENCES AG
Reel/Frame 069226/0875 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2024
From: ATAI LIFE SCIENCES AG
To: EMPATHBIO, INC.
Reel/Frame 069227/0048 →
Continuity (3)
Continuation 18147189 · Dec 28, 2022
Provisional Application 63294225 · Dec 28, 2021
Related Publication 20240400532A1 · Dec 5, 2024
References Cited (350)
US 3907864A · Biel et al. · 1975 [cited by applicant]
US 4017636A · Jones et al. · 1977 [cited by applicant]
US 4937360A · Liu et al. · 1990 [cited by applicant]
US 5061727A · Bloom et al. · 1991 [cited by applicant]
US 5932749A · Li et al. · 1999 [cited by applicant]
US 6436950B1 · Achari et al. · 2002 [cited by applicant]
US 7048545B2 · McClusky · 2006 [cited by applicant]
US 9878992B2 · Bhamidipati et al. · 2018 [cited by applicant]
US 9907812B2 · Bapat et al. · 2018 [cited by applicant]
US 10000555B2 · Doronina et al. · 2018 [cited by applicant]
US 11414423B1 · Olson et al. · 2022 [cited by applicant]
US 11845736B2 · Rao et al. · 2023 [cited by applicant]
US 11912680B2 · Perni · 2024 [cited by examiner]
US 11993577B2 · Fawaz et al. · 2024 [cited by applicant]
US 12221428B2 · Cozzi et al. · 2025 [cited by applicant]
US 20030171303A1 · Gallop et al. · 2003 [cited by applicant]
US 20030207884A1 · Haap et al. · 2003 [cited by applicant]
US 20050130244A1 · Zheng et al. · 2005 [cited by applicant]
US 20060035863A1 · Barbeau · 2006 [cited by applicant]
US 20060205779A1 · Mu et al. · 2006 [cited by applicant]
US 20060205946A1 · Ji et al. · 2006 [cited by applicant]
US 20070027208A1 · Caron et al. · 2007 [cited by applicant]
US 20080045588A1 · Gant et al. · 2008 [cited by applicant]
US 20080146567A1 · Kolczewski et al. · 2008 [cited by applicant]
US 20080293695A1 · Bristol et al. · 2008 [cited by applicant]
US 20090111741A1 · Aldrich et al. · 2009 [cited by applicant]
US 20090131516A1 · Mickle et al. · 2009 [cited by applicant]
US 20090143408A1 · Eissenstat et al. · 2009 [cited by applicant]
US 20100137428A1 · Bozzoli et al. · 2010 [cited by applicant]
US 20130317020A1 · Ruah et al. · 2013 [cited by applicant]
US 20180243241A1 · Popp et al. · 2018 [cited by applicant]
US 20180344728A1 · Bosse et al. · 2018 [cited by applicant]
US 20200369707A1 · Verhoeven et al. · 2020 [cited by applicant]
US 20210113559A1 · Boss et al. · 2021 [cited by applicant]
US 20210145851A1 · Stamets · 2021 [cited by applicant]
US 20210332012A1 · Olson et al. · 2021 [cited by applicant]
US 20210346341A1 · Liechti · 2021 [cited by applicant]
US 20220151986A1 · Liechti et al. · 2022 [cited by applicant]
US 20220267252A1 · Trachsel et al. · 2022 [cited by applicant]
US 20220354822A1 · Barrow et al. · 2022 [cited by applicant]
US 20230097530A1 · Short et al. · 2023 [cited by applicant]
US 20230109467A1 · Anzalone et al. · 2023 [cited by applicant]
US 20230113351A1 · Blumstock et al. · 2023 [cited by applicant]
US 20230129723A1 · Short et al. · 2023 [cited by applicant]
US 20230227420A1 · Rao et al. · 2023 [cited by applicant]
US 20230278977A1 · Fawaz et al. · 2023 [cited by applicant]
US 20230310368A1 · Barrow et al. · 2023 [cited by applicant]
US 20240082212A1 · Short et al. · 2024 [cited by applicant]
US 20240208920A1 · Fawaz et al. · 2024 [cited by applicant]
US 20240217944A1 · Fawaz · 2024 [cited by applicant]
US 20240408054A1 · Short et al. · 2024 [cited by applicant]
US 20240425470A1 · Khan et al. · 2024 [cited by applicant]
US 20250026731A1 · Rao et al. · 2025 [cited by applicant]
US 20250152553A1 · Khan et al. · 2025 [cited by applicant]
AU 2018268311B2 · 2022 [cited by applicant]
CN 101822841A · 2010 [cited by applicant]
CN 110294789A · 2019 [cited by applicant]
DK 3271357T3 · 2020 [cited by applicant]
EP 2687854A1 · 2014 [cited by applicant]
NZ 239929A · 1994 [cited by applicant]
WO WO2005038049A2 · 2005 [cited by applicant]
WO WO2007090733A1 · 2007 [cited by examiner]
WO WO2008033351A2 · 2008 [cited by applicant]
WO WO2008046135A1 · 2008 [cited by applicant]
WO WO2009049233A1 · 2009 [cited by applicant]
WO WO2009089494A2 · 2009 [cited by applicant]
WO WO2009095479A2 · 2009 [cited by applicant]
WO WO2012177986A2 · 2012 [cited by applicant]
WO WO2014013063A1 · 2014 [cited by applicant]
WO WO2016148306A1 · 2016 [cited by applicant]
WO WO2017147375A1 · 2017 [cited by applicant]
WO WO2018210988A1 · 2018 [cited by applicant]
WO WO2019018584A1 · 2019 [cited by applicant]
WO WO2020077217A1 · 2020 [cited by applicant]
WO WO2020101543A1 · 2020 [cited by applicant]
WO WO2020252384A1 · 2020 [cited by applicant]
WO WO2021252538A2 · 2021 [cited by applicant]
WO WO2022006192A1 · 2022 [cited by applicant]
WO WO2022010937A1 · 2022 [cited by applicant]
WO WO2022032147A1 · 2022 [cited by applicant]
WO WO2022053696A1 · 2022 [cited by applicant]
WO WO2022061242A1 · 2022 [cited by applicant]
WO WO2022069690A2 · 2022 [cited by applicant]
WO WO2022106947A1 · 2022 [cited by applicant]
WO WO2022150525A1 · 2022 [cited by applicant]
WO WO2022182602A2 · 2022 [cited by applicant]
WO WO2022232948A1 · 2022 [cited by applicant]
WO WO2022235530A1 · 2022 [cited by applicant]
WO WO2022251690A1 · 2022 [cited by applicant]
WO WO2022256720A2 · 2022 [cited by applicant]
WO WO2023283373A1 · 2023 [cited by applicant]
WO WO2023283386A2 · 2023 [cited by applicant]
WO WO2023019369A1 · 2023 [cited by applicant]
WO WO2023034510A1 · 2023 [cited by applicant]
WO WO2023044027A1 · 2023 [cited by applicant]
WO WO2023056102A1 · 2023 [cited by applicant]
WO WO2023056472A1 · 2023 [cited by applicant]
WO WO2023129958A2 · 2023 [cited by applicant]
WO WO2023131841A1 · 2023 [cited by applicant]
WO WO2023250247A2 · 2023 [cited by applicant]
WO WO2024052880A1 · 2024 [cited by applicant]
WO WO2024054279A1 · 2024 [cited by applicant]
WO WO2024102845A2 · 2024 [cited by applicant]
WO WO2024145663A2 · 2024 [cited by applicant]
WO WO2024148267A1 · 2024 [cited by applicant]
WO WO2024166057A1 · 2024 [cited by applicant]
WO WO2024166058A1 · 2024 [cited by applicant]
WO WO2024166059A1 · 2024 [cited by applicant]
WO WO2024254411A2 · 2024 [cited by applicant]
WO WO2024254505A2 · 2024 [cited by applicant]
WO WO2025010308A2 · 2025 [cited by applicant]
Acquas. “Differential effects of intravenous R, S-(±)-3, 4-methylenedioxymethamphetamine (MDMA, Ecstasy) and its S (+)-and R (-)-enantiomers on dopamine transmission and extracellular signal regulated kinase phosphoryla… [cited by applicant]
