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Original Article |

Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults FREE

John McGrath, MD, PhD, FRANZCP; Joy Welham, MAPs; James Scott, MBBS, FRANZCP; Daniel Varghese, MBBS, FRANZCP; Louisa Degenhardt, PhD; Mohammad Reza Hayatbakhsh, MD, PhD; Rosa Alati, PhD; Gail M. Williams, PhD; William Bor, MBBS, DPM, FRANZCP; Jake M. Najman, PhD
[+] Author Affiliations

Author Affiliations: Queensland Brain Institute (Dr McGrath) and Department of Psychiatry (Drs McGrath and Scott), University of Queensland, St Lucia, Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol (Dr McGrath and Ms Welham), Child and Youth Mental Health Service, Royal Children's Hospital (Dr Scott), School of Population Health (Drs Hayatbakhsh, Alati, Williams, and Najman), and Centre for Youth Substance Abuse Research (Dr Alati), University of Queensland, Herston, and Department of Psychiatry, Princess Alexandra Hospital, Woolloongabba (Dr Varghese), Queensland, National Drug and Alcohol Research Centre, University of New South Wales, Sydney (Dr Degenhardt), and Mater Children's Hospital, South Brisbane (Dr Bor), Australia.


Arch Gen Psychiatry. 2010;67(5):440-447. doi:10.1001/archgenpsychiatry.2010.6.
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Published online

Context  Prospective cohort studies have identified an association between cannabis use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables. The use of sibling pair analysis reduces the influence of unmeasured residual confounding.

Objective  To explore the association between cannabis use and psychosis-related outcomes.

Design  A sibling pair analysis nested within a prospective birth cohort.

Setting  Births at a Brisbane, Australia, hospital.

Participants  Three thousand eight hundred one young adults born between 1981 and 1984 as part of the Mater-University Study of Pregnancy.

Main Outcome Measures  Cannabis use and 3 psychosis-related outcomes (nonaffective psychosis, hallucinations, and Peters et al Delusions Inventory score) were assessed at the 21-year follow-up. Associations between duration since first cannabis use and psychosis-related outcomes were examined using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up. Within 228 sibling pairs, the association between within-pair differences in duration since first cannabis use and Peters et al Delusions Inventory score was examined with general linear modeling. The potential impact of attrition was examined.

Results  Duration since first cannabis use was associated with all 3 psychosis-related outcomes. For those with duration since first cannabis use of 6 or more years, there was a significantly increased risk of (1) nonaffective psychosis (adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.5), (2) being in the highest quartile of Peters et al Delusions Inventory score (adjusted odds ratio, 4.2; 95% confidence interval, 4.2-5.8), and (3) hallucinations (adjusted odds ratio, 2.8; 95% confidence interval, 1.9-4.1). Within sibling pairs, duration since first cannabis use and higher scores on the Peters et al Delusions Inventory remained significantly associated.

Conclusions  Early cannabis use is associated with psychosis-related outcomes in young adults. The use of sibling pairs reduces the likelihood that unmeasured confounding explains these findings. This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.Published online March 1, 2010 (doi:10.1001/archgenpsychiatry.2010.6).

Figures in this Article

Prospective cohort studies have found that early-onset cannabis use is associated with an increased risk of psychosis-related outcomes.17 Based on these studies and a range of other lines of evidence, reviews have generally concluded that cannabis use is a risk-modifying factor for these outcomes (ie, cannabis use is causally related to psychosis-related outcomes).813 However, there are lingering concerns that the association may reflect methodological biases and unmeasured residual confounding.14,15 In a recent meta-analysis, Moore and colleagues11 noted that after adjusting for various methodological issues, there were often substantial reductions in the effect size between cannabis use and later psychosis-related outcomes. Because the pooled effect size reported by Moore and colleagues was modest (adjusted odds ratio, 1.41; 95% confidence interval [CI], 1.20-1.65), the role of residual confounding cannot be discounted. In light of the limitations of observational epidemiology,16 it is understandable that there is debate about the public health implications of these findings.15,17

Despite the oft-repeated concerns about the role of residual confounding, the research community has yet to explore the association between cannabis and psychosis outcomes using sibling pair designs. Twin and other sibling pair studies provide a quasi-experimental design that can help address the issue of residual confounding. Sibling pair designs capitalize on between-sibling differences while reducing the influence of unmeasured confounding factors, since differences are less likely to be attributable to shared genetic and environmental exposures. Twin studies have explored cannabis use as a “gateway” to other illicit drug use,18 but, to our knowledge, no study has used a sibling pair design to examine the association between cannabis use and psychosis-related outcomes. If a significant association between cannabis use and psychosis-related outcomes was not detected in sibling pairs, it would seriously weaken the argument that cannabis use was a risk-modifying factor for psychosis-related outcomes. The aims of this study were to explore the association between cannabis use and multiple psychosis-related outcomes in a birth cohort and to further examine if these associations persisted within nested sibling pairs.

PARTICIPANTS

The Mater-University Study of Pregnancy, and its outcomes, is a prospective study of 7223 women and their singleton offspring who received antenatal care at a major public hospital in Brisbane, Australia, between 1981 and 1984. The cohort members (and their mothers) were followed up at 5, 14, and 21 years (eFigure 1). Of the original sample, follow-up responses were obtained for 3801 children (53%) at the 21-year follow-up. Full details of the Mater-University Study of Pregnancy study design, sampling strategy, attrition, and follow-up sample characteristics are available elsewhere.19

MEASUREMENT OF MAIN EXPOSURES

At the 21-year follow-up, cannabis use was retrospectively assessed via a self-report questionnaire. Cohort members were asked “In the last month, how often did you use cannabis, marijuana, pot, etc?” Options for response were have never used, used every day, every few days, once or so, and not in the last month. A second question sought the age at which use of cannabis began. Based on these variables, and the cohort members' age at interview, we derived a measure of duration since first cannabis use. This variable was categorized into 4 levels, with those who had never used cannabis in 1 group (the reference group) and those who had used cannabis divided into 3 approximately equal groups (≤3 years, 4 or 5 years, ≥6 years). Because members of this birth cohort were assessed within a relatively narrow age range, longer duration since first cannabis use is equivalent to an earlier age at first cannabis use.

To explore the validity of this item, we examined the association between duration since first cannabis use (a retrospective measure) vs a prospective measure of alcohol and illicit drug use that was assessed at the 14-year follow-up as part of the widely used Youth Self-Report20 (“I use alcohol and drugs for nonmedicinal purposes”).

