BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation
Volume 2, Issue 4 , Pages 229-233, October 2009

Cannabis-based treatment induces polarity-reversing plasticity assessed by theta burst stimulation in humans

  • Giacomo Koch, MD, PhD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa Lucia, Rome, Italy
    • Corresponding Author InformationCorrespondence: Dr Giacomo Koch, Stroke Unit, Dipartimento di Neuroscienze, Università Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
    • ,
  • Francesco Mori, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Claudia Codecà, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Hajime Kusayanagi, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Fabrizia Monteleone, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Fabio Buttari, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Stefania Fiore, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • ,
  • Giorgio Bernardi, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa Lucia, Rome, Italy
    • ,
  • Diego Centonze, MD

      Affiliations

    • Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy
    • Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa Lucia, Rome, Italy

Received 1 January 2009; received in revised form 26 February 2009; accepted 2 March 2009. published online 06 April 2009.

Background

In animal models, the cannabinoid system has been convincingly implicated in the regulation of long-lasting synaptic plasticity. Both long-term potentiation (LTP) and depression (LTD) phenomena can be induced in the human motor cortex by transcranial magnetic theta burst stimulation (TBS).

Objective/Hypothesis

Here, we explored the potential involvement of the cannabinoid system in TBS-induced synaptic plasticity in humans.

Methods

We tested the effects of a cannabis-based preparation (Sativex) on continuous TBS (cTBS) and intermittent TBS (iTBS) protocols in subjects with multiple sclerosis.

Results

We observed a shift in the polarity of synaptic plasticity induced by cTBS. In these subjects, in fact, cTBS induced the expected inhibition of motor-evoked potentials (MEPs) before Sativex exposure, whereas it caused a persisting enhancement of MEP amplitude 4 weeks after. The LTP-like phenomenon induced by iTBS was conversely unaffected by Sativex.

Conclusions

Our results indicate that cannabis ingredients have metaplastic effects on the motor cortex, and strongly suggest that the cannabinoid system is involved in the modulation of synaptic plasticity not only in rodents but also in humans.

Keywords: cannabinoid receptors, LTD, LTP, metaplasticity, Sativex, TBS

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 This investigation was supported by the Italian National Ministero dell'Università e della Ricerca, by the Italian National Ministero della Salute to GK and DC, by the Fondazione Italiana Sclerosi Multipla (FISM) to DC, and by the Agenzia Spaziale Italiana to GB.

PII: S1935-861X(09)00013-8

doi:10.1016/j.brs.2009.03.001

BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation
Volume 2, Issue 4 , Pages 229-233, October 2009

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