Anderson et al., “Absolute configuration and psychotomimetic activity”, ‘QuaSAR’ Research Monograph, National Institute on Drug Abuse (1978); 22: 8-15. [cited by applicant]
Angerer et al., “Acute psychotropic, autonomic, and endocrine effects of 5,6-methylenedioxy-2-aminoindane (MDAI) compared with 3,4-methylenedioxymethamphetamine (MDMA) in human volunteers: A self-administration study.” … [cited by applicant]
Auvelity, (dextromethorphan HBr and bupropion HCl) extended-release tablets, Prescribing Information, Axsome Therapeutics, Inc., 2022. 19 pages. [cited by applicant]
Baker et al., “Critical evaluation of methodology commonly used in sample collection, storage and preparation for the analysis of pharmaceuticals and illicit drugs in surface water and wastewater by solid phase extracti… [cited by applicant]
Baker, et al., “Drugs of abuse in wastewater and suspended particulate matter—Further developments in sewage epidemiology.” Environ Int. Nov. 1, 2012: 48: 28-38. doi: 10.1016/j.envint.2012.06.014. Epub Jul. 24, 2012. [cited by applicant]
Baker et al., “Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry.” J Chromatogr A. Mar… [cited by applicant]
Baker, et al., “Multi-residue determination of the sorption of illicit drugs and pharmaceuticals to wastewater suspended particulate matter using pressurized liquid extraction, solid phase extraction and liquid chromato… [cited by applicant]
Barreiro, J.C., et al., “A High-Resolution Magic Angle Spinning NMR Study of the Enantiodiscrimination of 3,4-Methylenedioxymethamphetamine (MDMA) by an Immobilized Polysaccharide-Based Chiral Phase”, PLoS One, vol. 11,… [cited by applicant]
Bartz, J., et al., “Oxytocin can hinder trust and cooperation in borderline personality disorder.” Soc Cogn Affect Neurosci., Oct. 2011; 6(5): 556-63. [cited by applicant]
Battaglia et al., “Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites.” Eur J Pharmacol. Apr. 27, 1988; 149(1-2): 159-63. doi: 10.1016/0014-2999(88)90056-8. [cited by applicant]
Baumann et al., “Effects of dose and route of administration on pharmacokinetics of (+ or -)-3,4-methylenedioxymethamphetamine in the rat.” Drug Metab Dispos. Nov. 2009; 37(11): 2163-70. doi: 10.1124/dmd.109.028506. Epu… [cited by applicant]
Berge et al., “Pharmaceutical salts.” J Pharm Sci. Jan. 1977; 66(1): 1-19. [cited by applicant]
Biezonski et al., “Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats.” Eur J Pharmacol. Feb. 15, 2013; 701(1-3): 176-80. doi: 10.1016/j… [cited by applicant]
Blanchard et al., “Ethoexperimental approaches to the biology of emotion.” Annu Rev Psychol. 1988: 39: 43-68. doi: 10.1146/annurev.ps.39.020188.000355. [cited by applicant]
Bobes, J., “How is recovery from social anxiety disorder defined?” The Journal of Clinical Psychiatry. J Clin Psychiatry. 1998: 59 Suppl 17:12-19. [cited by applicant]
Brooks et al., “The significance of chirality in drug design and development.” Curr Top Med Chem. 2011 ; 11 (7): 760-770. Author Manuscript, published Jan. 12, 2018 (Year: 2018). [cited by applicant]
Brøsen, K., et al., “Extensive Metabolizers of Debrisoquine Become Poor Metabolizers during Quinidine Treatment.” Pharmacol Toxicol. Apr. 1987; 60(4): 312-4. doi: 10.1111/j.1600-0773.1987.tb01758.x. [cited by applicant]
Carbonaro, T. et al., “Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.” Psychopharmacology (Berl). Feb. 2018; 235(2): 521-534. do… [cited by applicant]
Carhart-Harris et al., “Trial of psilocybin versus escitalopram for depression”, New England Journal of Medicine (2021); 384(15): 1402-1411. doi: 10.1056/NEJMoa2032994. [cited by applicant]
Carhart-Harris, “Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.” Sci Rep. Oct. 13, 2017; 7(1): 13187. doi: 10.1038/s41598-017-13282-7. 11 pages. [cited by applicant]
Cascorbi, I., “Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication.” Eur J Clin Invest. Nov. 2003: 33 (Suppl 2): 17-22. doi: 10.1046/j.1365-2362.33.s2.3.x. [cited by applicant]
Castrignano, et al., “Enantiomeric profiling of chiral drug biomarkers in wastewater with the usage of chiral liquid chromatography coupled with tandem mass spectrometry.” J Chromatogr A. Mar. 18, 2016:1438:84-99. doi: … [cited by applicant]
Castrignano, et al., Enantiomeric profiling of chiral illicit drugs in a pan-European study, Water Res. Mar. 1, 2018: 130: 151-160. doi: 10.1016/j.watres.2017.11.051. Epub Dec. 1, 2017. [cited by applicant]
Chaly and Diksic, “High yield synthesis of 6-[18F]fluoro-L-dopa by regioselective fluorination of protected L-dopa with [18F]acetylhypofluorite.” J Nucl Med. Dec. 1986; 27(12): 1896-901. [cited by applicant]
Chen, et al., “Investigation of the relationship between phenol ionization and affinity of norepinephrine for adrenergic receptors using ring-fluorinated analogs.” Medicinal Chemistry Research, 1994, 3(9) pp. 589-597. [cited by applicant]
Chen, et al., “Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and 2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic activity.” J Med Chem. Nov. 26, 1993; 36(24):… [cited by applicant]
Clinical Trials.gov., ID NCT03537014, “A Multi-site Phase 3 study of MDMA-Assisted Psychotherapy for PTSD (MAPP1).” National Library of Medicine, Sponsor Lykos Therapeutics, ((Aug. 18, 2021) Study Record Version 46) (Ye… [cited by applicant]
ClinicalTrials.gov ID NCT05277636, “Acute Effects of R- and S-MDMA in Healthy Subjects (R-S-MDMA).” National Library of Medicine, Sponsor University Hospital, Basel, Switzerland, Study start, Oct. 1, 2022, 13 pages. [cited by applicant]
Clouting, H., “The Commercial Chemistry of MDMA: From Research to Patient Access,” MAPS Bulletin Special Edition, Spring 2020, pp. 8-10. [cited by applicant]
Cohen, I., et al., “Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database.” Scientific Reports, (2021) 11: 5997, 9 pages. [cited by applicant]
Collins et al., “Identification and characterization of N-tert-butoxycarbonyl-MDMA: a new MDMA precursor”, Drug Testing and Analysis (Mar. 2017); 9(3): 399-404. doi: 10.1002/dta.2059. Epub Sep. 29, 2016. [cited by applicant]
