Sex, drugs, and arousal-two randomized trials on the effects of ketamine on sexual arousal and calcarine gyrus activity.
Manfred Klöbl, Thomas Liebe, Gregor Dörl, Peter Stöhrmann, Clemens Schmidt, Elisa Briem, Christian Milz, Gabriel Schlosser, Maximilian Kathofer, David Gomola, Godber Mathis Godbersen, Julia Sophia Crone, Rupert Lanzenberger, Marie Spies
Therapeutic Advances in Psychopharmacology 2026 DOI: 10.1177/20451253251406059 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, placebo-controlled crossover study Double-blind Qualitative Peer reviewed |
|---|---|
| Sample size | 67 |
| Population | Healthy volunteers |
| Interventions | intranasal S-ketamine intravenous racemic ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Resting-state Sex differences Sexual arousal |
| Registration | NCT05320120 NCT05320107 |
| Key points | Ketamine reduces sexual arousal in a sex-specific manner, with subacute S-ketamine lowering arousal to heterosexual stimuli in women and to lesbian stimuli in men, while late racemic ketamine reduces arousal to heterosexual stimuli in men and increases aversion to gay stimuli in women. |
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).
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cites 15
- Ketamine activates psychosis and alters limbic blood flow in schizophrenia Neuroreport April 1, 1995
- Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug British Journal of Addiction August 1, 1992
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate American Journal of Health-System Pharmacy June 1, 2002
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
and 10 more in the library