Two-month administration of methylphenidate improves olfactory sensitivity and suppresses appetite in individuals with obesity

Abstract

Introduction: Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake and body weight on individuals with obesity. 
 Methods: In a randomized, double-blind study, 12 participants (age 28.9±6.7 yrs) (BMI 36.1±4.5 kg/m2) were assigned to MPH (0.5mg/kg) (n=5) or Placebo (n=7) twice daily for 2 months. Appetite (Visual Analog Scale), odour threshold (Sniffin’ Sticks®), energy intake (food menu), and body weight (DEXA scan) were measured at day 1 and day 60. 
 Results: MPH intake significantly increased odour threshold scores (6.3±1.4 vs. 9.4±2.1 and 7.9±2.3 vs. 7.8±1.9, respectively; p=0.029) vs. Placebo. There was a significantly greater suppression of appetite sensations (desire to eat (p=0.001), hunger (p=0.008), and prospective food consumption (p=0.003)) and an increase in fullness (p=0.028) over time in the MPH vs. Placebo. 
 Conclusions: MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.

Effects of 2 months of methylphenidate on energy expenditure in individuals with obesity: A randomized, double‐blind, placebo‐controlled pilot study

“…This correction of bio‐behavioral adaptations to weight loss is unique among pharmacotherapies, as no approved drugs have demonstrated such an effect on REE, indicating MPH has the potential to tilt the scales of energy balance by decreasing EI and increasing REE, which is ideal to potentiate weight loss. The 2.7 kg average weight loss previously described (El Amine et al., 2022 ) was achieved in the absence of diet or exercise, a result comparable to other pharmacotherapy interventions at 8 weeks (Khera et al., 2016 ). Importantly, the tolerability of MPH within both our cohort, as well as in other assessments, is comparable or better than other available pharmacotherapy interventions (El Amine et al., 2022 ; Khera et al., 2016 ; Stuhec et al., 2019 ).…”

“…MPH has been shown to decrease EI (Goldfield et al., 2007 ) in acute doses and decrease appetite with both acute administrations among individuals with normal weight (Goldfield et al., 2007 ) and chronic administrations among those living with obesity (El Amine et al., 2022 ). Based on these pilot data and the large effect sizes shown, we highlight the possibility for the first time that MPH may chronically increase REE in participants with obesity, an effect that was apparent even in the presence of a 2.7 kg weight loss, countering the ubiquitous adaptive thermogenic process that is typically accompanied by reductions in REE both acutely and chronically (Hintze et al., 2018 ).…”

“…Therefore, identifying therapeutic avenues with the potential to correct these bio‐behavioral adaptations to weight loss on energy balance are appealing. We have previously reported that Methylphenidate (MPH) reduces energy intake (EI) and suppresses appetite acutely in individuals with normal weight (Goldfield et al., 2007 ), as well as over a 2‐months intervention in individuals living with obesity (El Amine et al., 2022 ). What is more, we have also shown that fast‐release MPH acutely increases resting EE (REE) by approximately 7% and the thermic effect of feeding (TEF) by ~5% in individuals with normal weight (Lorello et al., 2008 ).…”

Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol

“…Considering that this is an in vitro system, the findings are compelling since structural cortical changes and catecholaminergic transmission have been the target of various epidemiological studies and drug clinical trials, both in children and adults with ADHD. 87 , 88 , 89 , 90 It is biologically plausible that medications that cross the placenta and the blood-brain barrier, may interfere with normal fetal brain neurodevelopment, previously shown for valproic acid, and more recently for topiramate. 91 This is especially relevant for substances that cross the blood-brain barrier, which is considered functional by the 8th week of gestation.…”

Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol

“…The genes were enriched for BPs involved in cell morphogenesis and adhesion, but also synaptic transmission and signalling with a focus on catecholamines and GABAergic transmission. Considering that this is an in vitro system, the findings are compelling since structural cortical changes and catecholaminergic transmission have been the target of various epidemiological studies and drug clinical trials, both in children and adults with ADHD [77][78][79][80] . It is biologically plausible that medications that cross the placenta and the blood-brain barrier, may interfere with normal fetal brain neurodevelopment, previously shown for valproic acid, and more recently for topiramate 81 .…”