The descriptive findings from this study suggest that the majority of cocaine (79.6%), cannabis (50.7%), and opiate (63.1%) users in our sample had some level of dependence to the substances, while a minority of amphetamine (27.9%) users had developed dependence. Nearly half of the respondents who abuse cocaine (47.7%) or cannabis (44.8%) reported experiencing psychotic symptoms during the use or withdrawal of those specific substances, while more than half of the respondents who were dependent on cocaine (80%), cannabis (63.5%), amphetamines (56.1%), and opiates (53.1%) reported psychotic symptoms. Furthermore, the rate of psychotic symptoms experienced by users who were dependent on these substances increased as the severity of dependence increased from mild to severe. For example, 55.8% of participants with mild cocaine dependence experienced psychotic symptoms, while this prevalence increased to 77.7% and 88.7% in participants with moderate or severe cocaine dependence. This finding supports a strong dose-response relationship, suggested by Thirthalli and Benegal [26
], between the experience of psychotic symptoms and severity of substance use.
The general population prevalence of isolated psychotic symptoms has varied from 17.5% in the Netherlands [4
] through 25% in New Zealand [36
] to 28% in the US [37
]. The higher proportions found among abusers and dependent users of the substances in this study are consistent with other reports that more substance users experience psychotic symptoms [21
]. Cocaine has a strong dopamine uptake inhibition action [38
] and cannabinoid receptors regulate the release of dopamine [39
]; thus this may explain the higher proportion of subjects moderately or severely dependent on cocaine or cannabis who are experiencing psychotic symptoms. Amphetamines also act on the brain by stimulating dopamine release [41
]. Thus, to the extent that the substances differ in their neurochemical actions on the brain, their differential effects may yield important clues in the causation of psychotic symptoms.
Although psychotic symptoms were found to be common among these substance users, the risk for development of psychotic symptoms was found to vary by substance and severity of the substance use. Given our limitation in statistical power and sample, the risk ratios must be interpreted with caution. After adjusting for age, gender, and employment, our findings suggest that when compared to cocaine users with no diagnosis, an increasing severity of cocaine use from abuse (OR=12.2) to mild dependence (OR=17.1) to moderate dependence (OR=47.0) to severe dependence (OR=114.0) is associated with a greater risk of drug-induced psychotic symptoms during use or withdrawal. A similar pattern, although quantitatively less acute, was found for cannabis, opiates, and amphetamines. Thus, the risk of psychotic symptoms from use or withdrawal with respect to cocaine, cannabis, opiates, and amphetamines users displayed an increase with the progression of abuse to dependence severity for each specific substance. This supports a strong dose-response relationship between the experience of psychotic symptoms and severity of cocaine, cannabis, opiate, and amphetamine use after adjusting for covariates.
Psychotic symptoms in the general population have been associated with risk factors such as a younger age and unemployment [37
]. Consistent with prior research, we found that a younger age was related to a greater risk of psychotic symptoms, but only among individuals using cocaine. This study also found that psychotic symptoms are highly prevalent during substance use and/or withdrawal, which is independent from a diagnosed psychotic illness (e.g., schizophrenia, bipolar disorder). However, it is not yet clear whether the presence of psychotic symptoms in individuals without a psychotic disorder contribute to the development of a psychotic illness later in life. Thus, research is needed to examine whether a history of psychotic symptoms due to substance use and/or withdrawal affects an individual’s neurobiology, thus increasing the risk of developing a psychotic disorder such as schizophrenia or bipolar disorder.
Our findings also have implications for the pathophysiology of psychotic disorders. For instance, given the increase in risk for psychosis among substance dependent individuals and that recent studies have demonstrated a link between adolescent substance use and the onset of psychosis in young adulthood [12
], research is needed to study the neurobiology of substance induced psychosis. Thus, such studies will inform primary prevention for substance abusers at risk for psychosis. Our findings also speak to the importance of developing services to target out-of-treatment substance users who abuse or are dependent upon amphetamines, cannabis, cocaine, or opiates as they are at a heightened risk for developing psychotic symptoms.
There are some important methodological limitations in this study. First, this study recruited substance abusers who represent a population of non-treatment seekers. It is possible that psychotic symptoms may have provided a barrier to their treatment access. Second, only drug-related psychotic symptoms were reported, thus we provide a limited perspective on how psychotogenic substances are experienced. Third, our measure of psychosis was limited to the items of the CIDI-SAM, and was not representative of all domains of psychosis outlined in the DSM-IV [44
]. Fourth, 74% of the subjects were dependent on more than one substance and the reader might question whether subjects could correctly attribute their psychotic symptoms to a particular substance. However, prior work with this sample regarding withdrawal suggests that they can correctly attribute their psychotic symptoms to specific substances [30
]. Lastly, in order to reveal the risk relationship for the severity of dependence to psychotic symptoms, a larger sample of participants with dependence on amphetamines is needed.
In conclusion, our findings suggest a strong dose-response relationship between the prevalence of psychotic symptoms and severity of cocaine, cannabis, opiate, and amphetamine use among out-of-treatment users of these substances. Services need to be designed to engage these individuals in the treatment process.