La adicción es un trastorno neuropsicológico que se caracteriza por un deseo persistente e intenso de consumir una droga o de participar en una conducta que produce una recompensa natural, a pesar del daño sustancial y otras consecuencias negativas. El consumo repetitivo de drogas suele alterar la función cerebral de manera que perpetúa el ansia y debilita (pero no anula por completo) el autocontrol . [1] Este fenómeno (las drogas que reconfiguran la función cerebral ) ha llevado a entender la adicción como un trastorno cerebral con una variedad compleja de factores psicosociales y neurobiológicos (y, por lo tanto, involuntarios) [a] que están implicados en el desarrollo de la adicción. [2] [3] [4]
Los signos clásicos de adicción incluyen la participación compulsiva en estímulos gratificantes , la preocupación por sustancias o conductas y el consumo continuo a pesar de las consecuencias negativas. Los hábitos y patrones asociados con la adicción se caracterizan típicamente por una gratificación inmediata (recompensa a corto plazo), [5] [6] junto con efectos nocivos retardados (costos a largo plazo). [3] [7]
Entre los ejemplos de adicción a sustancias se incluyen el alcoholismo , la adicción al cannabis , la adicción a las anfetaminas , la adicción a la cocaína , la adicción a la nicotina , la adicción a los opioides y la adicción a la comida o a la alimentación . Las adicciones conductuales pueden incluir la adicción al juego , la adicción a las compras , el acoso , la adicción a Internet , la adicción a las redes sociales , el trastorno obsesivo-compulsivo , la adicción a los videojuegos y la adicción sexual . El DSM-5 y el CIE-10 solo reconocen las adicciones al juego como adicciones conductuales, pero el CIE-11 también reconoce las adicciones al juego. [8]
Definiciones
" Adicción " y " conducta adictiva " son polisemas que denotan una categoría de trastornos mentales , de síntomas neuropsicológicos o de hábitos y estilos de vida meramente desadaptativos /dañinos . [9] Un uso común de "adicción" en medicina es para los síntomas neuropsicológicos que denotan impulsos generalizados/excesivos e intensos de participar en una categoría de compulsiones o impulsos conductuales hacia recompensas sensoriales (por ejemplo , alcohol , betel quid , drogas, sexo, juegos de azar, videojuegos). [10] [11] [12] [ 13] [14] Los trastornos adictivos o trastornos de adicción son trastornos mentales que implican altas intensidades de adicciones (como síntomas neuropsicológicos) que inducen discapacidades funcionales (es decir, limitan las actividades sociales/familiares y ocupacionales de los sujetos); las dos categorías de tales trastornos son las adicciones al uso de sustancias y las adicciones conductuales . [15] [9] [13] [14]
El DSM-5 clasifica la adicción como la etapa más grave del trastorno por consumo de sustancias, debido a la pérdida significativa de control y la presencia de conductas compulsivas a pesar del deseo de dejar de consumirlas. [16] Es una definición que utilizan muchos artículos e informes científicos. [17] [18] [19]
La " dependencia " es también un polisema que denota síntomas neuropsicológicos o trastornos mentales. En el DSM-5, las dependencias difieren de las adicciones e incluso pueden ocurrir normalmente sin adicciones; [20] además, las dependencias por consumo de sustancias son etapas graves de las adicciones por consumo de sustancias (es decir, trastornos mentales) que implican problemas de abstinencia . [21] En la CIE-11, "dependencia por consumo de sustancias" es un sinónimo de "adicción por consumo de sustancias" (es decir, síntomas neuropsicológicos) que pueden, pero no necesariamente, implicar problemas de abstinencia. [22]
Adicción a sustancias
Adicción a las drogas
La adicción a las drogas , que pertenece a la clase de trastornos relacionados con sustancias , es un trastorno cerebral crónico y recurrente que presenta la búsqueda y el abuso de drogas, a pesar de sus efectos nocivos. [25] Esta forma de adicción cambia los circuitos cerebrales de tal manera que el sistema de recompensa del cerebro se ve comprometido, [26] causando consecuencias funcionales para el manejo del estrés y el autocontrol. [25] El daño a las funciones de los órganos involucrados puede persistir durante toda la vida y causar la muerte si no se trata. [25] Las sustancias involucradas en la adicción a las drogas incluyen alcohol, nicotina, marihuana, opioides, cocaína, anfetaminas e incluso alimentos con alto contenido de grasa y azúcar. [27] Las adicciones pueden comenzar experimentalmente en contextos sociales [28] y pueden surgir del uso de medicamentos recetados o una variedad de otras medidas. [29]
Se ha demostrado que la adicción a las drogas funciona en los modelos fenomenológicos , de condicionamiento ( operante y clásico ), cognitivos y en el modelo de reactividad ante señales . Sin embargo, ningún modelo ilustra completamente el abuso de sustancias. [30]
Los factores de riesgo de adicción incluyen:
- Comportamiento agresivo (particularmente en la infancia)
- Disponibilidad de sustancia [28]
- Situación económica de la comunidad
- Experimentación [28]
- Epigenética
- Impulsividad (atencional, motora o no planificada) [31]
- Falta de supervisión de los padres [28]
- Falta de habilidades de rechazo por parte de los compañeros [28]
- Trastornos mentales [28]
- Método en el que se toma la sustancia [25]
- Consumo de sustancias en jóvenes [28]
Adicción a la comida
Los criterios de diagnóstico para la adicción a la comida o a la alimentación no se han categorizado ni definido en referencias como el Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM o DSM-5) y se basan en experiencias subjetivas similares a los trastornos por consumo de sustancias. [32] [31] La adicción a la comida se puede encontrar en personas con trastornos alimentarios, aunque no todas las personas con trastornos alimentarios tienen adicción a la comida y no todas las personas con adicción a la comida tienen un trastorno alimentario diagnosticado. [32] El consumo frecuente y excesivo a largo plazo de alimentos con alto contenido en grasas, sal o azúcar, como el chocolate, puede producir una adicción [33] [34] similar a las drogas, ya que activan el sistema de recompensa del cerebro, de modo que el individuo puede desear los mismos alimentos en un grado creciente con el tiempo. [35] [32] [31] Las señales enviadas al consumir alimentos muy palatables tienen la capacidad de contrarrestar las señales del cuerpo de saciedad y se producirán antojos persistentes. [35] Aquellos que muestran signos de adicción a la comida pueden desarrollar tolerancias alimentarias, en las que comen más, a pesar de que la comida se vuelve menos satisfactoria. [35]
Se sabe que el dulce sabor del chocolate y sus ingredientes farmacológicos crean un fuerte deseo o una sensación de "adicción" en el consumidor. [36] Una persona que tiene un fuerte gusto por el chocolate puede referirse a sí misma como un adicto al chocolate .
Los factores de riesgo para desarrollar adicción a la comida incluyen comer en exceso y la impulsividad. [31]
La Escala de Adicción a la Comida de Yale (YFAS), versión 2.0, es la medida estándar actual para evaluar si un individuo exhibe signos y síntomas de adicción a la comida. [37] [32] [31] Fue desarrollada en 2009 en la Universidad de Yale sobre la hipótesis de que los alimentos altos en grasa, azúcar y sal tienen efectos similares a los adictivos que contribuyen a hábitos alimentarios problemáticos. [38] [35] La YFAS está diseñada para abordar 11 trastornos adictivos y relacionados con sustancias (SRAD) utilizando un cuestionario de autoinforme de 25 ítems, basado en los criterios de diagnóstico para SRAD según el DSM-5. [39] [32] Un posible diagnóstico de adicción a la comida se predice por la presencia de al menos dos de 11 SRAD y un deterioro significativo en las actividades diarias. [40]
Se ha demostrado que la Escala de Impulsividad de Barratt , específicamente la escala BIS-11, y las subescalas de Conducta Impulsiva de Urgencia Negativa y Falta de Perseverancia de la UPPS-P tienen relación con la adicción a la comida. [31]
Adicción conductual
El término adicción conductual se refiere a una compulsión a participar en una recompensa natural , que es un comportamiento que es inherentemente gratificante (es decir, deseable o atractivo), a pesar de las consecuencias adversas. [6] [33] [34] La evidencia preclínica ha demostrado que los aumentos marcados en la expresión de ΔFosB a través de la exposición repetida y excesiva a una recompensa natural inducen los mismos efectos conductuales y neuroplasticidad que ocurren en una adicción a las drogas. [33] [41] [42] [43]
La adicción puede existir en ausencia de drogas psicotrópicas, lo que fue popularizado por Peele. [44] Estas se denominan adicciones conductuales. Estas adicciones pueden ser pasivas o activas, pero comúnmente contienen características de refuerzo, que se encuentran en la mayoría de las adicciones. [44] La conducta sexual, comer, apostar, jugar videojuegos y comprar están asociados con conductas compulsivas en humanos y se ha demostrado que activan la vía mesolímbica y otras partes del sistema de recompensa. [33] Con base en esta evidencia, la adicción sexual , la adicción al juego , la adicción a los videojuegos y la adicción a las compras se clasifican en consecuencia. [33 ]
Sexual
La adicción sexual implica una participación en un comportamiento sexual excesivo, compulsivo o problemático que persiste a pesar de las consecuencias fisiológicas, psicológicas, sociales y ocupacionales negativas. [45] La adicción sexual puede denominarse hipersexualidad o trastorno de conducta sexual compulsiva . [45] El DSM-5 no reconoce la adicción sexual como un diagnóstico clínico. El trastorno de hipersexualidad y el trastorno de adicción a Internet estaban entre las adicciones propuestas en el DSM-5, pero luego fueron rechazados debido a la evidencia insuficiente disponible en apoyo de la existencia de estos trastornos como condiciones de salud mental discretas. [46] Las revisiones de la investigación clínica en humanos y los estudios preclínicos que involucran ΔFosB han identificado la actividad sexual compulsiva, específicamente, cualquier forma de relación sexual , como una adicción (es decir, adicción sexual). [33] [41] Se ha demostrado que la sensibilización cruzada de recompensa entre la anfetamina y la actividad sexual, lo que significa que la exposición a una aumenta el deseo por ambas, ocurre como un síndrome de desregulación de la dopamina . [33] [41] [42] [43] La expresión de ΔFosB es necesaria para este efecto de sensibilización cruzada, que se intensifica con el nivel de expresión de ΔFosB. [33] [42] [43]
Juego
El juego proporciona una recompensa natural que se asocia con el comportamiento compulsivo. [33] La evidencia de neuroimagen funcional muestra que el juego activa el sistema de recompensa y la vía mesolímbica en particular. [33] Se sabe que la dopamina está involucrada en el aprendizaje, la motivación, así como en el sistema de recompensa. [47] [26] Se ha debatido el papel exacto de la dopamina en la adicción al juego. [47] Se han encontrado roles sugeridos para los receptores de dopamina D2 , D3 y D4 , así como para los receptores D3 en la sustancia negra en modelos de ratas y humanos, mostrando una correlación con la gravedad del comportamiento de juego. [47] Esto a su vez se relacionó con una mayor liberación de dopamina en el estriado dorsal . [47]
Las adicciones al juego están relacionadas con comorbilidades como trastornos de salud mental , abuso de sustancias , trastorno por consumo de alcohol y trastornos de la personalidad . [48]
Los factores de riesgo para la adicción al juego incluyen el comportamiento antisocial, la personalidad impulsiva, [31] el sexo masculino, la búsqueda de sensaciones, [49] el consumo de sustancias y la edad joven.