Connarn et al., “Pharmacokinetics and Pharmacogenomics of Bupropion in Three Different Formulations with Different Release Kinetics in Healthy Human Volunteers.” AAPS J. Sep. 2017; 19(5): 1513-1522. doi: 10.1208/s12248-… [cited by applicant]
Corkery et al., “Deaths in the Lesbian, Gay, Bisexual and Transgender United Kingdom Communities Associated with GHB and Precursors.” Curr Drug Metab. 2018; 19(13): 1086-1099. doi: 10.2174/1389200218666171108163817. [cited by applicant]
Crean, R.D., et al., “Oral Administration of (±)3,4-Methylenedioxymethamphetamine and (+) Methamphetamine Alters Temperature and Activity in Rhesus Macaques”, Pharmacol Biochem Behav, vol. 87, No. 1, Author Manuscript P… [cited by applicant]
Crisp et al., “The antinociceptive effects of 3, 4-methylenedioxymethamphetamine (MDMA) in the rat”, Pharmacology Biochemistry and Behavior (1989); 34(3): 497-501. doi: 10.1016/0091-3057(89)90547-9. [cited by applicant]
Curry. “Separating the agony from ecstasy: R(-)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice”, Neuropharmacology (2018); 128: 196-206. doi: 10.1016/… [cited by applicant]
Dalgleish, T., et al., “Transdiagnostic Approaches to Mental Health Problems: Current Status and Future Directions.” Journal of Consulting and Clinical Psychology, 2020, vol. 88, No. 3, 179-195. [cited by applicant]
Danforth et al., “Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.” Psychopharmacology (2018) 235: 3137-3148 https:/ /doi.or… [cited by applicant]
De La Torre and Farre, “Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans.” Trends Pharmacol Sci. Oct. 2004;25(10):505-8. doi: 10.1016/j.tips.2004.08.001., 4 pages. [cited by applicant]
De La Torre et al., “MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?”, Frontiers in Genetics (2012); 3: 235; 8 pages .doi: 10.3389/fgene.2012.00235. [cited by applicant]
De La Torre et al., “Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans.” Br J Clin Pharmacol. Feb. 2000; 49(2): 104-9. doi: 10.1046/j. 1365-2125.2000.00121.x. [cited by applicant]
De Vos et al., “Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics.” Front Psychiatry. Sep. 10, 2021: 12: 724606. doi: 10.3389/fpsyt.2021.724606. eCollection 20… [cited by applicant]
Deluca et al., “Searching the Internet for drug-related web sites: analysis of online available information on ecstasy (MDMA).” Am J Addict. Nov.-Dec. 2007; 16(6):479-83. doi: 10.1080/10550490701641181. [cited by applicant]
Doly et al., “Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice.” PLoS One. Nov. 23, 2009; 4(11): e7952. doi: 10.1371/journal.pone.0007952. 10 pages. [cited by applicant]
Duman et al., “Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants.” Nat Med. Mar. 2016; 22(3): 238-49. doi: 10.1038/nm.4050. [cited by applicant]
Dunlap et al., “Dark classics in chemical neuroscience: 3, 4-methylenedioxymethamphetamine”, ACS Chemical Neuroscience (2018); 9(10): 2408-2427. doi: 10.1021/acschemneuro.8b00155. Epub Jul. 12, 2018. [cited by applicant]
Eiden, et al., “VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse.” Ann N Y Acad Sci. Jan. 2011: 1216: 86-98. doi: 10.1111/j.1749-6632.2010.05906.x. [cited by applicant]
Ellinwood Jr et al., “Fundamental mechanisms underlying altered behavior following chronic administration of psychomotor stimulants.” Biological Psychiatry, Oct. 1, 1980, 15(5):749-757. [cited by applicant]
Erowid, “Like a Happy Smiley Speed MOMA, Escitalopram & Divalproex.” May 29, 2021, Erowid.org Retrieved May 29, 2021. URL: https://www.erowid.org/experiences/exp.php?ID=89532. 6 pages. [cited by applicant]
Erowid, “Unexpectedly Hard Tripping . . . All Good, Too.” Jul. 7, 2021, Erowid, Retrieved Jul. 7, 2021. URL:https://www.erowid.org/experiences/exp.php?ID=108919. 3 pages. [cited by applicant]
Eurofins SafetyScreen87 Panel, Panlabs, available online at https://www.eurofinsdiscovery.com/catalog/safetyscreen87-panel-tw/PP223, date unknown, document copyright date 2023, 4 pages. [cited by applicant]
Fallon et al., “Stereospecific Analysis and Enantiomeric Disposition of 3,4-Methylenedioxymethamphetamine (Ecstasy) in Humans,” Clinical Chemistry (1999) 45:7, 1058-1069. [cited by applicant]
Fantegrossi et al., “3, 4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) and its stereoisomers as reinforcers in rhesus monkeys: serotonergic involvement.” Psychopharmacology (Berl). Jun. 2002; 161(4):356-64. doi: 10.1… [cited by applicant]
Fantegrossi et al., “Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and its enantiomers in the mouse”, Psychopharmacology (2005); 181(3): 529-536. doi: 10.1007/s00213-005-0005-8. Epub Oct.… [cited by applicant]
Fantegrossi et al., “Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice.” Psychopharmacology (2004) 173:270-277. [cited by applicant]
Fantegrossi et al., “Pharmacological characterization of the effects of 3, 4-methylenedioxymethamphetamine (“ecstasy”) and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crow… [cited by applicant]
Fantegrossi, “In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.” Exp Clin Psychopharmacol. Feb. 2008; 16(1): 1-12. doi: 10.1037/1064-1297.16.1.1. [cited by applicant]
Feduccia, “MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?” Progress in Neuropsychopharmacology & Biological Psychiatry vol. 84, pp. 221-228, 2019. [cited by applicant]
Felim et al., “Synthesis and in Vitro Cytotoxicity Profile of the R-Enantiomer of 3,4-Dihydroxymethamphetamine (R-(-)-HHMA): Comparison with Related Catecholamines,” Chem. Res. Toxicol. 2010, 23, 211-219. [cited by applicant]
Filler, R., “Fluorine-containing catecholamines. Synthesis of DL-2,5,6-trifluorodopa.” Journal of fluorine chemistry, 1981, vol. 18(4), p. 483-495. [cited by applicant]
Fitzgerald et al., “Stereoselective pharmacokinetics of 3, 4-methylenedioxymethamphetamine in the rat.” Chirality. 1990;2(4):241-8. doi: 10.1002/chir.530020409. [cited by applicant]
Forsling et al., “The effect of 3,4-methylenedioxymethamphetamine (MDMA,‘ecstasy’) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus.” British Journal of Pharmacology (2002); 135… [cited by applicant]
Frith et al., “Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat.” Fundam Appl Toxicol. Jul. 1987; 9(1): 110-9. doi: 10.1016/0272-0590(87)90158-8. [cited by applicant]
