Endocannabinoids control spasticity in a multiple sclerosis model

SPECIFICAIMSSynthetic cannabinoid agonists and antagonists, acting at cannabinoid receptors, inhibit or exacerbate spasticity, respectively, in an animal model of multiple sclerosis (MS) and chronic relapsing experimental allergic encephalomyelitis (CREAE). There are also anecdotal reports on the alleviation of these MS signs in humans by marijuana smoking. Here, we have investigated the existence of a possible tone of endogenous cannabinoids controlling spasticity in CREAE mice by examining whether: 1) endocannabinoid levels in nervous tissues are altered during spasticity; 2) exogenously administered endocannabinoids inhibit spasticity; and 3) pharmacological manipulation of endocannabinoid levels and action alters spasticity.PRINCIPAL FINDINGS1. Endocannabinoid levels increase in spastic miceCREAE was induced in Biozzi ABH mice (Harlan Olac, Bicester, U.K.) after subcutaneous injection of 1 mg of syngeneic spinal cord homogenate emulsifed in Freund’s complete adjuvant (Difco, Poole, U.K.) on day 0 and ...