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Relationships between sleep and addiction Enviar correspondencia a: Francesca Cañellas, Servei de Psiquiatria. Hospital Universitari Son Espases, C/Valldemosa n° 79. 07010 Palma de Mallorca. Cbd Para Dormir Dosis Cbd Hemp Oil For Als – Mister ToolBag Most Effective cbd para dormir dosis Mister ToolBag cbd and plavix Facts About Cbd. A voice cbd para dormir dosis Rewind

Relationships between sleep and addiction

Enviar correspondencia a: Francesca Cañellas, Servei de Psiquiatria. Hospital Universitari Son Espases, C/Valldemosa n° 79. 07010 Palma de Mallorca. España, [email protected] – Tel: +34871206673

Resumen

La interacción entre los trastornos del sueño y el abuso de sustancias es ya conocida, pero seguramente más compleja de lo que se pensaba. Existe tanto una relación positiva entre tener un trastorno por uso de substancias y sufrir un trastorno de sueño, como viceversa. Los efectos sobre el sueño dependen de la substancia utilizada, pero se ha demostrado que tanto durante su uso como en período de abstinencia los consumidores tienen diferentes problemas de sueño y fundamentalmente un sueño más fragmentado. Sabemos que hay que tener en cuenta los problemas de sueño para evitar recaídas en la adicción.

Investigaciones recientes indican que el sistema hipocretinérgico definido por el neuropéptido hipocretina/orexina (Hcrt/ox), localizado en el hipotálamo lateral e implicado entre otros en la regulación del ciclo sueño-vigilia, jugaría un papel importante en las conductas adictivas. Diferentes estudios han demostrado interacciones entre el sistema hipocretinérgico, los circuitos de respuesta aguda al estrés y los sistemas de recompensa. También sabemos que la activación optogenética selectiva del sistema hipocretinérgico incrementa la probabilidad de la transición del sueño a la vigilia, y también es suficiente para iniciar un comportamiento compulsivo de recaída adictiva. La activación del sistema hipocretinérgico podría explicar la hipervigilia asociada al estrés y a la adicción. El mayor conocimiento de esta interacción permitiría entender mejor los mecanismos de la adicción y encontrar nuevas estrategias para el tratamiento de las adicciones.

Abstract

While it is well known that there is an interaction between sleep disorders and substance abuse, it is certainly more complex than was previously thought. There is a positive relationship both between having a substance use disorder and suffering from a sleep disorder, and vice versa. The effects on sleep depend on the substance used, but it has been shown that both during use and in withdrawal periods consumers have various sleep problems, and basically more fragmented sleep. We know that sleep problems must be taken into account to prevent addiction relapses.

Recent research shows that the hypocretinergic system defined by neuropeptide hypocretin/orexin (Hcrt/ox), located in the lateral hypothalamus and involved in, among other things, the regulation of the sleep-wake cycle, may play an important role in addictive behaviors. Different studies have demonstrated interactions between the hypocretinergic system, acute response to stress circuits and reward systems. We also know that selective optogenetic activation of the hypocretinergic system increases the probability of transition from sleep to wakefulness, and is sufficient for initiating an addictive compulsive behavior relapse. Hypocretinergic system activation could explain the hyperarousal associated with stress and addiction. Improved knowledge of this interaction would help us to understand better the mechanisms of addiction and find new strategies for the treatment of addictions.

La interacción entre los trastornos del sueño y el abuso de sustancias es compleja. Hasta hace poco conocíamos una relación bidireccional positiva entre el riesgo de tener un trastorno por uso de substancias y sufrir un trastorno de sueño: las personas con abuso o dependencia de sustancias tienen mayor prevalencia de alteraciones del sueño y las que presentan alteraciones del sueño tienen mayor riesgo de presentar problemas relacionados con el uso de sustancias que la población general (Cañellas et al., 1998; Ford y Kamerow, 1989).

