- RATIONALE: Frequent cannabis use is a risk marker for schizophrenia and delusions, but the neurocognitive mechanisms of this relationship remain unclear. OBJECTIVES: We sought evidence that cannabis users have deficits in processing relationships between meaningful stimuli, similar to abnormalities reported in schizophrenia, and that these deficits are associated with delusion-like ideation. We used the N400 event-related brain potential (ERP) waveform as a neurophysiological probe of activation of concepts in semantic memory. We hypothesized that cannabis users would exhibit larger (more negative) than normal N400 amplitudes in response to stimuli meaningfully related to a preceding prime-reflecting deficient activation of concepts related to the prime. We further hypothesized that the magnitude of this abnormality would correlate with severity of delusion-like ideation. METHODS: We recorded ERPs in 24 frequent cannabis users and 24 non-using comparison participants who viewed prime words followed by targets which were either words related or unrelated to the prime or pronounceable nonwords. The participants' task was to indicate whether the target was a word. Delusion-like ideation was measured via the Schizotypal Personality Questionnaire. RESULTS: Contrary to our hypothesis, cannabis users exhibited smaller than normal N400s to both related and unrelated targets. These abnormalities correlated with delusion-like ideation in cannabis users only. CONCLUSIONS: The results are consistent with a generalized abnormality of activation within semantic memory neural networks in cannabis users. Further research is needed to investigate whether such an abnormality plays a role in the development of delusion-like ideation in cannabis users.