Novel pharmacotherapeutic treatments for cocaine addiction

Abstract

Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage.

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…Considering the primary involvement of dopamine in the abuse-related behavioral effects of cocaine, it is unsurprising that brain dopamine transporters and receptors have been targeted frequently in the development of pharmacotherapies for cocaine use disorder (e.g., Davies et al, 1993;Carroll et al, 1999;Grabowski et al, 2004;Heidbreder and Newman, 2010). In addition, drugs have been developed to indirectly modulate the effects of cocaine through 5-HT, glutamate and g-aminobutyric acid (GABA) and other systems (e.g., Cousins et al, 2002;Johnson, 2005;Negus et al, 2007;Bubar and Cunningham, 2008;Kalivas and Volkow, 2011;Shorter and Kosten, 2011;Li et al, 2013).…”

Nuevas vacunas contra la morfina-heroína

“…Estas nuevas estrategias experimentales están basadas en el diseño y síntesis de diversas formulaciones estructurales de vacunas terapéuticas contra la adicción a cocaína, [10][11][12][13] nicotina [14][15][16] y heroína/morfina, 17-20 las cuales, al ser dosificadas en esquemas de inmunización activa en modelos animales como el roedor o en el humano, inducen la producción de anticuerpos séricos específicos que reconocen y se unen a estas sustancias en el espacio intravascular sistémico. Estos anticuerpos anti-droga poseen la capacidad de secuestrar al compuesto adictivo circulante en el torrente sanguíneo ya que los anticuerpos son macromoléculas (≈150 kD) que normalmente no permean la barrera hematoencefálica, formando así complejos moleculares anticuerpo-droga de alto peso molecular, que "secuestran" e impiden el paso de la droga a través de la barrera hematoencefálica.…”

Dysregulation of RGS Proteins by Psychostimulants

“…In recent years, focus has been shifted to compounds that are indirect D2 receptor agonists or D2 receptor modulators. Recent clinical trials with indirect dopamine receptor agonists such as AMPH derivatives are promising [see review in [21]. Therefore, it is imperative to understand the regulatory machineries underlying receptor adaptations to psychostimulant exposure, which will provide opportunities for identifying novel drug targets.…”