Vaccines against morphine/heroine and its use as effective medication for preventing relapse to opiate addictive behaviors

Abstract

cues remains very high in individuals, even after many years of abstinence and after the last withdrawal symptom has receded. 7-9 Most of our knowledge and comprehension of drug habits and chronic relapse to drug-intake behaviors is based on the several decades of devoted search for the neurobiological mechanisms of motivation and choice for biological rewards, such as food and sex, as well as the understanding of the cognitive and experientially social-produced rewards (i.e., friendship, family and social status). 7,10 Moreover, the physiological mechanisms of the neural pathways and neuroplasticity events that underlie the generation of adaptive behavioral responses to motivationally relevant events and natural rewards, have led to a significant understanding of the pathological deregulation of cellular and molecular mechanisms and circuitry functions induced by drug addiction. 1,7,10 These altered changes in cellular and molecular mechanisms in drug addiction led researchers to postulate that "Addiction represents a pathological usurpation of the neural mechanisms of learning and memory that under normal circumstances serve to shape survival behaviors related to the pursuit of rewards and the cues that predict them." 1 In addition to this postulate, the advances in the search of the neural mechanisms of drug addiction showed that persistence vulnerability to drug-relapse in addicts after prolonged drug-free periods is caused by enduring, long-lasting changes in brain function (i.e., neuroadaptative plastic mechanisms) as a result of repeated drug use, genetic disposition and environmental associations learned with continuous drug use. 7 It has long been recognized that reward-processing depends on mesocorticolimbic dopamine (DA) system, comprising DA neurons in the ventral tegmental area (VTA) and their projections to the nucleus accumbens (NAc), amygdala, prefrontal cortex (PFCx) and other forebrain regions. 1,7,11 Addictive drugs act on the DA reward system, although the brain evolved to respond not to drugs but to natural rewards, such as food and sex. Appropriate responses to natural rewards have been evolutionarily important for survival, reproduction and for shaping several functions and behaviors. In the turn of the evolutionary ladder, humans discovered how to stimulate this system artificially with drugs. 12,13 The chemicals that the human abuse are structurally diverse and produce different behavioral effects in the user. However all share the common feature that they can interact, modulate Current pharmacotherapies for treating morphine/heroin dependence are designed to substitute or block addiction by targeting the drug itself rather than the brain. The heroin addict is still being exposed to addictive opiates, and consequently may develop tolerance to and experience withdrawal and drug's toxic effects from the treatment with high incidence of relapse to addictive drug consumption. As for other drugs of abuse, an alternative approach for morphine/heroin addiction is an antibody-based antagonism of...

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

“…Vaccines against methamphetamine have been developed for the potential treatment of methamphetamine addiction (Duryee et al, 2009;Gentry et al, 2009;Xu et al, 2007). A heroin/morphine vaccine was also effective in decreasing heroin self-administration in rats (Anton and Leff, 2006;Anton et al, 2009).…”

Nuevas vacunas contra la morfina-heroína

“…17,18 El objetivo inicial fue lograr que su mecanismo fuera válido y aplicable para producir efectos terapéuticos inmunoprotectores contra recaídas al consumo adictivo de morfina/heroína en un modelo animal con roedores (fase pre-clínica). Una de las grandes ventajas de este modelo estructural de vacuna bivalente morfina/heroína (M-TT) es que los elementos que la conforman están certificados por la FDA para uso humano, lo cual le permite ser usada rápidamente en protocolos clínicos.…”

“…Posteriormente hay un progresivo decaimiento de los anticuerpos anti-morfina/heroína, llegando a niveles no detectables de 10 a 12 meses después de su última inmunización. Esto sugiere que la vacuna M-TT no sólo es efectiva en generar grandes cantidades de anticuerpos sino también es capaz de activar a largo plazo la memoria inmunológica humoral contra estos opioides 17,18,48 Cierta especificidad a la morfina. Reacción cruzada a la codeína.…”

Inmunoprotección activa contra cocaína

“…1,2 Además, su aplicación como terapéutica a largo plazo no produce efectos secundarios tóxicos colaterales, a menudo detectados con las farmacopeas clásicas antiadictivas empleadas comúnmente contra la adicción a esta sustancia psicoestimulante. 4,9,10 Esta estrategia farmacológica experimental, de naturaleza "inmunoprotectora", ha demostrado ser un tratamiento eficaz para atenuar significativamente y/o inhibir las conductas de búsqueda y consumo adictivo a la morfina/heroína, [11][12][13] nicotina, 14 metanfetaminas 15 y cocaína, 1,16-23 tanto a nivel preclínico, en el modelo del roedor, 16,21,22,24,25 como en el humano. 9,10,26 En este último caso, un ejemplo notable del desarrollo de estudios de fases clínicas I-III, es para el caso particular de la cocaína.…”