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Entactogen Effects of Ketamine: A Reverse-Translational Study
Evan M Hess1, Dede K Greenstein1, Olivia L Hutchinson1
1Department of Psychiatry (Hess, Hutchinson, Gould), Department of Neurobiology (Gould), and Department of Pharmacology (Gould), University of Maryland School of Medicine, Baltimore; Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda, Md. (Greenstein, Zarate); Baltimore Veterans Affairs Medical Center, Veterans Affairs Maryland Health Care System, Baltimore (Gould).
Objective:
The authors sought to assess the prosocial, entactogen effects of ketamine.
Methods:
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.
Results:
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.
Conclusions:
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.