MEASUREMENT OF OUTCOME VARIABLES

We examined 3 psychosis-related outcomes. At the 21-year follow-up, 2575 of the 3801 cohort members were administered the computerized lifetime version of the Composite International Diagnostic Interview (CIDI).21 Not all cohort members received the CIDI, but this was because of insufficient funding rather than any systematic bias (see later for analyses related to missing values). For the current study, we defined “caseness” as having an International Statistical Classification of Diseases, 10th Revision (ICD-10)22 diagnosis of nonaffective psychosis based on meeting the criteria for the diagnoses of either schizophrenia (ICD-10 code F20), persistent delusional disorder (ICD-10 code F22), or acute and transient psychotic disorders (ICD-10 code F23). We also examined the 21-item version of the Peters et al Delusions Inventory (PDI), an instrument used to measure delusional-like experiences in clinical and community populations.23,24 Finally, we examined 2 specific CIDI items designed to assess the presence of auditory and visual hallucinations. Cohort members were grouped into those who endorsed no hallucination items vs 1 or more.

MEASUREMENT OF POTENTIAL CONFOUNDERS AND OTHER EXPLANATORY FACTORS

It is feasible that early psychotic-like experiences could influence both subsequent cannabis use and psychosis-related outcomes at the 21-year follow-up. At the 14-year follow-up, 2 items from the Youth Self-Report20 were chosen for their face validity as psychotic-like experiences: “I hear sounds or voices that other people think aren't there” and “I see things that other people think aren't there.” Based on this same cohort, we previously reported that these items were associated with both an increased risk of nonaffective psychosis25 and high scores on the PDI26 at the 21-year follow-up. Subjects were dichotomized into those who responded “never” vs “sometimes” or “often.”

Parental mental illness is a potential confounding factor because this could influence both the risk of cannabis use and psychotic-related outcomes in the offspring.2730 At the 5, 14, and 21-year follow-ups, mothers of the cohort members were asked to report on specific parental mental illnesses (maternal or paternal history of schizophrenia, alcohol abuse/dependence, and depression or anxiety disorders). Subjects were dichotomized into parental history of mental disorder present or absent.

MAIN AND PLANNED SENSITIVITY ANALYSES

We used maximum likelihood logistic regression to examine the associations between duration since first cannabis use and each of the 3 main outcomes variables in separate analyses (ie, nonaffective psychosis, PDI total score, and the CIDI hallucination items). In keeping with previous analyses,26 the total score of the PDI was divided into quartiles. For model 1, the analyses were adjusted for sex and age of the cohort members at the 21-year follow-up (age at testing varied slightly at each follow-up). For model 2, we also included adjustments for 2 additional variables: (1) parental mental illness and (2) hallucinations at age 14 years as assessed on the Youth Self-Report.

Several planned sensitivity analyses were undertaken. For the assessment of the PDI total score and CIDI hallucination items, we conducted the analyses again excluding cohort members who (1) received a CIDI-derived diagnosis of nonaffective psychosis (to examine psychotic-like experiences in the cohort members without diagnostic-level psychotic disorders) or (2) reported any cannabis use in the month prior to the 21-year follow-up interview (to reduce the potential influence of acute intoxication or withdrawal on the outcome measures). Cannabis use has also been associated with later depression and anxiety.11 Using the major CIDI-derived diagnoses of depression (ICD-10 codes F32, F33, and F34) and anxiety disorders (ICD-10 codes F40, F41, and F43), we examined the association between duration since first cannabis use and the psychosis-related outcomes in models that adjusted for the presence of these disorders. To focus on issues related to reverse causality, we also examined the association between endorsement of hallucination items at age 14 years on the Youth Self-Report and both frequency of cannabis use and duration since first cannabis use (assessed at the 21-year follow-up), excluding those who used cannabis before age 15 years.

SIBLING PAIR ANALYSIS

While the Mater-University Study of Pregnancy cohort was restricted to singleton offspring, during the period of recruitment several hundred sibling pairs were recruited into the study (there were no sibships with greater than 2 members included in the cohort). We identified 228 sibling pairs who participated in the 21-year follow-up and who provided information on the variables of interest (60 male sibling pairs, 65 female sibling pairs, and 103 mixed-sex sibling pairs). The maximum between-sibling age difference was 4 years, with 92% of the siblings differing in age by 3 years or less. Eighty-three percent of the mothers of the sibling pairs reported no change in partners over the period of the birth of the 2 siblings.

Following methods outlined elsewhere,31,32 an index sibling was randomly selected, and difference scores between the siblings for (1) years since first cannabis use and (2) PDI total score were generated (index sibling minus other sibling). For example, within a sibling pair, if (1) the index sibling had 6 years since first cannabis use and a PDI total score of 10 items while (2) the other sibling had 2 years since first cannabis use and a PDI total score of 3 items, then (3) the years since first cannabis use difference score would be 4 years and the PDI difference score would be 7 items. For each sibling pair, the association between years since first cannabis use difference score (the predictor variable) vs the PDI difference score (the outcome variable) was examined, when adjusted for differences in sibling age and sex. Sibling pairs that included a cohort member with an ICD-10 diagnosis of nonaffective psychosis were excluded from the main analysis.

It could be argued that siblings discordant for cannabis use (ie, one sibling who had never used cannabis and a sibling who had used cannabis for several years) may differ in a range of factors that could impact both the exposure variables (ie, propensity to use illicit drugs) and subsequent mental health. Thus, we undertook an additional planned sensitivity analysis where we restricted the sibling pairs to those who both used cannabis. This analysis allowed an even greater focus on the critical nonshared exposure (ie, duration since first cannabis use) and the psychosis-related outcomes.

POTENTIAL IMPACT OF MISSING DATA AND ATTRITION

We explored the influence of attrition using 2 methods. First, we used SAS Proc MI and MIanalzye (SAS Institute Inc, Cary, North Carolina) to explore the data under the assumption that data were missing randomly. For the multiple imputation, we included the variables of interest used in the earlier-mentioned models and also variables known to be associated with attrition in this cohort (ie, birth weight and various maternal variables at first clinic visit related to age, education, marital status, mental health, and smoking).19 We used logistic regression based on 20 imputed data sets. Finally, based on the assumption that the data were missing in a nonrandom fashion, we undertook a post hoc modeling exercise to explore the robustness of the main findings under a set of assumptions that would be potentially challenging to these findings.

Analyses were performed using SAS version 9.1 (SAS Institute Inc). Written informed consent was obtained from the mother at all data collection phases and from the young adult at the 21-year follow-up. Ethical approval for this study was obtained from the University of Queensland Ethics Committee.