Gauvin et al., “Establishing performance characteristics for positive control article selection in drug self-administration studies.” Journal of Pharmacological and Toxicological Methods vol. 97, May-Jun. 2019, pp. 13-2… [cited by applicant]
Glue, P., et al., “Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteerst.” J Clin Pharmacol. 2015. doi:10.1002/jcph.471. Epub Feb. 25, 2015. … [cited by applicant]
Gold and Koob, “MDMA produces stimulant-like conditioned locomotor activity.” Psychopharmacology (Berl). 1989; 99(3): 352-6. doi: 10.1007/BF00445556. [cited by applicant]
Gopisankar, M. G., “CYP2D6 pharmacogenomics.” The Egyptian Journal of Medical Human Genetics 18 (2017) 309-313. [cited by applicant]
Green et al., “The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”)”, Pharmacol Rev, Sep. 2003; 55(3): 463-508. Epub Jul. 17, 2003. [cited by applicant]
Green, R., et al., “MDMA: on the translation from rodent to human dosing.” Psychopharmacology (Berl). Jun. 2009; 204(2): 375-8. doi: 10.1007/s00213-008-1453-8. Epub Jan. 13, 2009. [cited by applicant]
Haberzettl et al., “Animal models of the serotonin syndrome: a systematic review.” Behav Brain Res. Nov. 1, 2013: 256: 328-45. doi: 10.1016/j.bbr.2013.08.045. Epub Sep. 1, 2013. [cited by applicant]
Hagele et al., “Enantioselective separation of Novel Psychoactive Substances using a Lux® AMP 3 μm column and HPLC-UV.” J Pharm Biomed Anal. Feb. 5, 2020:179:112967. doi: 10.1016/j.jpba.2019.112967. Epub Nov. 5, 2019. 2… [cited by applicant]
Halberstadt and Geyer, “Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement,” Psychopharmacology (Berl). Jun. 2013;227(4):727-3… [cited by applicant]
Halberstadt et al., “Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species.” Neuropharmacology. May 1, 2020: 167: 107933. d… [cited by applicant]
Han et al., “Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs.” BMC Pharmacol. Mar. 3, 2006: 6: 6. doi: 10.1186/1471-2210-6-6. 7 pages. [cited by applicant]
Heather, E., “The Synthesis and Chemical Profiling of 3,4-Methylene-dioxymethamphetamine (MDMA) and Analogues,” Thesis, University of Technology Sydney, Oct. 2020, 232 pages. [cited by applicant]
Hensley, et al., “Simultaneous determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA) enantiomers by GC-MS.” Journ… [cited by applicant]
Herr et al., “Re-evaluation of the discriminative stimulus effects of lysergic acid diethylamide with male and female Sprague-Dawley rats.” Behav Pharmacol. Dec. 2020; 31(8): 776-786. [cited by applicant]
Heydari, A., et al., “Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine.” Drug Metab Dispos. Nov. 2004; 32(11): 1213-7. doi: 10.1124/dmd.104.001180. Epub Aug. 24, 2004. [cited by applicant]
Hilaire et al., “The role of serotonin in respiratory function and dysfunction.” Respiratory Physiology & Neurobiology vol. 174, Issues 1-2, Nov. 30, 2010, pp. 76-88. [cited by applicant]
Hiramatsu et al., “Enantiomeric differences in the effects of 3, 4-methylenedioxymethamphetamine on extracellular monoamines and metabolites in the striatum of freely-moving rats: an in vivo microdialysis study”, Neurop… [cited by applicant]
Holze et al., “Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects”, Neuropsychopharmacology (2020); 45(3): 462-471. doi: 10.1038/s41386-019-0569-3. Epub Nov. 16, 2019. [cited by applicant]
Huot et al., “Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) Enantiomers In Vitro and in the MPTP-Lesioned Primate: R-MDMA Reduces Severity of Dyskinesia, Whereas S-MDMA Extends Duration of ON-Time”, The J… [cited by applicant]
Hysek et al., “Duloxetine inhibits effects of MDMA (“ecstasy”) in vitro and in humans in a randomized placebo-controlled laboratory study”, PloS One (2012); 7(5): e36476; 15 pages. doi: 10.1371/journal.pone.0036476. Epu… [cited by applicant]
Hysek et al., “Effects of the α2-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers”, The Journal of Pharmacology and Experimental Therap… [cited by applicant]
Hysek et al., “MDMA enhances emotional empathy and prosocial behavior.” Soc Cogn Affect Neurosci. Nov. 2014; 9(11): 1645-52. doi: 10.1093/scan/nst161. Epub Oct. 4, 2013. [cited by applicant]
Hysek et al., “Thenorepinephrine transporter inhibitor reboxetine reduces stimulant effects of MOMA (“ecstasy”) in humans”, Clinical Pharmacology and Therapeutics (2011); 90: 246-255. doi: 10.1038/clpt.2011.78. Epub Jun… [cited by applicant]
Inouye et al., “MDMA-assisted therapy for borderline personality disorder.” Journal of Psychedelic Studies, 7 (2023) 3, 227-237, DOI:10.1556/2054.2023.00196. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2023/058939 mailed Mar. 20, 2025, 8 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2022/042353 dated Nov. 7, 2023, 27 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2022/043833 dated Mar. 28, 2024, 5 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2022/045587 dated Apr. 11, 2024, 11 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2022/077432 dated Apr. 11, 2024, 9 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2023/079137 mailed May 22, 2025, 9 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/IB2023/058939 dated Dec. 1, 2023, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/042353, mailed on Dec. 8, 2022, 9 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/043833 dated Jan. 12, 2023, 13 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/045587 dated Feb. 1, 2023, 25 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/077432 dated Dec. 15, 2022, 14 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/082468, mailed on Jun. 6, 2023, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2023/079137 dated Apr. 29, 2024, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2023/086567, dated May 24, 2024, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/010486 mailed May 17, 2024. 10 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/032949, mailed Nov. 26, 2024. 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/033081, dated Oct. 24, 2024, 14 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/036639, mailed Sep. 23, 2024, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/054056, mailed Feb. 10, 2025, 18 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2024/061447, mailed Feb. 26, 2025, 10 pages. [cited by applicant]
