Clozapine, Explained

The picture shows striatal cholinergic interneurons (cell body in yellow) whose neurites (in red) make multiple connections to surrounding neurons. Dopamine through D2R has an important modulatory role on these connections in response to cocaine. R.G. Lewis, UCI School of Medicine

Clozapine has long been the most effective antipsychotic for people whose symptoms do not respond to standard treatments, yet no one has been able to fully explain why. For years, psychiatry has assumed that antipsychotic drugs work mainly by blocking dopamine or serotonin receptors, even though clozapine does not fit comfortably into either explanation. In a recent article, we suggest that the answer may have been hiding in plain sight: clozapine behaves very differently from other antipsychotics in the body’s cholinergic (acetylcholine) system, a difference that turns out to be central rather than incidental (Morrison et al 2025).

This matters because it helps make sense of both clozapine’s unmatched effectiveness and the recent success of a new generation of drugs that do not rely on dopamine blockade. These muscarinic-acting treatments appear to follow the same principle clozapine hinted at decades ago, but with better tolerability. If this approach continues to hold up, it could change how we understand psychosis and mark the beginning of a genuinely new era in antipsychotic treatment (Morrison et al 2025).

When Psychoanalysis Met the Brain

Salvador Dalí. (Spanish, 1904-1989). The Persistence of Memory. 1931

Widely regarded as a classic in modern psychiatry, Eric Kandel’s “Biology and the Future of Psychoanalysis” occupies a distinctive place at the intersection of neuroscience and depth psychology. Published in 1999 by a Nobel Prize–winning neuroscientist, in the final years of the “Decade of the Brain,” the paper reflects a moment when advances in brain science were reshaping psychiatry’s intellectual landscape. Rather than casting biology as a reductive alternative to psychoanalysis, Kandel argues that these advances offer the empirical tools psychoanalysis has long lacked, enabling its foundational concepts—such as the unconscious, and early experience—to be examined scientifically.

The paper is especially compelling in its careful use of neuroscientific research, including work on memory and stress-related neurobiology, to demonstrate how psychoanalytic ideas can be mapped onto identifiable neural systems. This integration preserves the explanatory depth of psychoanalysis while situating it within a testable biological framework. In doing so, Kandel offered a forward-looking vision for psychiatry, suggesting that the future intellectual vitality of psychoanalysis depends on its engagement with modern neuroscience rather than its isolation from it.