In total, 3801 subjects (1806 males) were included in the analyses, with mean (SD) age of 20.1 (0.90) years (range, 18 to 23 years). Overall, 65 subjects received a diagnosis of nonaffective psychosis (ICD-10 code F20 schizophrenia, n = 53; ICD-10 code F22 persistent delusional disorder, n = 3; and ICD-10 code F23 acute and transient psychotic disorders, n = 9), while 233 endorsed at least 1 CIDI hallucination item. The total PDI score ranged from zero to 21 endorsed items (mean [SD], 5.1 [3.6] items; median, 4.0 items). The quartiles for the PDI total score divided the subjects into (1) 2 or less, (2) 3 or 4, (3) between 5 and 7, and (4) 8 and more items. The association between a range of demographic and potential confounding variables is shown in Table 1. In keeping with previous analyses, sex, age at testing, parental mental illness, and hallucinations at age 14 years were significantly associated with some or all of the psychosis-related outcomes.

Table Graphic Jump LocationTable 1 Psychosis-Related Outcomes at the 21-Year Follow-up by Demographic and Covariate Factors

At the 14-year follow-up, 283 cohort members (7.9%) reported using alcohol or illicit drugs. At the 21-year follow-up, 17.7% reported using cannabis for 3 or fewer years, 16.2% for 4 to 5 years, and 14.3% used for 6 or more years. Among those who had ever used, 52.6% had not used in the previous month, 11.0% reported daily use, 13.8% reported use “every few days,” and 22.6% reported use “once or so per month.” With respect to the validity of the main exposure measure, there was a significant and strong relationship between the prospective assessment of alcohol or illicit drug use at the 14-year follow-up and longer duration since first cannabis use at the 21-year follow-up (Wald test = 231; df = 3; P < .001). Those who reported alcohol or illicit drug use at the 14-year follow-up were 15 times more likely to subsequently report 6 years’ or more duration since first cannabis use (odds ratio, 14.7; 95% CI, 10.2-21.2).

Tables 2, 3, and 4 show the association between duration since first cannabis use and the 3 psychosis-related outcome measures. Only those with the longest duration since first cannabis use were at significantly increased risk of nonaffective psychosis: those with 6 or more years duration since first cannabis use (ie, use since around 15 years of age) were twice as likely to receive a diagnosis of nonaffective psychosis.

Table Graphic Jump LocationTable 2 Association Between Duration Since First Cannabis Use and Nonaffective Psychosis at the 21-Year Follow-up
Table Graphic Jump LocationTable 3 Association Between Duration Since First Cannabis Use and PDI Total Score Quartiles
Table Graphic Jump LocationTable 4 Association Between Duration Since First Cannabis Use and the Presence of Hallucinations at the 21-Year Follow-up

In Table 3, only the highest vs lowest PDI total score quartile odds ratios are shown. Compared with those who did not use cannabis, cannabis users were significantly more likely to be in the highest quartile of the PDI scores. Those with a duration since first cannabis use of 6 or more years were 4 times more likely to be in the top PDI score quartile and twice as likely to endorse CIDI hallucination items (Table 4). There were significant linear trends between the exposure variable and all 3 psychosis-related measures: the longer the duration since first cannabis use, the higher the risk of the adverse outcomes.

For the PDI score and hallucination outcomes, we conducted a sensitivity analysis excluding individuals with nonaffective psychosis and those who had used cannabis in the month prior to the 21-year follow-up (eTable 1). The association between years since first cannabis use and PDI total score remained significant for those who had 4 years or more since first cannabis use. With respect to CIDI hallucination items, only those who had 4 or 5 years since first cannabis use had a significantly increased risk of reporting hallucinations at age 21 years. When we made additional adjustments to the model to include the presence of a depressive or anxiety disorder (eTable 2), the point estimates for all 3 analyses dropped slightly and the CIs became more imprecise, suggesting that these factors influenced the associations of interest. Only the analyses related to years since first cannabis use and (1) PDI total scores and (2) hallucinations remained statistically significant.

With respect to the potential for reverse causality, we found that hallucinations at the 14-year follow-up were significantly associated with longer duration since first cannabis use by the 21-year follow-up (Table 5). Furthermore, compared with those who did not report hallucinations, those with hallucinations at the 14-year follow-up were twice as likely to be using cannabis on a daily basis at the 21-year follow-up (model 1, adjusted odds ratio, 2.1; 95% CI, 1.4-2.9).

Table Graphic Jump LocationTable 5 Association Between Hallucinations at 14-Year Follow-up and Duration Since First Cannabis Use Assessed at 21-Year Follow-upa

Within the sibling pair sample, there were 10 pairs who were discordant for nonaffective psychosis (there were no pairs concordant for nonaffective psychosis at the 21-year follow-up). For the discordant sibling pairs, we calculated the difference in years since first cannabis use for the affected minus the nonaffected sibling. The median difference was 1.5 years (mean [SD], 0.4 [3.3] years, range, −6 to 4 years). However, within this small sample, there was no significant difference in years since first cannabis use between the affected vs nonaffected siblings when adjusted for age and sex (F1,5 = 0.60; P = .49). Concerning the main analysis, within the nonaffected sibling pairs (sib pairs = 218), there was a significant association between years since first cannabis use and PDI total difference scores when adjusted for differences in age and sex (F1,213 = 18.5; P < .001). Compared with their sibling, those with more years since first cannabis use were more likely to have higher PDI total scores. The model (which explained 19% of the variance) found that for every additional year since first exposure to cannabis, the sibling with the earlier age at first use had scored approximately 1 PDI item higher compared with their sibling (per annum increase in PDI total score = 0.8; 95% CI, 0.7-0.9). The Figure shows a scatterplot with each point representing 1 sibling pair. When sibling pairs were restricted to those where both siblings had used cannabis (100 sibling pairs), the significant relationship between years of cannabis use and PDI scores persisted (F1,95 = 6.4; P = .01) (eFigure 2).

Place holder to copy figure label and caption
Figure

Sibling pair analysis. Correlation between within-pair difference in years of cannabis use vs difference in Peters et al Delusions Inventory (PDI) total score. Each dot represents 1 sibling pair. Negative values indicate that the index sibling had lower values on the variable of interest compared with his or her sibling. Vertical and horizontal blue lines represent zero (ie, no difference between the siblings). The solid line is the regression and the dotted lines show the 95% confidence intervals (based on mean values).