Invitation to Pay Additional Fees for International Application No. PCT/US2023/086567, mailed Mar. 18, 2024. 2 pages. [cited by applicant]
Invitation to Pay Additional Fees for International Application No. PCT/US2024/010486 mailed Mar. 12, 2024, 2 pages. [cited by applicant]
Invitation to Pay Additional Fees for International Application No. PCT/US2024/032949, mailed Aug. 6, 2024, 2 pages. [cited by applicant]
Invitation to Pay Additional Fees for International Application No. PCT/US2024/033081, mailed Aug. 15, 2024, 3 pages. [cited by applicant]
Invitation to Pay Fee for International Application No. PCT/US2022/045587 dated Nov. 18, 2022, 3 pages. [cited by applicant]
Invitation to Pay for International Application No. PCT/US2022/082468 dated Mar. 16, 2023, 2 pages. [cited by applicant]
Jeppesen, U., et al., “Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.” Eur J Clin Pharmacol (1996) 51: 73-78. [cited by applicant]
Johnson et al., “Effects of enantiomers of MDA, MDMA and related analogues on [3H] serotonin and [3H] dopamine release from superfused rat brain slices.” Eur J Pharmacol. Dec. 16, 1986;132(2-3):269-76. doi: 10.1016/0014… [cited by applicant]
Kalant, Harold, “The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs.” CMAJ. Oct. 2, 2001; 165(7): 917-28. [cited by applicant]
Kalivas et al., “MDMA Elicits Behavioral and Neurochemical Sensitization in Rats.” Neuropsychopharmacology vol. 18, pp. 469-479 (1998). [cited by applicant]
Kamilar-Britt and Bedi, “The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals.” Neurosci Biobehav Rev. Oct. 2015: 57: 433-46. doi: 10.1016/j.neubiorev.20… [cited by applicant]
Kashdan, T. B. & Mcknight, P. E., “The darker side of social anxiety: When aggressive impulsivity prevails over shy inhibition.” Current Directions in Psychological Science. Feb. 2010;19(1):47-50. [cited by applicant]
Kilpatrick et al., “National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria.” J Trauma Stress. Oct. 2013;26(5):537-47. doi: 10.1002/jts.21848. [cited by applicant]
Kirilly, E, et al., “Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats.” Int J Neuropsychopharmacol. Feb. 2006; 9(1): 63-76. [cited by applicant]
Kiyatkin, “Environmental Conditions Modulate Neurotoxic Effects of Psycho motor Stimulant Drugs of Abuse.” Int Rev Neurobiol. 2012 ; 102: 147-171. doi:10.1016/B978-0-12-386986-9.00006-5. [cited by applicant]
Koenig and Hilber, “The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation.” Molecules 2015, 20, 2208-2228; doi:10.3390/molecules20022208. [cited by applicant]
Kolbrich et al., “Physiological and subjective responses to controlled oral 3, 4-methylenedioxymethamphetamine administration”, Journal of Clinical Psychopharmacology (2008); 28(4): 432-440. doi: 10.1097/JCP.0b013e31817… [cited by applicant]
Kotlyar et al., “Inhibition of CYP2D6 Activity by Bupropion.” J Clin Psychopharmacol. Jun. 2005; 25(3): 226-9. doi: 10.1097/01.jcp.0000162805.46453.e3. [cited by applicant]
Kozma, D., et al., “Optical resolution of N-methylamphetamine via diastereoisomeric salt formation with 2R,3R-O,O′-di-p-toluoyltartaric acid,” Chirality, 1999, vol. 11, Issue 5-6, pp. 373-375. [cited by applicant]
Ladd, et al., Improved synthesis of fluoroveratroles and fluorophenethylamines via organolithium reagents, Journal of Organic Chemistry, 1981, pp. 203-206. [cited by applicant]
Leapman, et al., Application of parallel recorded EELS to analysis of beam-sensitive organic compounds, Biomed. Eng. Instrum., Proceedings—Annual Meeting, Electron Microscopy Society of America, 1988, pp. 632-633. [cited by applicant]
Leapman, et al., Applications of electron energy loss spectroscopy in biology: detection of calcium and fluorine, Proceedings—Annual Meeting, Electron Microscopy Society of America, 1982, pp. 412-415. [cited by applicant]
Lettfuss et al. “Is behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA) mediated in part by cholinergic receptors?” Behav Brain Res. May 1, 2013: 244: 116-9. doi: 10.1016/j.bbr.2013.01.033. Epub Feb. 1,… [cited by applicant]
Levine et al. (editor), “Principles of Forensic Toxicology,” Springer, Fifth Edition, 2020, 680 pages. [cited by applicant]
Lewis et al., “Synthesis of R-and S-MDMA via nucleophilic ring-opening of homochiral N- tosylaziridines”, Jul. 12, 2023 (Jul. 12, 2023), Australian Journal of Chemistry, 76(5), pp. 299-310. [cited by applicant]
Lourenco et al., Chiral separation of 3, 4-methylenedioxymethamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling and its effects on oxidative stress status in rat liver, Journal of Phar… [cited by applicant]
Ly et al., “Psychedelics promote structural and functional neural plasticity.” Cell Rep. Jun. 12, 2018; 23(11): 3170-3182. doi: 10.1016/j.celrep.2018.05.022. [cited by applicant]
Lyon et al., “3, 4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT [cited by applicant]
Madry, et al., Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes, Analytical and Bioanalytical Chemistry, Jan. 2016, pp. 545-556. [cited by applicant]
Madsen et al., “A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding.” Eur Neuropsychopharmacol. Apr. 2020: 33: 71-80. doi… [cited by applicant]
Martins, et al., Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry, Journal of Chromatography B, Oct. 15, 200… [cited by applicant]
Martins, et al., “Time-resolved hair analysis of MDMA enantiomers by GC/MS-NCI.” Forensic Sci Int. Oct. 25, 2007;172(2-3):150-5. doi: 10.1016/j.forsciint.2007.01.008. Epub Feb. 14, 2007. [cited by applicant]
Mas et al., “Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.” J Pharmacol Exp Ther. Jul. 1999;290(1):136-45. [cited by applicant]
Matsushima et al., “Optical isomer analysis of 3, 4-methylenedioxyamphetamine analogues and their stereoselective disposition in rats.” J Anal Toxicol. Jan.-Feb. 1998;22(1):33-9. doi: 10.1093/jat/22.1.33. [cited by applicant]
McEwen et al., “Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex.” Neuropsychopharmacology. Jan. 2016; 41(1): 3-23. doi: 10.1038/npp.2015.171. Epub Jun. 16, 2015. [cited by applicant]
