Investigational drug therapies in phase I and phase II clinical trials for alcohol use disorders

A balancing act: the role of pro‐ and anti‐stress peptides within the central amygdala in anxiety and alcohol use disorders

“…Excessive alcohol use costs the US more than $249 billion annually (Sacks et al, 2015). Relapse and cravings are a major hurdle for the treatment of alcohol use disorder (AUD), with many current treatments unable to adequately protect against the negative affect and cravings associated with abstinence following long-term alcohol use (Hunt et al, 1971;Sinha, 2012;Walker & Lawrence, 2018). It has long been acknowledged that stress and anxiety play a key role in consumption, escalation and relapse to alcohol seeking (Kushner et al, 1990;Sinha, 2012).…”

Translational approach to understanding momentary factors associated with alcohol consumption

“…For instance, Rubio, Martínez‐Gras, and Manzanares (2009) demonstrated reductions in craving, and alcohol consumption associated with topiramate treatment may be related to changes in trait impulsivity. It should be mentioned, however, that anticonvulsants, such as topiramate, have been shown to cause cognitive decline (Walker & Lawrence, 2018). Preclinical studies showed that the noradrenaline/5‐HT reuptake inhibitor atomoxetine, several 5‐HT antagonists, a 5‐HT agonist WAY‐163909 and several other monoaminergic compounds decreased impulsivity in both animals and humans (for a review, see Winstanley, 2011).…”

“…Preclinical studies showed that the noradrenaline/5‐HT reuptake inhibitor atomoxetine, several 5‐HT antagonists, a 5‐HT agonist WAY‐163909 and several other monoaminergic compounds decreased impulsivity in both animals and humans (for a review, see Winstanley, 2011). Two monoaminergic compounds, modafinil and guanfacine, are currently under development for treatment of alcohol use disorder and have been demonstrated to significantly improve self‐report measures of impulsivity (Walker & Lawrence, 2018). Given the crucial role of the frontal cortex in mediating impulsive actions (Dalley et al, 2011), the glutamatergic system and especially metabotropic glutamate receptors are considered promising targets (Winstanley, 2011).…”

“…Another μ‐opioid receptor antagonist and a partial κ‐opioid receptor agonist, nalmefene, have recently been approved for reduction of alcohol consumption. However, the effectiveness of these medications in reducing the probability of alcohol consumption remains limited or beneficial only in a subset of the population due to issues such as compliance, side effects, and lack of a personalized medicine approach (Walker & Lawrence, 2018). The identification of momentary state‐dependent factors and high‐risk situations associated with increased probability of drug use could suggest novel strategies for the development of individual therapeutic approaches.…”

Pattern of neural activation following yohimbine‐induced reinstatement of alcohol seeking in rats

“…Despite the extensive disease burden of alcohol use disorders (AUD) effective pharmacotherapies are still lacking. While FDA approved medications are efficacious in certain subpopulations with AUD, they are all inadequate at a population level (Jupp & Lawrence, ; Lyon, ; Walker & Lawrence, ). A major obstacle in treating addiction is the high rate of relapse, with up to 90% of addicts relapsing within 12 months of abstinence (Dejong, ).…”