Graphic Jump Location

The association between years since first cannabis use and PDI total score was reexamined using imputed missing data (eTable 3). The significant findings persisted and the point estimates and CIs remained essentially unchanged. Finally, we modeled a conservative missing data scenario where we assumed that (1) all subjects with missing data on years since first cannabis use were users and randomly allocated them between 1 to 8 years' duration since first cannabis use and (2) those with missing values were more likely to have lower PDI total scores (to challenge our main empirical finding) and randomly allocated these subjects to the lower 2 PDI score quartiles. The resulting effect sizes for model 2 fell sharply, but compared with those who never used cannabis, the association between 6 or more years' duration since first cannabis use and higher PDI total scores remained statistically significant.

Longer duration since first cannabis use was associated with multiple psychosis-related outcomes in young adults. Furthermore, we report for the first time, to our knowledge, that this association persisted when examined in sibling pairs, thus reducing the likelihood that the association was due to unmeasured shared genetic and/or environmental influences. There was a “dose-response” relationship between the variables of interest: the longer the duration since first cannabis use, the higher the risk of psychosis-related outcomes. The key findings were robust in the face of various planned sensitivity analyses and conservative tests related to attrition.

Compared with those who had never used cannabis, young adults who had 6 or more years since first use of cannabis (ie, who commenced use when around 15 years or younger) were twice as likely to develop a nonaffective psychosis and were 4 times as likely to have high scores on the PDI. Further analyses demonstrated that these findings were not due to a small group of individuals with psychotic disorders nor to individuals who were acutely intoxicated with cannabis when completing the PDI.

Sibling pair analysis provides the opportunity to control for a range of unmeasured potential confounding variables. We identified a small but significant positive association between years since first cannabis use and scores on the well-validated measures of delusional-like experiences. Reassuringly, this association persisted when we restricted the analysis to sibling pairs concordant for any cannabis use. This more stringent analysis provided a sharper focus on the critical nonshared exposure (ie, duration since first cannabis use).

With respect to genetic background, the cohort members within the sibling pairs shared the same mother, and the majority (we assume) shared the same father. Because of the age proximity of the siblings, we can also feel confident that a range of family milieu and socioeconomic factors remained reasonably constant for the sibling pairs during early childhood. Of course, a range of exposures would still differ between the siblings (eg, the use of alcohol and illicit substances), and we would expect these nonshared exposures to become more prominent with age (eg, after the cohort members left the family home).

The nature of the relationship between psychosis and cannabis use is by no means simple. In keeping with previous findings,33 we confirmed that those with early-onset hallucinations were more likely to have longer duration since first cannabis use and to use cannabis more frequently at the 21-year follow-up. This demonstrates the complexity of the relationship: those individuals who were vulnerable to psychosis (ie, those who had isolated psychotic symptoms) were more likely to commence cannabis use, which could then subsequently contribute to an increased risk of conversion to a nonaffective psychotic disorder. In addition, analyses that incorporated adjustments for depressive and anxiety-related disorders led to a reduction in the strength of the association between cannabis use and psychosis-related outcomes. This suggests that depression and/or anxiety disorders may mediate or moderate the pathways between cannabis use and psychosis-related outcomes. We plan to further explore these issues in more detail in future studies.

The main analyses relied on retrospective self-assessment of duration since first cannabis use rather than prospective self-report or objective drug screens.34 The main predictor variable did not capture cumulative exposure to cannabis. It is feasible that some cohort members may have started cannabis use at a relatively young age and then stopped. These subjects would have been allocated the same duration since first cannabis use as those with early and persistent usage. Those with psychosis-related outcomes may have been less reliable in estimating the age at first using cannabis, but there is no a priori reason to suspect that these individuals would systematically underreport or overreport this variable. Furthermore, the strong association between alcohol and illicit drug use assessed at the 14-year follow-up and longer duration since first cannabis use assessed at the 21-year follow-up lends weight to the validity of the later variable.

Our diagnosis of nonaffective psychosis at age 21 years was not clinically validated, and our findings related to nonaffective psychosis (which were the most fragile of the 3 psychosis-related outcomes) should be interpreted cautiously. We hope to address the clinical validity of the CIDI-derived diagnoses in the cohort in future follow-ups. Diagnostic instruments were not administered at the 14-year follow-up; thus, we cannot confidently exclude the possibility that some of the cohort members may have developed psychosis as young adolescents, which may have contributed to subsequent cannabis use. In addition, the assessment of psychotic-like experiences at the 14-year follow-up were based on 2 hallucination items only; no items related to delusional beliefs were available at this follow-up.

Like other birth cohort studies, attrition was evident by the 21-year follow-up.25 While this was primarily due to lack of resources to track all original cohort members rather than refusal to participate, participants lost to follow-up differed on a range of variables.19 However, results of reanalyses based on imputed data were essentially unchanged from the results based on actual data. We also undertook post hoc modeling to test the robustness/fragility of our main finding in the face of “challenging” scenarios related to differential attrition. The direction and significance of the key findings persisted in these analyses.

Our study has demonstrated an association between duration since first cannabis use and psychosis-related outcomes in young adults. The findings are consistent with the 2 other birth cohort studies that have addressed this issue.6,7 Of particular interest, these findings persisted within sibling pairs, thus reducing the chance that these associations were influenced by unmeasured residual confounding. This study has also highlighted the complexity of the relationship between risk factors and mediating variables on psychosis-related outcomes, since those with early-onset psychotic symptoms were also likely to report early cannabis use. This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults. Apart from the implications for policy makers and health planners,15 we hope our findings will encourage further clinical and animal model–based research to unravel the mechanisms linking cannabis use and psychosis.35

Correspondence: John McGrath, MD, PhD, FRANZCP, Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, QLD 4076, Australia (john_mcgrath@qcmhr.uq.edu.au).

Submitted for Publication: July 6, 2009; final revision received September 9, 2009; accepted September 13, 2009.

Published Online: March 1, 2010 (doi:10.1001/archgenpsychiatry.2010.6).

Author Contributions: Dr McGrath and Ms Welham developed the study aim and design. Drs Williams, Najman, and Bor set up and are responsible for the Mater-University Study of Pregnancy (MUSP) and its outcomes. Dr McGrath and Ms Welham wrote the first draft of the paper and undertook the analysis. All authors contributed to the final version of the paper.

Financial Disclosure: None reported.

Funding/Support: This work was funded by the National Health and Medical Research Council of Australia. Dr Alati is funded by a National Health and Medical Research Council Career Development Award in Population Health (ID 519721).

