: Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug has ebbed and flowed. In the last three decades, heroin use has increased again, and yet the pharmacology of heroin is still poorly understood. After entering the body, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM), which is then deacetylated to morphine. Thus, drug addiction literature has long settled on the notion that heroin is little more than a pro-drug. In contrast to these former views, we will argue for a more complex interplay among heroin and its active metabolites: 6-MAM, morphine, and morphine-6-glucuronide (M6G). In particular, we propose that the complex temporal pattern of heroin effects results from the sequential, only partially overlapping, actions not only of 6-MAM, morphine, and M6G, but also of heroin per se, which, therefore, should not be seen as a mere brain-delivery system for its active metabolites. We will first review the literature concerning the pharmacokinetics and pharmacodynamics of heroin and its metabolites, then examine their neural and behavioral effects, and finally discuss the possible implications of these data for a better understanding of opioid reward and heroin addiction. By so doing we hope to highlight research topics to be investigated by future clinical and pre-clinical studies.

Heroin and its metabolites: relevance to heroin use disorder / Milella, MICHELE STANISLAW; D’Ottavio, Ginevra; DE PIRRO, Silvana; Barra, Massimo; Caprioli, Daniele; Badiani, Aldo. - In: TRANSLATIONAL PSYCHIATRY. - ISSN 2158-3188. - 13:1(2023), p. 120. [10.1038/s41398-023-02406-5]

Heroin and its metabolites: relevance to heroin use disorder

Michele Stanislaw Milella
Primo
;
Ginevra D’Ottavio
Secondo
;
Silvana De Pirro;Daniele Caprioli
Penultimo
;
Aldo Badiani
Ultimo
2023

Abstract

: Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug has ebbed and flowed. In the last three decades, heroin use has increased again, and yet the pharmacology of heroin is still poorly understood. After entering the body, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM), which is then deacetylated to morphine. Thus, drug addiction literature has long settled on the notion that heroin is little more than a pro-drug. In contrast to these former views, we will argue for a more complex interplay among heroin and its active metabolites: 6-MAM, morphine, and morphine-6-glucuronide (M6G). In particular, we propose that the complex temporal pattern of heroin effects results from the sequential, only partially overlapping, actions not only of 6-MAM, morphine, and M6G, but also of heroin per se, which, therefore, should not be seen as a mere brain-delivery system for its active metabolites. We will first review the literature concerning the pharmacokinetics and pharmacodynamics of heroin and its metabolites, then examine their neural and behavioral effects, and finally discuss the possible implications of these data for a better understanding of opioid reward and heroin addiction. By so doing we hope to highlight research topics to be investigated by future clinical and pre-clinical studies.
2023
heroin; 6MAM; morphine; pharmacokinetics; reward; addiction
01 Pubblicazione su rivista::01a Articolo in rivista
Heroin and its metabolites: relevance to heroin use disorder / Milella, MICHELE STANISLAW; D’Ottavio, Ginevra; DE PIRRO, Silvana; Barra, Massimo; Caprioli, Daniele; Badiani, Aldo. - In: TRANSLATIONAL PSYCHIATRY. - ISSN 2158-3188. - 13:1(2023), p. 120. [10.1038/s41398-023-02406-5]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1677557
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 15
social impact