Preliminary data indicate that delta-9-tetrahydrocannabinol (THC) is an effective drug in the treatment of experimental autoimmune encephalomyelitis (EAE), a model for the human inflammatory demyelinating disease of the central nervous system multiple sclerosis (MS). The purpose of this proposed project is to determine the scope and mechanism of THC's benefit in EAE and also, possibly, in the treatment of experimental autoimmune neuritis (EAN), a model of the human peripheral neuropathy Guillain-Barre' Syndrome (GBS). Current treatments for MS and GBS include the administration of exogenous steroids. THC, an active component of marijuana, has been shown to be immunosuppressive and this effect may be induced by modulating endogenous steroid levels. To investigate the possible efficacy of THC in the treatment of immune-mediated diseases of the nervous system, different models of EAE and EAN will be studied in a number of species by: (1) determining the ability of THC to prevent disease development by maintaining experimental animals on an appropriate prophylactic dose before and after challenging them with disease-inducing inocula; (2) using the cute form of each disease, THC's ability to suppress disease will be determined by treating animals at different times during the prodromal stage and after the onset of clinical signs; (3) employing chronic- relapsing models of both diseases, studies will be conducted to evaluate the possible benefit THC therapy may have by treating animals during periods of exacerbations and remissions; and, (4) concurrent studies which will determine the mechanism of THC's effect on these diseases by employing immunologic, biochemical, and morphologic techniques to examine correlative phenomena in vivo and in vitro. Such investigations may ultimately lead to a better understanding of the pathophysiology of EAE and EAN and provide a novel and effective treatment for human inflammatory demyelinating diseases. In addition, these studies may establish a rational basis for treating an even broader range of immune- mediated diseases, which represent major human health problems, with THC.
