Joar Guterstam

Amphetamine use disorder (AmUD) afflicts approximately 19.000 individuals in Sweden and is associated with negative psychosocial consequences, including criminality, increased somatic and psychiatric morbidity, and increased mortality (seven-fold compared to the general population). Despite this, very few, if any, effective treatments are available. Thus treatment of AmUD represents an unmet medical need.In analogy with opiate use disorder (OUD) researchers have tried to treat AmUD with central stimulants (CS) as a substitution treatment. However, both unique studies and meta-analyses are negative. One reason for this may be that the doses used have been too low. Also the now widely spread substitution treatment programmes for OUD (LARO) initially lacked dose-finding studies, which, however, later was corrected, resulting in changed recommendations and better effects. Controlled studies of CS-treatment for individuals with AmUD or cocaine use disorder and co-morbid ADHD have clearly indicated that higher than normal doses are needed to treat this co-morbidity. This is most likely due to both pre- and postsynaptic measures of brain dopamine systems being severely compromised in stimulant use disorders, as consistently found in brain imaging studies.Here we will explore the feasibility of performing a 24 week multi-centre RCT on the efficacy and safety of lis-dexamphetamine in a dose up- and down-titrating manner for the treatment of AmUD.

Internet-delivered cognitive behavior therapy (CBT) for social anxiety disorder is an evidence-based treatment in regular health care. Still, a considerable proportion of treated patients do not respond. There is also a debate on the importance of patients expectations’ for therapeutic outcomes. However, experimental evidence is lacking to answer this question. Our aim is thus to investigate the placebo response in social anxiety disorder, and the link between initial placebo responsiveness and subsequent outcome of CBT. First, we will manipulate expectations of anxiety relief. A benzodiazepine (a common anti-anxiety drug) will be administered with correct or incorrect information about clinical efficacy during a public speaking task. Self-reports and moment-to-moment variability in neural response will be measured with functional magnetic resonance imaging (fMRI) during the manipulation of expectations. The balanced placebo design allows us to dissect the total treatment effect into its components: drug, placebo, and interactions between the two. Second, patients undergo internet-delivered CBT after completing the placebo experiments. This project aims to unravel expectations´ influence on treatment response, and has a two-fold significance, 1) the scientific understanding of the neural mechanisms of treatment expectations, central for placebo, and 2) the development of pre-treatment predictors of CBT outcome which could improve precision in clinical decision making.