Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans

Abstract

MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its prosocial effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5 mg/kg), intranasal oxytocin (20 IU or 40 IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5 mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7 pg/ml at approximately 90–120 minutes, compared to 18.6 pg/ml after placebo. Intranasal oxytocin (40 IU, but not 20 IU) increased plasma oxytocin levels to 48.0 pg/ml, 30–60 min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., ‘High’ and ‘Like Drug’), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects.

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial

“…In 1999, Blaicher et al (34) found that the plasma concentration of oxytocin was significantly higher in both men and women 1 minute after orgasm than at baseline and would decrease after 5 minutes. In our study, the plasma levels of oxytocin doubled after drug administration as shown in other clinical investigations (35)(36)(37)(38), hence ruling out possible objections regarding the applied oxytocin dose.…”

Oxytocin-induced membrane hyperpolarization in pain-sensitive dorsal root ganglia neurons mediated by Ca2+/nNOS/NO/KATP pathway

“…In humans, the concentrations of OT in plasma range from 1.70 to 45.0 pmol/L (Carmichael et al, 1987;Alfven, 2004;Gossen et al, 2012;Dal Monte et al, 2014;Kirkpatrick et al, 2014;Yuen et al, 2014). It is well recognized that baseline plasma OT concentrations do not vary significantly among men (2.7 ± 0.4 pmol/L), nonpregnant women (2.5 ± 0.4 pmol/L), or pregnant women before labor (2.3 ± 0.2 pmol/L).…”

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

“…In addition, central infusions of OT up-regulate hypothalamic OT mRNA and increase circulating OT levels [27]. Given that circulating levels of OT are elevated by 40 or 60 min following intranasal administration in nonhuman primates [214] and humans [167,168,215] it is possible that intranasal OT is entering the circulation directly or indirectly following the release of endogenous OT into the CNS and peripheral circulation. Future studies that examine CNS levels of radiolabelled OT following intranasal administration into OT deficient mice with intact or severed vagal afferent signaling to the hindbrain will be helpful in addressing the extent to which OT enters the CNS without impacting release of endogenous OT within the CNS.…”

“…Current data, however, suggest that the intranasal route of administration is not associated with unwanted side effects [220], including adverse effects on blood pressure or heart rate relative to vehicle treatment in rats [210], healthy adults [34,167,215] and pre-diabetic obese men and women [33]. In addition, chronic subcutaneous infusions of OT failed to impact systolic blood pressure [28] or heart rate [28,93] in DIO [28], db/db [28,93] or hyperlipidemic ApoE deficient mice [187].…”