We conducted a systematic review on resting state cerebral blood flow activities found in first-episode psychosis (FEP) and during acute effects of cannabinoids and opioids, mental states that can be profoundly different from normal functioning. The main goal was to identify connections of cerebral blood flow measure and regional brain activity patterns associated with subjective experiences and to find out whether there are similarities between the three mental states. The present study reviewed systematically the current state of research with respect to cannabinoids and opioids on resting state activity patterns as investigated by different neuroimaging techniques. Twenty-two studies encompassing different neuroimaging techniques were selected. Cerebral perfusion and resting blood flow measure by single-photon emission computed tomography (SPECT), positron emission tomography (PET), perfusion-weighted imaging (PWI), arterial spin labeling (ASL), and resting-state functional magnetic resonance imaging (resting-state fMRI) during acute cannabinoids or opioids challenges were compared to findings in patients with FEP. The total number of subjects included in this review encompassed 279 FEP/controls (mean age = 28 ± 8.6 years, 40.1% females), 315 participants with cannabinoids (mean age = 29 ± 7.1 years, 31.8% females) and 113 participants with opioids (mean age = 30 ± 3.9 years, 17.3% females). We found that effects on regional activity were highly conflicting within the same condition group. However, we critical compared baseline acitivty patterns between FEP and acute cannabinoid or opioids effects. There was some consistent evidence suggesting positive symptoms of FEP and depersonalization experiences after cannabis administration both result in an increased anterior cingulate activity, an important area in the default mode network.