Sex, drugs, and arousal-two randomized trials on the effects of ketamine on sexual arousal and calcarine gyrus activity.

Ketamine reduces sexual arousal in a sex-specific manner, which may explain why it is used recreationally in chemsex settings despite dampening sexual experience. In two placebo-controlled crossover studies with 67 healthy volunteers, subacute S-ketamine lowered arousal to heterosexual stimuli in women and to lesbian stimuli in men, while decreasing sexual aversion to gay stimuli in both sexes. Late racemic ketamine reduced arousal to heterosexual stimuli in men but increased aversion to gay stimuli in women. Ketamine also modulated calcarine gyrus activity differently in men and women. These sex-dependent effects on brain activity and sexual response may relate to ketamine's known sex-specific influences on stress resilience and psychosis-like symptoms.

Study at a glance

Abstract

Ketamine, a well-established antidepressant and dissociative anesthetic, is also used recreationally in the club and chemsex scene. Survey and qualitative data suggest that while ketamine facilitates chemsex encounters, it diminishes the intensity of the sexual experience. To investigate this phenomenon from a neuroscientific perspective while considering ketamine's sex-specific effects. Two randomized, placebo-controlled crossover studies using intranasal S-ketamine (double-blinded) or intravenous racemic ketamine (single-blinded). Subjective sexual arousal in response to a newly compiled set of erotic stimuli was assessed following subacute S-ketamine and late racemic ketamine administration across two studies. Overall, 67 healthy volunteers (26 females) participated in the studies. Functional magnetic resonance imaging (fMRI) was performed during sexual arousal assessment under late racemic ketamine exposure, with both studies also incorporating resting-state fMRI assessments. Subacute S-ketamine reduced sexual arousal to heterosexual stimuli in women (β = -0.21, CI95 = (-0.36, -0.06)) and, to a lesser extent, to lesbian stimuli in men (β = -0.16, CI95 = (0.003, -0.33)). It also diminished sexual aversion to gay stimuli in both sexes (β ⩾ 0.18, CI95 ⩾ (0.03, 0.32)). Conversely, late racemic ketamine decreased sexual arousal to heterosexual stimuli in men (β = -0.17, CI95 = (-0.31, -0.02)) while exacerbating sexual aversion to gay stimuli in women (β = -0.24, CI95=(-0.36,-0.12)). Furthermore, late ketamine administration resulted in reduced calcarine gyrus activation in men compared to women, independent of sexual arousal (β ⩽ -0.23, CI95 ⩽ (-0.52, 0.05)). This finding was confirmed for resting activity under subacute ketamine (β = -0.18, CI95 = (-0.32, -0.04)). Our results align with reports of diminished sexual arousal under ketamine, while the reduced sexual aversion may play a role in facilitating chemsex. The heightened sexual aversion in women and the distinct calcarine gyrus activity modulation may relate to previously documented sex-dependent ketamine effects on stress resilience and psychosis-like symptoms. Both studies were registered at clinicaltrials.gov: NCT05320120 (2022-04-08), NCT05320107 (2022-04-08).