In 1949, Axelrod began work at the National Heart Institute, forerunner of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). He examined the mechanisms and effects of caffeine, which led him to an interest in the sympathetic nervous system and its main neurotransmitters, epinephrine and norepinephrine. During this time, Axelrod also conducted research on codeine, morphine, methamphetamine, and ephedrine and performed some of the first experiments on LSD. Realizing that he could not advance his career without a PhD, he took a leave of absence from the NIH in 1954 to attend George Washington University Medical School. Allowed to submit some of his previous research toward his degree, he graduated one year later, in 1955. Axelrod then returned to the NIH and began some of the key research of his career.