Miczek, K., “A new test for aggression in rats without aversive stimulation: Differential effects of d-amphetamine and cocaine.” Psychopharmacology (Berl). Feb. 28, 1979; 60(3): 253-9. doi: 10.1007/BF00426664. [cited by applicant]
Miksys, et al., “Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model.” Drug Metab Dispos. Oct. 2005; 33(10): 1495-502. doi: 10.1124/dmd.105.005488. Epub Jul. 20, 2005. [cited by applicant]
Milhazes, et al., Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors, Analytica Chimica Ac… [cited by applicant]
Mitchell. “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study”, Nature Medicine (2021); 27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub May 10, 2021. [cited by applicant]
Mithoefer et al., “The safety and efficacy of {+/−}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pi… [cited by applicant]
Multidisciplinary Association for Psychedelic Studies (MAPS), “A Manual for Adherence Ratings of MDMA-Assisted Therapy for Treatment of Posttraumatic Stress Disorder, Version 6.” MAPS, Santa Cruz, CA, Aug. 2021, 52 page… [cited by applicant]
Murnane, et al., Discriminative stimulus effects of psychostimulants and hallucinogens in S (+)-3, 4-methylenedioxymethamphetamine (MDMA) and R (−)-MDMA trained mice, Journal of Pharmacology and Experimental Therapeutic… [cited by applicant]
Murnane et al., “Endocrine and neurochemical effects of 3, 4-methylenedioxymethamphetamine and its stereoisomers in rhesus monkeys”, Journal of Pharmacology and Experimental Therapeutics (2010); 334(2): 642-650. doi: 10… [cited by applicant]
Murnane, et al., “The neuropharmacology of prolactin secretion elicited by 3, 4-methylenedioxymethamphetamine (“ecstasy”): a concurrent microdialysis and plasma analysis study.” Horm Behav. Feb. 2012; 61(2): 181-90. doi… [cited by applicant]
Mustafa, et al., Review Paper: MDMA and the Brain: A Short Review on the Role of Neurotransmitters in Neurotoxicity, Basic and Clinical Neuroscience, 2020, pp. 381-388. [cited by applicant]
Nair et al., “Fully validated, multi-kilogram cGMP synthesis of Mdma”, ACS Omega (2021); 7(1): 900-907. doi: 10.1021/acsomega.1c05520. [cited by applicant]
Nash et al., “Effect of the R (-) and S (+) isomers of MDA and MDMA on phosphotidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors”, Neuroscience Letters (1994); 177(1-2): 111-115. doi: 10.101… [cited by applicant]
National Center for Biotechnology Information, “1-(1,3-benzodioxol-5-yl)-N ,3-dimethylbuta n-2-amine; hydrochloride: Pubchem CID 90667266” Pubchem entry (online), pp. 1-9, Mar. 11, 2015; Retrieved on Dec. 2, 2024 from t… [cited by applicant]
National Center for Biotechnology Information, “[1-[2-(3,4-Dimethoxyphenyl)ethyl] cycloprop yl] carbamic acid: Pubchem CID 150096163” Pubchem entry (online), pp. 1-7, Dec. 13, 2018; Retrieved on Dec. 2, 2024 from the In… [cited by applicant]
National Center for Biotechnology Information, “[1-[(3,4-Dimethoxyphenyl)methyl] cyclobutyl] carbamic acid: Pubchem CID 135313815” Pubchem entry (online), pp. 1-8, Dec. 15, 2018; Retrieved on Dec. 2, 2024 from the Inter… [cited by applicant]
National Center for Biotechnology Information, “[2-(I,3-Benzodioxol-5-yl)-2-methylpropyl] carbamic acid: Pubchem CID 115171385” Pubchem entry (online), pp. 1-7, Jan. 29, 2016; Retrieved on Dec. 2, 2024 from the Internet… [cited by applicant]
National Center for Biotechnology Information “2-(I,3-benzodioxol-5-yl)ethyl carbamothio ic S-acid: Pubchem CID 115170245” Pubchem entry (online), pp. 1-7, Jan. 29, 2016; Retrieved on Dec. 1, 2024 from the Internet: [UR… [cited by applicant]
National Center for Biotechnology Information, “Ethyl (2S)-3-(1,3-benzodioxol-5-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino] propanoate: Pubchem CID 57958894” Pubchem entry (online), pp. 1-9, Aug. 19, 2012; Retrieved o… [cited by applicant]
National Center for Biotechnology Information, “Ethyl N-[1-chloro-2-(3,4-dimethoxyphenyl) ethyl]carbamate: Pubchem CID 89487151” Pubchem entry (online), pp. 1-8, Feb. 13, 2015; Retrieved on Dec. 2, 2024 from the Interne… [cited by applicant]
National Center for Biotechnology Information, “Ethyl N-[2-(I,3-benzodioxol-5-yl)ethyl] carbamate: Pubchem CID 15229637” Pubchem entry (online), pp. 1-9, Feb. 9, 2007; Retrieved on Dec. 1, 2024 from the Internet: [URL: … [cited by applicant]
National Center for Biotechnology Information, “Mbdp hydrochloride: Pubchem CID 90667265” Pubchem entry (online), pp. 1-10, Mar. 11, 2015; Retrieved on Dec. 2, 2024 from the Internet: [URL: https://pubchem.ncbi.nlm.nih.… [cited by applicant]
National Center for Biotechnology Information, “Methyl N-[2-(1 ,3-benzodioxol-5-yl) ethyl]carbamodithioate: Pubchem CID 44125045” Pubchem entry (online), pp. 1-8, Jul. 27, 2009; Retrieved on Dec. 1, 2024 [URL: https://p… [cited by applicant]
National Center for Biotechnology Information, “Methyl N-[(2R)-I-(I,3-benzodioxol-5-yl)-3 -chloropropan-2-yl]carbamate: Pubchem CID 166107066” Pubchem entry (online), pp. 1-7, Dec. 20, 2022; Retrieved on Dec. 2, 2024 fr… [cited by applicant]
National Center for Biotechnology Information, “Methyl N-[I-(I , 3-benzodioxol-5-yl) propan- 2-yl]carbamate: Pubchem CID 168188536” Pubchem entry (online), pp. 1-9, May 30, 2023; Retrieved on Dec. 1, 2024 from the Inter… [cited by applicant]
National Center for Biotechnology Information, N-Methyl-1-(3,4-methylenedioxyphenyl)- 2-butananiine: Pubchem CID 124844 Pubchem entry (online), pp. 1-8, Jul. 19, 2005; Retrieved on Dec. 2, 2024 from the Internet: [URL: … [cited by applicant]
National Center for Biotechnology Information, N-Moc-MDMA: Pubchem CID 165361551 Pubchem entry (online), pp. 1-11, Oct. 11, 2022; Retrieved on Dec. 2, 2024 from the Internet: [URL: https://pubchem.ncbi.nlm.nih.gov/compo… [cited by applicant]
National Center for Biotechnology Infonnation, “Methyl N-[(2S)-1-(1,3-benzodioxol-5-yl)-3 -chloropropan-2-yl]carbamate: Pubchem CID 166107086” Pubchem entry (online), pp. 1-7, Dec. 20, 2022; Retrieved on Dec. 2, 2024 fr… [cited by applicant]
