A recent study demonstrated a 1,100% (12-fold) increase in substance abuse after acquiring Lyme borreliosis. Lyme borreliosis and substance abuse have never been adequately studied and deserves greater attention. A fatal case of Lyme borreliosis and substance abuse is presented, compared to a database, relevant citations are reviewed, brain tussue is analyzed, and findings are discussed. The patient had a delay in adequate diagnosis and treatment. Further disease progression contributed to him feeling desperate as a result of multiple late stage symptoms. He experimented with multiple substances in an effort for relief. The pathophysiological effects of the infection resulted in an increased number and severity of mulsitystem symptoms, disability, and substance abuse. During acute deterioration of his mental state from phencyclidine withdrawal, NMDA agonism increased, he committed a homicide, two assaults, and suicide. In reviewing other cases, late stage Lyme borreliosis is associated with many symptoms that may contribute to an increased risk of addictive disorders and substance abuse. These symptoms include chronic pain, anxiety, social anxiety, insomnia, anhedonia and fatigue. More effective diagnosis and treatment and attention to substance abuse potential in these patients may help prevent some cases of addictive disorders, substance abuse, and death.