Role of the Sponsors: The sponsor had no role in the design or conduct of the study, the analysis and interpretation of the results, or the preparation or approval of the manuscript.

Additional Contributions: We thank MUSP participants, the MUSP Research Team and Database manager, the MUSP data collection teams from phases 3 to 5, the Mater Misericordiae Hospital, and the schools of Social Science, Population Health, and Medicine at the University of Queensland for their support.

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Hall  W The psychotogenic effects of cannabis use: challenges in reducing residual uncertainties and communicating the risks. Addiction 2004;99 (4) 511- 512, author reply 515
PubMed Link to Article
Lynskey  MTHeath  ACBucholz  KKSlutske  WSMadden  PANelson  ECStatham  DJMartin  NG Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA 2003;289 (4) 427- 433
PubMed Link to Article
Najman  JMBor  WO'Callaghan  MWilliams  GMAird  RShuttlewood  G Cohort profile: the Mater-University of Queensland Study of Pregnancy (MUSP). Int J Epidemiol 2005;34 (5) 992- 997
PubMed Link to Article
Achenbach  TM Manual for the Youth Self-Report and 1991 Profile.  Burlington: University of Vermont Dept of Psychiatry; 1991
WHO Composite International Diagnostic Interview (CIDI), version 2.1.  Geneva, Switzerland: World Health Organisation; 1992
World Health Organization International Statistical Classification of Diseases, 10th Revision (ICD-10).  Geneva, Switzerland: World Health Organization; 1992
Peters  ERJoseph  SAGarety  PA Measurement of delusional ideation in the normal population: introducing the PDI (Peters et al. Delusions Inventory). Schizophr Bull 1999;25 (3) 553- 576
PubMed Link to Article
Peters  EJoseph  SDay  SGarety  P Measuring delusional ideation: the 21-item Peters et al. Delusions Inventory (PDI). Schizophr Bull 2004;30 (4) 1005- 1022
PubMed Link to Article
Welham  JIsohanni  MJones  PMcGrath  J The antecedents of schizophrenia: a review of birth cohort studies. Schizophr Bull 2009;35 (3) 603- 623
PubMed Link to Article
Scott  JMartin  GWelham  JBor  WNajman  JO’Callaghan  MWilliams  GAird  RMcGrath  J Psychopathology during childhood and adolescence predicts delusional-like experiences in adults: a 21-year birth cohort study. Am J Psychiatry 2009;166 (5) 567- 574
PubMed Link to Article
Varghese  DScott  JMcGrath  J Correlates of delusion-like experiences in a non-psychotic community sample. Aust N Z J Psychiatry 2008;42 (6) 505- 508
PubMed Link to Article
Hayatbakhsh  MRMamun  AANajman  JMO'Callaghan  MJBor  WAlati  R Early childhood predictors of early substance use and substance use disorders: prospective study. Aust N Z J Psychiatry 2008;42 (8) 720- 731
PubMed Link to Article
Macleod  JHickman  MBowen  EAlati  RTilling  KSmith  GD Parental drug use, early adversities, later childhood problems and children's use of tobacco and alcohol at age 10: birth cohort study. Addiction 2008;103 (10) 1731- 1743
PubMed Link to Article
Fergusson  DMBoden  JMHorwood  LJ The developmental antecedents of illicit drug use: evidence from a 25-year longitudinal study. Drug Alcohol Depend 2008;96 (1-2) 165- 177
PubMed Link to Article
Matte  TDBresnahan  MBegg  MDSusser  E Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. BMJ 2001;323 (7308) 310- 314
PubMed Link to Article
Lawlor  DANajman  JMBatty  GDO'Callaghan  MJWilliams  GMBor  W Early life predictors of childhood intelligence: findings from the Mater-University study of pregnancy and its outcomes. Paediatr Perinat Epidemiol 2006;20 (2) 148- 162
PubMed Link to Article
Ferdinand  RFSondeijker  Fvan der Ende  JSelten  JPHuizink  AVerhulst  FC Cannabis use predicts future psychotic symptoms, and vice versa. Addiction 2005;100 (5) 612- 618
PubMed Link to Article
Buchan  BJL Dennis  MTims  FMDiamond  GS Cannabis use: consistency and validity of self-report, on-site urine testing and laboratory testing. Addiction 2002;97 ((suppl 1)) 98- 108
PubMed Link to Article
McGrath  JJRichards  LJ Why schizophrenia epidemiology needs neurobiology—and vice versa. Schizophr Bull 2009;35 (3) 577- 581
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure

Sibling pair analysis. Correlation between within-pair difference in years of cannabis use vs difference in Peters et al Delusions Inventory (PDI) total score. Each dot represents 1 sibling pair. Negative values indicate that the index sibling had lower values on the variable of interest compared with his or her sibling. Vertical and horizontal blue lines represent zero (ie, no difference between the siblings). The solid line is the regression and the dotted lines show the 95% confidence intervals (based on mean values).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1 Psychosis-Related Outcomes at the 21-Year Follow-up by Demographic and Covariate Factors
Table Graphic Jump LocationTable 2 Association Between Duration Since First Cannabis Use and Nonaffective Psychosis at the 21-Year Follow-up
Table Graphic Jump LocationTable 3 Association Between Duration Since First Cannabis Use and PDI Total Score Quartiles
Table Graphic Jump LocationTable 4 Association Between Duration Since First Cannabis Use and the Presence of Hallucinations at the 21-Year Follow-up
Table Graphic Jump LocationTable 5 Association Between Hallucinations at 14-Year Follow-up and Duration Since First Cannabis Use Assessed at 21-Year Follow-upa

