Levocarnitine propionate hydrochloride

Cerebrovascular CYP450 is underexplored in humans. Twenty‐three participants (12 females) completed familiarization and two experimental visits utilizing double‐blind, randomized, crossover design. Participants ingested fluconazole (150 mg; FLZ, CYP450 inhibitor) or placebo (PLC, microcrystalline cellulose) followed by 120 min of supine rest. Five minutes of middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were collected during rest (PLC/FLZ BASE ) and lower body negative pressure (LBNP; −20 mmHg; PLC/FLZ LBNP ). There was no interaction for MCAv, cerebrovascular conductance index (CVCi), resistance area product (RAP), critical closing pressure (CrCP), or transfer function variables. Bonferroni tests revealed only FLZ attenuated MCAv (FLZ BASE 75.2 ± 11.3 cm•s −1 vs. FLZ LBNP 70.6 ± 11.2 cm•s −1 , p  = 0.015, d  = 0.713) and CVCi (FLZ BASE 0.76 ± 0.12 cm•s −1 •mmHg −1 vs. FLZ LBNP 0.71 ± 0.11 cm•s −1 •mmHg −1 , p =  0.003, d  = 0.865) during LBNP. LBNP lowered CrCP (PLC BASE 29.7 ± 9.3 mmHg vs. PLC LBNP 25.1 ± 11.3 mmHg, p  = 0.002, d =  0.940) within PLC. RAP increased during LBNP (PLC BASE 0.96 ± 0.29 vs. PLC LBNP 1.08 ± 0.32, p  = < 0.001, d  = 1.28; FLZ BASE 0.98 ± 0.24 vs. FLZ LBNP 1.07 ± 0.23, p  = < 0.001, d  = 1.10). These data suggest a participatory, nonobligatory role of CYP450 in human cerebrovascular control.

Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.

We aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.

We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.

OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, pFWE=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).

OXY’s effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.

DRKS00026218.