La adicción al juego se ha asociado con algunos rasgos de personalidad, entre ellos: evitación del daño, baja autodirección, insuficiencias en la toma de decisiones y planificación, impulsividad, así como individuos que buscan sensaciones. [49] Aunque algunos rasgos de personalidad pueden estar relacionados con la adicción al juego, no existe una descripción general de los individuos adictos al juego. [49]
Internet
La adicción a Internet no tiene una definición estandarizada, pero hay un amplio consenso en cuanto a la existencia de este problema. [50] El debate sobre la clasificación del uso problemático de Internet considera si debe considerarse una adicción conductual, un trastorno del control de los impulsos o un trastorno obsesivo-compulsivo. [51] [52] Otros sostienen que la adicción a Internet debe considerarse un síntoma de una condición de salud mental subyacente y no un trastorno en sí mismo. [53] La adicción a Internet se ha descrito como "una dependencia psicológica de Internet, independientemente del tipo de actividad una vez que se ha iniciado sesión". [50] El uso problemático de Internet puede incluir una preocupación por Internet y/o los medios digitales, un tiempo excesivo de uso de Internet a pesar de la angustia resultante en el individuo, un aumento en la cantidad de uso de Internet necesaria para lograr la misma respuesta emocional deseada, pérdida de control sobre los propios hábitos de uso de Internet, síntomas de abstinencia y un uso problemático continuo de Internet a pesar de las consecuencias negativas para la vida laboral, social, académica o personal. [54]
Estudios realizados en India, Estados Unidos, Asia y Europa han identificado tasas de prevalencia de adicción a Internet que varían en valor desde 1% a 19%, con la población adolescente teniendo tasas altas en comparación con otros grupos de edad. [55] [56] Las tasas de prevalencia han sido difíciles de establecer debido a la falta de criterios de diagnóstico universalmente aceptados, la falta de instrumentos de diagnóstico que demuestren validez y confiabilidad transculturales y la controversia existente en torno a la validez de etiquetar el uso problemático de Internet como un trastorno adictivo. [57] [56] La escala más común utilizada para medir la adicción es la Prueba de Adicción a Internet desarrollada por Kimberly Young . [56]
Las personas con adicción a Internet probablemente tengan un trastorno psiquiátrico comórbido. Los diagnósticos comórbidos identificados junto con la adicción a Internet incluyen trastornos del estado de ánimo afectivo, trastornos de ansiedad, trastornos por consumo de sustancias y trastorno por déficit de atención con hiperactividad. [57]
Juegos de vídeo
La adicción a los videojuegos se caracteriza por la Organización Mundial de la Salud (OMS) como una conducta de juego excesiva, potencialmente priorizada sobre otros intereses, a pesar de las consecuencias negativas que pueden surgir, durante un período de al menos 12 meses. [58] En mayo de 2019, la OMS introdujo el trastorno del juego en la 11.ª edición de la Clasificación Internacional de Enfermedades. [59] Se ha demostrado que la adicción a los videojuegos es más frecuente en hombres que en mujeres, 2,9 veces más. [60] Se ha sugerido que las personas de edades más jóvenes son más propensas a volverse adictas a los videojuegos. [60] Las personas con determinadas personalidades pueden ser más susceptibles a las adicciones a los juegos. [60] [61]
Los factores de riesgo de la adicción a los videojuegos incluyen:
- Masculino,
- Psicopatologías (por ejemplo, TDAH o TDM), y
- Ansiedad social. [62]
Compras
La adicción a las compras, o trastorno de compra compulsiva (TCC), es la necesidad excesiva de comprar o gastar, lo que puede tener consecuencias no deseadas. [63] Estas consecuencias pueden tener graves repercusiones, como un mayor endeudamiento del consumidor , relaciones afectadas negativamente, mayor riesgo de comportamiento ilegal e intentos de suicidio. [63] La adicción a las compras se produce en todo el mundo y ha mostrado una prevalencia del 5,8% en los Estados Unidos. [64] De forma similar a otras adicciones conductuales, el TCC puede estar relacionado con trastornos del estado de ánimo, trastornos por consumo de sustancias, trastornos alimentarios y otros trastornos que implican una falta de control. [64]
Signos y síntomas
Los signos y síntomas de la adicción pueden variar según el tipo de adicción. Los síntomas de la adicción a las drogas pueden incluir:
- Continuación del consumo de drogas a pesar del conocimiento de las consecuencias [32]
- No tener en cuenta la situación financiera a la hora de comprar medicamentos
- Garantizar un suministro estable del medicamento
- Experimentar síntomas de abstinencia al dejar de tomar el medicamento [65] [32]
- Necesidad de una mayor cantidad del fármaco a lo largo del tiempo para lograr efectos similares [32]
- La vida social y laboral se ve afectada por el consumo de drogas [32]
- Intentos fallidos de dejar el consumo de drogas [32]
- Necesidad de consumir drogas regularmente
Los signos y síntomas de la adicción pueden incluir:
Detección y evaluación
Evaluación neuroclínica de adicciones
La evaluación neuroclínica de adicciones se utiliza para diagnosticar trastornos de adicción. Esta herramienta mide tres dominios diferentes: función ejecutiva , prominencia de incentivos y emocionalidad negativa . [67] [68] El funcionamiento ejecutivo consiste en procesos que se verían alterados en la adicción. [68] En el contexto de la adicción, la prominencia de incentivos determina cómo se percibe la sustancia adictiva. [68] Se ha encontrado un aumento de las respuestas emocionales negativas en personas con adicciones. [68]
Consumo de tabaco, alcohol, medicamentos recetados y otras sustancias (TAPS)
Se trata de una herramienta de detección y evaluación en una sola, que evalúa las sustancias de uso común. Esta herramienta permite un diagnóstico sencillo, eliminando la necesidad de varias herramientas de detección y evaluación, ya que incluye tanto TAPS-1 como TAPS-2, herramientas de detección y evaluación respectivamente. El componente de detección pregunta sobre la frecuencia de uso de la sustancia específica (tabaco, alcohol, medicamentos recetados y otros). [69] Si una persona da positivo en la prueba, se iniciará el segundo componente. Este determina el nivel de riesgo de la sustancia. [69]
ARTESANÍA
El CRAFFT (Car-Relax-Alone-Forget-Family and Friends-Trouble) es una herramienta de detección que se utiliza en los centros médicos. El CRAFFT se encuentra en la versión 2.1 y tiene una versión para el uso de nicotina y tabaco llamada CRAFFT 2.1+N. [70] Esta herramienta se utiliza para identificar el uso de sustancias, el riesgo de conducir relacionado con las sustancias y las adicciones entre los adolescentes. Esta herramienta utiliza un conjunto de preguntas para diferentes escenarios. [71] En el caso de una combinación específica de respuestas, se pueden utilizar diferentes conjuntos de preguntas para obtener una respuesta más precisa. Después de las preguntas, se utilizan los criterios del DSM-5 para identificar la probabilidad de que la persona tenga un trastorno por uso de sustancias. [71] Después de que se realicen estas pruebas, el médico debe administrar las "5 R" del asesoramiento breve.
Las cinco R del asesoramiento breve incluyen:
- REVISIÓN de los resultados de la evaluación
- RECOMIENDO no utilizar
- Asesoramiento sobre riesgos al conducir/conducir
- RESPUESTA: provocar declaraciones de automotivación.
- REFUERZA la autoeficacia [71]
Prueba de detección de abuso de drogas (DAST-10)
La prueba de detección del abuso de drogas (DAST, por sus siglas en inglés) es una herramienta de autoinforme que mide el uso problemático de sustancias. [72] Las respuestas a esta prueba se registran como respuestas de sí o no y se puntúan con un número entre cero y 28. El abuso o dependencia de drogas se indica con una puntuación de corte de 6. [72] Se utilizan tres versiones de esta herramienta de detección: DAST-28, DAST-20 y DAST-10. Cada uno de estos instrumentos tiene derechos de autor del Dr. Harvey A. Skinner. [72]
Prueba de consumo de alcohol, tabaco y sustancias (ASSIST)
El test de consumo de alcohol, tabaco y otras sustancias (ASSIST) es un cuestionario basado en una entrevista que consta de ocho preguntas desarrollado por la OMS. [73] Las preguntas se refieren al consumo a lo largo de la vida; la frecuencia de consumo; la urgencia de consumo; la frecuencia de problemas de salud, financieros, sociales o legales relacionados con el consumo; el incumplimiento de las obligaciones; si alguien ha expresado inquietudes sobre el consumo; los intentos de limitar o moderar el consumo; y el consumo por inyección. [74]
Causas
Teorías de la personalidad
Las teorías de la personalidad de la adicción son modelos psicológicos que asocian rasgos de personalidad o modos de pensamiento (es decir, estados afectivos ) con la proclividad de un individuo a desarrollar una adicción. El análisis de datos demuestra que los perfiles psicológicos de los consumidores y no consumidores de drogas tienen diferencias significativas y la predisposición psicológica a consumir diferentes drogas puede ser diferente. [75] Los modelos de riesgo de adicción que se han propuesto en la literatura psicológica incluyen: un modelo de desregulación afectiva de afectos psicológicos positivos y negativos , la teoría de la sensibilidad al refuerzo de la impulsividad y la inhibición conductual, y un modelo de impulsividad de sensibilización a la recompensa e impulsividad. [76] [77] [78] [79] [80]
Neuropsicología
El modelo transteórico del cambio (TTM) puede señalar cómo alguien puede estar conceptualizando su adicción y los pensamientos en torno a ella, incluso sin ser consciente de su adicción. [81]
El control cognitivo y el control de estímulos , que se asocian con el condicionamiento operante y clásico , representan procesos opuestos (es decir, interno versus externo o ambiental, respectivamente) que compiten por el control de las conductas provocadas de un individuo. [82] El control cognitivo, y particularmente el control inhibitorio sobre la conducta , se ve afectado tanto en la adicción como en el trastorno por déficit de atención con hiperactividad . [83] [84] Las respuestas conductuales impulsadas por estímulos (es decir, el control de estímulos) que se asocian con un estímulo gratificante particular tienden a dominar la conducta de uno en una adicción. [84]
Control de estímulos de la conducta
En el condicionamiento operante, el comportamiento se ve influenciado por estímulos externos, como una droga. La teoría del aprendizaje basada en el condicionamiento operante es útil para entender por qué las consecuencias estimulantes o que alteran el estado de ánimo del consumo de drogas pueden reforzar el consumo continuado (un ejemplo de refuerzo positivo ) y por qué la persona adicta intenta evitar la abstinencia mediante el consumo continuado (un ejemplo de refuerzo negativo ). El control de estímulos consiste en utilizar la ausencia del estímulo o la presencia de una recompensa para influir en el comportamiento resultante. [81]
Control cognitivo del comportamiento
El control cognitivo es la selección intencional de pensamientos, conductas y emociones, en función de nuestro entorno. Se ha demostrado que las drogas alteran la forma en que funciona nuestro cerebro y su estructura. [85] [26] Las funciones cognitivas como el aprendizaje, la memoria y el control de los impulsos se ven afectadas por las drogas. [85] Estos efectos promueven el consumo de drogas, así como dificultan la capacidad de abstenerse de él. [85] El aumento de la liberación de dopamina es prominente en el consumo de drogas, específicamente en el estriado ventral y el núcleo accumbens . [85] La dopamina es responsable de producir sentimientos placenteros, así como de impulsarnos a realizar actividades importantes de la vida. Las drogas adictivas provocan un aumento significativo de este sistema de recompensa, lo que provoca un gran aumento de la señalización de dopamina, así como un aumento de la conducta de búsqueda de recompensa, lo que a su vez motiva el consumo de drogas. [85] [26] Esto promueve el desarrollo de una relación desadaptativa entre la droga y el estímulo. [86] El consumo temprano de drogas conduce a estas asociaciones desadaptativas, que luego afectan los procesos cognitivos utilizados para afrontar la situación, que son necesarios para abstenerse con éxito de ellas. [85] [81]
Factores de riesgo
Existen varios factores de riesgo genéticos y ambientales para desarrollar una adicción. [2] [87] Los factores de riesgo genéticos y ambientales representan cada uno aproximadamente la mitad del riesgo de una persona de desarrollar una adicción; [2] se desconoce la contribución de los factores de riesgo epigenéticos al riesgo total. [87] Incluso en personas con un riesgo genético relativamente bajo, la exposición a dosis suficientemente altas de una droga adictiva durante un período prolongado (por ejemplo, semanas o meses) puede provocar una adicción. [2] Los eventos adversos en la infancia se asocian con resultados negativos para la salud, como el trastorno por consumo de sustancias. El abuso infantil o la exposición a delitos violentos se relaciona con el desarrollo de un trastorno del estado de ánimo o de ansiedad, así como con el riesgo de dependencia de sustancias. [88]
Factores genéticos
Los factores genéticos, junto con los factores socioambientales (p. ej., psicosociales ), se han establecido como contribuyentes significativos a la vulnerabilidad a la adicción. [2] [87] [89] [32] Los estudios realizados en 350 pacientes dependientes de drogas hospitalizados mostraron que más de la mitad cumplía los criterios de abuso de alcohol, con un papel de factores familiares predominantes. [90] Los factores genéticos representan el 40-60% de los factores de riesgo para el alcoholismo. [91] Se han indicado tasas similares de heredabilidad para otros tipos de adicción a las drogas, específicamente en genes que codifican el receptor nicotínico de acetilcolina alfa5 . [92] Knestler planteó la hipótesis en 1964 de que un gen o grupo de genes podría contribuir a la predisposición a la adicción de varias maneras. Por ejemplo, los niveles alterados de una proteína normal debido a factores ambientales pueden cambiar la estructura o el funcionamiento de neuronas cerebrales específicas durante el desarrollo. Estas neuronas cerebrales alteradas podrían afectar la susceptibilidad de un individuo a una experiencia inicial de consumo de drogas. En apoyo de esta hipótesis, los estudios realizados en animales han demostrado que factores ambientales como el estrés pueden afectar la expresión genética de un animal. [92]
En los seres humanos, los estudios sobre la adicción en gemelos han proporcionado algunas de las pruebas de mayor calidad de este vínculo, con resultados que indican que si un gemelo se ve afectado por la adicción, es probable que el otro gemelo también lo esté, y a la misma sustancia. [93] Otra evidencia de un componente genético son los resultados de las investigaciones de estudios familiares que sugieren que si un miembro de la familia tiene antecedentes de adicción, las probabilidades de que un pariente o familiar cercano desarrolle esos mismos hábitos son mucho mayores que las de uno que no ha sido introducido a la adicción a una edad temprana. [94]
