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2025, Número 6

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Rev Fac Med UNAM 2025; 68 (6)


Los endocannabinoides y las orexinas en la modulación del ciclo vigilia-sueño y del abuso de sustancias (Segunda de dos partes)

Ostos VA, Daval MLV, Gómez VJP, Méndez DM, Herrera SA, Ruiz CAE, Prospero GGOE

Idioma: Español
Referencias bibliográficas: 89
Paginas: 8-24
Archivo PDF: 396.58 Kb.


RESUMEN

Los trastornos del sueño son altamente prevalentes entre personas con trastorno por uso de sustancias (TUS). Se ha reportado que aproximadamente siete de cada diez pacientes que ingresan a tratamiento por desintoxicación presentan dificultades para dormir y que una proporción similar de los usuarios de drogas consume como forma de automedicación para regular el ciclo sueño-vigilia. Este trastorno, además de afectar la calidad de vida, incrementa la vulnerabilidad a la recaída y la severidad del TUS. En México, el alcohol es la sustancia de abuso más consumida (más del 70 % de la población), mientras que, a nivel mundial, la marihuana es la droga ilícita de mayor uso, con 219 millones de consumidores reportados en 2021. De ahí la importancia, a nivel mexicano y mundial, de profundizar en la relación entre las disfunciones del sueño y los TUS, analizando los procesos neurobiológicos que las vinculan, entre ellos los regulados por los sistemas orexinérgico y endocannabinoide.
Este trabajo constituye la segunda parte de un análisis integral sobre los sistemas neurobiológicos que vinculan la regulación del sueño con la vulnerabilidad al consumo de drogas. En la primera parte se abordó la relevancia del ciclo sueño-vigilia, mediado por factores homeostáticos (Proceso S) y circadianos (Proceso C), así como la participación de diversos neurotransmisores. En esta segunda parte se profundiza en el papel del sistema endocannabinoide y del sistema de hipocretinas/orexinas en la regulación del sueño y su relación con los mecanismos de reforzamiento y adicción.
Tanto las orexinas como los endocannabinoides modulan los circuitos de motivación y recompensa, implicados en el consumo de alcohol, opioides y psicoestimulantes. Además, ambos sistemas participan activamente en la regulación del ciclo sueño-vigilia. La activación del sistema orexinérgico promueve la vigilia, mientras que su disfunción se ha asociado con narcolepsia. Por otro lado, se ha observado que la alteración del sistema endocannabinoide, generada por el consumo crónico de cannabis, produce trastornos del sueño que se mantienen incluso durante la abstinencia. La evidencia experimental en modelos murinos demuestra que antagonizar los receptores OX1R/OX2R o bloquear los receptores CB1R reduce la búsqueda y la recaída al consumo de drogas. Por ello, la modulación farmacológica de estos sistemas se plantea como una estrategia prometedora para tratar los trastornos del sueño y mejorar los resultados de rehabilitación en pacientes con TUS.


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