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Comprehensive Psychiatry 53 (2012) 1063–1070www.elsevier.com/locate/comppsych

Psychopathologic differences between cannabis-induced psychoses andrecent-onset primary psychoses with abuse of cannabis

Gabriel Rubioa,b, c,⁎, Jesús Marín-Lozanod, Francisco Ferreb,e, Isabel Martínez-Grasa,b, c,Roberto Rodriguez-Jimeneza,b, c, Javier Sanza,b, c, Miguel Angel Jimenez-Arrieroa,b, c,José Luis Carrascob,c, f, David Lorag, Rosa Juradoa,c, José Ramón López-Trabadaa,

Tomás Palomoa,b,ca12 de Octubre University Hospital, Madrid, Spain

bDepartment of Psychiatry, Faculty of Medicine, Complutense University, Madrid, SpaincBiomedical Research Center Network for Mental Health (CIBERSAM), Madrid, Spain

dLa Paz University Hospital, Madrid, SpaineGregorio Marañón University Hospital, Madrid, SpainfClínico San Carlos University Hospital, Madrid, Spain

gClinical Epidemiology Research Unit, 12 de Octubre University Hospital, Madrid, Spain

Abstract

The study aims to identify psychopathologic variables in cannabis-induced psychosis and recent-onset primary psychoses using theSymptom Checklist-90-R and the Psychiatric Research Interview for Substance and Mental Disorders. A sample of 181 subjects withpsychotic symptoms and cannabis use referred to the psychiatry inpatient units of 3 university general hospitals were assessed. The finalsample included 50 subjects with a diagnosis of cannabis-induced psychotic disorder (CIPD) and 104 subjects with primary psychoticdisorders. Using receiver operating characteristic curves, the most efficient psychopathologic variables for classifying CIPD wereinterpersonal sensitivity, “depression,” phobic anxiety, and Scale to Assess Unawareness of Mental Disorders subscales. The area under thereceiver operating characteristic curve of the model including depression and “misattribution” scores was 96.78% (95% confidence interval,94.43-99.13). Depressive symptoms could be used to distinguish CIPD from other primary psychotic disorders. Clinical variables related to“neurotic” symptoms could be involved in the susceptibility to cannabis-induced psychosis.© 2012 Elsevier Inc. All rights reserved.

1. Introduction

Cannabis use is widespread in the general population ofthe United States, European Union, and Spain [1-3]. It is alsocommon in subjects with severe mental disorders [4,5]. Theassociation between cannabis use and psychoses is well-known [4,6,7]. Cannabis use provokes induced psychosis[8], and in subjects with schizophrenia, cannabis abuse wasrelated to earlier onset [9], worse prognosis [10-13], andcognitive impairment [14,15]. In some cases, cannabis can

Conflict of interest: None.⁎ Corresponding author. Hospital Universitario 12 de Octubre, Glorieta

de Málaga s/n, 28041 Madrid, Spain. Tel.: +34 913908022; fax: +34913908538.

E-mail address: gabrielrubio@med.ucm.es (G. Rubio).

0010-440X/$ – see front matter © 2012 Elsevier Inc. All rights reserved.doi:10.1016/j.comppsych.2012.04.013

increase the susceptibility for a state of chronic psychosis[16]. Cannabis use is also very common in patients withbipolar disorders (BDs) [17-19]; it is associated with anearlier age at onset [20], lower compliance, and higher levelsof overall illness severity [21,22].

The similarities between the clinical features of cannabis-induced psychotic disorder (CIPD) and recent-onset primarypsychoses (mainly schizophrenia) with concurrent cannabisuse give rise to diagnostic and management difficulties inpatients with these disorders [23]. Recent studies haveattempted to establish the clinical differences between CIPDand primary psychotic disorders (PPDs) (see review byMathers et al [5]); however, these have either been cross-sectional studies in which the symptoms of the 2 disordershave been compared [24-26] or else follow-up studies todetermine which patients are finally diagnosed with