Investigaciones recientes apuntan que la interacción entre adicciones y niveles de vigilancia es más compleja. El ciclo vigilia sueño esta regulado por un conjunto de redes neuronales que controlan diferentes aspectos de la transición entre los diferentes estados de vigilancia. En concreto, el sistema definido por el neuropéptido hipocretina/orexina (Hcrt/ox), localizado en el hipotálamo lateral (de Lecea et al., 1998; Sakurai et al., 1998), juega un papel crucial en la estabilidad del ciclo, ya que su deficiencia da lugar a la narcolepsia con cataplejía (Hungs y Mignot 2001). El sistema Hcrt está implicado en el control de numerosas variables, como el estado metabólico, ritmo circadiano, duración previa del sueño, niveles de estrés, etc. y transmite esta información de forma integrada a otros circuitos esenciales para el mantenimiento de la vigilia (Sutcliffe y de Lecea, 2002).

La implicación tan significativa del sistema hipocretinérgico en la vigilia llevó a la hipótesis de un posible papel de este circuito en la hipervigilia asociada al estrés y la adicción, como describiremos más adelante.

Acción de las principales drogas sobre el sueño

En el estudio ECA (Ford y Kamerow, 1989) se describió que los pacientes que referían preocupaciones sobre el sueño tenían un riesgo relativo 2.32 veces mayor de desarrollar problemas relacionados con el alcohol, detectándose especialmente en los que presentaban historia de ansiedad y disforia. Aunque también se ha descrito esta relación con otras sustancias, la mayoría de los estudios han sido realizados en alcohólicos (Irwin et al. 2006). El insomnio, en la adolescencia, está relacionado con el desarrollo posterior de trastornos mentales, asociándose al uso de alcohol, cannabis, otras drogas, depresión y a ideas e intentos de suicidio. Además, el insomnio es más frecuente en los adolescentes, que fuman, beben y duermen menos tiempo durante el fin de semana (Roane et al., 2008).

Aunque las acciones sobre el sueño dependen de la droga consumida, y el objetivo de esta editorial no es repasar detalladamente cuales son específicamente estas alteraciones, nos detendremos a señalar algunas que son características y frecuentes, debido a su importancia en el manejo de los pacientes con trastorno del uso de substancias.

La mayoría de estudios se han realizado con el alcohol, que es el ansiolítico e hipnótico más ampliamente utilizado en el mundo occidental desde hace milenios. En consumo agudo esta sustancia ejerce un efecto inductor del sueño, pero en consumo continuado deteriora su calidad, problema que se agrava todavía más durante el periodo de abstinencia. A dosis bajas, como podría ser el consumo social reconocido como “normal” en los países latinos, con unos niveles plasmáticos de alcohol bajos, no tiene claros efectos sobre la arquitectura del sueño. A dosis más altas produce un efecto similar al de un hipnótico de acción corta: disminuye la latencia de sueño, así como los despertares, la fase de sueño 1 y la densidad de movimientos oculares rápidos (REM) en la primera mitad de la noche; mientras que en la segunda mitad se aprecian fenómenos de rebote con aumento de la fase de sueño 1, aumento de despertares y un incremento de sueño REM. En pacientes alcohólicos crónicos, se ha encontrado una disminución del sueño lento profundo, del sueño REM y un sueño más fragmentado. Durante la fase de abstinencia estas alteraciones se agravan. Los sujetos duermen menos, el sueño está más fragmentado y tienen una disminución del sueño lento, mientras que la duración del REM y la densidad de los movimientos oculares rápidos están incrementadas (Brower et al., 2011). De hecho, uno de los factores de recaída en el consumo de alcohol, tras un periodo de abstinencia puede ser la persistencia de alteraciones del sueño. Por ello se recomienda dar inductores del sueño durante la fase de abstinencia aguda y, si el insomnio persiste, utilizar antidepresivos sedativos como la trazodona, para mejorar la calidad de sueño y prevenir las recaídas (Kolla et al 2011).

En un trabajo reciente, realizado por el equipo de Roncero (2011) en una unidad de desintoxicación, se resumen los diferentes efectos sobre el sueño de diferentes substancias y en periodo de abstinencia. Los estimulantes disminuyen la sensación de necesidad sueño, en muchas ocasiones los pacientes no tienen la percepción subjetiva de alteración del sueño o sueño no reparador. La cocaína tiene un efecto euforizante sobre el ánimo, disminuye el tiempo total del sueño y altera su continuidad. Durante el periodo de abstinencia o disminución del consumo regular, aumenta el tiempo total de sueño y la somnolencia diurna.

