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Although typically associated with headaches, migraine refers to a particularly painful neurological disorder characterized by severe head and eye pain, distortions in eyesight, slurred or slowed speech and thoughts, and numbness in the face, mouth, limbs, or hands. With over 40 million people in the U.S. affected by migraine, the social consequences can be as impactful as the physical consequences. While research has revealed that “migrainers” feel stigmatized by their condition, given the potential for a migraine attack to occur at any time without clear provocation and with little treatment options available, we instead conceptualize migraine as a source of strain. Thus, drawing from general strain theory and using multiple waves of data from the Midlife in the United States (MIDUS) data, we examine the linkage between migraine and illicit substance use. Initial analyses show that migrainers report much higher levels of illicit substance use than non-migrainers. Within the context of general strain, we find that this effect is partially influenced by negative affective states. Overall, findings suggest that the social experiences of a biological disorder may be stronger and more disruptive to life experiences than the physical symptoms of the disorder.