Pia Steensland, Karolinska Institutet – Alcohol Dependence Treatment

Alcohol releases dopamine in our brains, which makes it hard to know when to stop.

Pia Steensland, associate professor of psychology at Karolinksa Institutet, examines her research into finding a new way to treat alcohol dependency.

Pia Steensland, BPharm, PhD, Associate Professor at Karolinska Institutet, is a leading expert on behavioral psychopharmacology. The overall goal of Dr Steensland’s research is to increase the understanding of the pathophysiology of alcohol use disorder (AUD) with the ultimate goal to identify potential novel effective medications by using validated preclinical models of long-term voluntary alcohol consumption. Dr Steensland gained her PhD at Uppsala University in Sweden 2002, and after a longer maternity leave she was a successful postdoc scholar at the Ernest Gallo Clinic and Research Center (Gallo), University of California San Francisco, USA (2006-2008). At Gallo she identified the smoking cessation agent varenicline as a novel potential treatment of AUD using validated animal models (Steensland et al, PNAS 2007). Her findings led to the initiation of several clinical studies confirming the efficacy of varenicline in decreasing alcohol consumption in AUD patients. Dr Steensland was recruited to Karolinska Institutet in 2008, and based on her wide methodological background within behavioral psychopharmacology, she established an Experimental Addiction Research Platform at the department of Clinical Neuroscience. Dr Steensland was awarded a junior research position through the Swedish Research Council in 2010 and an Associate Professors degree in neuropharmacology at Karolinska Institutet in 2011. Dr Steensland’s current research focuses on the dopamine stabilizer (-)-OSU6162 (developed by Nobel Laureate Arvid Carlsson) and its potential as a novel treatment of AUD. Through a successful series of preclinical studies she has shown that (-)-OSU6162 possess several desirable characteristics of a medication for AUD (Steensland et al 2012, Biological Psychiatry). Recently, using a translational platform in collaboration with Professor Johan Franck and Assistant Professor Nitya Jayaram-Lindström, Dr Steensland conducted a proof-of-concept human laboratory study showing that (-)-OSU6162 attenuates priming-induced alcohol craving in alcohol dependent patients (Khemiri et al 2015). The successful preclinical and clinical evaluation of (-)-OSU6162, highlights the potential of Dr Steensland’s research to accelerate the development of novel AUD medications.

Alcohol Dependence Treatment

Alcohol dependence is a chronic relapsing disorder, but the few available medications have limited clinical efficacy. Dopamine and the brain reward system is one potential treatment target due to its involvement in the development of alcohol dependence.

When drinking alcohol, dopamine is released creating euphoria. However, with repeated intoxication, adaptations occur in the brain reward system and less dopamine is released. With time, more alcohol is needed to cause intoxication and eventually you need to maintain drinking to prevent feelings of depression – addiction has set in.

Our research focuses on a compound called OSU6162, or OSU for short, that is developed by Nobel laureate Arvid Carlsson. In contrast to traditional dopamine compounds, OSU has mild side effects and the unique ability to increase or decrease the dopamine levels depending on the concurrent dopamine level in the brain.

We have previously shown that OSU can attenuate voluntary drinking, relapse and withdrawal symptoms in long-term drinking rats.

Our recent clinical “proof-of-concept” study in alcohol dependent patients shows that a two-week-treatment with OSU, compared to placebo, attenuates the craving for alcohol after drinking one alcoholic beverage.

OSU’s mechanism of action is not fully understood, however, our recent animal study shows that OSU can counteract a dopamine deficit state in the brain reward system of long-term drinking rats. We therefore believe that OSU can reduce alcohol craving in dependent people by normalizing the downregulated dopamine levels.

A clinical study with more patients and a longer treatment period is now needed to determine whether OSU also can attenuate drinking and prevent relapse in alcohol dependent patients.