Hallucinations arise from at least three distinct pharmacological pathways: activation of dopamine D2 receptors by psychostimulants, activation of serotonin 5HT2A receptors by psychedelics, and blockage of glutamate NMDA receptors by dissociative anesthetics. In schizophrenia, the relative roles of NMDA and dopamine receptors remain debated, and slight clinical differences appear depending on the cause. This narrative review synthesizes how leading researchers have approached whether the concept of hallucination is clinically and neurobiologically homogeneous. Some favor a single mechanism, while others propose integrated theories based on pharmacological psychosis models. The authors suggest that although common neurobiological pathways may exist, each system likely has unique properties that explain observed clinical differences.
A systematic review of 31 studies involving 2639 participants found that 12 studies reported a significant decrease in craving for alcohol, opioids, cocaine, or tobacco after psychedelic use. However, all but two studies had moderate to high risk of bias due to methodological issues, so the promising anti-craving effects must be interpreted cautiously. The review highlights the need for larger, well-controlled trials to better understand psychedelics' effects on craving, a core symptom of substance use disorders and a predictor of relapse.