Full length articleA longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults
Introduction
Understanding the impact of cannabis use on cognitive function in mid-life adults is increasingly important. Cannabis is already consumed by an estimated 178 million people worldwide (United Nations Office on Drugs and Crime, 2015) and 13.1 million people are dependent on the drug (Degenhardt et al., 2013). However, its use is projected to rise significantly in older cohorts (50+ years) with the ageing of the baby-boomer generation (Colliver et al., 2006, Wu and Blazer, 2011). The medicalisation of cannabis is also likely to see increased use in older adults to treat chronic pain (Martin-Sanchez et al., 2009) and as an antiemetic in cancer treatment (Borgelt et al., 2013). For example, Pacula et al. (2015) cite 18 US states where legislation has been established around the medicinal use of cannabis, this trend beginning in California in 1996 with the establishment of medical marijuana dispensaries.
Most research on the relationship between cannabis use and cognitive function comes from studies of young adults (Becker et al., 2010, Block and Ghoneim, 1993, Carlin and Trupin, 1977, Croft et al., 2001, Dafters et al., 2004, Dougherty et al., 2013, Ehrenreich et al., 1999, Fried et al., 2002, Gouzoulis-Mayfrank et al., 2000, Pope and Yurgelun-Todd, 1996, Rodgers, 2000, Solowij, 1995). A meta-analysis of this research found that cannabis use was associated with worse performance on verbal learning and memory (i.e., immediate and delayed recall on the Californian Verbal Learning Test and the Rey Auditory Verbal Learning Test), with effect sizes ranging between 0.21 and 0.27, but not on tasks involving attention, executive function, motor function, reaction time or language ability (Grant et al., 2003). However, more recent research suggests deficits may also be present in other domains, including attention and concentration and abstract reasoning (Crane et al., 2013). Longitudinal studies have also found deficits relative to premorbid ability (Fried et al., 2005, Meier et al., 2012), including greater cognitive decline into adulthood (Meier et al., 2012). Although some performance decrements recover with cessation of cannabis use (Fried et al., 2005, Tait et al., 2011) full recovery is not always observed (Meier et al., 2012).
Few studies have examined how these cognitive deficits manifest in later adulthood, where they may be exacerbated by cumulative exposure to cannabis, interact with natural age-related declines in processing speed (Anstey et al., 2014, Singh-Manoux et al., 2012), or arise from secondary adverse effects of cannabis on educational and vocational attainment (Horwood et al., 2010)—both of which are protective against age-related cognitive decline (Anstey et al., 2013). Both Solowij et al. (2002) and Pope et al. (2001) found verbal learning deficits in older cannabis users (aged 32–55 years), compared to a non-using control group; however, Pope et al. (2001) found deficits remitted following a 28 day washout period from cannabis use, suggesting that deficits may be restricted to periods of heavy use (Pope et al., 2001).
In this paper we use an alternative approach to previous research by examining within-person changes in cognitive function that co-occur with changes in cannabis use in a longitudinal cohort. Within-person effects estimate the average change in an outcome (i.e., cognitive test performance) during time periods when an individual is exposed to a particular risk factor (i.e., cannabis use) relative to when they are not exposed (i.e., not using cannabis). This approach provides superior control for time-invariant factors (e.g., heritable traits, personality, sex) than statistical adjustment, and also reduces confounding by unmeasured time-invariant confounds (Gunasekara et al., 2014). It has been used to strengthen evidence for a causal relationship between substance use and various health and social outcomes (Fergusson et al., 2002, Livingston, 2011, McKetin et al., 2013). Time-varying factors still need to be adjusted for because they can confound these types of analyses.
We assessed the relationship between current levels of cannabis use and cognitive functioning across three waves of data in a population-based longitudinal cohort of adults in their forties and examined whether deficits were related to current levels of cannabis use by testing within-person changes in cognitive performance during periods of cannabis use. We hypothesised (a) that heavy cannabis users would perform more poorly on tests of verbal recall; and (b) that this effect would be due to a significant within-person association between cannabis use and cognitive function, indicating worse cognitive function during periods of more frequent cannabis use relative to periods of no use. We also explored whether cannabis use modified age-related changes in cognitive performance, which could indicate early cognitive decline.
Section snippets
Participants and procedure
Participants were 2,530 people aged 40–46 years, who were recruited from the Personality and Total Health (PATH) through life cohort in 2000–2001. Participants were randomly drawn from the electoral roll of the Australian Capital Territory and Queanbeyan in Australia (Anstey et al., 2012). Voting is compulsory in Australia and therefore electoral roll samples provide a good reflection of the adult general population. The response rate was 64.6%. A comparison with the Australian census data show
Characteristics of participants at baseline
Participants were English speaking (100%), mostly Caucasian (98%) and employed (91%); 16% were current tobacco smokers and 14% exceeded the cut-off of ≥ 8 for risky drinking on the AUDIT. Ten per cent of the sample (n = 576) had used cannabis at one of the three waves, with cannabis use reported at 6% of all assessments (n = 331), and with 2% (n = 106) involving using cannabis weekly or more often. Amongst participants who had used cannabis, 31% (n = 176) of observations represented a change in cannabis
Discussion
The finding that mid-life cannabis users has worse verbal recall is consistent with past research in young adults (Grant et al., 2003); however, this was only evident for a between-person effect, reflecting an overall average lower performance of heavy cannabis users relative to people who do not use the drug. The lack of a significant within-person effect of cannabis use on verbal recall indicates that verbal recall was no worse when people were using cannabis weekly or more often compared to
Conclusion
Mid-life cannabis use (≥ weekly use) was associated with worse verbal episodic memory as reflected by poor verbal recall. Deficits in verbal recall may place cannabis users at elevated risk of cognitive decline in later life, or even dementia, as episodic memory decline is the first cognitive symptom of Alzheimer’s disease (Gainotti et al., 2014). Further research is needed to establish whether these decrements are due to lasting brain changes associated with cannabis use or other correlates of
Contributors
All authors contributed to the writing and review of the manuscript.
Role of funding source
The funders of the study played no role in the design and conduct of the study; collection, management, analysis, interpretation of the data; or the preparation, review or approval of the manuscript.
Conflict of interest
No conflict declared.
Acknowledgements
PATH was funded by National Health and Medical Research Council Grants 229936, 973302, 179839, 179805, 418039, 1002160. Kaarin Anstey is funded by NHMRC Fellowship No.1002560 and Nicolas Cherbuin by ARC Fellowship No. 12010227. Rebecca McKetin is funded by a Curtin Senior Research Fellowship. The authors are grateful to Patricia Jacomb, Karen Maxwell, Peter Butterworth, Simon Easteal, Helen Christensen and the PATH interviewers.
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