Los datos que implican a genes específicos en el desarrollo de la adicción a las drogas son contradictorios en la mayoría de los casos. Muchos estudios sobre la adicción que tienen como objetivo identificar genes específicos se centran en variantes comunes con una frecuencia de alelos superior al 5 % en la población general. Cuando se asocian con una enfermedad, estas solo confieren una pequeña cantidad de riesgo adicional con una razón de probabilidades del 1,1 al 1,3 %; esto ha llevado al desarrollo de la hipótesis de la variante rara, que afirma que los genes con frecuencias bajas en la población (<1 %) confieren un riesgo adicional mucho mayor en el desarrollo de la enfermedad. [95]
Los estudios de asociación de todo el genoma (GWAS, por sus siglas en inglés) se utilizan para examinar las asociaciones genéticas con la dependencia, la adicción y el consumo de drogas. [89] Estos estudios rara vez identifican genes de proteínas descritas previamente mediante modelos de knockout en animales y análisis de genes candidatos. En cambio, se identifican comúnmente grandes porcentajes de genes involucrados en procesos como la adhesión celular. Los efectos importantes de los endofenotipos no suelen poder captarse mediante estos métodos. Los genes identificados en los GWAS para la adicción a las drogas pueden estar involucrados en el ajuste del comportamiento cerebral antes de las experiencias con las drogas, después de ellas o en ambos. [96]
Factores ambientales
Los factores de riesgo ambientales de la adicción son las experiencias de un individuo durante su vida que interactúan con la composición genética del individuo para aumentar o disminuir su vulnerabilidad a la adicción. [2] Por ejemplo, después del brote nacional de COVID-19, más personas dejaron de fumar (en comparación con las que comenzaron a hacerlo); y los fumadores, en promedio, redujeron la cantidad de cigarrillos que consumían. [97] De manera más general, se ha implicado a varios factores ambientales diferentes como factores de riesgo de adicción, incluidos varios estresores psicosociales. El Instituto Nacional sobre Abuso de Drogas (NIDA) y los estudios citan la falta de supervisión parental, la prevalencia del consumo de sustancias entre pares, la disponibilidad de sustancias y la pobreza como factores de riesgo para el consumo de sustancias entre niños y adolescentes. [98] [28] El modelo de adicción de la enfermedad cerebral postula que la exposición de un individuo a una droga adictiva es el factor de riesgo ambiental más significativo para la adicción. [99] Muchos investigadores, incluidos los neurocientíficos, indican que el modelo de la enfermedad cerebral presenta una explicación engañosa, incompleta y potencialmente perjudicial de la adicción. [100]
El modelo de la teoría psicoanalítica define la adicción como una forma de defensa contra sentimientos de desesperanza e impotencia, así como un síntoma de incapacidad para regular emociones poderosas relacionadas con experiencias adversas en la infancia (ACE), diversas formas de maltrato y disfunción experimentadas en la infancia. En este caso, la sustancia adictiva proporciona un alivio breve pero total y sentimientos positivos de control. [81] El estudio de experiencias adversas en la infancia de los Centros para el Control y la Prevención de Enfermedades ha demostrado una fuerte relación dosis-respuesta entre las ACE y numerosos problemas de salud, sociales y de comportamiento a lo largo de la vida de una persona, incluido el trastorno por consumo de sustancias. [101] El desarrollo neurológico de los niños puede verse alterado de forma permanente cuando están expuestos crónicamente a eventos estresantes como abuso físico, emocional o sexual, negligencia física o emocional, presenciar violencia en el hogar o que uno de los padres esté encarcelado o tenga una enfermedad mental. Como resultado, el funcionamiento cognitivo del niño o la capacidad para hacer frente a emociones negativas o disruptivas pueden verse afectados. Con el tiempo, el niño puede adoptar el consumo de sustancias como mecanismo de afrontamiento o como resultado de un menor control de los impulsos, en particular durante la adolescencia. [101] [28] [81] Una gran cantidad de niños que han sufrido abusos han desarrollado algún tipo de adicción en su adolescencia o vida adulta. [102] Este camino hacia la adicción que se abre a través de experiencias estresantes durante la infancia se puede evitar mediante un cambio en los factores ambientales a lo largo de la vida de un individuo y oportunidades de ayuda profesional. [102] Si uno tiene amigos o compañeros que se involucran en el consumo de drogas de manera favorable, aumentan las probabilidades de que desarrollen una adicción. Los conflictos familiares y la gestión del hogar son una causa para que uno se involucre en el consumo de drogas. [103]
Teoría del control social
Según la teoría del control social de Travis Hirschi, los adolescentes con vínculos más fuertes con la familia, la religión, la academia y otras instituciones sociales tienen menos probabilidades de involucrarse en conductas delictivas y desadaptativas, como el consumo de drogas que conduce a la adicción. [104]
Edad
La adolescencia representa un período de mayor vulnerabilidad para desarrollar una adicción. [105] En la adolescencia, los sistemas de incentivos y recompensas del cerebro maduran mucho antes que el centro de control cognitivo. Esto, en consecuencia, otorga a los sistemas de incentivos y recompensas una cantidad desproporcionada de poder en el proceso de toma de decisiones conductuales. Por lo tanto, los adolescentes son cada vez más propensos a actuar según sus impulsos y participar en conductas de riesgo y potencialmente adictivas antes de considerar las consecuencias. [106] Los adolescentes no solo tienen más probabilidades de iniciar y mantener el consumo de drogas, sino que una vez adictos son más resistentes al tratamiento y más propensos a recaer. [107] [108]
La mayoría de las personas se exponen a drogas adictivas y las consumen por primera vez durante la adolescencia. [109] En los Estados Unidos, hubo poco más de 2,8 millones de nuevos usuarios de drogas ilícitas en 2013 (7.800 nuevos usuarios por día); [109] entre ellos, el 54,1% eran menores de 18 años. [109] En 2011, había aproximadamente 20,6 millones de personas en los Estados Unidos mayores de 12 años con una adicción. [110] Más del 90% de las personas con una adicción comenzaron a beber, fumar o consumir drogas ilícitas antes de los 18 años. [110]
Trastornos comórbidos
Las personas con trastornos de salud mental comórbidos (es decir, coexistentes) como depresión, ansiedad, trastorno por déficit de atención e hiperactividad (TDAH) o trastorno por estrés postraumático tienen más probabilidades de desarrollar trastornos por consumo de sustancias. [111] [112] [113] [28] El NIDA cita el comportamiento agresivo temprano como un factor de riesgo para el consumo de sustancias. [98] La Oficina Nacional de Investigación Económica encontró que existe una "conexión definitiva entre la enfermedad mental y el consumo de sustancias adictivas" y una mayoría de pacientes de salud mental participan en el consumo de estas sustancias: 38% alcohol, 44% cocaína y 40% cigarrillos. [114]
Epigenética
La epigenética es el estudio de los cambios fenotípicos estables que no implican alteraciones en la secuencia del ADN. [115] Se ha descubierto que el consumo de drogas ilícitas causa cambios epigenéticos en la metilación del ADN , así como en la remodelación de la cromatina . [116] El estado epigenético de la cromatina puede suponer un riesgo para el desarrollo de adicciones a sustancias. [116] Se ha descubierto que los factores estresantes emocionales, así como las adversidades sociales, pueden conducir a una respuesta epigenética inicial, que provoca una alteración en las vías de señalización de recompensa. [116] Este cambio puede predisponer a uno a experimentar una respuesta positiva al consumo de drogas. [116]
Herencia epigenética transgeneracional
Los genes epigenéticos y sus productos (por ejemplo, las proteínas) son los componentes clave a través de los cuales las influencias ambientales pueden afectar los genes de un individuo: [87] sirven como el mecanismo responsable de la herencia epigenética transgeneracional , un fenómeno en el que las influencias ambientales sobre los genes de un padre pueden afectar los rasgos asociados y los fenotipos conductuales de su descendencia (por ejemplo, las respuestas conductuales a los estímulos ambientales). [87] En la adicción, los mecanismos epigenéticos juegan un papel central en la fisiopatología de la enfermedad; [2] se ha observado que algunas de las alteraciones del epigenoma que surgen a través de la exposición crónica a estímulos adictivos durante una adicción pueden transmitirse a través de generaciones, afectando a su vez el comportamiento de los hijos (por ejemplo, las respuestas conductuales del niño a las drogas adictivas y las recompensas naturales). [87] [117]
Las clases generales de alteraciones epigenéticas que se han implicado en la herencia epigenética transgeneracional incluyen la metilación del ADN, las modificaciones de las histonas y la regulación negativa o positiva de los microARN . [87] Con respecto a la adicción, se necesita más investigación para determinar las alteraciones epigenéticas hereditarias específicas que surgen de varias formas de adicción en humanos y los fenotipos conductuales correspondientes de estas alteraciones epigenéticas que ocurren en la descendencia humana. [87] [117] Con base en evidencia preclínica de investigación animal , ciertas alteraciones epigenéticas inducidas por la adicción en ratas pueden transmitirse de padres a hijos y producir fenotipos conductuales que disminuyen el riesgo de la descendencia de desarrollar una adicción. [nota 1] [87] De manera más general, los fenotipos conductuales hereditarios que se derivan de alteraciones epigenéticas inducidas por la adicción y se transmiten de padres a hijos pueden servir para aumentar o disminuir el riesgo de la descendencia de desarrollar una adicción. [87] [117]
Mecanismos
La adicción es un trastorno del sistema de recompensa del cerebro que se desarrolla a través de mecanismos transcripcionales y epigenéticos como resultado de niveles crónicamente altos de exposición a un estímulo adictivo (p. ej., comer alimentos, el uso de cocaína, participar en actividad sexual, participación en actividades culturales de alta emoción como el juego, etc.) durante un tiempo prolongado. [2] [118] [33] DeltaFosB (ΔFosB), un factor de transcripción genética , es un componente crítico y un factor común en el desarrollo de prácticamente todas las formas de adicciones conductuales y a las drogas. [118] [33] [119] [34] Dos décadas de investigación sobre el papel de ΔFosB en la adicción han demostrado que la adicción surge y el comportamiento compulsivo asociado se intensifica o atenúa, junto con la sobreexpresión de ΔFosB en las neuronas espinosas medianas de tipo D1 del núcleo accumbens. [2] [118] [33] [119] Debido a la relación causal entre la expresión de ΔFosB y las adicciones, se utiliza preclínicamente como un biomarcador de adicción . [2] [118] [119] La expresión de ΔFosB en estas neuronas regula directa y positivamente la autoadministración de drogas y la sensibilización a la recompensa a través del refuerzo positivo, al tiempo que disminuye la sensibilidad a la aversión. [nota 2] [2] [118]
El uso crónico de drogas adictivas causa alteraciones en la expresión génica en la proyección mesocorticolímbica . [34] [127] [128] Los factores de transcripción más importantes que producen estas alteraciones son ΔFosB, proteína de unión al elemento de respuesta a AMPc ( CREB ) y factor nuclear kappa B ( NF-κB ). [34] ΔFosB es el mecanismo biomolecular más significativo en la adicción porque la sobreexpresión de ΔFosB en las neuronas espinosas medianas de tipo D1 en el núcleo accumbens es necesaria y suficiente para muchas de las adaptaciones neuronales y efectos conductuales (por ejemplo, aumentos dependientes de la expresión en la autoadministración de drogas y sensibilización a la recompensa) observados en la adicción a las drogas. [34] La expresión de ΔFosB en las neuronas espinosas medianas de tipo D1 del núcleo accumbens regula directa y positivamente la autoadministración de drogas y la sensibilización a la recompensa a través del refuerzo positivo mientras disminuye la sensibilidad a la aversión. [nota 2] [2] [118] Se ha implicado a ΔFosB en la mediación de adicciones a muchas drogas y clases de drogas diferentes, incluyendo alcohol, anfetamina y otras anfetaminas sustituidas , cannabinoides , cocaína , metilfenidato , nicotina , opiáceos , fenilciclidina y propofol , entre otros. [118] [34] [127] [129] [130] ΔJunD , un factor de transcripción, y G9a , una histona metiltransferasa , ambos se oponen a la función de ΔFosB e inhiben los aumentos en su expresión. [2] [34] [131] El aumento de la expresión de ΔJunD en el núcleo accumbens (a través de la transferencia génica mediada por un vector viral ) o de la expresión de G9a (a través de medios farmacológicos) reduce, o con un gran aumento puede incluso bloquear, muchas de las alteraciones neuronales y conductuales que resultan del uso crónico de dosis altas de drogas adictivas (es decir, las alteraciones mediadas por ΔFosB). [119] [34]
ΔFosB desempeña un papel importante en la regulación de las respuestas conductuales a las recompensas naturales, como la comida sabrosa, el sexo y el ejercicio. [34] [132] Las recompensas naturales, como las drogas de abuso, inducen la expresión genética de ΔFosB en el núcleo accumbens, y la adquisición crónica de estas recompensas puede resultar en un estado adictivo patológico similar a través de la sobreexpresión de ΔFosB. [33] [34] [132] En consecuencia, ΔFosB es el factor de transcripción clave involucrado en las adicciones a las recompensas naturales (es decir, adicciones conductuales) también; [34] [33] [132] en particular, ΔFosB en el núcleo accumbens es fundamental para los efectos de refuerzo de la recompensa sexual. [132] Las investigaciones sobre la interacción entre las recompensas naturales y las drogas sugieren que los psicoestimulantes dopaminérgicos (por ejemplo, la anfetamina) y el comportamiento sexual actúan sobre mecanismos biomoleculares similares para inducir ΔFosB en el núcleo accumbens y poseen efectos de sensibilización cruzada bidireccional que están mediados por ΔFosB. [33] [42] [43] Este fenómeno es notable ya que, en los seres humanos, se ha observado un síndrome de desregulación de la dopamina, caracterizado por la participación compulsiva inducida por drogas en recompensas naturales (específicamente, actividad sexual, compras y juegos de azar), en algunas personas que toman medicamentos dopaminérgicos . [33]
Los inhibidores de ΔFosB (medicamentos o tratamientos que se oponen a su acción) pueden ser un tratamiento eficaz para la adicción y los trastornos adictivos. [133]
La liberación de dopamina en el núcleo accumbens desempeña un papel en las cualidades de refuerzo de muchas formas de estímulos, incluidos los estímulos de refuerzo natural como la comida sabrosa y el sexo. [134] [135] [32] La neurotransmisión de dopamina alterada se observa con frecuencia después del desarrollo de un estado adictivo. [33] [26] En humanos y animales de laboratorio que han desarrollado una adicción, son evidentes las alteraciones en la neurotransmisión de dopamina u opioides en el núcleo accumbens y otras partes del cuerpo estriado. [33] El uso de ciertas drogas (p. ej., cocaína) afecta a las neuronas colinérgicas que inervan el sistema de recompensa, lo que a su vez afecta la señalización de dopamina en esta región. [136]
Sistema de recompensas
Vía mesocorticolímbica
Comprender las vías en las que actúan las drogas y cómo pueden alterarlas es fundamental para estudiar la base biológica de la adicción a las drogas. La vía de recompensa, conocida como vía mesolímbica [26] o su extensión, la vía mesocorticolímbica , se caracteriza por la interacción de varias áreas del cerebro.