El consumo de cannabis a dosis altas disminuye el sueño REM y el sueño de ondas lentas. El uso de cannabis también se relaciona con el aumento del número de movimientos periódicos de las extremidades durante el sueño y sueño más fragmentado. La abstinencia de cannabis reduce la calidad del sueño, aumenta la latencia y produce sueños extraños. La abstinencia después de la exposición de 4–5 cigarrillos/día, incluso tras un período corto, se ha asociado con aumento de la latencia y de la fase REM.

Los opioides producen reacciones de alertamiento dependientes de la dosis, con aumento de la actividad muscular medida en el EMG y de los movimientos corporales. El EEG muestra un aumento de la actividad alfa, y una disminución de las fases de sueño lento profundo y del sueño REM. Los sujetos en tratamiento agudo con metadona, refieren dormir mejor. Muestran un discreto aumento del sueño lento profundo y una disminución de las frecuencias EEG rápidas durante el sueño. Durante la fase de administración crónica de metadona el sueño nocturno no esta alterado, aunque un porcentaje de pacientes refiere insomnio de conciliación y mantenimiento. Durante las primeras 3–5 semanas de abstinencia los sujetos refieren un aumento de la actividad onírica e insomnio. Durante la abstinencia de opiáceos en dependientes, aumentan los sueños y la fase REM y delta. Tras la retirada, se describe un periodo de insomnio de varias semanas de duración. El insomnio persistente puede provocar una recaída en el consumo de heroína.

Relación Entre Los Circuitos Neuronales de Recompensa y Ciclo Vigilia/Sueño

Estudios neuroanatómicos y electrofisiológicos han demostrado interacciones entre el sistema hipocretinérgico y los circuitos de respuesta aguda al estrés (Winsky-Sommerer et al., 2004). Asimismo, estudios en ratas demostraron que la aplicación farmacológica de Hcrt-1 era suficiente para inducir una recaída adictiva (Boutrel et al., 2005). Una literatura ya abundante demuestra que, en efecto, existe una importantísima relación entre el sistema hipocretinérgico con el sistema dopaminérgico mesocorticolímbico. También contribuyen a esta interacción con los sistemas de recompensa, los circuitos hipotalámicos adyacentes (p.ej, neuronas que contienen MCH (hormona concentradora de melanina), neurotensina o sensibles a leptina (lepRB).

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Recientemente estudios optogenéticos en roedores han permitido establecer relaciones causales entre la actividad de circuitos neuronales y comportamientos complejos. Así, la activación optogenética selectiva del sistema hipocretinérgico, incrementa la probabilidad de la transición del sueño a la vigilia (Adamantidis el al., 2007), y también es suficiente para iniciar un comportamiento compulsivo de recaída adictiva. Como decíamos en los apartados anteriores, la literatura ha revelado numerosas asociaciones entre el abuso de drogas y deficiencias clínicas en la arquitectura del sueño. Por otra parte, varios estudios clínicos han mostrado que los pacientes narcolépticos deficientes en Hcrt, que reciben dosis frecuentes de psicoestimulantes (anfetaminas, metilfenidato o modafinil) para el tratamiento de la somnolencia diurna excesiva, son relativamente resistentes a la adicción.

El papel del sistema hipocretinérgico en la adicción sería el de actuar conjuntamente con el sistema dopaminérgico y añadir un valor positivo a la recompensa (de Lecea et al., 2006). La activación del sistema dopaminérgico puede tener consecuencias en el papel de las neuronas hipocretinérgicas durante el sueño, ya que controlan la generación del ritmo theta en el hipocampo y facilitan las transiciones sueño vigilia. Esto explicaría porqué los pacientes adictos muestran un sueño fragmentado con múltiples despertares nocturnos.

Además de la interacción Hcrt-dopamina, hay otros circuitos compartidos entre la regulación del estado de vigilia y la recompensa cerebral. En concreto, la actividad del sistema noradrénergico del locus coeruleus, esta altamente correlacionada con los estados de vigilia e inversamente proporcional al sueño (Aston-Jones y Shipley, 1987). También el sistema serotonérgico es importante para la regulación de la entrada en sueño REM, y contribuye de forma notable como neuromodulador en el estado de animo en general y en conductas adictivas.