References

Andréasson  SAllebeck  PEngstrom  ARydberg  U Cannabis and schizophrenia: a longitudinal study of Swedish conscripts. Lancet 1987;2 (8574) 1483- 1486
PubMed Link to Article
Zammit  SAllebeck  PAndreasson  SLundberg  ILewis  G Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 2002;325 (7374) 1199
PubMed Link to Article
van Os  JBak  MHanssen  MBijl  RVde Graaf  RVerdoux  H Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol 2002;156 (4) 319- 327
PubMed Link to Article
Henquet  CKrabbendam  LSpauwen  JKaplan  CLieb  RWittchen  HUvan Os  J Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 2005;330 (7481) 11
PubMed Link to Article
Weiser  MReichenberg  ARabinowitz  JKaplan  ZCaspi  AYasvizky  RMark  MKnobler  HYNahon  DDavidson  M Self-reported drug abuse in male adolescents with behavioral disturbances, and follow-up for future schizophrenia. Biol Psychiatry 2003;54 (6) 655- 660
PubMed Link to Article
Arseneault  LCannon  MPoulton  RMurray  RCaspi  AMoffitt  TE Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002;325 (7374) 1212- 1213
PubMed Link to Article
Fergusson  DMHorwood  LJSwain-Campbell  NR Cannabis dependence and psychotic symptoms in young people. Psychol Med 2003;33 (1) 15- 21
PubMed
Hall  WDegenhardt  L Cannabis use and the risk of developing a psychotic disorder. World Psychiatry 2008;7 (2) 68- 71
PubMed
Murray  RMMorrison  PDHenquet  CDi Forti  M Cannabis, the mind and society: the hash realities. Nat Rev Neurosci 2007;8 (11) 885- 895
PubMed Link to Article
Macleod  JOakes  RCopello  ACrome  IEgger  MHickman  MOppenkowski  TStokes-Lampard  HDavey Smith  G Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet 2004;363 (9421) 1579- 1588
PubMed Link to Article
Moore  THZammit  SLingford-Hughes  ABarnes  TRJones  PBBurke  MLewis  G Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007;370 (9584) 319- 328
PubMed Link to Article
Semple  DMMcIntosh  AMLawrie  SM Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol 2005;19 (2) 187- 194
PubMed Link to Article
Henquet  CMurray  RLinszen  Dvan Os  J The environment and schizophrenia: the role of cannabis use. Schizophr Bull 2005;31 (3) 608- 612
PubMed Link to Article
Fergusson  DMHorwood  LJRidder  EM Tests of causal linkages between cannabis use and psychotic symptoms. Addiction 2005;100 (3) 354- 366
PubMed Link to Article
Degenhardt  LHall  WLynskey  MMcGrath  JMcLaren  JCalabria  BWhiteford  HVos  T Should burden of disease estimates include cannabis use as a risk factor for psychosis? PLoS Med 2009;6 (9) e1000133
PubMed Link to Article
Smith  GD Reflections on the limitations to epidemiology. J Clin Epidemiol 2001;54 (4) 325- 331
PubMed Link to Article
Hall  W The psychotogenic effects of cannabis use: challenges in reducing residual uncertainties and communicating the risks. Addiction 2004;99 (4) 511- 512, author reply 515
PubMed Link to Article
Lynskey  MTHeath  ACBucholz  KKSlutske  WSMadden  PANelson  ECStatham  DJMartin  NG Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA 2003;289 (4) 427- 433
PubMed Link to Article
Najman  JMBor  WO'Callaghan  MWilliams  GMAird  RShuttlewood  G Cohort profile: the Mater-University of Queensland Study of Pregnancy (MUSP). Int J Epidemiol 2005;34 (5) 992- 997
PubMed Link to Article
Achenbach  TM Manual for the Youth Self-Report and 1991 Profile.  Burlington: University of Vermont Dept of Psychiatry; 1991
WHO Composite International Diagnostic Interview (CIDI), version 2.1.  Geneva, Switzerland: World Health Organisation; 1992
World Health Organization International Statistical Classification of Diseases, 10th Revision (ICD-10).  Geneva, Switzerland: World Health Organization; 1992
Peters  ERJoseph  SAGarety  PA Measurement of delusional ideation in the normal population: introducing the PDI (Peters et al. Delusions Inventory). Schizophr Bull 1999;25 (3) 553- 576
PubMed Link to Article
Peters  EJoseph  SDay  SGarety  P Measuring delusional ideation: the 21-item Peters et al. Delusions Inventory (PDI). Schizophr Bull 2004;30 (4) 1005- 1022
PubMed Link to Article
Welham  JIsohanni  MJones  PMcGrath  J The antecedents of schizophrenia: a review of birth cohort studies. Schizophr Bull 2009;35 (3) 603- 623
PubMed Link to Article
Scott  JMartin  GWelham  JBor  WNajman  JO’Callaghan  MWilliams  GAird  RMcGrath  J Psychopathology during childhood and adolescence predicts delusional-like experiences in adults: a 21-year birth cohort study. Am J Psychiatry 2009;166 (5) 567- 574
PubMed Link to Article
Varghese  DScott  JMcGrath  J Correlates of delusion-like experiences in a non-psychotic community sample. Aust N Z J Psychiatry 2008;42 (6) 505- 508
PubMed Link to Article
Hayatbakhsh  MRMamun  AANajman  JMO'Callaghan  MJBor  WAlati  R Early childhood predictors of early substance use and substance use disorders: prospective study. Aust N Z J Psychiatry 2008;42 (8) 720- 731
PubMed Link to Article
Macleod  JHickman  MBowen  EAlati  RTilling  KSmith  GD Parental drug use, early adversities, later childhood problems and children's use of tobacco and alcohol at age 10: birth cohort study. Addiction 2008;103 (10) 1731- 1743
PubMed Link to Article
Fergusson  DMBoden  JMHorwood  LJ The developmental antecedents of illicit drug use: evidence from a 25-year longitudinal study. Drug Alcohol Depend 2008;96 (1-2) 165- 177
PubMed Link to Article
Matte  TDBresnahan  MBegg  MDSusser  E Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. BMJ 2001;323 (7308) 310- 314
PubMed Link to Article
Lawlor  DANajman  JMBatty  GDO'Callaghan  MJWilliams  GMBor  W Early life predictors of childhood intelligence: findings from the Mater-University study of pregnancy and its outcomes. Paediatr Perinat Epidemiol 2006;20 (2) 148- 162
PubMed Link to Article
Ferdinand  RFSondeijker  Fvan der Ende  JSelten  JPHuizink  AVerhulst  FC Cannabis use predicts future psychotic symptoms, and vice versa. Addiction 2005;100 (5) 612- 618
PubMed Link to Article
Buchan  BJL Dennis  MTims  FMDiamond  GS Cannabis use: consistency and validity of self-report, on-site urine testing and laboratory testing. Addiction 2002;97 ((suppl 1)) 98- 108
PubMed Link to Article
McGrath  JJRichards  LJ Why schizophrenia epidemiology needs neurobiology—and vice versa. Schizophr Bull 2009;35 (3) 577- 581
PubMed Link to Article

