Psychotic disorders, particularly schizophrenia, are severe psychiatric conditions in which the ability to evaluate reality is profoundly impaired. These disorders are defined as a cluster of serious psychiatric conditions characterised by abnormal perception and thought. Both negative symptoms, reflected in the reduction or absence of normal functions (e.g., alogia, avolition, and diminished self-care), and positive symptoms, reflected in the exaggeration of normal functions (e.g., delusions, hallucinations, and disorganised speech or behaviour), are typically observed.

In primary psychotic disorders, notably schizophrenia, structural neuroimaging reveals a consistent pattern of widespread grey and white matter alterations that serves as a vital benchmark for differentiating substance-induced states. The most robustly replicated findings include diminished total brain and grey matter volumes alongside the enlargement of the lateral and third ventricles, a feature often detectable at the first episode of psychosis. Furthermore, widespread reductions in cortical thickness are observed—particularly within the frontal and temporal lobes—while significant volume loss is frequently identified in the hippocampus, amygdala, and thalamus. Conversely, certain subcortical regions, such as the caudate nucleus, putamen, and nucleus accumbens, often exhibit increased volume; these hypertrophic changes are generally attributed to the secondary effects of long-term antipsychotic treatment. Finally, compromised white matter integrity, evidenced by reduced fractional anisotropy in tracts such as the corpus callosum, suggests a profound disruption in connectivity between distant cortical regions.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), substance-induced psychosis is defined by the presence of delusions and/or hallucinations that emerge during or shortly after substance ingestion or acute withdrawal. A key clinical feature is that these symptoms are generally expected to remit following approximately one month of abstinence [1]. When symptom clusters extend beyond this duration, considerable difficulties are encountered in differentiating substance-related psychosis from schizophrenia and other primary psychotic disorders in clinical practice [2]. In a follow-up study, patients with primary psychosis and those with substance-induced psychosis admitted to a psychiatric unit were compared at baseline and at subsequent intervals until discharge. Patients with substance-induced psychosis recovered more rapidly than those with a primary psychotic disorder, with the difference being most pronounced during the first 15 days. Nevertheless, both groups exhibited comparable positive symptom severity, while more severe behavioural disturbances were observed among patients with substance-induced psychosis [3]. Contrary evidence has been reported in a study where patients with substance-induced psychosis did not exhibit a faster rate of remission following substance withdrawal compared to those with a primary psychotic disorder and co-occurring substance use. On the contrary, a slower reduction in hallucinations relative to baseline levels was observed [4].

The use of addictive substances has increasingly become a major public health concern worldwide. According to the European Monitoring Centre for Drugs and Drug Addiction, approximately 30% of adults in the European Union aged 15–64 have used illicit substances, particularly cannabis, at least once in their lifetime. Among young adults aged 15–34, considered the group most vulnerable to addiction, it has been estimated that 16% used cannabis within the past year, with prevalence reported to be approximately twice as high among men [5]. It has been estimated that approximately 4% of the global population, including both young adults and adults, have used cannabis at least once. Moreover, cannabis use has been reported to have increased by nearly 20% over the past decade [6]. An important consideration in substance-induced psychosis is the dose–response relationship in cannabis use, as the risk of psychosis has been shown to increase significantly with higher levels of tetrahydrocannabinol (THC) [7, 8]. A particularly alarming trend in public health is that the age of initiation for substance use is becoming progressively younger. In 2023, cannabis use within the past year was reported by 21.8% of individuals aged 12 years or older, corresponding to approximately 61.8 million people. Prevalence was highest among young adults aged 18–25 (36.5%, or 12.4 million), followed by adults aged 26 and older (20.8%, or 46.5 million), and adolescents aged 12–17 (11.2%, or 2.9 million) [9].

Cocaine, one of the most commonly used illicit substances, is estimated to affect nearly 25 million people worldwide, particularly in Americas, and Europe [10]. Among users, between half and three-quarters are reported to experience vivid hallucinations, delusions, and paranoid thoughts [11–13].

Methamphetamine use, increasingly encountered in psychiatric practice due to its availability and relatively low cost, is frequently associated with acute psychotic symptoms. In one study, nearly one-quarter of individuals using methamphetamine were reported to exhibit a psychotic disorder, indicating a markedly elevated risk and underscoring the severity of the problem [14].

Research on the prevalence of substance-related psychosis remains limited. In one study, the incidence of primary psychotic disorder was reported as 24.1 per 100,000 persons per year, while the incidence of primary psychotic disorder with comorbid substance misuse was 9.7, exceeding that of substance-related psychotic disorder, which was 6.5 [15]. With respect to treatment referral rates, substance-related psychosis has been reported to account for approximately 6–10% of patients presenting with first-episode psychosis compared with those presenting with primary psychotic or affective disorders [16, 17].

Distinguishing substance-induced psychosis from primary psychotic disorders remains a major clinical challenge. Although certain indicators exist, differentiation is often difficult, which likely affects research on substance-related psychosis, including structural neuroimaging studies reviewed here. It should also be considered that individuals predisposed to primary psychotic disorders may be more likely to use substances, while conversely, substance use may accelerate the course of an underlying psychotic condition [18]. Notably, substance-induced psychosis may occur at older ages and outside the typical onset range expected for primary psychotic disorders, further complicating diagnosis [17, 19]. Furthermore, individuals with substance-induced psychosis have been reported to show greater insight into their psychotic symptoms—particularly delusions and hallucinations—and to exhibit fewer negative symptoms compared with those with primary psychotic disorders [17, 19]. Regarding positive symptoms, some studies have reported higher levels in substance-induced psychosis, whereas others have found no such difference [15, 17, 19, 20].

Although primary psychotic disorders and substance-induced psychoses differ in certain respects, a diagnosis of schizophrenia or bipolar disorder is often made in the long term following substance use. For instance, approximately one-third of individuals diagnosed with amphetamine-induced psychosis are subsequently diagnosed with schizophrenia or bipolar disorder. Conversely, this proportion is reduced to approximately one-quarter among those diagnosed with hallucinogen-induced psychosis. Cannabis appears to play the most prominent role, with nearly half of those experiencing cannabis-induced psychosis later diagnosed with schizophrenia [21].

Extensive efforts have been made to explain the diverse clinical features of primary psychotic disorders, particularly schizophrenia, through structural and functional neuroimaging. However, neuroimaging studies on psychotic states arising from substance use disorders remain limited. This review therefore aims to summarise the available structural neuroimaging research and provide insights for future work in this field.