1064 G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

schizophrenia [23,27]. Hence, little is known about thebaseline psychopathologic features and the clinical course ofpatients who are not diagnosed with schizophrenia or BD.Despite the clinical importance of this issue, there has beensurprisingly little research into the differences betweenprimary and CIPDs. It is not known whether there arespecific vulnerability factors for cannabis-induced psychosisthat differ from those related to primary psychosis.Furthermore, the medium- and long-term outcomes inindividuals who have been diagnosed with cannabis-inducedpsychosis remain unclear; it is not known how many of themhave a true CIPD or finally develop chronic psychoticdisorders induced by drugs. Knowledge of these clinicalfeatures could facilitate prevention of cannabis-inducedpsychosis in at-risk individuals and improve the outcomeand prognosis in patients.

To clarify this issue, we conducted a follow-up study ofsubjects diagnosed with CIPD. In this article, we present theresults of the short-term psychotic period.

The main objectives of the study were to establish thepsychopathologic differences between PPD with cannabisconsumption and CIPD during the first weeks of treatment ininpatient facilities.

2. Methods

2.1. Sample selection

Over a 36-month period, from January 2005 to January2008, consecutive patients admitted to the psychiatry inpatientunits of 3 university general hospitals in Madrid (Spain) forpsychotic symptoms and cannabis use were screened for entryinto the study. Most subjects were identified during their firstadmission. They were recruited to the study when they wereable to give voluntary informed consent. The inclusion criteriaincluded age older than 18 years, at least 1 confirmedpsychotic symptom during the study period, and use ofcannabis within the previous 30 days.

Urine analyses were performed on all subjects to confirmor exclude the presence of other recreational drugs—hallucinogens, amphetamines, cocaine, opiates, barbiturates,benzodiazepines, and alcohol. These toxicological analyseswere performed at the time of clinical diagnosis and at least 3times a week until the study interview, a period that neverexceeded 1 month. All participants had a positive toxicologyscreen for cannabis at enrollment.

Clinical assessments for the study were performed duringthe time they remained in the hospital, at baseline (during thefirst 3 days after admission to a psychiatric unit), and beforedischarge, except for personality evaluation, which was onlyperformed at the 4-week interview. A total of 82 participantshad to be admitted on an involuntary basis (21 belonged tothe CIPD group).

The research protocol was approved by the institutionalreview board of the hospitals from which study subjectswere recruited.

2.2. Instruments

Psychopathologic symptoms were assessed using theSymptom Checklist-90-R (SCL-90-R) [28,29]. The SCL-90-R is a 90-item, multidimensional, self-report symptominventory designed to measure a broad range of currentpsychopathology symptoms. It contains 9 symptom scales thatare rated on a 5-point Likert scale of distress ranging from “notat all” to “extremely.” The internal consistency α coefficientsfor the 9 symptom dimensions vary between 0.77 and 0.90.The SCL-90-R has a high diagnostic sensitivity (80%-90%)but a low diagnostic specificity (20%-60%).

The Scale to Assess Unawareness of Mental Disorders(SUMD) [30] was used to evaluate an individual's insightinto having a mental illness. This instrument yields thefollowing 2 scores: the unawareness of symptoms score (k =0.64) and the “misattribution” of symptoms score (k = 0.62).The first score assesses the awareness of the existence of apsychotic symptom, and the second assesses the individual'sunderstanding that a psychotic symptom is a manifestation ofa mental illness. Subjects were given perfect scores onattribution for responses that indicated that the individualknew that the symptom being rated was because of a mentalillness or caused by the use of cannabis.

Research diagnoses were made using the PsychiatricResearch Interview for Substance and Mental Disorders(PRISM) [31], which was developed to assess psychiatricand substance use comorbidity based on the Diagnostic andStatistical Manual of Mental Disorders, Fourth Edition(DSM-IV) criteria [32].