- Las proyecciones del área tegmental ventral (ATV) son una red de neuronas dopaminérgicas con receptores de glutamato postsinápticos co-localizados ( AMPAR y NMDAR ). Estas células responden cuando hay estímulos indicativos de una recompensa. [32] El ATV apoya el desarrollo del aprendizaje y la sensibilización y libera dopamina (DA) en el prosencéfalo . [138] Estas neuronas proyectan y liberan DA en el núcleo accumbens, [139] a través de la vía mesolímbica . Prácticamente todas las drogas que causan adicción aumentan la liberación de DA en la vía mesolímbica. [140] [26]
- El núcleo accumbens (NAcc) es una de las salidas de las proyecciones del VTA. El núcleo accumbens en sí mismo está compuesto principalmente por neuronas espinosas medianas (MSN) GABAérgicas . [141] El NAcc está asociado con la adquisición y la provocación de conductas condicionadas, y está involucrado en la mayor sensibilidad a las drogas a medida que progresa la adicción. [138] [31] La sobreexpresión de ΔFosB en el núcleo accumbens es un factor común necesario en prácticamente todas las formas conocidas de adicción; [2] ΔFosB es un potente modulador positivo de conductas reforzadas positivamente . [2]
- La corteza prefrontal , que incluye las cortezas cingulada anterior y orbitofrontal , [142] [31] es otra salida del VTA en la vía mesocorticolímbica; es importante para la integración de la información que ayuda a determinar si se desencadenará una conducta. [143] Es fundamental para formar asociaciones entre la experiencia gratificante del consumo de drogas y las señales del entorno. Es importante destacar que estas señales son fuertes mediadores de la conducta de búsqueda de drogas y pueden desencadenar una recaída incluso después de meses o años de abstinencia. [144] [26]
Otras estructuras cerebrales que están involucradas en la adicción incluyen:
- La amígdala basolateral se proyecta hacia el NAcc y se cree que es importante para la motivación. [143]
- El hipocampo está involucrado en la adicción a las drogas debido a su papel en el aprendizaje y la memoria. Gran parte de esta evidencia proviene de investigaciones que muestran que la manipulación de las células en el hipocampo altera los niveles de DA en el NAcc y las tasas de activación de las células dopaminérgicas del VTA. [139]
Papel de la dopamina y el glutamato
La dopamina es el principal neurotransmisor del sistema de recompensa del cerebro. Desempeña un papel en la regulación del movimiento, la emoción, la cognición, la motivación y los sentimientos de placer. [145] Las recompensas naturales, como comer, así como el consumo de drogas recreativas provocan una liberación de dopamina y están asociadas con la naturaleza reforzadora de estos estímulos. [145] [146] [32] Casi todas las drogas adictivas, directa o indirectamente, actúan sobre el sistema de recompensa del cerebro aumentando la actividad dopaminérgica. [147] [26]
La ingesta excesiva de muchos tipos de drogas adictivas produce una liberación repetida de grandes cantidades de dopamina, lo que a su vez afecta directamente a la vía de recompensa a través de una mayor activación del receptor de dopamina. Los niveles prolongados y anormalmente altos de dopamina en la hendidura sináptica pueden inducir una regulación negativa del receptor en la vía neuronal. La regulación negativa de los receptores de dopamina mesolímbicos puede dar lugar a una disminución de la sensibilidad a los reforzadores naturales. [145]
La conducta de búsqueda de drogas es inducida por proyecciones glutamatérgicas desde la corteza prefrontal al núcleo accumbens. Esta idea está respaldada por datos de experimentos que muestran que la conducta de búsqueda de drogas puede prevenirse tras la inhibición de los receptores de glutamato AMPA y la liberación de glutamato en el núcleo accumbens. [142]
Sensibilización de recompensa
La sensibilización a la recompensa es un proceso que provoca un aumento en la cantidad de recompensa (específicamente, la prominencia del incentivo [nota 5] ) que el cerebro asigna a un estímulo gratificante (por ejemplo, una droga). En términos simples, cuando se produce la sensibilización a la recompensa de un estímulo específico (por ejemplo, una droga), aumenta el "deseo" o deseo de un individuo por el estímulo en sí y sus señales asociadas . [150] [149] [151] La sensibilización a la recompensa ocurre normalmente después de niveles crónicamente altos de exposición al estímulo. [26] Se ha demostrado que la expresión de ΔFosB en las neuronas espinosas medianas de tipo D1 en el núcleo accumbens regula de manera directa y positiva la sensibilización a la recompensa que involucra drogas y recompensas naturales. [2] [118] [119]
El "deseo inducido por señales" o "deseo desencadenado por señales", una forma de ansia que ocurre en la adicción, es responsable de la mayor parte del comportamiento compulsivo que exhiben las personas con adicciones. [149] [151] Durante el desarrollo de una adicción, la asociación repetida de estímulos por lo demás neutrales e incluso no gratificantes con el consumo de drogas desencadena un proceso de aprendizaje asociativo que hace que estos estímulos previamente neutrales actúen como reforzadores positivos condicionados del consumo adictivo de drogas (es decir, estos estímulos comienzan a funcionar como señales de drogas ). [149] [152] [151] Como reforzadores positivos condicionados del consumo de drogas, a estos estímulos previamente neutrales se les asigna una prominencia de incentivo (que se manifiesta como un ansia) -a veces en niveles patológicamente altos debido a la sensibilización a la recompensa- que puede transferirse al reforzador primario (por ejemplo, el consumo de una droga adictiva) con el que se emparejó originalmente. [149] [152] [151]
Las investigaciones sobre la interacción entre las recompensas naturales y las drogas sugieren que los psicoestimulantes dopaminérgicos (por ejemplo, la anfetamina) y el comportamiento sexual actúan sobre mecanismos biomoleculares similares para inducir ΔFosB en el núcleo accumbens y poseen un efecto de sensibilización cruzada de recompensa bidireccional [nota 6] que está mediado por ΔFosB. [33] [42] [43] En contraste con el efecto sensibilizador de recompensa de ΔFosB, la actividad transcripcional de CREB disminuye la sensibilidad del usuario a los efectos gratificantes de la sustancia. La transcripción de CREB en el núcleo accumbens está implicada en la dependencia psicológica y los síntomas que implican una falta de placer o motivación durante la abstinencia de la droga . [2] [137] [148]
Mecanismos neuroepigenéticos
La regulación epigenética alterada de la expresión génica dentro del sistema de recompensa del cerebro desempeña un papel significativo y complejo en el desarrollo de la adicción a las drogas. [131] [153] Las drogas adictivas están asociadas con tres tipos de modificaciones epigenéticas dentro de las neuronas. [131] Estas son (1) modificaciones de histonas, (2) metilación epigenética del ADN en sitios CpG en (o adyacentes a) genes particulares, y (3) regulación negativa o positiva epigenética de microARN que tienen genes diana particulares. [131] [34] [153] Como ejemplo, mientras que cientos de genes en las células del núcleo accumbens (NAc) muestran modificaciones de histonas después de la exposición a drogas -en particular, estados alterados de acetilación y metilación de residuos de histonas [153] - la mayoría de los demás genes en las células del NAc no muestran tales cambios. [131]
Diagnóstico
Clasificación
DSM-5
La quinta edición del DSM utiliza el término trastorno por consumo de sustancias para referirse a un espectro de trastornos relacionados con el consumo de drogas. El DSM-5 elimina los términos abuso y dependencia de las categorías diagnósticas, y en su lugar utiliza los especificadores de leve , moderado y grave para indicar el grado de uso desordenado. Estos especificadores están determinados por el número de criterios diagnósticos presentes en un caso determinado. En el DSM-5, el término adicción a las drogas es sinónimo de trastorno grave por consumo de sustancias . [18] [24]
El DSM-5 introdujo una nueva categoría diagnóstica para las adicciones conductuales. El juego problemático es la única condición incluida en esta categoría en la quinta edición. [20] El trastorno por juego en Internet se incluye como una "condición que requiere más estudio" en el DSM-5. [154]
En ediciones anteriores se ha utilizado la dependencia física y el síndrome de abstinencia asociado para identificar un estado adictivo. La dependencia física se produce cuando el cuerpo se ha adaptado incorporando la sustancia a su funcionamiento "normal" (es decir, alcanza la homeostasis ) y, por lo tanto, los síntomas de abstinencia física se producen al dejar de consumirla. [155] La tolerancia es el proceso por el cual el cuerpo se adapta continuamente a la sustancia y requiere cantidades cada vez mayores para lograr los efectos originales. La abstinencia se refiere a los síntomas físicos y psicológicos experimentados al reducir o suspender una sustancia de la que el cuerpo se ha vuelto dependiente. Los síntomas de abstinencia generalmente incluyen, entre otros, dolores corporales, ansiedad , irritabilidad , antojos intensos de la sustancia, disforia , náuseas , alucinaciones , dolores de cabeza , sudores fríos, temblores y convulsiones. Durante la abstinencia física aguda de opioides, los síntomas del síndrome de piernas inquietas son comunes y pueden ser profundos. Este fenómeno originó la expresión "dejar el hábito".
