Early-onset cannabis use and cognitive deficits: what is the nature of the association?
Introduction
Does long-term heavy use of cannabis produce residual deficits in cognitive functioning? Most recent studies agree that heavy users exhibit temporary deficits for hours or days after stopping cannabis (Pope et al., 1995, Pope and Yurgelun-Todd, 1996, Fletcher et al., 1996, Struve et al., 1999, Patrick and Struve, 2000, Solowij, 1998, Pope et al., 2001a, Pope et al., 2001b, Solowij et al., 2002)—perhaps attributable to withdrawal effects or to a residue of cannabinoids lingering in the brain (Pope et al., 1995, Pope et al., 2001a, Pope et al., 2001b, Haney et al., 1999, Kouri and Pope, 2000). However, there is less consensus about whether cannabis can produce cumulative neurotoxicity—that is, potentially irreversible deficits associated with total lifetime cannabis exposure (Pope, 2002). A recent meta-analysis seems to argue against this possibility (Grant et al., 2001), as does a longitudinal population study of heavy cannabis users (Lyketsos et al., 1999) and recent data from our own laboratory (Pope et al., 2001a, Pope et al., 2001b, Pope et al., 2002). Other studies, however, have suggested an association between lifetime cannabis exposure and electroencephalographic (Struve et al., 1998) or neuropsychologic abnormalities (Solowij, 1998). Recently, another study (Solowij et al., 2002) has reported a significant association between lifetime cannabis use and neuropsychological test performance among users seeking treatment.
One explanation for these discrepant findings may be that cannabis is more toxic for some populations than others. For example, individuals with longer durations of cannabis use have likely started use earlier in life, and perhaps cannabis is more toxic for the developing brain than for the mature brain. Evidence supporting this hypothesis comes from studies showing apparently irreversible effects on behavior and brain morphology in rats exposed to cannabinoids while immature (Stiglick and Kalant, 1985, Landfeld et al., 1988). And in humans, one recent study found that 48 early-onset cannabis users (onset before age 17), but not 51 late-onset users (onset at 17 or later), exhibited significantly longer reaction times than controls in a visual scanning task (Ehrenreich et al., 1999). Another recent study also compared 29 long-term cannabis users who had initiated use before age 17 with 28 users who had initiated use at age 17 or later (Wilson et al., 2000). Magnetic resonance images of the brain showed that early-onset users had a lower percentage of gray matter and a higher percentage of white matter, relative to whole-brain volume, than the late-onset users. Positron emission tomography studies in the same subjects showed that male early-onset users had higher cerebral blood flow than males who initiated use after age 17. Finally, early-onset users of both sexes were shorter in height and lower in weight than late-onset users. The authors speculated that these differences might be related to the effects of cannabis on gonadal and pituitary hormones in early adolescence.
To explore further the relationship between onset of cannabis use and neuropsychological dysfunction, we analyzed data from a study of cognitive performance in 122 long-term cannabis users and 87 controls, conducted at our laboratory between 1997 and 2001.
Section snippets
Method
The detailed methods of this study, together with the results obtained from the first 180 subjects, have been presented previously (Pope et al., 2001a, Pope et al., 2001b); a subsequent publication (Pope et al., 2002) presents augmented results with 29 additional female subjects. The present paper uses the full sample of 209 subjects to assess the relationship between age of onset of cannabis use and neuropsychological performance.
Primary analyses
The three groups differed in age, but were otherwise similar on ethnicity, sex, and levels of education and income of the subjects’ parents (Table 1). However, we found significant differences between groups on the education and income of the subjects themselves. Only 22 (32%) of the early-onset users had graduated from a 4-year college, as compared with 32 (60%) of late-onset users and 71 (82%) of controls (P=0.001 for early-onset vs. late onset, P=0.007 for late-onset vs. controls, and P
Discussion
We compared 69 long-term cannabis users who had begun smoking cannabis before age 17 (‘early-onset users’), 53 long-term users who had begun smoking at age 17 or later (‘late-onset users’), and 87 control subjects who had smoked cannabis only a few times in their lives. Subjects with a significant history of other forms of drug or alcohol use, or with potentially confounding medical or psychiatric disorders, were excluded. All subjects received a battery of ten standard neuropsychological tests
Acknowledgements
This research was supported in part by NIDA Grant 5 R37 DA-10346 (to Dr Pope) and DA12483-1 (to Dr Yurgelun-Todd).
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