From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?

Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.     

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

ABSTRACT

Designing an oncology clinical program is more challenging than designing a single study. The standard approaches have been proven to be not very successful during the last decade; the failure rate of Phase 2 and Phase 3 trials in oncology remains high. Improving a development strategy by applying innovative statistical methods is one of the major objectives of a drug development process. The oncology sub-team on Adaptive Program under the Drug Information Association Adaptive Design Scientific Working Group (DIA ADSWG) evaluated hypothetical oncology programs with two competing treatments and published the work in the Therapeutic Innovation and Regulatory Science journal in January 2014. Five oncology development programs based on different Phase 2 designs, including adaptive designs and a standard two parallel arm Phase 3 design were simulated and compared in terms of the probability of clinical program success and expected net present value (eNPV). In this article, we consider eight Phase2/Phase3 development programs based on selected combinations of five Phase 2 study designs and three Phase 3 study designs. We again used the probability of program success and eNPV to compare simulated programs. For the development strategies, we considered that the eNPV showed robust improvement for each successive strategy, with the highest being for a three-arm response adaptive randomization design in Phase 2 and a group sequential design with 5 analyses in Phase 3.     

“I wonder what age you grow out of it?”: Negotiation of recreational drug use and the transition to adulthood among an Australian ethnographic sample

Aims: Positioned by work of normalisation researchers, this article examines how “recreational” styles of drug use were negotiated by young adults in relation to emerging “adult” identities. Methods: Ethnographic fieldwork was conducted in Perth, Western Australia. This involved 18 months of field observations within a network of approximately 60 non-service-engaged 18–31 year olds among whom amphetamine-type stimulant use was a common activity and 25 in-depth interviews with a sub-sample (average age, 25 years) who used illicit drugs at least monthly. Findings: While most participants began to “age out” of drug use by their mid-twenties, the process was uneven and individualised. Some did not perceive a need to “quit” using drugs at all. While health and wellbeing and work-related responsibilities informed decisions by many to use less frequently of “quit”, negotiation of non-stigmatised and “normal” identities – especially among friends and partners – appeared to most strongly inform decision-making. Conclusions: Values associated with “ageing out” of illicit drug use are more nuanced and contested than have been depicted within typical accounts of “normalised” drug use. This study found that they are complicated by uncertain and protracted transitions into adulthood in contemporary society but also by the continued stigmatisation of drug users.