Los investigadores médicos que estudian activamente la adicción han criticado la clasificación DSM de la adicción por ser defectuosa e implicar criterios de diagnóstico arbitrarios. [156]
CIE-11
La undécima revisión de la Clasificación Internacional de Enfermedades , comúnmente conocida como CIE-11 , conceptualiza el diagnóstico de manera algo diferente. La CIE-11 distingue primero entre problemas con el uso de sustancias psicoactivas ("Trastornos debidos al uso de sustancias") y adicciones conductuales ("Trastornos debidos a conductas adictivas"). [14] Con respecto a las sustancias psicoactivas, la CIE-11 explica que las sustancias incluidas inicialmente producen "efectos psicoactivos agradables o atractivos que son gratificantes y reforzantes con el uso repetido, [pero] con el uso continuado, muchas de las sustancias incluidas tienen la capacidad de producir dependencia. Tienen el potencial de causar numerosas formas de daño, tanto a la salud mental como física". [157] En lugar del enfoque del DSM-5 de un diagnóstico ("Trastorno por uso de sustancias") que cubre todos los tipos de uso problemático de sustancias, la CIE-11 ofrece tres posibilidades diagnósticas: 1) Episodio de uso nocivo de sustancias psicoactivas, 2) Patrón nocivo de uso de sustancias psicoactivas y 3) Dependencia de sustancias. [157]
Prevención
Responsabilidad por abuso
El abuso o la adicción son tendencias a consumir drogas en situaciones no médicas, generalmente para producir euforia, cambios de humor o sedación. [158] El abuso se produce cuando la persona que consume drogas desea algo que no puede obtener de otra manera, y la única forma de conseguirlo es mediante el consumo de drogas. Cuando se analiza el abuso, existen varios factores que determinan si se abusa de la droga, como la composición química de la droga, los efectos en el cerebro, la edad, la vulnerabilidad y la salud (mental y física) de la población estudiada. [158] Hay algunas drogas con una composición química específica que provocan un alto riesgo de abuso, como la cocaína, la heroína, los inhalantes, la marihuana, el MDMA (éxtasis), la metanfetamina, el PCP, los cannabinoides sintéticos, las catinonas sintéticas (sales de baño), la nicotina (p. ej., el tabaco) y el alcohol. [159]
Vacunas potenciales contra la adicción a sustancias
Las vacunas contra la adicción se han investigado como una posibilidad desde principios de la década de 2000. [160] La teoría general de una vacuna destinada a "inmunizar" contra la adicción a las drogas u otro abuso de sustancias es que condicionaría al sistema inmunológico a atacar y consumir o deshabilitar de otro modo las moléculas de dichas sustancias que causan una reacción en el cerebro, impidiendo así que el adicto pueda percibir el efecto de la droga. Las adicciones que se han planteado como objetivos para dicho tratamiento incluyen la nicotina , los opioides y el fentanilo . [161] [162] [163] [164] Se ha identificado que las vacunas son potencialmente más efectivas que otros tratamientos contra la adicción, debido a "la larga duración de la acción, la certeza de la administración y una posible reducción de la toxicidad para órganos importantes". [165]
Entre las vacunas específicas contra la adicción que se están desarrollando se incluyen:
- NicVAX , una vacuna conjugada destinada a reducir o eliminar la dependencia física de la nicotina. [166] Esta vacuna patentada está siendo desarrollada por Nabi Biopharmaceuticals [167] de Rockville, MD. con el apoyo del Instituto Nacional sobre Abuso de Drogas de EE . UU. NicVAX consiste en el hapteno 3'-aminometilnicotina que ha sido conjugado (unido) a la exotoxina A de Pseudomonas aeruginosa . [168]
- TA-CD , una vacuna activa [169] desarrollada por el Grupo Xenova que se utiliza para anular los efectos de la cocaína . Se crea combinando norcocaína con toxina del cólera inactivada . Funciona de forma muy similar a una vacuna normal. Una molécula de proteína grande se adhiere a la cocaína, lo que estimula la respuesta de los anticuerpos , que destruyen la molécula. Esto también evita que la cocaína cruce la barrera hematoencefálica , anulando el efecto eufórico y gratificante de la cocaína causado por la estimulación de la liberación de dopamina en la vía de recompensa mesolímbica . La vacuna no afecta el "deseo" del usuario por la cocaína, solo los efectos físicos de la droga. [170]
- TA-NIC , utilizado para crear anticuerpos humanos para destruir la nicotina en el cuerpo humano de modo que ya no sea efectiva. [171]
En septiembre de 2023, se informó además que una vacuna "se ha probado contra la heroína y el fentanilo y está en camino de ser probada contra la oxicodona ". [172]
Tratamiento y manejo
Para que el tratamiento de la adicción, que tiene una base farmacológica o biológica, sea eficaz, debe ir acompañado de otras intervenciones, como la terapia cognitivo-conductual (TCC), la psicoterapia individual y de grupo, las estrategias de modificación de la conducta , los programas de doce pasos y los centros de tratamiento residencial. [173] [28] El TTM se puede utilizar para determinar cuándo puede comenzar el tratamiento y qué método será más eficaz. Si el tratamiento comienza demasiado pronto, puede provocar que la persona se ponga a la defensiva y se resista al cambio. [81] [174]
Epidemiología
Debido a las variaciones culturales, la proporción de personas que desarrollan una adicción a las drogas o al comportamiento dentro de un período de tiempo específico (es decir, la prevalencia ) varía con el tiempo, según el país y según la demografía de la población nacional (por ejemplo, según el grupo de edad, el nivel socioeconómico, etc.). [87] Cuando la adicción se considera inaceptable, habrá menos personas adictas.
Asia
La prevalencia de la dependencia del alcohol no es tan alta como en otras regiones. En Asia, no sólo los factores socioeconómicos sino también los factores biológicos influyen en el comportamiento de consumo de alcohol. [175]
El trastorno por adicción a Internet es más frecuente en Filipinas, según el IAT (Internet Addiction Test), con un 5 %, y la CIAS-R (Revised Chen Internet Addiction Scale), con un 21 %. [176]
Australia
The prevalence of substance use disorder among Australians was reported at 5.1% in 2009.[177] In 2019 the Australian Institute of Health and Welfare conducted a national drug survey that quantified drug use for various types of drugs and demographics.[178] The national[specify] found that in 2019, 11% of people over 14 years old smoke daily; that 9.9% of those who drink alcohol, which equates to 7.5% of the total population age 14 or older, may qualify as alcohol dependent; that 17.5% of the 2.4 million people who used cannabis in the last year may have hazardous use or a dependence problem; and that 63.5% of about 300000 recent users of meth and amphetamines were at risk for developing problem use.[178]
Europe
In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8% for cannabis use, 0.77% for amphetamine use, 0.37% for opioid use, and 0.35% for cocaine use in 2017. The mortality rates for alcohol and illicit drugs were highest in Eastern Europe.[179] Data shows a downward trend of alcohol use among children 15 years old in most European countries between 2002 and 2014. First-time alcohol use before the age of 13 was recorded for 28% of European children in 2014.[28]
United States
Based on representative samples of the US youth population in 2011[update], the lifetime prevalence[note 7] of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively.[180] Based on representative samples of the US adult population in 2011[update], the 12-month prevalence of alcohol and illicit drug addictions were estimated at 12% and 2–3% respectively.[180] The lifetime prevalence of prescription drug addictions is around 4.7%.[181]
As of 2021,[update] 43.7 million people aged 12 or older surveyed by the National Survey on Drug Use and Health in the United States needed treatment for an addiction to alcohol, nicotine, or other drugs. The groups with the highest number of people were 18–25 years (25.1%) and "American Indian or Alaska Native" (28.7%).[182] Only about 10%, or a little over 2 million, receive any form of treatments, and those that do generally do not receive evidence-based care.[183][184] One-third of inpatient hospital costs and 20% of all deaths in the US every year are the result of untreated addictions and risky substance use.[183][184] In spite of the massive overall economic cost to society, which is greater than the cost of diabetes and all forms of cancer combined, most doctors in the US lack the training to effectively address a drug addiction.[183][184]
Estimates of lifetime prevalence rates in the US are 1–2% for compulsive gambling, 5% for sexual addiction, 2.8% for food addiction, and 5–6% for compulsive shopping.[33] The time-invariant prevalence rate for sexual addiction and related compulsive sexual behavior (e.g., compulsive masturbation with or without pornography, compulsive cybersex, etc.) within the US ranges from 3–6% of the population.[41]
According to a 2017 poll conducted by the Pew Research Center, almost half of US adults know a family member or close friend who has struggled with a drug addiction at some point in their life.[185]
In 2019, opioid addiction was acknowledged as a national crisis in the United States.[186] An article in The Washington Post stated that "America's largest drug companies flooded the country with pain pills from 2006 through 2012, even when it became apparent that they were fueling addiction and overdoses."
The National Epidemiologic Survey on Alcohol and Related Conditions found that from 2012 to 2013 the prevalence of Cannabis use disorder in U.S. adults was 2.9%.[187]
Canada
A Statistics Canada Survey in 2012 found the lifetime prevalence and 12-month prevalence of substance use disorders were 21.6%, and 4.4% in those 15 and older.[188] Alcohol abuse or dependence reported a lifetime prevalence of 18.1% and a 12-month prevalence of 3.2%.[188] Cannabis abuse or dependence reported a lifetime prevalence of 6.8% and a 12-month prevalence of 3.2%.[188] Other drug abuse or dependence has a lifetime prevalence of 4.0% and a 12-month prevalence of 0.7%.[188] Substance use disorder is a term used interchangeably with a drug addiction.[189]
In Ontario, Canada between 2009 and 2017, outpatient visits for mental health and addiction increased from 52.6 to 57.2 per 100 people, emergency department visits increased from 13.5 to 19.7 per 1000 people and the number of hospitalizations increased from 4.5 to 5.5 per 1000 people.[190] Prevalence of care needed increased the most among the 14–17 age group overall.[190]
South America
The realities of opioid use and opioid use disorder in Latin America may be deceptive if observations are limited to epidemiological findings. In the United Nations Office on Drugs and Crime report,[191] although South America produced 3% of the world's morphine and heroin and 0.01% of its opium, prevalence of use is uneven. According to the Inter-American Commission on Drug Abuse Control, consumption of heroin is low in most Latin American countries, although Colombia is the area's largest opium producer. Mexico, because of its border with the United States, has the highest incidence of use.[192]
Addiction and the humanities
History and etymology
The etymology of the term addiction throughout history has been misunderstood and has taken on various meanings associated with the word.[193] An example is the usage of the word in the religious landscape of early modern Europe.[194] "Addiction" at the time meant "to attach" to something, giving it both positive and negative connotations. The object of this attachment could be characterized as "good or bad".[195] The meaning of addiction during the early modern period was mostly associated with positivity and goodness;[194] during this early modern and highly religious era of Christian revivalism and Pietistic tendencies,[194] it was seen as a way of "devoting oneself to another".[195]
Modern research on addiction has led to a better understanding of the disease with research on the topic dating back to 1875, specifically on morphine addiction.[196] This furthered the understanding of addiction being a medical condition. It was not until the 19th century that addiction was seen and acknowledged in the Western world as a disease, being both a physical condition and mental illness.[197] Today, addiction is understood both as a biopsychosocial and neurological disorder that negatively impacts those who are affected by it, most commonly associated with the use of drugs and excessive use of alcohol.[3] The understanding of addiction has changed throughout history, which has impacted and continues to impact the ways it is medically treated and diagnosed.
The suffixes "-holic" and "-holism"
In contemporary modern English "-holic" is a suffix that can be added to a subject to denote an addiction to it. It was extracted from the word alcoholism (one of the first addictions to be widely identified both medically and socially) (correctly the root "alcohol" plus the suffix "-ism") by misdividing or rebracketing it into "alco" and "-holism". There are correct medico-legal terms for such addictions: dipsomania is the medico-legal term for alcoholism;[198] other examples are in this table:
Arts
The arts can be used in a variety of ways to address issues related to addiction. Art can be used as a form of therapy in the treatment of substance use disorders. Creative activities like painting, sculpting, music, and writing can help people express their feelings and experiences in safe and healthy ways. The arts can be used as an assessment tool to identify underlying issues that may be contributing to a person's substance use disorder. Through art, individuals can gain insights into their own motivations and behaviors that can be helpful in determining a course of treatment. Finally, the arts can be used to advocate for those suffering from a substance use disorder by raising awareness of the issue and promoting understanding and compassion. Through art, individuals can share their stories, increase awareness, and offer support and hope to those struggling with substance use disorders.
As therapy
Addiction treatment is complex and not always effective due to engagement and service availability concerns, so researchers prioritize efforts to improve treatment retention and decrease relapse rates.[199][200] Characteristics of substance abuse may include feelings of isolation, a lack of confidence, communication difficulties, and a perceived lack of control.[201] In a similar vein, people suffering from substance use disorders tend to be highly sensitive, creative, and as such, are likely able to express themselves meaningfully in creative arts such as dancing, painting, writing, music, and acting.[202] Further evidenced by Waller and Mahony (2002)[203] and Kaufman (1981),[204] the creative arts therapies can be a suitable treatment option for this population especially when verbal communication is ineffective.