The PRISM interview took place when patients wereclinically sufficiently stable to participate (during the first 10days of the inpatient period and at 6-month follow-up). Thevalidity of the Spanish version of the DSM-IV PRISM hasbeen evaluated using the Longitudinal, Expert, All Datastandard [33] and has shown good concordance for anycurrent psychotic disorder (k = 0.85) and past substance-induced disorder (k = 0.68). Reliability for diagnosesrelevant to this report was good for current and lifetimeschizophrenia with cannabis abuse and for CIPD (0.61-0.80).For this study, we used diagnoses made at 6-month follow-up (of 4 subjects who had been initially diagnosed asschizophreniform disorder, at 6-month follow-up, 1 of themwas diagnosed as CIPD and the others remained in the PPD).Cannabis-induced psychotic disorder was diagnosed whenpsychotic symptoms were developed after the beginning ofcannabis abuse, their psychotic symptoms had disappearedduring the first months of treatment, and at 6-month follow-up antipsychotics had been removed.

To determine Axis II diagnoses, patients also completedthe patient questionnaire for the Structured Clinical Inter-view for DSM-IV Personality Disorders [34].

2.3. Procedure

During the first days (days 1-3) of admission to theinpatient unit, patients signed the informed consent and were

1065G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

evaluated in accordance with the study protocol: SCL-90-Rscales and SUMD. Clinicians involved in the project used thepharmacologic treatment that they considered most appro-priate for each case during the study. Before discharge fromthe inpatient unit and at 6-month follow-up, patients wereinterviewed using the PRISM to diagnose Axis I episodesand also using the Structured Clinical Interview for DSM-IVAxis II Personality Disorders to diagnose personalitydisorders. At discharge, patients were referred to the programfor induced psychosis at “12 de Octubre” UniversityHospital for follow-up.

2.4. Statistical analysis

Demographic, clinical, and psychopathologic variablesare presented as mean ± SD, and categorical variables, asabsolute and relative frequencies. Statistical significance(P b .05) was determined by the Student t test for continuousvariables and by χ2 or Fisher exact test for categoricalvariables, as appropriate.

Receiver operating characteristic (ROC) curves wereplotted for the psychologic scales administered at baseline

Enrollment Assessed(N

Patiecomp

researc(N

Diagnostic groups determined before discharge

Cannabis-induced psychotic disorder

(CIPD) (n = 49)

Confirmation of diagnostic groups at 6-month follow-up

Cannabis-induced psychotic disorder (CIPD) (N = 50)

Fig. Diagram showing the number of p

(SCL-90-R and SUMD), and the following parameters werecalculated to measure the efficiency of clinical prediction:sensitivity (proportion of participants who were correctlyidentified), specificity (proportion of nonresponders whowere correctly identified), negative predictive value, positivepredictive value, and likelihood ratios [35]. Confidenceintervals (CIs) are included [36].

Taking into account the distribution of subjects over thepsychologic dimensions, we only selected those variableswith good sensitivity and specificity and with cutoff valuesthat comprised an adequate number of subjects [37].

There are several procedures that were applied to developthe predictive logistic model. First, variables that presentedhigh correlations with other variables (Spearman correlationN0.7) were excluded to avoid problems of colinearity.Second, continuous covariates were converted to categoricalvariables using fixed cutoff points, such as quartiles, andwere thus included as ordinal covariates. Finally, hands-onmodeling was performed with the addition or removal ofcovariates in logical order rather than solely according tostatistical significance. The best model was selected accord-ing to predictive ability.

for eligibility = 181)

Excluded Urine analysis positive for: - Cocaine plus alcohol (n = 18) - Opiates (n = 3) Refused to participate (n = 6)

nts who leted the h interview = 154)

Primary psychotic disorders withconcurrent cannabis use disorders

(PPD) (n = 105)

Primary psychotic disorder (PPD)(N = 104)

atients in each stage of the study.

able 2sychiatric diagnoses made before discharge

xis I, n (%)Primary psychoses 105 (68.18)Schizophrenia (n = 56)BD (n = 28)Schizophreniform disorder (n = 4)

1066 G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

The predictive model was evaluated by discriminativecapacity, area under the ROC curve [38], and explainedvariability (the Nagelkerke R2) [39].

Statistical analyses were performed using the SPSS v15.0(SPSS, Inc, Chicago, IL) and SAS v9.1 (SAS Institute, Inc,Cary, NC) statistical software packages.

