, Volume 64, Issue 1, pp 67–74 | Cite as

High frequency deep transcranial magnetic stimulation acutely increases β-endorphins in obese humans

  • Anna Ferrulli
  • Concetta Macrì
  • Ileana Terruzzi
  • Federico Ambrogi
  • Valentina Milani
  • Michela Adamo
  • Livio LuziEmail author
Original Article



In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation (dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects.


This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients).


No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (p = 0.048); a significant increase of ghrelin in LF (p = 0.041) was also demonstrated.


A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.


Obesity Transcranial magnetic stimulation Food craving β-endorphin Ghrelin 



This study was supported by the Italian Ministry of Health (RF-2011–02349303).


Prof. Livio Luzi was a recipient of a grant from the Italian Ministry of Health (RF-2011–02349303).

Author contributions

LL and IT contributed to designing the research study. LL, AF, and CM conducted experiments; specifically, LL provided research conduct oversight; AF contributed to performing dTMS after a specific training, and to providing medical oversight; CM contributed to collecting blood samples. AF and MA contributed to acquiring data; FA and VM performed statistical analysis. AF, LL, MA, FA and VM contributed to writing the manuscript. As corresponding author, LL confirms that he had full access to all the data in the study and has final responsibility for the decision to submit for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Endocrinology and Metabolism Division and Metabolism Research CenterIRCCS Policlinico San DonatoSan Donato MilaneseItaly
  2. 2.Laboratory of Nutrigenomics, Metabolism and Cell Differentiation, Diabetes Research InstituteSan Raffaele HospitalMilanItaly
  3. 3.Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly
  4. 4.Scientific Directorate, IRCCS Policlinico San DonatoMilanItaly
  5. 5.Department of Biomedical Sciences for HealthUniversity of MilanMilanItaly

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