Designer drugs, like Spice, are synthetic psychoactive analogs of illegal substances with understudied health effects since they have traditionally been sold in packages labeled “not for human consumption” and the molecular structures can be specifically altered to circumvent legislation. Recent legislation has focused on regulating packaging and has reduced, but not eliminated, the distribution of Spice in Alaska. Legally obtained Spice samples from three geographic regions in Alaska were analyzed using liquid injection gas chromatography-mass spectrometry (GC-MS). Most (70%) of the samples contained illegal cannabinoids that have been regulated by the Drug Enforcement Agency and 47% contained multiple active ingredients. We hypothesized that the heterogeneity of the active ingredients between brands and across regions could be used to indicate small- or larger-scale manufacturing, and the results indicate multiple manufacturing scales. Evidence for small-scale manufacturing included inconsistent packaging, several of which contained similar active ingredient profiles in different brands purchased from a single store. Evidence for large-scale production was also found with some brands having consistent active ingredient profiles across regions. This study provides preliminary data for the geographic variability of active ingredients in Spice as an indicator of mechanisms of manufacture and distribution to inform legislators and law enforcement and help prioritizing resource allocation in an effort to quell Spice use in Alaska.