Primary advantages of art therapy in the treatment of addiction have been identified as:[205][206]
- Assess and characterize a client's substance use issues
- Bypassing a client's resistances, defenses, and denial
- Containing shame or anger
- Facilitating the expression of suppressed and/or complicated emotions
- Highlighting a client's strengths
- Providing an alternative to verbal communication (via use of symbols) and conventional forms of therapy
- Providing clients with a sense of control
- Tackling feelings of isolation
Art therapy is an effective method of dealing with substance abuse in comprehensive treatment models. When included in psychoeducational programs, art therapy in a group setting can help clients internalize taught concepts in a more personalized manner.[207] During the course of treatment, by examining and comparing artwork created at different times, art therapists can be helpful in identifying and diagnosing issues, as well as charting the extent or direction of improvement as a person detoxifies.[207] Where increasing adherence to treatment regimes and maintaining abstinence is the target; art therapists can aid by customizing treatment directives (encourage the client to create collages that compare pros and cons, pictures that compare past and present and future, and drawings that depict what happened when a client went off medication).[207]
Art therapy can function as a complementary therapy used in conjunction with more conventional therapies and can can integrate with harm reduction protocols to minimize the negative effects of drug use.[208][206] An evaluation of art therapy incorporation within a pre-existing Addiction Treatment Programme based on the 12 step Minnesota Model endorsed by the Alcoholics Anonymous found that 66% of participants expressed the usefulness of art therapy as a part of treatment.[209][206] Within the weekly art therapy session, clients were able to reflect and process the intense emotions and cognitions evoked by the programme. In turn, the art therapy component of the programme fostered stronger self-awareness, exploration, and externalization of repressed and unconscious emotions of clients, promoting the development of a more integrated 'authentic self'.[210][206]
Despite the large number of randomized control trials, clinical control trials, and anecdotal evidence supporting the effectiveness of art therapies for use in addiction treatment, a systematic review conducted in 2018 could not find enough evidence on visual art, drama, dance and movement therapy, or 'arts in health' methodologies to confirm their effectiveness as interventions for reducing substance misuse.[211] Music therapy was identified to have potentially strong beneficial effects in aiding contemplation and preparing those diagnosed with substance use for treatment.[211]
As an assessment tool
The Formal Elements Art Therapy Scale (FEATS) is an assessment tool used to evaluate drawings created by people suffering from substance use disorders by comparing them to drawings of a control group (consisting of individuals without SUDs).[212][206] FEATS consists of twelve elements, three of which were found to be particularly effective at distinguishing the drawings of those with SUDs from those without: Person, Realism, and Developmental. The Person element assesses the degree to which a human features are depicted realistically, the Realism element assesses the overall complexity of the artwork, and the Developmental element assesses "developmental age" of the artwork in relation to standardized drawings from children and adolescents.[212] By using the FEATS assessment tool, clinicians can gain valuable insight into the drawings of individuals with SUDs, and can compare them to those of the control group. Formal assessments such as FEATS provide healthcare providers with a means to quantify, standardize, and communicate abstract and visceral characteristics of SUDs to provide more accurate diagnoses and informed treatment decisions.[212]
Other artistic assessment methods include the Bird's Nest Drawing: a useful tool for visualizing a client's attachment security.[213][206] This assessment method looks at the amount of color used in the drawing, with a lack of color indicating an 'insecure attachment', a factor that the client's therapist or recovery framework must take into account.[214]
Art therapists working with children of parents suffering from alcoholism can use the Kinetic Family Drawings assessment tool to shed light on family dynamics and help children express and understand their family experiences.[215][206] The KFD can be used in family sessions to allow children to share their experiences and needs with parents who may be in recovery from alcohol use disorder. Depiction of isolation of self and isolation of other family members may be an indicator of parental alcoholism.[215]
Advocacy
Stigma can lead to feelings of shame that can prevent people with substance use disorders from seeking help and interfere with provision of harm reduction services.[216][217][218] It can influence healthcare policy, making it difficult for these individuals to access treatment.[219]
Artists attempt to change the societal perception of addiction from a punishable moral offense to instead a chronic illness necessitating treatment. This form of advocacy can help to relocate the fight of addiction from a judicial perspective to the public health system.[220]
Artists who have personally lived with addiction and/or undergone recovery may use art to depict their experiences in a manner that uncovers the "human face of addiction". By bringing experiences of addiction and recovery to a personal level and breaking down the "us and them", the viewer may be more inclined to show compassion, forego stereotypes and stigma of addiction, and label addiction as a social rather than individual problem.[220]
According to Santora[220] the main purposes in using art as a form of advocacy in the education and prevention of substance use disorders include:
- Addiction art exhibitions can come from a variety of sources, but the underlying message of these works is the same: to communicate through emotions without relying on intellectually demanding/gatekept facts and figures. These exhibitions can either stand alone, reinforce, or challenge facts.
- A powerful educational tool for increasing awareness and understanding of addiction as a medical illness. Exhibitions featuring personal stories and images can help to create lasting impressions on diverse audiences (including addiction scientists/researchers, family/friends of those affected by addiction etc.), highlighting the humanity of the problem and in turn encouraging compassion and understanding.
- A way to destigmatize substance use disorders and shift public perception from viewing them as a moral failing to understanding them as a chronic medical condition which requires treatment.
- Provide those who are struggling with addiction assurance and encouragement of healing, and let them know that they are not alone in their struggle.
- The use of visual arts can help bring attention to the lack of adequate substance use treatment, prevention, and education programs and services in a healthcare system. Messages can encourage policymakers to allocate more resources to addiction treatment and prevention from federal, state, and local levels.
The Temple University College of Public Health department conducted a project to promote awareness around opioid use and reduce associated stigma by asking students to create art pieces that were displayed on a website they created and promoted via social media.[221] Quantitative and qualitative data was recorded to measure engagement, and the student artists were interviewed, which revealed a change in perspective and understanding, as well as greater appreciation of diverse experiences. Ultimately, the project found that art was an effective medium for empowering both the artist creating the work and the person interacting with it.[221]
Another author critically examined works by contemporary Canadian artists that deal with addiction via the metaphor of a cultural landscape to "unmap" and "remap" ideologies related to Indigenous communities and addiction to demonstrate how colonial violence in Canada has drastically impacted the relationship between Indigenous peoples, their land, and substance abuse.[222]
A project known as "Voice" was a collection of art, poetry and narratives created by women living with a history of addiction to explore women's understanding of harm reduction, challenge the effects of stigma and give voice to those who have historically been silenced or devalued.[223] In the project, nurses with knowledge of mainstream systems, aesthetic knowing, feminism and substance use organized weekly gatherings, wherein women with histories of substance use and addiction worked alongside a nurse to create artistic expressions. Creations were presented at several venues, including an International Conference on Drug Related Harm, a Nursing Conference and a local gallery to positive community response.[223]
Narrative Approach and Addiction
The narrative medicine to addiction focuses on recognizing, absorbing, and interpreting the stories of those suffering from addiction, allowing for better understanding of their experiences[224] with narrative analysis being used to study the discourse of those with addiction. This knowledge can be used to develop better care plans with the potential to increase patient compliance and make treatment more effective.
A narrative study demonstrated and studied cognitive and emotional tendencies among substance abusers during treatment periods to learn more about motivation and ambivalence inherent in recovery over the course of a residential treatment program.[225] Seven narrative types emerged from the overall analysis: optimistic, overly optimistic, pessimistic, overly pessimistic, "tough life," troubled/confused, and balanced. Narratives tended to express a basic level of emotionality in early stages of treatment ("optimistic", "pessimistic" narrative). Over time, as clients progressed through the program, their stories became more complex and detailed, including their drug abuse and recovery efforts, more skeptical positions towards treatment began to emerge. Clients began to distinguish between the positive and negative aspects of treatment, creating more "balanced" narratives in the process.[225]
Due to higher medication consumption, social isolation, financial worries, and other factors, older adults are particularly vulnerable to substance use problems.[226] Incidence of addiction among this population is inaccurately reported. Narrative therapy can provide an avenue to unearth stories of addiction in an empowering manner, and thus serves as a viable therapeutic tool in applied gerontology.[226] When treating substance abuse in older adults, it is essential to ensure that the client is respected and comfortable disclosing information. This should be done at the outset of treatment when the therapist and older adult are developing the therapeutic relationship.[227] The social breakdown model is an important tool that can consider the compounded effects of ageism, physical changes, social changes, and substance abuse. The narrative approach integrates the social breakdown model with substance abuse challenges and can be an effective way to address addiction in this population.[227]
A study conducted in 2009 in the Republic of Moldova looked into the social dynamics of initiating injection drug usage by examining 42 audio-recorded, semi-structured interviews with present and former injectors.[228] A thematic analysis suggested that self-injection was viewed as a symbolic transition of identity, enabled by interpersonal interactions and collective influences. Personal narratives of self-transition were connected to larger narratives of social transitions. The personal narratives of self-initiation and transition are contextualized and understood in terms of political (social) narratives within the core concept of the 'transitional society'.[228] Another study examined the narratives of 'initiators': people who help people who inject drugs (PWID) with their first injection.[229] Through their accounts, respondents described initiation events as meaningful transitions to a life characterized by predictable downfalls of homelessness, infections, and social stigma. Initiators used examples from their own personal experience to explain the process of initiation and assistance, attributing personal agency and predicting specific injection-related harms for initiates. They distinguished between two forms of harm: potentially avoidable proximal harm caused by risky injection practices (e.g. overdose, HIV) and perceived inevitable distal harm caused by long-term injection (e.g. socioeconomic decline).[229] In this way, these narratives reflect a balance of individual agency, harm reduction intentions, and accepted notions of 'life after initiation' interact with the narrative experiences and intentions of PWIDs.[228][229]
Philosophy
From a philosophy perspective, the behavior of many with addiction that is not explained by executive dysfunction or biological reasons can be explained by folk psychology – specifically the belief–desire model.[26] According to this model, a person acquires and uses a substance or does an addictive activity in belief that it will help them achieve a goal.
Social scientific models
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Biopsychosocial–cultural–spiritual
While regarded biomedically as a neuropsychological disorder, addiction is multi-layered, with biological, psychological, social, cultural, and spiritual (biopsychosocial–cultural–spiritual) elements.[230][231] A biopsychosocial–cultural–spiritual approach fosters the crossing of disciplinary boundaries, and promotes holistic considerations of addiction.[232][233][234] A biopsychosocial–cultural–spiritual approach considers, for example, how physical environments influence experiences, habits, and patterns of addiction.
Ethnographic engagements and developments in fields of knowledge have contributed to biopsychosocial–cultural–spiritual understandings of addiction, including the work of Philippe Bourgois, whose fieldwork with street-level drug dealers in East Harlem highlights correlations between drug use and structural oppression in the United States.[235] Prior models that have informed the prevailing biopsychosocial–cultural–spiritual consideration of addiction include:
Cultural model
The cultural model, an anthropological understanding of the emergence of drug use and abuse, was developed by Dwight Heath.[236] Heath undertook ethnographic research and fieldwork with the Camba people of Bolivia from June 1956 to August 1957.[237] Heath observed that adult members of society drank 'large quantities of rum and became intoxicated for several contiguous days at least twice a month'.[236] This frequent, heavy drinking from which intoxication followed was typically undertaken socially, during festivals.[237] Having returned in 1989, Heath observed that while much had changed, 'drinking parties' remained, as per his initial observations, and 'there appear to be no harmful consequences to anyone'.[238] Heath's observations and interactions reflected that this form of social behavior, the habitual heavy consumption of alcohol, was encouraged and valued, enforcing social bonds in the Camba community.[237] Despite frequent intoxication, "even to the point of unconsciousness", the Camba held no concept of alcoholism (a form of addiction), and no visible social problems associated with drunkenness, or addiction, were apparent.[236]
As noted by Merrill Singer, Heath's findings, when considered alongside subsequent cross-cultural experiences, challenged the perception that intoxication is socially 'inherently disruptive'.[236] Following this fieldwork, Heath proposed the 'cultural model', suggesting that 'problems' associated with heavy drinking, such as alcoholism – a recognised form addiction – were cultural: that is, that alcoholism is determined by cultural beliefs, and therefore varies among cultures. Heath's findings challenged the notion that 'continued use [of alcohol] is inexorably addictive and damaging to the consumer's health'.[237][236]
The cultural model did face criticism by Sociologist Robin Room and others, who felt anthropologists could "downgrade the severity of the problem".[236] Merrill Singer found it notable that the ethnographers working within the prominence of the cultural model were part of the 'wet generation': while not blind to the 'disruptive, dysfunctional and debilitating effects of alcohol consumption', they were products 'socialized to view alcohol consumption as normal'.[236]
Subcultural model
Historically, addiction has been viewed from the etic perspective, defining users through the pathology of their condition.[239] As reports of drug use rapidly increased, the cultural model found application in anthropological research exploring western drug subculture practices.[236]
The approach evolved from the ethnographic exploration into the lived experiences and subjectivities of 1960s and 1970s drug subcultures.[236] The seminal publication "Taking care of business", by Edward Preble and John J. Casey, documented the daily lives of New York street-based intravenous heroin users in rich detail, providing unique insight into the dynamic social worlds and activities that surrounded their drug use.[240] These findings challenge popular narratives of immorality and deviance, conceptualizing substance abuse as a social phenomenon. The prevailing culture can have a greater influence on drug taking behaviors than the physical and psychological effects of the drug itself.[241][better source needed] To marginalized individuals, drug subcultures can provide social connection, symbolic meaning, and socially constructed purpose that they may feel is unattainable through conventional means.[241] The subcultural model demonstrates the complexities of addiction, highlighting the need for an integrated approach. It contends that a biosocial approach is required to achieve a holistic understanding of addiction.[236]
Critical medical anthropology model
Emerging in the early 1980s, the critical medical anthropology model was introduced, and as Merrill Singer offers 'was applied quickly to the analysis of drug use'.[236] Where the cultural model of the 1950s looked at the social body, the critical medical anthropology model revealed the body politic, considering drug use and addiction within the context of macro level structures including larger political systems, economic inequalities, and the institutional power held over social processes.[236]
Highly relevant to addiction, the three issues emphasized in the model are:
- Self-medication
- The social production of suffering
- The political economy (Licit and Illicit Drugs)[236]
These three key points highlight how drugs may come to be used to self-medicate the psychological trauma of socio-political disparity and injustice, intertwining with licit and illicit drug market politics.[236] Social suffering, "the misery among those on the weaker end of power relations in terms of physical health, mental health and lived experience", is used by anthropologists to analyze how individuals may have personal problems caused by political and economic power.[236] From the perspective of critical medical anthropology heavy drug use and addiction is a consequence of such larger scale unequal distributions of power.[236]
The three models developed here – the cultural model, the subcultural model, and the Critical Medical Anthropology Model – display how addiction is not an experience to be considered only biomedically. Through consideration of addiction alongside the biological, psychological, social, cultural and spiritual (biopsychosocial–spiritual) elements which influence its experience, a holistic and comprehensive understanding can be built.
