CB1 receptor antagonism/inverse agonism increases motor system excitability in humans

A. Oliviero, A. Arevalo-Martin, M. Rotondi, D. García-Ovejero, L. Mordillo-Mateos, A. Lozano-Sicilia, I. Panyavin, L. Chiovato, J. Aguilar, G. Foffani, V. Di Lazzaro, E. Molina-Holgado

Research output: Contribution to journalArticle


CB1 receptor is highly expressed in cerebral structures related to motor control, such as motor cortex, basal ganglia and cerebellum. In the spinal cord, the expression of CB1 receptors has also been observed in ventral motor neurons, interneurons and primary afferents, i.e., in the cells that may be part of the circuits involved in motor control. It is known that the antagonist/inverse agonist of CB1 receptors Rimonabant penetrates the blood-brain barrier and produces a broad range of central psychoactive effects in humans. Based on the occurrence of central effects in humans treated with Rimonabant and on the location of CB1 receptors, we hypothesized that the application of Rimonabant can also affect the motor system. We tested the effects of a single dose of 20. mg of Rimonabant on the excitability of motor cortex and of spinal motor neurons in order to detect a possible drug action on motor system at cortical and spinal levels. For this purpose we use classical protocols of transcranial magnetic and electrical stimulation (TMS and TES). Single and paired pulse TMS and TES were used to assess a number of parameters of cortical inhibition and cortical excitability as well as of the excitability of spinal motor neurons. We demonstrated that a single oral dose of 20. mg of Rimonabant can increase motor system excitability at cortical and spinal levels. This opens new avenues to test the CB1R antagonists/inverse agonists for the treatment of a number of neurological dysfunctions in which can be useful to increase the excitability levels of motor system. Virtually all the disorders characterized by a reduced output of the motor cortex can be included in the list of the disorders that can be treated using CB1 antagonists/reverse agonists (e.g. stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, fatigue syndromes, parkinsonisms, etc.).

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalEuropean Neuropsychopharmacology
Issue number1
Publication statusPublished - Jan 2012


  • CB1
  • Motor cortex
  • Rimonabant
  • Spinal cord
  • Transcranial magnetic stimulation

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

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    Oliviero, A., Arevalo-Martin, A., Rotondi, M., García-Ovejero, D., Mordillo-Mateos, L., Lozano-Sicilia, A., Panyavin, I., Chiovato, L., Aguilar, J., Foffani, G., Di Lazzaro, V., & Molina-Holgado, E. (2012). CB1 receptor antagonism/inverse agonism increases motor system excitability in humans. European Neuropsychopharmacology, 22(1), 27-35. https://doi.org/10.1016/j.euroneuro.2011.04.004