Cabe señalar que el ciclo vigilia sueño se manifiesta a través cambios de actividad globales de la corteza cerebral en el electroencefalograma. Además, los circuitos de motivación y recompensa convergen en la corteza prefrontal. Así pues también hay mecanismos de control “bottom-up” que comparten las transiciones de sueño a vigilia y las de vigilia a hipervigilia. Es de esperar que cuando se establezcan nuevas implicaciones de circuitos neuronales en el comportamiento adictivo, se revelen también nuevas asociaciones con las redes neuronales responsables de la regulación del ciclo de sueño vigilia. El mayor conocimiento de esta interacción permitiría entender mejor los mecanismos de la adicción y encontrar nuevas estrategias para el tratamiento de las adicciones (Plaza-Zabala, Maldonado y Berrendero 2012).

Footnotes

Conflicto de intereses

Los autores declaran no tener ningún conflicto de intereses en esta publicación.

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Then, he knew that his life was saved by this young man, he turned over and climbed up, first bowed to Bai Gang, then turned to Liu Kunshan and said, Is this old brother a friend of Brother Liu Liu Kunshan couldn t help cbd para dormir dosis his ears warm, and said We have met several times cannabis tea bags Liu Cbd Ground Coffee cbd and plavix Fengwu also got up and gave Bai Gang a cbd para dormir dosis deep bow Thanks cbd para dormir dosis to Brother Tian s potent cbd oil rescue, Cbd Ground Coffee cbd and plavix I will be under Yongzhi Bai Gang hurriedly returned the bow and smiled Brother Liu is wrong.

With How To Make Cbd Oil cbd para dormir dosis a sound, cbd para dormir dosis Charlot Webs Cbd Oil Free Trial he swooped forward, and with a single stroke of Snow Mud Claws ,the swords and palms were thrown together, hitting Kong Liang in front of him.

Shan Hui said happily I guessed it right The cbd para dormir dosis pits that have already been bombed will not be bombed again, Bai Lang You lie here, I ll go over there Bai Lang suddenly realized, all the grudges were eliminated, he clasped his arms anxiously, and said with a wry smile, There is no need to pass, I hope death can be at the cbd and plavix In 2020 same point Shan Huixin was shocked when she heard it, but she was so happy that tears fell.

Ge Yunshang laughed and said, What are you thinking about Don t drink ginseng soup first, then drink gruel, and then eat steamed cbd para dormir dosis Medicinal Benefits Of Cbd buns to eat vegetables, so as not to hurt the stomach.

In an instant, the palms were handed over, and the thunder that broke the sky and the ground sounded, and the swords clashed into a wonderful music.

It can be cbd para dormir dosis seen that even if someone lived there, that person has already left.

If you don t want to frame us, you might cbd para dormir dosis cbd para dormir dosis as well go after breakfast What kind of name do you use Bai Gang thought for a while and said, Although I How To Make Cbd Oil cbd para dormir dosis want to see Kong Liang for something, but I don t know each other, I want to use the reputation of the Taoist priest to ask for advice, and then state my intention.

He walked out of the back garden and reached a cliff thousands of feet.

Looking closer, the man looks like an old man with five strands of long Cbd Ground Coffee cbd and plavix beard, wearing a Han Dynasty robe, sitting cross legged on a futon.

Seeing her full of filial attire, Bai Gang couldn t help but secretly surprised and said, Who is she wearing filial piety for Could it be cbd para dormir dosis that the Tongtian Poison Dragon is dead Hearing her mournful cbd and plavix In 2020 voice again It s been a hundred days since you fell.

Hu Yanniang cbd edibles gummies suddenly raised her head and said sadly I have become like this, and I have already planned to refuse the world.

Bai Gang hurriedly straightened her up and said softly, Your injury is serious, cbd para dormir dosis don t be angry yet, it s important to concentrate on breathing He cbd para dormir dosis paused, feeling that he should heal her, and continued cbd and plavix to ask Said Would you Can I help you to get through your qi and menstruation When he mentioned the injury, Tian Hong s anger was hard to dissipate, and he spat You have such a good intention, why do you stand by and don t come to rescue Bai zatural cbd oil reviews Gang was already low pitched, and he Cbd Ground Coffee cbd and plavix was still a little cbd para dormir dosis annoyed by her, but in retrospect, it was inevitable that he was negligent, so he had to explain It s my fault, but it wasn t intentional, don t take offense, Let me first Tian Hong became even more irritated when she saw that he was being honest, and shouted You go Just ignore me Bai Gang gently put her sword back into the sword pin for her, put his mouth in her ear, and said softly, Sister Hong Can t you forgive me too After talking for a long time, he didn t see How To Make Cbd Oil cbd para dormir dosis the other party s answer.