Social learning models
Social learning theory
Albert Bandura's 1977 social learning theory posits that individuals acquire addictive behaviors by observing and imitating models in their social environment.[242][243] The likelihood of engaging in and sustaining similar addictive behaviors is influenced by the reinforcement and punishment observed in others. The principle of reciprocal determinism suggests that the functional relationships between personal, environmental, and behavioral factors act as determinants of addictive behavior.[244] Thus, effective treatment targets each dynamic facet of the biopsychosocial disorder.
Transtheoretical model (stages of change model)
The transtheoretical model of change suggests that overcoming an addiction is a stepwise process that occurs through several stages.[245]
Precontemplation: This initial stage precedes individuals considering a change in their behavior. They might be oblivious to or in denial of their addiction, failing to recognize the need for change.
Contemplation is the stage in which individuals become aware of the problems caused by their addiction and are considering change. Although they may not fully commit, they weigh the costs and benefits of making a shift.
Preparation: Individuals in this stage are getting ready to change. They might have taken preliminary steps, like gathering information or making small commitments, in preparation for behavioral change.
Action involves actively modifying behavior by making specific, observable changes to address the addictive behavior. The action stage requires significant effort and commitment.
Maintenance: After successfully implementing a change, individuals enter the maintenance stage, where they work to sustain the new behavior and prevent relapse. This stage is characterized by ongoing effort and consolidation of gains.
Termination/relapse prevention: Recognizing that relapse is a common part of the change process, this stage focuses on identifying and addressing factors that may lead to a return to old behaviors. Relapse is viewed as an opportunity for learning and strategy adjustment, with the ultimate goal of eliminating or terminating the targeted behavior.
The transtheoretical model can be helpful in guiding development of tailored behavioral interventions that can promote lasting change. Progression through these stages may not always follow a linear path, as individuals may move back and forth between stages. Resistance to change is recognized as an expected part of the process.
Addiction causes an "astoundingly high financial and human toll" on individuals and society as a whole.[246][180][183] In the United States, the total economic cost to society is greater than that of all types of diabetes and all cancers combined.[183] These costs arise from the direct adverse effects of drugs and associated healthcare costs (e.g., emergency medical services and outpatient and inpatient care), long-term complications (e.g., lung cancer from smoking tobacco products, liver cirrhosis and dementia from chronic alcohol consumption, and meth mouth from methamphetamine use), the loss of productivity and associated welfare costs, fatal and non-fatal accidents (e.g., traffic collisions), suicides, homicides, and incarceration, among others.[246][180][183][247] The US National Institute on Drug Abuse has found that overdose deaths in the US have almost tripled among male and females from 2002 to 2017, with 72,306 overdose deaths reported in 2017 in the US.[248] 2020 marked the year with highest number of overdose deaths over a 12-month period, with 81,000 overdose deaths, exceeding the records set in 2017.[249]
See also
Endnotes
- ^ In other words, a person cannot control the neurobiological processes that occur in the body in response to using an addictive drug. A person can make a voluntary choice to, for example, start using a drug (or not), or to seek help after becoming addicted, although resisting the urge to use drug(s) becomes increasingly difficult as addiction worsens. See [1] for detailed discussion.
Notes
- ^ According to a review of experimental animal models that examined the transgenerational epigenetic inheritance of epigenetic marks that occur in addiction, alterations in histone acetylation – specifically, di-acetylation of lysine residues 9 and 14 on histone 3 (i.e., H3K9ac2 and H3K14ac2) in association with BDNF gene promoters – have been shown to occur within the medial prefrontal cortex (mPFC), testes, and sperm of cocaine-addicted male rats.[87] These epigenetic alterations in the rat mPFC result in increased BDNF gene expression within the mPFC, which in turn blunts the rewarding properties of cocaine and reduces cocaine self-administration.[87] The male but not female offspring of these cocaine-exposed rats inherited both epigenetic marks (i.e., di-acetylation of lysine residues 9 and 14 on histone 3) within mPFC neurons, the corresponding increase in BDNF expression within mPFC neurons, and the behavioral phenotype associated with these effects (i.e., a reduction in cocaine reward, resulting in reduced cocaine-seeking by these male offspring).[87] Consequently, the transmission of these two cocaine-induced epigenetic alterations (i.e., H3K9ac2 and H3K14ac2) in rats from male fathers to male offspring served to reduce the offspring's risk of developing an addiction to cocaine.[87] As of 2018,[update] neither the heritability of these epigenetic marks in humans nor the behavioral effects of the marks within human mPFC neurons has been established.[87]
- ^ a b A decrease in aversion sensitivity, in simpler terms, means that an individual's behavior is less likely to be influenced by undesirable outcomes.
- ^ In other words, c-Fos repression allows ΔFosB to more rapidly accumulate within the D1-type medium spiny neurons of the nucleus accumbens because it is selectively induced in this state.[2] Before c-Fos repression, all Fos family proteins (e.g., c-Fos, Fra1, Fra2, FosB, and ΔFosB) are induced together, with ΔFosB expression increasing to a lesser extent.[2]
- ^ According to two medical reviews, ΔFosB has been implicated in causing both increases and decreases in dynorphin expression in different studies;[118][148] this table entry reflects only a decrease.
- ^ Incentive salience, the "motivational salience" for a reward, is a "desire" or "want" attribute, which includes a motivational component, that the brain assigns to a rewarding stimulus.[149][150] As a consequence, incentive salience acts as a motivational "magnet" for a rewarding stimulus that commands attention, induces approach, and causes the rewarding stimulus to be sought out.[149]
- ^ In simplest terms, this means that when either amphetamine or sex is perceived as more alluring or desirable through reward sensitization, this effect occurs with the other as well.
- ^ The lifetime prevalence of an addiction is the percentage of individuals in a population that developed an addiction at some point in their life.
- Image legend
- ^ (Text color) Transcription factors
References
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pre-existing vulnerabilities and persistent drug use lead to a vicious circle of substantive disruptions in the brain that impair and undermine choice capacities for adaptive behavior, but do not annihilate them.
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Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
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Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance.
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Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder. - ^ a b c d NIDA (13 July 2020). "Drug Misuse and Addiction". National Institute of Drug Abuse. U.S. Department of Health and Human Services. Retrieved 15 November 2022.
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Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some people taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."
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ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
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Sexual addiction, which is also known as hypersexual disorder, has largely been ignored by psychiatrists, even though the condition causes serious psychosocial problems for many people. A lack of empirical evidence on sexual addiction is the result of the disease's complete absence from versions of the Diagnostic and Statistical Manual of Mental Disorders. ... Existing prevalence rates of sexual addiction-related disorders range from 3% to 6%. Sexual addiction/hypersexual disorder is used as an umbrella construct to encompass various types of problematic behaviors, including excessive masturbation, cybersex, pornography use, sexual behavior with consenting adults, telephone sex, strip club visitation, and other behaviors. The adverse consequences of sexual addiction are similar to the consequences of other addictive disorders. Addictive, somatic and psychiatric disorders coexist with sexual addiction. In recent years, research on sexual addiction has proliferated, and screening instruments have increasingly been developed to diagnose or quantify sexual addiction disorders. In our systematic review of the existing measures, 22 questionnaires were identified. As with other behavioral addictions, the appropriate treatment of sexual addiction should combine pharmacological and psychological approaches.
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Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
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Today, arguably more than at any time in history, the constructs of attention, executive functioning, and cognitive control seem to be pervasive and preeminent in research and theory. Even within the cognitive framework, however, there has long been an understanding that behavior is multiply determined, and that many responses are relatively automatic, unattended, contention-scheduled, and habitual. Indeed, the cognitive flexibility, response inhibition, and self-regulation that appear to be hallmarks of cognitive control are noteworthy only in contrast to responses that are relatively rigid, associative, and involuntary.
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Core EFs are inhibition [response inhibition (self-control – resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)], working memory, and cognitive flexibility (including creatively thinking "outside the box," seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances). ... EFs and prefrontal cortex are the first to suffer, and suffer disproportionately, if something is not right in your life. They suffer first, and most, if you are stressed (Arnsten 1998, Liston et al. 2009, Oaten & Cheng 2005), sad (Hirt et al. 2008, von Hecker & Meiser 2005), lonely (Baumeister et al. 2002, Cacioppo & Patrick 2008, Campbell et al. 2006, Tun et al. 2012), sleep deprived (Barnes et al. 2012, Huang et al. 2007), or not physically fit (Best 2010, Chaddock et al. 2011, Hillman et al. 2008). Any of these can cause you to appear to have a disorder of EFs, such as ADHD, when you do not. You can see the deleterious effects of stress, sadness, loneliness, and lack of physical health or fitness at the physiological and neuroanatomical level in prefrontal cortex and at the behavioral level in worse EFs (poorer reasoning and problem solving, forgetting things, and impaired ability to exercise discipline and self-control). ...
EFs can be improved (Diamond & Lee 2011, Klingberg 2010). ... At any age across the life cycle EFs can be improved, including in the elderly and in infants. There has been much work with excellent results on improving EFs in the elderly by improving physical fitness (Erickson & Kramer 2009, Voss et al. 2011) ... Inhibitory control (one of the core EFs) involves being able to control one's attention, behavior, thoughts, and/or emotions to override a strong internal predisposition or external lure, and instead do what's more appropriate or needed. Without inhibitory control we would be at the mercy of impulses, old habits of thought or action (conditioned responses), and/or stimuli in the environment that pull us this way or that. Thus, inhibitory control makes it possible for us to change and for us to choose how we react and how we behave rather than being unthinking creatures of habit. It doesn't make it easy. Indeed, we usually are creatures of habit and our behavior is under the control of environmental stimuli far more than we usually realize, but having the ability to exercise inhibitory control creates the possibility of change and choice. ... The subthalamic nucleus appears to play a critical role in preventing such impulsive or premature responding (Frank 2006). - ^ a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 313–21. ISBN 978-0-07-148127-4.
• Executive function, the cognitive control of behavior, depends on the prefrontal cortex, which is highly developed in higher primates and especially humans.
• Working memory is a short-term, capacity-limited cognitive buffer that stores information and permits its manipulation to guide decision-making and behavior. ...
These diverse inputs and back projections to both cortical and subcortical structures put the prefrontal cortex in a position to exert what is called "top-down" control or cognitive control of behavior. ... The prefrontal cortex receives inputs not only from other cortical regions, including association cortex, but also, via the thalamus, inputs from subcortical structures subserving emotion and motivation, such as the amygdala (Chapter 14) and ventral striatum (or nucleus accumbens; Chapter 15). ...
In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 15), or in attention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result. ... ADHD can be conceptualized as a disorder of executive function; specifically, ADHD is characterized by reduced ability to exert and maintain cognitive control of behavior. Compared with healthy individuals, those with ADHD have diminished ability to suppress inappropriate prepotent responses to stimuli (impaired response inhibition) and diminished ability to inhibit responses to irrelevant stimuli (impaired interference suppression). ... Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the striatum) in tasks that demand inhibitory control of behavior. Subjects with ADHD exhibit less activation of the medial prefrontal cortex than healthy controls even when they succeed in such tasks and utilize different circuits. ... Early results with structural MRI show thinning of the cerebral cortex in ADHD subjects compared with age-matched controls in prefrontal cortex and posterior parietal cortex, areas involved in working memory and attention. - ^ a b c d e f Gould TJ (December 2010). "Addiction and cognition". Addiction Science & Clinical Practice. 5 (2): 4–14. PMC 3120118. PMID 22002448.
