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Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT).
Witowski, Christopher G; Hess, Mika R; Jones, Nate T; Pellitteri Hahn, Molly C; Razidlo, John; Bhavsar, Riya; Beer, Christina; Gonzalez-Velazquez, Natalie; Scarlett, Cameron O; Wenthur, Cody J; von Salm, Jacqueline L.
Afiliación
- Witowski CG; Psilera Inc., 3802 Spectrum Blvd., Suite 136B, Tampa, FL 33612, United States.
- Hess MR; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Jones NT; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Pellitteri Hahn MC; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Razidlo J; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Bhavsar R; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Beer C; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Gonzalez-Velazquez N; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Scarlett CO; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States.
- Wenthur CJ; University of Wisconsin-Madison, School of Pharmacy, 777 Highland Ave., Madison, WI 53705, United States; Transdisciplinary Center for Research in Psychoactive Substances, 777 Highland Ave., Madison, WI 53705, United States. Electronic address: wenthur@wisc.edu.
- von Salm JL; Psilera Inc., 3802 Spectrum Blvd., Suite 136B, Tampa, FL 33612, United States. Electronic address: jsalm@psilera.com.
Eur J Pharm Sci ; 199: 106803, 2024 Aug 01.
Article en En
| MEDLINE| ID: mdl-38788435
- ABSTRACT
ABSTRACT
There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmaco*kinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.
Asunto(s)
Administración Cutánea; Preparaciones de Acción Retardada; Alucinógenos; N,N-Dimetiltriptamina; Animales; ; Alucinógenos/farmacocinética; Masculino; ; Preparaciones de Acción Retardada/farmacocinética; Femenino; Ratones; ; N,N-Dimetiltriptamina/farmacocinética; Parche Transdérmico; Absorción Cutánea/efectos de los fármacos; Encéfalo/metabolismo; Encéfalo/efectos de los fármacos; Conducta Animal/efectos de los fármacos
Palabras clave
DMT; Dimethyltryptamine; Extended-release; Pharmaco*kinetics; Psychedelics; Transdermal
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Administración Cutánea / N,N-Dimetiltriptamina / Preparaciones de Acción Retardada / Alucinógenos Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Administración Cutánea / N,N-Dimetiltriptamina / Preparaciones de Acción Retardada / Alucinógenos Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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