In addition to causing myriad health problems, injury and death, the harmful use of alcohol contributes to significant social and economic loss for individuals, families, and society. A new study has found that medication used to treat skin conditions might effectively combat problem drinking.
The damaging effects of alcohol on the body are well-known. A complex psychiatric disease, alcohol use disorder (AUD) is characterized by an inability to stop or control alcohol consumption despite its negative social, occupational, or health consequences. AUD is an umbrella term for alcohol abuse, alcohol dependence, alcohol addiction, and the colloquial term alcoholism.
While there is a greater understanding of AUD’s underlying genetic and molecular mechanisms, there has been little advancement in pharmacological treatment options for the disorder since 2004, when the US Food and Drug Administration (FDA) approved the use of acamprosate (Campral). There are only two other medications currently available to treat AUD – disulfiram (Antabuse) and naltrexone – prompting a team of researchers from around the US to look into the suitability of currently available medications for use as a new treatment option.
Researchers relied on previous studies that supported the influence of the body’s immune and inflammatory responses on binge drinking, motivation to drink, and alcohol dependence. Genome-wide association studies, which help scientists to identify the genes associated with a particular disease, suggested a link between the enzyme phosphodiesterase-4 (PDE4), particularly the subtype PDE4b, and alcohol and nicotine dependence.
PDE4 causes the degradation of cyclic adenosine monophosphate (cAMP), an intracellular molecule that plays an important role in the inflammatory process. Inhibiting the degradation of cAMP by PDE4 has been shown to have therapeutic utility, including an anti-inflammatory effect.
One such PDE4 inhibitor, apremilast (Otezla), an anti-inflammatory used to treat psoriasis and psoriatic arthritis, stood out. Researchers began testing the drug’s efficacy, first on mice and then on humans.
Through their experiments on mice, the researchers found that apremilast acted on the nucleus accumbens, the area of the brain that processes incoming reward and reinforcement stimuli related to addictive drugs, sex, and exercise.
They found that the drug reduced excessive alcohol intake in mice across a range of situations, including binge drinking, compulsive, and stress- and non-stress-induced drinking.
Seeking to validate the clinical effects they had seen in animal studies, researchers undertook a Phase IIa double-blind, placebo-controlled proof-of-concept study on humans. They found that apremilast, administered orally, was effective at reducing the number of daily drinks consumed by more than half. On average, alcohol intake fell from five drinks a day to two.
“I’ve never seen anything like that before,” said co-senior author Angela Ozburn, PhD. “This is incredibly promising for treatment of addiction in general.”
Importantly, the clinical study’s participants were not actively seeking any form of treatment for excessive alcohol consumption. Co-senior author, Barbara Mason, PhD, considers that apremilast may be even more effective in those motivated to address their problem drinking.
“Apremilast’s large effect size on reducing drinking, combined with its good tolerability in our participants, suggests that it is an excellent candidate for further evaluation as a novel treatment for people with alcohol use disorder,” Mason said.
The study was published in The Journal of Clinical Investigation.