Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial

Abstract

Background: Individuals with alcohol use disorder (AUD) are much more likely to meet criteria for posttraumatic stress disorder (PTSD) than the general population. Compared to AUD alone, those with comorbid AUD-PTSD experience worse outcomes. Prior literature suggests that oxytocin, a hypothalamic neuropeptide, may be effective in the treatment of both AUD and PTSD when administered intranasally, although specific mechanisms remain elusive.

Methods: Forty-seven male patients with comorbid AUD-PTSD were administered intranasal oxytocin in a randomized, double-blind, dose-ranging (20 IU, 40 IU, and matched placebo), within-participant design with study visits at least 1 week apart. A cue-induced craving paradigm was conducted using each participant's preferred alcoholic beverage versus a neutral water cue. Self-reported alcohol craving and heart rate (HR) were recorded and analyzed using linear mixed-effect models.

Results: While alcohol cues significantly induced self-reported craving and increased HR compared to neutral water cues, neither dosage of oxytocin compared to placebo reduced self-reported cue-induced alcohol craving nor cue-induced changes in HR in patients with PTSD-AUD.

Conclusions: These preliminary findings suggest that oxytocin does not affect cue-induced craving. Our results contribute to an ever-growing field of research investigating the effects of intranasal oxytocin on the symptoms of substance use disorders and will help further refine methodology and streamline future inquiries in this area.

Keywords: Alcohol Use Disorder; Comorbidity; Craving; Oxytocin; PTSD.

Fig. 1.

Summary flow of participant enrollment. C, controls; PT, patients.

Fig. 2.

Mean self-reported alcohol craving at each time point for patients and controls separated by Treatment condition (placebo, OT 20, OT 40). Construct validity: mean change (SEM), placebo condition, patient t_(4-1) = 22.94 (4.13), p-value < 0.001; control t_(4-1) = 5.68 (1.86), p-value = 0.004. Patient t_(3-1) = 1.91 (3.93), p-value = 0.63; control t_(3-1) = 0.19 (0.48), p-value = 0.70. Patient versus control: mean (SEM), placebo condition, patient t₁ = 27.17 (4.01) versus control t₁ = 2.14 (0.54); p-value < 0.001. OT, oxytocin; t_1-4, cue-induced craving paradigm time points; VAS, visual analog scale. Error bars = standard error of the mean (SEM).

Fig. 3.

Mean HR for patients and controls separated by Treatment condition (placebo, OT 20, OT 40). Baseline (prestudy drug and pre-CIC) is 5-minute resting mean HR. 1 to 4 on the x-axis for the water and alcohol cue exposure correspond to the mean HR for the 1-minute periods recorded immediately after each prompt in the CIC paradigm. Patient versus control: prestudy drug baseline, mean (SEM), placebo condition, patient = 73.58 (1.97), control = 71.10 (2.15), p-value = 0.43. Mean water cue exposure, patient = 69.41 (1.86), control = 67.32 (1.99), p-value = 0.45. Mean alcohol cue exposure, patient = 69.96 (1.86), control = 67.14 (2.03), p-value = 0.31. (mean alcohol cue exposure) – (mean water cue exposure), patient = 0.56 (0.26), control = −0.18(0.23), p-value = 0.04. bpm, beats per minute; CIC, cue-induced craving; HR, heart rate; OT, oxytocin. Error bars = standard error of the mean (SEM).