Psychotic disorder NOS (n = 11)Delusional disorder (n = 6)CIPD 49 (31.82)ther Axis I disordersCannabis dependence 115 (74.67)Alcohol dependence 83 (53.89)Nicotine dependence 154 (100)Social phobia 14 (9.10)OCD 7 (4.54)xis II, n (%)BPD 21 (13.64)Antisocial personality disorder 13 (8.44)Schizoid personality disorder 6 (3.89)Paranoid personality disorder 10 (6.50)Others 11 (7.14)

3. Results

During the study period, 181 consecutive patients werescreened for inclusion. Six patients refused to participate.Eighteen patients were excluded for cocaine and alcoholabuse and 3 for opiate abuse; 12 of those subjects alsosatisfied criteria for alcohol dependence. A total of 154patients therefore performed the study interview (see theFig). The patients were aged between 18 and 45 years.

The demographic and clinical characteristics of thesample are shown in Table 1; most subjects were men,

Table 1Demographic and clinical characteristics of the sample at baseline (N = 154)

VariableDemographic variablesMale, n (%) 134 (87.0)Age, mean (SD) 25.28 (4.01)Marital status, n (%)Never married 116 (75.32)Married/cohabiting 29 (18.83)Separated/divorced 7 (4.54)Educational level, n (%)Primary 34 (22.07)Secondary/high school 118 (76.62)University 2 (1.29)Employment, n (%)Employed 83 (53.89)Parental mental illness, n (%) 33 (21.42)Parental substance abuse, n (%) 25 (16.23)

Substance useCannabis useAge (y) at initiation of cannabis use, mean (SD) 15.51 (2.73)Joints/d, mean (SD) 6.10 (2.01)Other drugsSmokers, n (%) 154 (100)Cigarettes/d, mean (SD) 24.30(6.0)Alcohol consumptionDrinks/wk, mean (SD) 34.59 (6.3)

Psychologic assessmentsSCL-90-R subscalesSomatization 1.81 (0.40)Obsessive-compulsive 2.23 (0.38)Interpersonal sensitivity 2.16 (0.39)Depression 2.73 (0.51)Anxiety 2.56 (0.40)Hostility 1.62 (0.60)Phobic anxiety 1.93 (0.52)Paranoid ideation 2.23 (0.44)Psychotic ideation 2.78 (0.58)SUMD scaleUnawareness of symptoms 2.71 (0.82)Misattributions of symptoms 1.58 (0.90)

OS indicates not otherwise specified; OCD, obsessive compulsiveisorder.

TP

A

O

A

Nd

never married, and had high school education. A familyhistory of mental disorders was detected in 21% and ofsubstance abuse disorders in 16%. Patients smoked anaverage of 6 joints of cannabis a day and drank heavily (anaverage of 5 standard drinks per day). At 6-month follow-up,50 patients (33.1%) were classified as CIPD and theremainder (104 patients, or 66.9%) with PPD (Table 2).One patient switched from PPD to CIPD after discharge. Inthis last group, the most prevalent disorders were schizo-phrenia (59 patients) and BD (28 patients, manic episode).Psychotic disorder not otherwise specified (11 patients) anddelusional disorder (6 patients) were also observed.Personality disorders were diagnosed in 61 patients(39.61%), the most frequent being the borderline andantisocial personality disorders.

3.1. Relevant clinical and psychopathologic differencesbetween CIPD and PPD groups

3.1.1. Demographic and background variablesThe demographic variables showed that patients in the

CIPD group were older and more likely to be employed.With regard to psychiatric comorbidity, there were nosignificant differences in premorbid personality disorders,but social phobia was more prevalent in the CIPD group(Table 3).

A family history of parental substance use disorders wasdetected in 28% of patients with CIPD but in only 10% ofthose with PPD. Only 2 patients in the group of subjects withPPD had a history of parental psychosis. Variables related tocannabis consumption indicated that subjects with CIPDsmoked larger amounts of cannabis. About 80% smokedmore than 8 joints a day, and the diagnosis of cannabisdependence was more prevalent in this group.

