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The therapeutic potential of psychedelics in headache and chronic pain disorders is documented over decades of anecdotal and early investigational reports, which have paved the way for the first controlled studies of psilocybin and lysergic acid diethylamide (LSD) in these disorders. The reported lasting clinical effects after limited dosing with psychedelics present a novel means for disease management, but considerable further study will be required to address disease-specific treatments, uncover mechanism(s) of action, and verify safety. In this chapter, these topics are reviewed with particular attention to the neurobiological systems that offer potential sources of psychedelics' unique clinical effects in headache and pain.
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