National Center for Biotechnology Information, “Methyl N-[4-(3,4-dimethoxyphenyl) oxan-4- yl]carbamate: Pubchem CID 142770320” Pubchem entry (online), pp. 1-8, Dec. 7, 2019; Retrieved on Dec. 2, 2024 from the Internet: … [cited by applicant]
Navarro and Maldonado, “Behavioral profile of 3,4-methylenedioxy-methamphetamine (MDMA) in agonistic encounters between male mice.” Prog Neuropsychopharmacol Biol Psychiatry. Feb. 1999; 23(2): 327-34. doi: 10.1016/s0278… [cited by applicant]
Navarro and Maldonado, “Effects of acute, subchronic and intermittent MDMA (‘Ecstasy’) administration on agonistic interactions between male mice.” Aggressive Behavior (2004) vol. 30, Issue 1, p. 84-91. [cited by applicant]
Nelson and Chiavegatto, “Molecular basis of aggression.” Trends Neurosci. Dec. 2001; 24(12): 713-9. doi: 10.1016/s0166-2236(00)01996-2. [cited by applicant]
Nenajdenko et al., “A new convenient approach to chiral β-aryl (heteroaryl) alkylamines”, Tetrahedron: Asymmetry (2001); 12(18): 2517-2527. [cited by applicant]
Neumann et al., “Aggression and anxiety: social context and neurobiological links, Front Behav Neurosci.” Mar. 30, 2010: 4: 12. doi: 10.3389/fnbeh.2010.00012. eCollection 2010, 16 pages. [cited by applicant]
Nichols et al., “Derivatives of 1-(1, 3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class”, Journal of Medicinal Chemistry (1986); 29(10): 2009-2015. doi: 10.1021/jm00160a035. [cited by applicant]
Nie, et al., “Synthesis of fluorodopamines: effect of aryl fluoro substituents on affinities for adrenergic and dopaminergic receptors.” Medicinal Chemistry Research, Jan. 1996, pp. 318-332. [cited by applicant]
O'Mathuna, B., et al., “The Consequences of 3,4-Methylenedioxymethamphetamine Induced CYP2D6 Inhibition in Humans.” J Clin Psychopharmacol. Oct. 2008; 28(5): 523-9. doi: 10.1097/JCP.0b013e318184ff6e. [cited by applicant]
Organic Chemistry Portal, Amino Protecting Groups, Stability, available online at: https://www.organic-chemistry.org/protectivegroups/amino.shtm, 1999, pp. 1-3. [cited by applicant]
Parrot, A C, “Is ecstasy Mdma? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity.” Psychopharmacology (Berl). May 2004; 173(3-4): 234-41. doi: 10.… [cited by applicant]
Parrott AC, “Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research.” Hum Psychopharmacol. Dec. 2001; 16(8): 557-577. [cited by applicant]
Peters. “Drug testing in blood: validated negative-ion chemical ionization gas chromatographic-mass spectrometric assay for enantioselective measurement of the designer drugs MDEA, MDMA, and MDA and its application to s… [cited by applicant]
Peters, et al., Concentrations and ratios of amphetamine, methamphetamine, MDA, MDMA, and MDEA enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by GC-NICI-… [cited by applicant]
Peters, et al., Drug testing in blood: validated negative-ion chemical ionization gas chromatographic-mass spectrometric assay for determination of amphetamine and methamphetamine enantiomers and its application to toxi… [cited by applicant]
Peters, et al., Negative-ion chemical ionization gas chromatography-mass spectrometry assay for enantioselective measurement of amphetamines in oral fluid: application to a controlled study with MDMA and driving under t… [cited by applicant]
Pitts et al., “3, 4-Methylenedioxymethamphetamine increases affiliative behaviors in squirrel monkeys in a serotonin 2A receptor-dependent manner”, Neuropsychopharmacology (2017); 42(10): 1962-1971. doi: 10.1038/npp.201… [cited by applicant]
Pitts. “(±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA”, Psychopharmacology (2018); 235: 377-392. doi: 10.1007/s00213-017-4812-5. Epub Dec. 16, 2017. [cited by applicant]
Pizarro et al., “Synthesis and Capillary Electrophoretic Analysis of Enantiomerically Enriched Reference Standards of MDMA and its Main Metabolites,” Bioorganic & Medicinal Chemistry (2002) 10: 1085-1092. [cited by applicant]
Pizarro. “Stereochemical analysis of 3, 4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3, 4-dihydroxymethamphetamine)”, Drug Metabolism and Disposition … [cited by applicant]
Pizzaro et al., “Determination of MDMA and its Metabolites in Blood and Urine by Gas Chromatography-Mass Spectrometry and Analysis of Enantiomers by Capillary Electrophoresis.” J Anal Toxicol. Apr. 2002; 26(3): 157-65. … [cited by applicant]
Pokorny et al., “Effect of Psilocybin on Empathy and Moral Decision-Making.” International Journal of Neuropsychopharmacology (2017) 20(9): 747-757. [cited by applicant]
Pubchem 297429685 deposited on Jan. 27 (Jan. 27, 2016) p. 1-5. 2, structure. [cited by applicant]
Pubchem 459067002 deposited on Dec. 20, 2021 (Dec. 20, 2021) p. 1-5. [cited by applicant]
Pubchem SID 235735835, Feb. 13, 2015, 8 pages. [cited by applicant]
Pubchem SID 243280603, Mar. 16, 2015, 7 pages. [cited by applicant]
Pubchem, Substance Record for SID 104098418, Jan. 2011, 6 pages. [cited by applicant]
Pubcem, Substance Record for SID 117678335, Apr. 2011, 6 pages. [cited by applicant]
Pubchem, Substance Record for SID 38492237, Dec. 5, 2007, 5 pages. [cited by applicant]
Pubchem, Substance Record for SID 406789554, Jul. 18, 2020, 6 pages. [cited by applicant]
Pubchem, Substance Record for SID 439624087, Jan. 15, 2021, 6 pages. [cited by applicant]
Pubill, et al., Neuronal nicotinic receptors as new targets for amphetamine-induced oxidative damage and neurotoxicity, Pharmaceuticals, Jun. 15, 2011, pp. 822-847. [cited by applicant]
Rasmussen et al., “Chiral separation and quantification of R/S-amphetamine, R/S-methamphetamine, R/S-MDA, R/S-MDMA, and R/S-MDEA in whole blood by GC-EI-MS,” Journal of Chromatography B, (2006) 842: 136-141. [cited by applicant]
Rickli et al., “Pharmacological profile of novel psychoactive benzofurans”, British Journal of Pharmacology (2015); 172(13): 3412-3425. doi: 10.1111/bph.13128. Epub Apr. 24, 2015. [cited by applicant]
Rothman et al., “Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin”, Synapse. Jan. 2001; 39(1): 32-41. [cited by applicant]
Rudnick, et al., The molecular mechanism of “ecstasy” [3, 4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release, Proceedings of the National Academy of Sciences,… [cited by applicant]
Saez-Briones and Hernandez, “MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology.” Curr Neuropharmacol. Sep. 2013; 11(5): 521-… [cited by applicant]