Table 3Significant demographic and clinical differences between cannabis-induced psychoses and primary psychoses

Variable CIPD (n = 50) PPDs (n = 104) P

Age (y), mean (SD) 27.96 (4.60) 24.95 (4.31) t = −5.133, df = 152, P = .001Employed, n (%) 39 (78.00) 44 (42.30) χ2 = 15.90, df =1, P = .001Parental substance abuse, n (%) 14 (28.00) 11 (10.57) χ2 = 6.30, df =1, P = .05Parental psychotic disorders, n (%) 0 (0) 2 (1.92) Fisher test, 0.46Cannabis dependence, n (%) 38 (76.00) 33 (31.73) χ2 = 18.59, df = 1, P = .001Joints/d, mean (SD) 8.53 (2.1) 5.07 (1.78) t = −10.402, df = 152, P = .001SCL-90-R subscale scoresSomatization 2.01 (0.36) 1.75 (0.43) t = 3.45, df = 152, P = .001Obsessive-compulsive 2.43 (0.32) 2.15 (0.48) t = 3.63, df = 152, P = .001Interpersonal sensitivity 2.53 (0.35) 1.75 (0.58) t = 8.71, df = 152, P = .001Depression 2.43 (0.31) 1.42 (0.61) t = 10.86, df = 1, P = .001Anxiety 1.96 (0.42) 1.81 (0.41) t = 2.68, df = 152, P = .04Hostility 1.15 (0.64) 1.34 (0.64) t = 1.65, df = 152, P = .09Phobic anxiety 1.87 (0.62) 1.32 (0.60) t = 5.25, df = 152, P = .001Paranoid ideation 1.62 (0.36) 1.77 (0.64 t = −1.52, df = 1, P = .132Psychotic ideation 1.65 (0.57) 1.85 (0.59) t = −1.98, df = 152, P = .05SUMD scale scoresUnawareness of symptoms 2.14 (0.89) 3.18 (1.17) t = −5.47, df = 152, P = .001Misattribution of symptoms 2.08 (0.89) 3.04 (0.89) t = −6.22, df = 152, P = .001Axis I, n (%)Social phobia 10 (20.0) 4 (3.84) χ2 = 8.70, df = 1, P = .003

Diagnoses confirmed at 6-month follow-up.

1067G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

3.1.2. Psychopathologic variables at baselineAt baseline, subjects with CIPD had significantly higher

scores than patients with PPD in the following SCL-90-Rsubscales: obsessive ideation, interpersonal sensitivity,“depression,” anxiety, and phobic anxiety (“neurotic pro-file”). However, they exhibited lower scores in paranoidideation and in SUMD subscales. Social phobia wasdiagnosed in 20% of subjects included in the CIPD group(vs 3.8% in the PPD group).

3.2. Logistic analysis and explicative model

The results of the area under the ROC curve and theefficiency of each cutoff point for each one of the subscalesare shown in Table 4. The SCL-90-R subscales with thegreatest areas under the curve were those of depression,interpersonal sensitivity, and phobic anxiety. The cutoffpoints for depression and interpersonal sensitivity with thebest sensitivity:specificity ratio were greater than 2. With acutoff point of 2.1 in the depression subscale and of 2.2 in theinterpersonal sensitivity subscale, the positive likelihoodratios were 4.7 (3.1-7.23) and 3.2 (2.3-4.6), respectively.

Given the significant association between the subscales, aclassification model was elaborated, which was finally formedby the variables depression andmisattribution. The first had anodds ratio of 15.11 (5.95-38.36), and the second, of 0.087(0.0034-0.223). Used in combination, these variables correctlyclassified patients in 96% (95% CI, 94.43-99.13) of cases.

