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

BackgroundIn 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 beinduced in the human motor cortex by transcranial magnetic theta burst stimulation (TBS).Objective/HypothesisHere, we explored the potential involvement of the cannabinoid system in TBS-induced synapticplasticity in humans.MethodsWe tested the effects of a cannabis-based preparation (Sativex) on continuous TBS (cTBS) andintermittent TBS (iTBS) protocols in subjects with multiple sclerosis.ResultsWe 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-likephenomenon induced by iTBS was conversely unaffected by Sativex.ConclusionsOur results indicate that cannabis ingredients have metaplastic effects on the motor cortex, and stronglysuggest that the cannabinoid system is involved in the modulation of synaptic plasticity not only inrodents but also in human