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However, the components that are responsible for the heritability of characteristics that make an individual more susceptible to drug addiction in humans remain largely unknown given that patterns of inheritance cannot be explained by simple genetic mechanisms (Cloninger et al., 1981; Schuckit et al., 1972). The environment plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse. ...
The evidence presented here demonstrates that rapid environmental adaptation occurs following exposure to a number of stimuli. Epigenetic mechanisms represent the key components by which the environment can influence genetics, and they provide the missing link between genetic heritability and environmental influences on the behavioral and physiological phenotypes of the offspring. - ^ Douglas KR, Chan G, Gelernter J, Arias AJ, Anton RF, Weiss RD, et al. (January 2010). "Adverse childhood events as risk factors for substance dependence: partial mediation by mood and anxiety disorders". Addictive Behaviors. 35 (1): 7–13. doi:10.1016/j.addbeh.2009.07.004. PMC 2763992. PMID 19720467.
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- ^ a b c d e f g h i j Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am. J. Drug Alcohol Abuse. 40 (6): 428–37. doi:10.3109/00952990.2014.933840. PMID 25083822. S2CID 19157711.
ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades[...]As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
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[...]ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence.
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[Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its targets. This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the histone acetyltransferase, CREB binding protein (CBP) to acetylate histones and facilitate gene activation. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure. ΔFosB is also upregulated by chronic psychostimulant treatments, and is known to activate certain genes (eg, cdk5) and repress others (eg, c-fos) where it recruits HDAC1 as a corepressor. ... Chronic exposure to psychostimulants increases glutamatergic [signaling] from the prefrontal cortex to the NAc. Glutamatergic signaling elevates Ca2+ levels in NAc postsynaptic elements where it activates CaMK (calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5.
Figure 2: Psychostimulant-induced signaling events - ^ Broussard JI (January 2012). "Co-transmission of dopamine and glutamate". The Journal of General Physiology. 139 (1): 93–96. doi:10.1085/jgp.201110659. PMC 3250102. PMID 22200950.
Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex (PFC), as well as projections from midbrain dopamine neurons. Previous studies have demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses (Goto and Grace, 2005). The converse was also shown to be true; stimulation at PFC potentiates PFC–NAc synapses but depresses hippocampal–NAc synapses. In light of the new functional evidence of midbrain dopamine/glutamate co-transmission (references above), new experiments of NAc function will have to test whether midbrain glutamatergic inputs bias or filter either limbic or cortical inputs to guide goal-directed behavior.
- ^ Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)". KEGG Pathway. Retrieved 31 October 2014.
Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. ... Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain.
- ^ Cadet JL, Brannock C, Jayanthi S, Krasnova IN (2015). "Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat". Molecular Neurobiology. 51 (2): 696–717 (Figure 1). doi:10.1007/s12035-014-8776-8. PMC 4359351. PMID 24939695.
- ^ a b c Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews Neuroscience. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.
Figure 4: Epigenetic basis of drug regulation of gene expression - ^ a b c d Nestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clinical Psychopharmacology and Neuroscience. 10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMC 3569166. PMID 23430970.
The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB ... In contrast, the ability of ΔFosB to repress the c-Fos gene occurs in concert with the recruitment of a histone deacetylase and presumably several other repressive proteins such as a repressive histone methyltransferase
- ^ Nestler EJ (October 2008). "Transcriptional mechanisms of addiction: Role of ΔFosB". Philosophical Transactions of the Royal Society B: Biological Sciences. 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924.
Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure
- ^ a b Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–98. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.
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- ^ Kanehisa Laboratories (2 August 2013). "Alcoholism – Homo sapiens (human)". KEGG Pathway. Retrieved 10 April 2014.
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- ^ a b c d e Nestler EJ (January 2014). "Epigenetic mechanisms of drug addiction". Neuropharmacology. 76 (Pt B): 259–68. doi:10.1016/j.neuropharm.2013.04.004. PMC 3766384. PMID 23643695.
Short-term increases in histone acetylation generally promote behavioral responses to the drugs, while sustained increases oppose cocaine's effects, based on the actions of systemic or intra-NAc administration of HDAC inhibitors. ... Genetic or pharmacological blockade of G9a in the NAc potentiates behavioral responses to cocaine and opiates, whereas increasing G9a function exerts the opposite effect (Maze et al., 2010; Sun et al., 2012a). Such drug-induced downregulation of G9a and H3K9me2 also sensitizes animals to the deleterious effects of subsequent chronic stress (Covington et al., 2011). Downregulation of G9a increases the dendritic arborization of NAc neurons, and is associated with increased expression of numerous proteins implicated in synaptic function, which directly connects altered G9a/H3K9me2 in the synaptic plasticity associated with addiction (Maze et al., 2010).
G9a appears to be a critical control point for epigenetic regulation in NAc, as we know it functions in two negative feedback loops. It opposes the induction of ΔFosB, a long-lasting transcription factor important for drug addiction (Robison and Nestler, 2011), while ΔFosB in turn suppresses G9a expression (Maze et al., 2010; Sun et al., 2012a). ... Also, G9a is induced in NAc upon prolonged HDAC inhibition, which explains the paradoxical attenuation of cocaine's behavioral effects seen under these conditions, as noted above (Kennedy et al., 2013). GABAA receptor subunit genes are among those that are controlled by this feedback loop. Thus, chronic cocaine, or prolonged HDAC inhibition, induces several GABAA receptor subunits in NAc, which is associated with increased frequency of inhibitory postsynaptic currents (IPSCs). In striking contrast, combined exposure to cocaine and HDAC inhibition, which triggers the induction of G9a and increased global levels of H3K9me2, leads to blockade of GABAA receptor and IPSC regulation. - ^ a b c d Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, et al. (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964.
It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.
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Although the ΔFosB signal is relatively long-lived, it is not permanent. ΔFosB degrades gradually and can no longer be detected in [the] brain after 1–2 months of drug withdrawal ... Indeed, ΔFosB is the longest-lived adaptation known to occur in [the] adult brain, not only in response to drugs of abuse, but to any other perturbation (that doesn't involve lesions) as well.
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Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch – from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure – cited earlier (Renthal et al. in press). The mechanism responsible for ΔFosB repression of c-fos expression is complex and is covered below. ...
Examples of validated targets for ΔFosB in nucleus accumbens ... GluR2 ... dynorphin ... Cdk5 ... NFκB ... c-Fos
Table 3 - ^ a b c d e f Berridge KC (April 2012). "From prediction error to incentive salience: mesolimbic computation of reward motivation". Eur. J. Neurosci. 35 (7): 1124–43. doi:10.1111/j.1460-9568.2012.07990.x. PMC 3325516. PMID 22487042.
Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. ... Associative learning and prediction are important contributors to motivation for rewards. Learning gives incentive value to arbitrary cues such as a Pavlovian conditioned stimulus (CS) that is associated with a reward (unconditioned stimulus or UCS). Learned cues for reward are often potent triggers of desires. For example, learned cues can trigger normal appetites in everyone, and can sometimes trigger compulsive urges and relapse in individuals with addictions.
Cue-triggered 'wanting' for the UCS
A brief CS encounter (or brief UCS encounter) often primes a pulse of elevated motivation to obtain and consume more reward UCS. This is a signature feature of incentive salience.
Cue as attractive motivational magnets
When a Pavlovian CS+ is attributed with incentive salience it not only triggers 'wanting' for its UCS, but often the cue itself becomes highly attractive – even to an irrational degree. This cue attraction is another signature feature of incentive salience ... Two recognizable features of incentive salience are often visible that can be used in neuroscience experiments: (i) UCS-directed 'wanting' – CS-triggered pulses of intensified 'wanting' for the UCS reward; and (ii) CS-directed 'wanting' – motivated attraction to the Pavlovian cue, which makes the arbitrary CS stimulus into a motivational magnet. - ^ a b Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (second ed.). New York: McGraw-Hill Medical. pp. 147–48, 366–67, 375–76. ISBN 978-0-07-148127-4.
VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc. ... If motivational drive is described in terms of wanting, and hedonic evaluation in terms of liking, it appears that wanting can be dissociated from liking and that dopamine may influence these phenomena differently. Differences between wanting and liking are confirmed in reports by humans with addictions, who state that their desire for drugs (wanting) increases with continued use even when pleasure (liking) decreases because of tolerance. - ^ a b c d Edwards S (2016). "Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder". Neuroscience for Addiction Medicine: From Prevention to Rehabilitation - Constructs and Drugs. Progress in Brain Research. Vol. 223. pp. 63–76. doi:10.1016/bs.pbr.2015.07.005. ISBN 978-0-444-63545-7. PMID 26806771.
An important dimension of reinforcement highly relevant to the addiction process (and particularly relapse) is secondary reinforcement (Stewart, 1992). Secondary reinforcers (in many cases also considered conditioned reinforcers) likely drive the majority of reinforcement processes in humans. In the specific case of drug addiction, cues and contexts that are intimately and repeatedly associated with drug use will themselves become reinforcing ... A fundamental piece of Robinson and Berridge's incentive-sensitization theory of addiction posits that the incentive value or attractive nature of such secondary reinforcement processes, in addition to the primary reinforcers themselves, may persist and even become sensitized over time in league with the development of drug addiction (Robinson and Berridge, 1993).
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Studies investigating general HDAC inhibition on behavioral outcomes have produced varying results but it seems that the effects are specific to the timing of exposure (either before, during or after exposure to drugs of abuse) as well as the length of exposure
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The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2013), which uses the term substance use disorder, is flawed. Criteria used to make the diagnosis of substance use disorders include tolerance and somatic dependence/withdrawal, even though these processes are not integral to addiction as noted. It is ironic and unfortunate that the manual still avoids use of the term addiction as an official diagnosis, even though addiction provides the best description of the clinical syndrome.
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Initial drug use can be attributed to the ability of the drug to act as a reward (ie, a pleasurable emotional state or positive reinforcer), which can lead to repeated drug use and dependence.8,9 A great deal of research has focused on the molecular and neuroanatomical mechanisms of the initial rewarding or reinforcing effect of drugs of abuse. ... At present, no pharmacological therapy has been approved by the FDA to treat psychostimulant addiction. Many drugs have been tested, but none have shown conclusive efficacy with tolerable side effects in humans.172 ... A new emphasis on larger-scale biomarker, genetic, and epigenetic research focused on the molecular targets of mental disorders has been recently advocated.212 In addition, the integration of cognitive and behavioral modification of circuit-wide neuroplasticity (i.e., computer-based training to enhance executive function) may prove to be an effective adjunct-treatment approach for addiction, particularly when combined with cognitive enhancers.198,213–216 Furthermore, in order to be effective, all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation, such as CBT, individual and group psychotherapy, behavior-modification strategies, twelve-step programs, and residential treatment facilities.
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Sixteen percent of the non-institutionalized U.S. population age 12 and over – more than 40 million Americans – meets medical criteria for addiction involving nicotine, alcohol or other drugs. This is more than the number of Americans with cancer, diabetes or heart conditions. In 2014, 22.5 million people in the United States needed treatment for addiction involving alcohol or drugs other than nicotine, but only 11.6 percent received any form of inpatient, residential, or outpatient treatment. Of those who do receive treatment, few receive evidence-based care. (There is no information available on how many individuals receive treatment for addiction involving nicotine.)
Risky substance use and untreated addiction account for one-third of inpatient hospital costs and 20 percent of all deaths in the United States each year, and cause or contribute to more than 100 other conditions requiring medical care, as well as vehicular crashes, other fatal and non-fatal injuries, overdose deaths, suicides, homicides, domestic discord, the highest incarceration rate in the world and many other costly social consequences. The economic cost to society is greater than the cost of diabetes and all cancers combined. Despite these startling statistics on the prevalence and costs of addiction, few physicians have been trained to prevent or treat it. - ^ a b c Volkow N (31 March 2016). "A Major Step Forward for Addiction Medicine". National Institute on Drug Abuse. National Institutes of Health. Archived from the original on 5 April 2016. Retrieved 3 April 2016.
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Further reading
- Pelchat ML (March 2009). "Food Addiction in Humans". The Journal of Nutrition. 139 (3): 620–622. doi:10.3945/jn.108.097816. PMID 19176747.
- Gordon HW (April 2016). "Laterality of Brain Activation for Risk Factors of Addiction". Current Drug Abuse Reviews. 9 (1): 1–18. doi:10.2174/1874473709666151217121309. PMC 4811731. PMID 26674074.
- Szalavitz M (2016). Unbroken Brain. St. Martin's Press. ISBN 978-1-250-05582-8.
External links
- "The Science of Addiction: Genetics and the Brain". learn.genetics.utah.edu. Learn.Genetics – University of Utah.
- Why do our brains get addicted? – a TEDMED 2014 talk by Nora Volkow, the director of the National Institute on Drug Abuse at NIH.
Kyoto Encyclopedia of Genes and Genomes (KEGG) signal transduction pathways:
- KEGG – human alcohol addiction
- KEGG – human amphetamine addiction
- KEGG – human cocaine addiction