4. Discussion

To our knowledge, this is the first rigorous study in whichthe distinction between cannabis-induced psychosis and PPDs

has been made using DSM-IV criteria. In our sample, 32.27%(50/154) of the sample was diagnosed as CIPD using thePRISM. The results of this study demonstrate that there areclinical and psychopathologic differences between cannabis-induced psychosis and primary psychosis with concurrentcannabis abuse in the short-term presentation. Subjects withCIPDhad psychopathologic symptoms belonging to a neuroticprofile (somatizations, obsessive-compulsive, interpersonalsensitivity, depression, anxiety, and phobic anxiety). Mis-attribution of the disorder and the prevalence of depressionalso differed between CIPD and PPD.

Although there are no studies that have used SCL-90-R todiscriminate between patients with and without inducedpsychosis, higher scores in the dimensions related to somaticanxiety symptoms and depression have been reported insubjects who use cannabis or ecstasy [40].

That subjects in the cannabis-induced psychosis grouphad a more “neurotic” rather than “psychotic” psychopath-ologic profile compared with those with primary psychosiscould have 2 possible explanations that are not mutuallyexclusive: (a) that the symptom profile in the subjects in theCIPD group was conditioned by the higher level of cannabisconsumption and (b) that the symptoms were dependent onpersonality traits, that is, on the cannabis-personalityinteraction (interpersonal sensitivity and phobic anxiety).

With regard to the first explanation, cannabis can mimicboth the positive and negative symptoms of schizophrenia[41,42]. Cannabis can also produce anxiety states [43]. It iswell-known that panic attacks occur in subjects withcannabis intoxication, but they can also develop in patientswith other psychiatric disorders, as we have found in thisstudy (borderline personality disorder [BPD], social phobia,and obsessive-compulsive disorder) [44]. This said, if the

Table4

Receiveroperatingcharacteristic

curvevalues

andcutoffpointsforSCL-90-RandSUMD

subscaleswith

discriminativecapacity

forclassifyingcann

abis-induced

psychoses(CIPD)

ROCcurve

Score

Sensitiv

itySpecificity

Positive

predictiv

evalue

Negative

predictiv

evalue

Positive

likelihoodratio

Negative

likelihoodratio

Efficiency

Areaun

der

thecurve

95%

CI

Value

95%

CI

Value

95%

CI

Value

95%

CI

Value

95%

CI

Value

95%

CI

Value

95%

CI

SCL-90-R

Obsessive-

compulsive

0.66

0.58-0.75

2.2

81.63

69.7-93.5

42.86

32.9-52.8

40.00

29.9-50.1

83.33

72.4-94.2

1.43

1.1-1.7

0.43

0.2-0.8

55.19

Interpersonal

sensitivity

0.87

0.82-0.93

2.2

87.76

77.5-97.9

73.33

64.4-82.2

60.56

48.4-72.6

92.7

86.6-98.9

3.2

2.3-4.6

0.17

0.08

-0.3

77.92

Depression

0.92

0.87-0.96

2.1

85.71

74.9-96.5

81.9

74.0-89.7

68.85

56.4-81.29

92.47

86.5-98.3

4.7

3.1-7.23

0.17

0.09

-0.3

83.12

Anx

iety

0.60

0.51-0.69

2.0

63.27

–53

.33

––

––

––

––

–56

.49

Pho

bicanxiety

0.72

0.63-0.80

1.60

61.22

46.5-75.8

71.43

62.3-80.5

50.00

36.5-63.4

79.79

71.4-88.4

2.14

1.47

-3.12

0.54

0.37

-0.79

68.18

SUMD

Unawareness

ofsymptom

s0.74

0.67-0.82

2.0

61.22

46.5-75.9

75.24

66.5-83.9

53.57

39.6-67.5

80.61

72.2-88.9

2.47

1.6-3.69

0.52

0.36

-0.75

70.78

Misattribution

ofsymptom

s0.76

0.68-0.84

2.0

73.47

60.1-86.8

68.57

59.2-77.9

52.17

39.6-64.6

84.71

76.4-92.9

2.34

1.68

-3.25

0.39

0.24

-0.63

70.13

1068 G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

intensity of consumption is related to the severity ofsymptoms, subjects in the CIPD group would have notonly more neurotic symptoms but also more psychoticsymptoms; this was found in our sample.

