Entactogen Effects of Ketamine: A Reverse-Translational Study

The authors sought to assess the prosocial, entactogen effects of ketamine.

Pleasure from social situations was assessed in a sample of participants with treatment-resistant depression from randomized, double-blind, placebo-controlled studies, using four items of the Snaith-Hamilton Pleasure Scale (SHAPS) at five time points over 1 week following treatment with ketamine (0.5 mg/kg intravenously) or placebo. The primary endpoint was postinfusion self-reported pleasure on the four SHAPS items pertaining to social situations, including the item on helping others, between the ketamine and placebo groups. In a rodent experiment, the impact of ketamine on helping behavior in rats was assessed using the harm aversion task. The primary endpoint was a reduction in lever response rate relative to baseline, which indicated the willingness of rats to forgo obtaining sucrose to help protect their cage mate from electric shock.

Relative to placebo, ketamine increased ratings of feeling pleasure from being with family or close friends, seeing other people’s smiling faces, helping others, and receiving praise, for 1 week following treatment. In the rodent experiment, during the harm aversion task, ketamine-treated rats maintained lower response rates relative to baseline to a greater extent than what was observed in vehicle-treated rats for 6 days posttreatment and delivered fewer shocks overall.

In patients with treatment-resistant depression, ketamine treatment was associated with increased pleasure from social situations, such as feeling pleasure from helping others. Ketamine-treated rats were more likely to protect their cage mate from harm, at the cost of obtaining sucrose. These findings suggest that ketamine has entactogen effects.