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Does acute cannabis intoxication explain the psychosis link?
Posted on March 31, 2010
Dan Werb, MSc
British Columbia Centre for Excellence in HIV/AIDS
Conflict of Interest: None Declared
The recent 21-year study by McGrath et al. provides new insights into the association between cannabis use and psychosis,(1) as this type of long- term investigation has thus far been lacking. The authors should be commended for the scope of the study and their cautious presentation, though we note that the study as published leaves some questions unanswered. First, the authors examine three distinct psychosis-related outcomes (schizophrenia, persistent delusional disorder, and transient psychotic disorders), but aggregate these into one overall measure of "nonaffective psychosis". Of particular concern is that the measurement of transient psychosis, which can result from acute cannabis intoxication,(2) is not disaggregated from other measures of severe and chronic forms of psychosis such as schizophrenia. As such, it is impossible to make inferences about these diverse psychosis-related conditions among cannabis users. When considered individually, are any of these specific conditions statistically elevated among cannabis users and, if so, which conditions? Further, how are these outcomes distributed across the various levels of cannabis exposure? Without the crude data, we simply do not know what their study has actually identified. It would also be of interest to present how the prevalence of these psychosis-related outcomes among the sample compare with the expected prevalence among the population from which the sample was drawn. There are also some limitations of the study that warrant consideration of the potential impact of cannabis use on risk for psychosis. For instance, while the study spans 21 years, diagnostic data on psychosis are only measured at the 21 year follow up mark. As such, it raises the question that the onset of psychosis may have preceded the use of cannabis among study participants during the study period. This allows for the potential introduction of measurement bias into the findings and raises doubt as to the direction of causation between cannabis as reported in the study.(3) Finally, the measurement of cannabis use itself among study participants appears limited. The authors base their assessment of intensity of cannabis use on two measures: a cross-sectional measure of past month cannabis use carried out at 21 years, and a retrospective measure of age of initiation of cannabis use. However, this approach may make the study findings susceptible to misclassification.(3) In the method employed, is an individual who initiates cannabis use at age 14 and subsequently ceases use until a month prior to the 21-year follow-up interview assumed to have an equal intensity of cannabis use as an individual who initiates cannabis use at the same age and uses every day throughout the study period? Under this scenario, it is difficult to determine the relative effect sizes associated with different levels of cannabis use among study participants. It would be very informative if the authors could provide crude data and statistical comparisons for individual components on the aggregate measure of "nonaffective psychosis" and to reflect upon the above issues as possible sources of bias. Conflict of interest: The authors state that they have no conflicts of interest.
References:
1. McGrath J, Welham J, Scott J, et al. Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults. Arch Gen Psych. 2010;67(5).
2. Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. Lancet. 2007;370(9584):319-328.
3. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet. 2002;359:5.
4. Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Progress in Neuropsychopharmacology & Bio Psych. 2004;28(5):849-863.
Cannabis and Psychosis: A bi-directional relationship?
Posted on May 20, 2010
Thomas H Richardson, B.A.(Hons)
Mental Health Research and Development Unit, University of Bath
Conflict of Interest: None Declared
In the May issue of Archives of General Psychiatry, McGrath and colleagues(1) report a cohort study examining the relationship between cannabis and psychosis. A number of studies have previously examined this issue, but this work has the advantage of demonstrating a relationship in sibling pairs, thus controlling for potential confounding variables which often plague research in the area. As well as cannabis use predicting psychotic symptoms and diagnoses, early psychotic symptoms also predicted increased frequency and duration of cannabis use. As the authors discuss, this finding mirrors the work of Ferdinand et al(2) who showed that cannabis use predicts future psychosis, but psychosis also predicts future cannabis use. Work with those with diagnosed psychotic illnesses has also shown that increased frequency of use predicted relapse of psychosis, but increased psychotic symptoms also predicted relapse of cannabis use(3). However, other research suggests that psychosis does not always predict later cannabis use(4), and that cannabis use generally precedes the emergence of psychotic symptoms(5).
McGrath et al(1) say that their study has highlighted the “complexity of the relationship” as cannabis use may predict later psychosis, or alternatively psychosis may predict later cannabis use. However the authors do not discuss the possibility that both temporal patterns are important and the causal relationship is bi-directional. That is, cannabis may induce psychotic symptoms as well as be used frequently by those who already have a diagnosed psychotic illness. Cannabis is often used by patients with psychosis for self-medication(6), and being high risk for psychosis increases the likelihood of experiencing psychosis from cannabis use5. Thus it is plausible that those with early onset sub-clinical psychosis are more likely to use cannabis heavily in the future as an attempt at self-medication, which may in turn trigger a full blown psychotic episode. McGrath et al(1) found that increased duration of cannabis use increased the risk of psychotic outcomes even after controlling for baseline psychotic symptoms, but nonetheless it is possible that different patterns of cannabis use and reasons for its use may have different causal relationships with psychotic symptoms.
In work on the relationship between bipolar disorder and substance use it has been argued that a number of different mechanisms are likely to all play a role in observed relationships(7). Perhaps we should begin to consider the possibility that one single casual mechanism is unlikely to explain the complex relationship between cannabis and psychosis. The authors suggest that “We plan to explore these issues in more detail in future studies”, and I hope that such work in the future will help address the complex yet intriguing possibility of a bi-directional relationship.
Thomas Richardson, BA(Hons)
Author Affiliation: Mental Health Research and Development Unit, University of Bath, U.K. Correspondence: Thomas Richardson, MHRDU, 22-23 Eastwood, University of Bath, Bath, BA2 7AY, U.K.(T.H.Richardson@bath.ac.uk). Financial Disclosure: None reported
1. McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh MR, Alati R, Williams GM, Bor W, Najman JM. Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults. Arch Gen Psychiatry. 2010;67(5):440- 447.
2. Ferdinand RF, Sondeijker F, van der Ende J, Selten J-P, Huizink A, Verhulst FC. Cannabis use predicts future psychotic symptoms, and vice versa. Addiction. 2005;100:612–618.
