Naltrexone alters the processing of social and emotional stimuli in healthy adults

Abstract

Endogenous opioids have complex social effects that may depend on specific receptor actions and vary depending on the “stage” of social behavior (e.g., seeking vs. responding to social stimuli). We tested the effects of a nonspecific opioid antagonist, naltrexone (NTX), on social processing in humans. NTX is used to treat alcohol and opiate dependence, and may affect both mu and kappa-opioid systems. We assessed attention (“seeking”), and subjective and psycho-physiological responses (“responding”) to positive and negative social stimuli. Based on literature suggesting mu-opioid blockade impairs positive social responses, we hypothesized that NTX would decrease responses to positive social stimuli. We also tested responses to negative stimuli, which might be either increased by NTX’s mu-opioid effects or decreased by its kappa-opioid effects. Thirty-four healthy volunteers received placebo, 25 mg, or 50 mg NTX across three sessions under double-blind conditions. At each session, participants completed measures of attention, identification, and emotional responses for emotional faces and scenes. NTX increased attention to emotional expressions, slowed identification of sadness and fear, and decreased ratings of arousal for social and nonsocial emotional scenes. These findings are more consistent with anxiolytic kappa-antagonist than mu-blocking effects, suggesting effects on kappa receptors may contribute to the clinical effects of NTX.

Opioids and Social Connection

“…More puzzling, some findings support the opposite pattern. Naltrexone increased attention to negative faces (anger, fear, sadness), which is consistent with how naltrexone is theorized to affect social perceptions (Wardle et al, 2016).…”

“…However, in a departure from the hypothesized pattern, naltrexone also increased attention to positive faces (happiness) and reduced sensitivity (reaction time) to recognizing negative facial expressions (fear and sadness; Wardle et al, 2016).…”

Sustained opioid antagonism modulates striatal sensitivity to baby schema in opioid use disorder

“…By the third week of XRNTX, the nonspecific brain response to infant faces regardless of their cuteness had declined while the striatal sensitivity to baby schema levels had returned. These findings extend the limited evidence that opioid antagonism reduces hedonic responses and enhances prosocial activities in animals (Alcaro & Panksepp, 2011; Martel, Nevison, Rayment, Simpson, & Keverne, 1993) and modulates these domains in humans (Inagaki, Ray, Irwin, Way, & Eisenberger, 2016; Johnson et al, 2014; Shi et al, 2016; Wardle, Bershad, & de Wit, 2016). Prior studies that used sweet taste perception as a model of hedonic processing in detoxified heroin addicts (Kampov-Polevoy, Garbutt, & Janowsky, 1997) found that XRNTX treatment reduced self-reported liking of the sweet solutions and lowered the threshold of sweet taste perception in detoxified opioid addicts, making them similar to healthy controls and suggesting that naltrexone “reset” the hedonic processing to normal levels (Green et al, 2013; Langleben, Busch, O’Brien, & Elman, 2012).…”

Pharmacological Effects of a Monoclonal Antibody against 6-Monoacetylmorphine upon Heroin-Induced Locomotor Activity and Pharmacokinetics in Mice

“…Agonist treatment also contributes to overdoses and may have cognitive side effects (Verdejo et al, 2005;Andersen et al, 2011;Bernard et al, 2015). Antagonist treatments include naltrexone and naloxone, which act by blocking the action of opioid drugs and may potentially interfere with the action of endogenous opioids (e.g., endorphins and enkephalins) (Nestler, 2002;Bodnar, 2016;Wardle et al, 2016).…”