A general cognitive improvement emerged in non-affective psychosis with and without

llicit drug use in the first month after an acute psychotic episode. As hypothesized, the

psychosis group with illicit drug use showed the largest increase in performance on the global

measure of cognitive functioning from baseline to follow-up, especially among the youngest

patients in this group. No significant differences in cognitive functioning were found at baseline

between the groups in this study. However, a larger increase in cognitive functioning emerged

in the psychosis group with illicit drug use as compared to the group without from admission to

follow-up. This indicates that the cognitive recovery process is more prominent in the illicit drug

using psychosis group in the acute phase as opposed to the non-affective psychosis only group.

Possibly, patients with non-affective psychosis and a history of illicit drug use, like for instance

cannabis, originally have a superior cognitive functioning (Løberg and Hugdahl,2009; Yuceletal.,

2012). Conceivably, use of illicit drugs can induce transient cognitive deficits, mimicking the

cognitive vulnerability that characterizes patients with schizophrenia at group level (Løberg and

Hugdahl,2009). The results from this study, with larger cognitive changes in the psychosis group

with illicit drug use, are in line with this assumption. Thus, the cognitive deficits initially in the

acute psychosis phase maybe attributed to the effects ofillicit drugs, like cannabis.

The analyzed interaction model accounted for age differences in the two groups and

showed the group difference to be stronger for younger patients. This means that the younger

patients in the psychosis group with illicit drug use had the largest cognitive change in the acute

phase, and younger age was not related to poly drug use or having a schizophrenia diagnoses as

opposed to an acute and transient psychosis diagnosis in the psychosis group with illicit drug

use group. Aplausible explanation for a larger cognitive change among the younger illicit drug

using patients is that their neuro cognitive set-up is more resilient and flexible; their younger

brains may have a larger capacity for plasticity (Kolb and Robbin,2011). Accordingly, the

recovery process of the brain functioning in the acute phase is larger among these patients.

However, one cannot rule out the possibility of a selection bias. Theoretically the younger

patients in this study could representa better functioning cognition sub-group. The association

between younger age and higher scores on the PANSS negative and general psycho pathology

subscales,and thus higher PANSS total scores, in the psychosis group with illicit drug use,

implies that the younger illicit drug using patients have more, not less, symptoms at admission.

However, inspite of more symptoms at baseline the youngest illicit drug using patients have the

most improvement on the neuro psychological tests in the acute phase. Interestingly, this effect

of age has been reported previously; a meta-analysis by Potvin et al.(2008) found that the

effect of better global cognition in schizophrenia patients with mixed substance use or cannabis

use decreased with increased age. Thus, it is important to be aware of the effect of age in

relation to cognitive functioning when drawing conclusions about cognition.

Use of illicit drugs like cannabis and amphetamines, may have led to disturbances in

dopaminergic and endogenous cannabinoid system and transient cognitive deficits, which

ultimately have resulted in expression of a psychotic disorder (Di Fortietal.,2007; Bossong and

Niesink,2010; Kuepperetal.,2010). This is supported by the fact that having a drug use disorder,

in particular cannabis and amphetamines use disorder (Callaghan etal.,2012), or earlier

cannabis use, is a risk factor for developing schizophrenia in a dose dependent manner

(Andreasson etal.,1987; Henquetetal.,2005; Moore etal.,2007). Thus, illicit drug-using patients

may have become psychotic through an alternative etiological pathway Løberg

andHugdahl,2009; Løberg etal.,2012). Supporting this, less neurological soft signs(Bersani

etal.,2002; Stirlingetal., 2005; Ruiz-Veguillaetal.,2012) and better social and leisure functioning

and more social contacts among drug using patients with schizophrenia, as compared to

psychosis patients without illicit drug use, have also been found (SalyersandMueser,2001). In

addition, non-affective psychosis patients with cannabis use seem to have a higher premorbid

IQ compared to those without illicit drug use (Leeson etal.,2012). Furthermore, studies have

generally reported an earlier onset of psychosis among cannabis using patients with

schizophrenia(Large etal.,2011;Leesonetal.,

2012;Mylesetal.,2012;DiFortietal.,2013;Donoghueetal., 2014), also suggesting an alternative

etiological pathway. Use of illicit drugs, like cannabis and amphetamines seems to have an

additive negative effect on brain functioning, and in some individuals the thres hold for

developing psychosisis lowered, presumably depending on the brains ability to tolerate the

effects of drugs, amount of drugs taken and genetic and cognitive vulnerability. The present

study is a naturalistic prospective study integrated in clinical practice. This increases the

generaliz ability and clinical relevance of the study, while at the sametime decreases the ability

to control for confounders and the ability to create a more homogenous drug user group, since

multiple drug use seems to be the norm. It may therefore be difficult to attribute the

differential effects on cognition a particular illicit drug. Confounders have been minimized by

controlling for group differences by statistical procedures, but it is a weakness of this study that

age onset of psychosis and number of psychotic episodes were not recorded, this was also the

case with frequency and duration of illicit drug use. Methodological strengths of the present

study were particularly that the patients were hospitalized during the follow-up to minimize

drug use and that neuropsychological screening instrument had alternative forms to avoid

practice effects. The present study did not include a control group of healthy individuals.

Cognitive functioning has been shown to predict functional everyday outcomes, like work

participation, better than positive symptoms (Green,1996;Venturaetal.,2009). RBANS total

score has also been shown to be strongly related to work participation in patients with

schizophrenia (Gold etal.,1999). Even though a general cognitive improvement took place in

both groups, indicating that neuropsychological functioning in the acute psychosis phase is not

stable, better cognition in particularly the younger psychosis patients that are using illicit drugs

emerged. This may have positive clinical implications, suggesting a potential for better

functional outcome. It seems plausible however, that a better prognosis is dependent on

abstinence from illicit drugs (Mullin et al.,2012;Guptaetal.,2013). In line with this, worse

cognitive functioning has been associated with continuous use of illicit drugs in psychosis (Rabin

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