Facing the intersection, there is a stone tablet engraved with five characters Home of the Dugu Weng ,and on the side of the characters Do not enter unless you do, How To Make Cbd Oil cbd para dormir dosis those who trespass will die, if you dare not believe it, but please give it cbd para dormir dosis Medicinal Benefits Of Cbd a try.

If you look back and move, you have to say thank you if you dare Bai Gang asked in surprise, Who are you talking about Ge empire cbd crystals Yunshang looked up at the sky and said coldly, Why do you need to admit that you don t want to young living cbd oil release date admit it yourself I m nosy I never got you She suddenly felt that there was something wrong with her words, and the red cloud rose up, and she how many grams should a person take for pain relieve of cbd oil lowered her head to peek at everyone.

When he mentioned his name, Huangfu Bixia suddenly became jealous, Bah ,and scolded You shameless Hu Meizi, do you think that by pretending like this, you can take on the reputation of a filial lupus and cbd daughter and move your aunt Get your sword back, grandma wants you to die Mister ToolBag cbd para dormir dosis Shan Huixin has been spoiled since she was a child, and she is arrogant to instruct cbd para dormir dosis others, but she is kind hearted.

Meng Bulijiao, traversing the south of the Yangtze River, never met an opponent, and was called the Dragon and Tiger Double Heroes by the people at that time.

Unexpectedly, Your Excellency treats Cbd Ground Coffee cbd and plavix you as a guest The old man tore his hoarse voice. Hehe smiled and said The old man is Kong Liang, and the offense was just out of negligence.

It turned out that everything was just a dream of Nanke.

Ge Yunshang shot into the air with a hammer, and felt that the cold light was dazzling again.

Grandma Feng Xue scolded him after eating him, but she thought back to her heart This kid is still cbd para dormir dosis kind, and Daan Lai is not from Lingyun s sect, but when it comes to the Han Dynasty, there is still a unique martial arts A Zhu Teng Cuiguo is worth 30 years of skill a white plum spirit fruit is worth three Jiazi s skill combined with two elixir, isn t it twice as powerful as my mother in law s scented oils for bath bombs skill She pondered doubtfully for a moment.

Go to cbd and plavix In 2020 the New Year to Laozi is cbd pure hemp oil good for essential tremors Yan Bai Gang saw a shop owner, and he didn t greet the guests kindly.

Both of them were in their forties and fifties.

He reluctantly asked The Taoist priest stayed at the gate of the Confucius Temple, saying that Bai Gang was here, where did he go now, is it What happened again Huangfu Bixia was the first to tell Bai Gang s loss.

The bones of the Holy Hand of cbd para dormir dosis Thousand Poisons were able to etch iron with fossils, cbd para dormir dosis but were destroyed by a puff of green smoke.

Fang Hui took the antidote and the small hammer, and said, Thank you As soon as she arrived in front of the room, she heard the voices of how many mg of thc is in 1500 mg cbd oil men Mister ToolBag cbd para dormir dosis and women talking in the room.

He thought that Uncle Hu was just a temporary feeling.

It s over But he was raising his palms to fight, but the drunken beggar in Shenzhou rushed over cbd para dormir dosis and shouted Don t kill him, the culprit has not yet been determined, he must be kept alive Jie Dao Junior obeys orders, but I m afraid that I cbd para dormir dosis won t be able to find him in the future Shenzhou drunk beggar laughed and said Let s do things to convince others and die without resentment, let him go now, and ask me for someone in the future.

Unexpectedly, on the night that my elder sister in law gave cbd para dormir dosis birth to Bai Gang, she immediately gave up and returned to the west.

The man s hands were not cbd and plavix weak, and when he saw the slap, he hurriedly dodged to avoid it, but his cheeks were still covered by cbd para dormir dosis the palm wind.

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