3. Hides L, Dawe S, Kvanagh DJ, Young RM. Psychotic symptom and cannabis relapse in recent-onset psychosis. Br J Psychiatry. 2006;189:137- 143.
4. Henquet C, Krabbendam L, Spauwen J, Kaplan C, Lieb R, Wittchn H-U, Van Os, J. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. Br Med J. 2005;330:11.
5. McLaren JA, Silins E, Hutchinson D, Mattick RP, Hall W. Assessing evidence for a causal link between cannabis and psychosis: A review of cohort studies. In J Drug Pol. 2010;21:10–19.
6. Schofield D, Tennant C, Nash L, Degenhardt L, Cornish A, Hobbs C, Brenann G. Reasons for cannabis use in psychosis. Aust NZ J Psychiatry. 2006;40:570–574.
7. Strakowski SM, DelBello MP. The co-occurrence of bipolar and substance use disorders. Clin Psych Rev. 2000;20(2):191-206.
Early Clinical Research on Toxic Effects of Chronic Marihuana (Marijuana) Use
Posted on May 18, 2010
Partam Manalai, M.D.
Chief Resident, St. Elizabeths Hospital
Conflict of Interest: None Declared
In response to: McGrath J,Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh, Alati R, Williams GM,Bor W, and Najman JM. Association between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults. Arch Gen Psychiatry. 2010;67(5): 440-447.
Title of the Letter:
Early Clinical Research on Toxic Effects of Chronic Marihuana (Marijuana) Use
Partam Manalai, M.D.*,** Gul. G. Manalai, M.D.** S. Kalman Kolansky, M.D.*
*Saint Elizabeths Hospital, Psychiatry Residency Training Program, Washington DC **Mood and Anxiety Program (MAP), University of Maryland Baltimore, Baltimore, MD
Authors: Partam Manalai, M.D. Chief Resident, Psychiatry Residency Training Program, Saint Elizabeths Hospital & Volunteer Research Assistant, MAP, Department of Psychiatry, University of Maryland 1100 Alabama Ave, SE Washington DC 20032 Email: partam.manalai@dc.gov Phone 202-489-4665
Gul G. Manalai, M.D. Volunteer Research Assistant 685 West Baltimore Street MSTF Building Room 916 Baltimore, MD 21201 Phone: 410-706-6799 gmanala@psych.umaryland.edu
S. Kalman Kolansky, M.D. Teaching and Supervising Faculty (Child Psychiatry) St. Elizabeths Hospital Residency Training Program 1100 Alabama Ave, SE Washington DC 20032 Phone: 202-299-5307 Email: saul.kolansky@dc.gov
Corresponding Author: Partam Manalai, M.D. Chief Resident Psychiatry Residency Training Program St. Elizabeths Hospital 1100 Alabama Ave, SE Washington DC 20032 Phone: 202-489-4665 Email: partam.manalai@dc.gov
Conflicts of Interests: None (NOTE: Harld Kolansky, M.D. and S. Kalman Kolansky, M.D. are brothers)
Early Clinical Research on Toxic Effects of Chronic Marihuana (Marijuana) Use
We congratulate McGrath et al. for their paper titled “Association between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults” published in Archives of General Psychiatry. However, we would like to mention the papers of Harold Kolansky, M.D. and William T. Moore, M.D. published on the subject more than 35 years ago but not mentioned in the citation (1-3). Harold Kolansky and William T. Moore were among the first authors to carefully study and characterize the long term effect of the active substance of cannabis, tetrahydrocannabinol (THC) on the central nervous system.
In their articles, published in JAMA in 1971 and 1975, Drs. Kolansky and Moore reported a mild to severe “decomposition of ego functioning (1)” associated with chronic cannabis use. In their article published on April 19, 1971, the authors studied the effects of chronic cannabis use in adolescent and young adults(1). Their study included 38 patients (ages 13 – 24) selected over 5 year period (1965-1970) in whom serious psychological effects seemed be traced to chronic heavy usage of marijuana. The authors found that “these patients consistently showed very poor social judgment, poor attention span, poor concentration, confusion, anxiety, depression, apathy, passivity, indifference, and often, slowed and slurred speech.” Four patients had attempted suicide and another four exhibited psychosis which Drs. Kolansky and Moore believed resulted from marihuana use. The authors conclude that in a group of adolescents and young adult, heavy cannabis use may produce severe psychological problems in the absence of any predisposing factors for psychiatric disorders.
In a follow up study published in JAMA (Oct 2, 1972), Kolansky and Moore expanded their work to include adults chronically using cannabis and reported that the “specific and separate behavioral changes” seen in adolescents are also observed in adults using cannabis (2). They describe a “stereotyped symptom complex”, characterized by apathy, sluggish mental and physical response, slowed verbal response, and poor hygiene with chronic cannabis use in adults. The users tended to be thinner, look older than their chronological age, and reported chronic tiredness and insomnia. The authors noted that the calmness and amotivation in these individuals would falsely be interpreted, by the patients and those around them, as “emotional maturity” and heightened insight. To reach a conclusive diagnosis, the authors interviewed the patients and their family 4 to 10 times to rule out other causes that might explain the syndrome. Over two years time period, 13 patients from their practice met the inclusion criteria. With such extensive psychiatric assessments, the possibility of alternative explanation for phenomenological observation in these 13 individuals seems unlikely. The authors tentatively classified the patients into three groups. The first group included patients whose symptomatolgy resolved 6 months after cannabis use was stopped (called “Biological Changes” by the authors). In the second group partial remission was seen after six months and symptoms resolved completely after 9 months after secession of cannabis use (the authors called this “Biochemical Change with Suspected Structural Change”). Finally, a group of patients continued to experience some residual symptoms 9 months after ceasing to use the drug (called “Biochemical Change with Possible Structural Change” by the authors). Kolansky and Moore also summarized the data on possible long term biological and neuropsychiatric changes associated with chronic cannabis use, including sequestration of THC in fatty tissues that prolog the half-life of the active ingredient in marihuana (3).
On a humorous note, in a personal communication from S. Kalman Kolansky, M.D. (a psychiatry resident in 1971) recalls when a fellow psychiatry resident had approached him saying “Your brother, Harold Kolansky, wrote a terrible article about marijuana”. When asked what was so “terrible” about the article, the other resident said “I didn’t read the article, but no one should criticize pot”. The plant seems to have successfully attracted its zealot fans.
With the ever-expanding number of publications and digitalization of medical literature, the research conducted before 1980 at times remains unnoticed; thus, a valuable source of information remains underutilized4. While future research is essential, we would like to credit Dr. Kolansky and Dr. Moore for their research on the toxic effects of chronic cannabis use in adolescents and adults.
References:
1. Kolansky H, Moore WT. Effects of marihuana on adolescents and young adults. J Psychiatr Nurs Ment Health Serv. 1971;9(6):9-16.
2. Kolansky H, Moore WT. Toxic effects of chronic marihuana use. Jama. 1972;222(1):35-41.
3. Kolansky H, Moore WT. Marihuana. Can it hurt you? Jama. 1975;232(9):923 -924.
4. Goodwin F. Case Presentation and Panel Discussion. Presented at: Suicide from the Inside Out: Implications for the Management of Suicidal Behavior in the Military and the VA. May 13, 2010; Baltimore, MD.
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