This research program delves into the interplay between anxiety-buffer disruption and drug abuse, grounded in the integration of Terror Management Theory (TMT) and attachment theory. Here, dominant cultural worldviews, self-esteem, and attachment security are conceptualized as critical anxiety buffers that shield individuals from existential threats, promoting emotional balance and stability. In our view, the disruption of these buffers, by eroding the validity of cultural worldviews and amplifying attachment anxiety (i.e., low self-esteem and doubts about availability of others’ support), could increase the accessibility of death-related thoughts and shatter emotional balance, thereby elevating the risk of substance use as a maladaptive strategy to cope with existential threats. In this research, we assess and experimentally manipulate levels of attachment anxiety and the invalidity of cultural worldviews, exploring their implications for drug use behaviors. The goal is to elucidate how compromised psychological buffers may escalate drug abuse and to inform targeted interventions designed to bolster psychological resilience and curb substance addiction.