Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study

The strongest evidence that cannabis use may be a risk factor for later psychosis comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold.¹,² This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause. We present the first prospective longitudinal study of adolescent cannabis use as a risk factor for adult schizophreniform disorder, taking into account childhood psychotic symptoms³ antedating cannabis use.

Methods and results

The Dunedin multidisciplinary health and development study (a study of a general population birth cohort of 1037 individuals born in Dunedin, New Zealand, in 1972-3)⁴ has a 96% follow up rate at age 26. It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed psychiatric symptoms at age 26 with a standardised interview schedule to obtain DSM-IV (diagnostic and statistical manual of mental disorders, 4th edition) diagnoses. We analysed data from a representative group of 759 (74%) living study members who had complete data on adult psychiatric outcomes, adolescent use of illicit substances, and childhood psychotic symptoms.

We divided the sample into three groups based on cannabis use at ages 15 and 18. The 494 controls (65.1% of the sample) had reported using cannabis “never” or “once or twice” at both ages; cannabis users by age 18 (236; 31.1%) first reported using cannabis “three times or more” at age 18; and cannabis users by age 15 (29; 3.8%) had reported using cannabis “three times or more” at age 15 (all of whom continued to use cannabis at age 18).

Psychiatric outcomes at age 26 were symptoms of schizophrenia and depression and diagnoses of schizophreniform disorder and depression.

Multiple linear regression analyses showed that cannabis users by age 15 and by age 18 had more schizophrenia symptoms than controls at age 26 (table). These results remained significant after psychotic symptoms at age 11 were controlled for. The effect was stronger with earlier use.

Logistic regression analyses showed that people who used cannabis by age 15 were four times as likely to have a diagnosis of schizophreniform disorder at age 26 than controls. After psychotic symptoms at age 11 were controlled for, the risk for adult schizophreniform disorder remained higher among those who used cannabis at age 15; however, this risk was reduced by 31% and was no longer significant.

Cannabis use by age 15 did not predict depressive outcomes at age 26. Use of other drugs in adolescence did not predict schizophrenia outcomes over and above the effect of cannabis use.

Comment

Using cannabis in adolescence increases the likelihood of experiencing symptoms of schizophrenia in adulthood. Our findings agree with those of the Swedish study¹ and add three new pieces of evidence. Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding.⁵ Thirdly, risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression. Our findings now require replication in large population studies with detailed measures of cannabis use and schizophrenia.

Although most young people use cannabis in adolescence without harm, a vulnerable minority experience harmful outcomes. A tenth of the cannabis users by age 15 in our sample (3/29) developed schizophreniform disorder by age 26 compared with 3% of the remaining cohort (22/730). Our findings suggest that cannabis use among psychologically vulnerable adolescents should be strongly discouraged by parents, teachers, and health practitioners. Policy makers and law makers should concentrate on delaying onset of cannabis use.

Table.

Association between cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 (n=759), controlling for childhood psychotic symptoms and use of other drugs in adolescence

Model*	Predictor	Schizophrenia outcomes						Depression outcomes
		Schizophrenia symptoms (scores 0-58)			Schizophreniform disorder (n=25; 3.3%)			Depressive symptoms (scores 0-54)			Depressive disorder (n=118; 15.5%)
		B¶ (SE)	P value		Odds ratio (95% CI)	P value		B§ (SE)	P value		Odds ratio (95% CI)	P value
1†	Cannabis users by age 15	6.91 (0.91)	0.001		4.50 (1.11 to 18.21)	0.035		0.25 (1.93)	0.897		1.02 (0.34 to 3.04)	0.971
	Cannabis users by age 18	1.04 (0.40)	0.009		1.65 (0.65 to 4.18)	0.293		1.98 (0.84)	0.018		1.62 (1.06 to 2.49)	0.028
2‡	Weak psychotic symptoms at age 11	0.68 (0.53)	0.201		4.65 (1.84 to 11.78)	0.001		1.60 (1.13)	0.159		1.45 (0.82 to 2.56)	0.203
	Strong psychotic symptoms at age 11	5.16 (1.39)	0.001		15.97 (3.38 to 75.47)	0.001		−0.55 (2.96)	0.852		0.54 (0.07 to 4.25)	0.554
	Cannabis users by age 15	6.56 (0.91)	0.001		3.12 (0.73 to 13.29)	0.124		0.13 (1.94)	0.946		1.01 (0.34 to 3.02)	0.987
	Cannabis users by age 18	1.03 (0.39)	0.009		1.42 (0.54 to 3.74)	0.473		1.96 (0.84)	0.020		1.61 (1.05 to 2.47)	0.031
3§	Other drug users at age 15 to 18	−0.3 (0.69)	0.615		0.30 (0.05 to 1.62)	0.160		2.48 (1.45)	0.086		1.23 (0.55 to 2.32)	0.743
	Cannabis users by age 15	7.2 (1.07)	0.001		11.38 (1.84 to 70.45)	0.009		−1.75 (2.26)	0.438		0.93 (0.27 to 3.17)	0.905
	Cannabis users by age 18	1.1 (0.42)	0.008		1.95 (0.76 to 5.01)	0.167		1.55 (0.88)	0.078		1.59 (1.01 to 2.49)	0.043

^*Model 1 includes the effects of adolescent cannabis use only; model 2 adds to model 1 controls for childhood psychotic symptoms; model 3 adds to model 1 controls for other drug use. 

^†Estimates for each step are given controlling for socioeconomic status and sex. The socioeconomic status of study members' families was coded into one of six categories based on educational level and income associated with occupations in New Zealand. The scale ranges from 1=unskilled labourer to 6=professional and reflects the average of the highest status of either parent across the seven assessments of the Dunedin study from birth through to age 15. 

^‡When study members were aged 11, five questions about psychotic symptoms were asked during the interview and were then scored by a psychiatrist (0=no; 1=yes, likely; 2=yes, definitely). Individuals reporting weak psychotic symptoms at age 11 (94 (12.4%) with score of 1) and those reporting strong symptoms (12 (1.6%) with score of ⩾2) were compared with individuals who reported no symptoms at all (653 (86.0%)). 

^§Comparison for other drug users at age 15 to 18 (78; 10.3%) was made with individuals who reported “never” using other drugs at ages 15 and 18 (681; 89.7%). Other drugs refer to substances such as glue, cocaine, and opiates. 

^¶Confidence intervals for regression coefficients (B) can be calculated using the standard error of the estimate, based on the formula: B±(1.96^*SE). 

Papers pp 1195, 1199