Sager et al., “In vitro to in vivo extrapolation of the complex drug-drug interaction of bupropion and its metabolites with CYP2D6; simultaneous reversible inhibition and CYP2D6 downregulation.” Biochem Pharmacol. Jan. … [cited by applicant]
Sandtner et al., “Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters.” Mol Pharmacol. Jan. 2016; 89(1): 165-75. doi:10.1124/mol.115.101394. Epub Oct. 30, 2015. [cited by applicant]
Schenk and Bradbury, “Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats.” Pharmacol Biochem Behav. May 2015: 132: 103-107. doi: 10.1016/j.pbb.2015.03.001. Ep… [cited by applicant]
Schmid et al., “Acute subjective effects in LSD-and MDMA-assisted psychotherapy”, Journal of Psychopharmacology (2021); 35(4): 362-374. doi: 10.1177/0269881120959604. Epub Oct. 8, 2020. [cited by applicant]
Schwaninger, et al., “Development and validation of LC-HRMS and GC-NICI-MS methods for stereoselective determination of MDMA and its phase I and II metabolites in human urine.” Journal of Mass Spectrometry, Jul. 2011, p… [cited by applicant]
Schwaninger, et al., “Stereoselective urinary MDMA (ecstasy) and metabolites excretion kinetics following controlled MDMA administration to humans.” Biochemical pharmacology, Jan. 1, 2012, pp. 131-138. [cited by applicant]
Segura, M., et al., “Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe.” Clin Pharmacokinet. 2005; 44(6): 649-60. doi: 10.21… [cited by applicant]
Setola, et al., 3, 4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro, Molecular Pharmacology, Jun. 1, 2003, pp. 1223-… [cited by applicant]
Simmler. “Pharmacological characterization of designer cathinones in vitro”, British Journal of Pharmacology (2013) 168(2): 458-470. doi: 10.1111/j.1476-5381.2012.02145.x. [cited by applicant]
Spanos and Yamamoto, “Acute and subchronic effects of methylenedioxymethamphetamine [(+/−)MDMA] on locomotion and serotonin syndrome behavior in the rat.” Pharmacol Biochem Behav. Apr. 1989; 32(4): 835-40. doi: 10.1016/… [cited by applicant]
Steele, et al., “Stereochemical effects of 3, 4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H] monoamines into synaptosomes from different regions of rat brain.”… [cited by applicant]
Steuer et al., “Impact of cytochrome P450 2D6 function on the chiral blood plasma pharmacokinetics of 3, 4-methylenedioxymethamphetamine (MDMA) and its phase I and II metabolites in humans”, PloS One (2016); 11(3): e015… [cited by applicant]
Strajhar, et al., Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study, The Journal of steroid biochemistry a… [cited by applicant]
Straumann, I., et al., “Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants.” Neuropsychopharmacology. Dec. 2024; 50(2): 362-371. doi: 10.1038/s41386-0… [cited by applicant]
Sun, et al., Facile and universal immobilization of L-lysine inspired by mussels, J. Mater. Chem., 2012, Journal of Materials Chemistry, 2012, pp. 10035-41. [cited by applicant]
Thomas, et al., “Characterization of 3, 4-methylenedioxypyrovalerone discrimination in female Sprague-Dawley rats.” Behavioural Pharmacology, Jul. 2021, pp. 524-532. [cited by applicant]
Thomas et al., “Psilocybin and Ketamine Acutely Promote Wakefulness, Suppress REM Sleep but Differentially Modulate High Frequency EEG Oscillatory Power in Wistar Kyoto Rats—a Preliminary Analysis.” ACNP 59th Annual Mee… [cited by applicant]
Thomsen, et al., “In Vitro Drug Metabolism by Human Carboxylesterase 1: Focus on Angiotensin-Converting Enzyme Inhibitors.” Drug Metab Dispos. Jan. 2014; 42(1): 126-33. doi: 10.1124/dmd.113.053512. Epub Oct. 18, 2013. [cited by applicant]
Torner, L., “Actions of Prolactin in the Brain: From Physiological Adaptations to Stress and Neurogenesis to Psychopathology.” Front Endocrinol (Lausanne). Mar. 30, 2016: 7: 25. doi: 10.3389/fendo.2016.00025. eCollectio… [cited by applicant]
Tournier, et al., Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), International Journal of Neuropsychopharmacology, Aug. 1, 2010, … [cited by applicant]
Traynor, J.M., et al., “MDMA-Assisted Psychotherapy for BorderlinePersonality Disorder”. Focus, 2022, 20(4):358-67, (focus.psychiatryonline.org). [cited by applicant]
U.S. Appl. No. 18/990,840, filed Dec. 20, 2024, by Rao et al. [cited by applicant]
Verrico. “MDMA (ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA induced neurotoxicity and treatment”, Psychopharmacology (2007); 189(4): 489-503. doi: 10.1007/s00213-005-01… [cited by applicant]
Verweij , A., “Impurities in illicit drug preparations; 3,4-methylenedioxyamphetamine and 3-4-methylenedioxymethylamphetamine”, Forensic. Sci. Rev., 1992, pp. 1-6. [cited by applicant]
Weinstock, et al., Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogs of fenoldopam, Journal of Medicinal Chemistry, 1986, … [cited by applicant]
Willins and Meltzer, “Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats.” J Pharmacol Exp Ther. Aug. 1997; 282(2): 699-706. [cited by applicant]
Winstock, et al., “Ecstasy pill testing: harm minimization gone too far?” Addiction, 2001, pp. 1139-1148. [cited by applicant]
Wu, et al., Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score, Breast Cancer Research and Treatment, 2012, pp. 677-683. [cited by applicant]
Young et al., “MDMA (N-methyl-3, 4-methylenedioxyamphetamine) and its stereoisomers: Similarities and differences in behavioral effects in an automated activity apparatus in mice”, Pharmacology Biochemistry and Behavior… [cited by applicant]
Young, M.B., et al., “3,4-Methylenedioxymethamphetamine facilitates fear extinction learning”, Transl Psychiatry. Sep. 15, 2015; 5(9): e634. 8 pages. [cited by applicant]
Yubero-Lahoz et al., “Changes in CYP1A2 Activity in Humans after 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) Administration Using Caffeine as a Probe Drug.” Drug Metab. Pharmacokinet. 27 (6): 605-613 (2012). [cited by applicant]
Zapata-Torres et al., “Quantum-chemical, NMR and X-ray diffraction studies on (±)-1-[3, 4-(methylenedioxy) phenyl]-2-methylaminopropane”, Journal of Molecular Graphics and Modelling (2008); 26(8): 1296-1305. [cited by applicant]
Cited By (1)
US 12,715,852