The other possibility is that subjects who developcannabis-induced psychosis are those who have personalitycharacteristics similar to those of the sample studied(predominance of interpersonal sensitivity and social phobicanxiety) and that, after consuming large quantities ofcannabis, they develop induced psychosis, that is, thepsychosis is due to a substance-personality trait interaction.

Recently, anxiety has been implicated in the onset ofsymptoms of delirious ideas of persecution (persecutorydelusions). In the model by Freeman et al [45], it wasconsidered that delirious ideas could develop because of theimplication of several factors: anomalous experiences, whichmay be caused by core cognitive dysfunction and street druguse; affective processes, especially anxiety, worry, andinterpersonal sensitivity; reasoning biases, particularly beliefconfirmation, jumping to conclusions, and belief inflexi-bility; and social factors, such as isolation and trauma. Inthe case of cannabis abusers in our sample, cannabis itselfcould also have played a role in the onset of persecutorydelusions through the induction of affective states such asdepression [46,47], anxiety [40], or exaggerated interper-sonal sensitivity or social anxiety, which could, in turn,explain the appearance of reasoning [45]. A depressedmood induced by drugs could also activate paranoid be-liefs. In fact, some current cognitive models of paranoiasuggest that paranoid patients are characterized by an un-derlying cognitive schemata with negative aspects similarto those found in depressed patients [48,49]. More spe-cifically, studies on attributional processes have found thatpatients with persecutory beliefs and patients with majordepression have a similar tendency to blame others fornegative events [50].

As we stated above, our final model correctly classifiedpatients with high scores in depression and with awarenessthat their clinical condition was caused by cannabis. Thislatter variable is a known characteristic that has often beenused to discriminate between induced and primary disorders[32,51]. Furthermore, although it would appear reasonable tothink that a depressed mood would serve to differentiatesubjects with induced psychosis from those with primaryaffective psychosis (BPD, manic phase), the discriminatorycapacity of these symptoms with regard to schizophrenicpsychosis has not yet been reported. There are several studiesthat have observed a relationship between cannabis anddepressive symptoms in both healthy and ill individuals[40,52-55], and it is possible that their presence could be acharacteristic of CIPD that could reasonably be used todistinguish CIPD from other disorders, although this willhave to be confirmed in future studies.

This study has several limitations. It was performed onpatients referred to acute care settings, which means that oursample included patients with more serious illness. The

1069G. Rubio et al. / Comprehensive Psychiatry 53 (2012) 1063–1070

findings cannot therefore be generalized to other settings,although further studies could add to our results. Thediagnosis of personality disorder was made during the firstmonths of the study, and it is possible that the cognitiveeffects of antipsychotic drugs and interference by thepsychotic symptoms could have altered the ability ofsubjects to recall their personality traits. Cannabis is themost widely used illegal substance in Spain, and itsconsumption is particularly high among young individualswho do not attribute any risk to its use [3]. Young Spaniardsconsider cannabis to be a “soft” substance used to relax andget high [3]. The wide availability of cannabis and theexpectations of its use could mean that the characteristics ofsubjects with CIPD in Spain differ from those of subjects inother countries with different patterns of consumption andwith others expectations of use.

5. Conclusions

Study findings suggest that depressive symptoms couldbe used to distinguish CIPD from other primary psychotic. Inour opinion, clinicians should consider this information andsuspect a CIPD when the severity of such symptoms ispronounced. We have found a relationship between anxietysymptoms/sensitive personality (trait or state) and the risk ofCIPD. If the present results are confirmed, in subjects withthese comorbid conditions who develop CIPD, pharmaco-logic and psychologic strategies need to be implemented totreat not only the psychotic symptoms and cannabisdependence but also the underlying psychiatric disorders.In summary, Axes I and II disorders may represent futurepaths for understanding the relationship between cannabisand psychotic symptoms.

Acknowledgment

This study was supported by the Carlos III HealthInstitute (PI 080287); Biomedical Research Center Networkfor Mental Health (CIBERSAM). The authors thank ProfCarmelo Vazquez for his constructive comments on earlierversions of this manuscript.

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