Elsevier

Drug and Alcohol Dependence

Volume 169, 1 December 2016, Pages 134-140
Drug and Alcohol Dependence

Full length article
A longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults

https://doi.org/10.1016/j.drugalcdep.2016.10.022Get rights and content

Highlights

  • Mid-life cannabis smokers have poorer verbal recall than non-users.

  • Verbal recall performance is not related to current level of cannabis use in mid-life.

  • Cannabis use was not associated with accelerated cognitive decline in mid-life.

Abstract

Background

The relationship between cannabis use and cognitive function in mid-life has rarely been examined despite verbal learning deficits in young adults.

Method

A longitudinal cohort study of 1,897 Australians recruited at 40–46 years of age and followed up 4 years (94%) and 8 years (87%) later. Random effects regression was used to assess within- and between-person associations between cannabis use and cognitive function across waves of data, and examine whether age-related changes in cognitive performance were modified by cannabis use. The first list of the California Verbal Learning Test (immediate and delayed recall), Symbol Digit Modality Test, Digit Backwards, simple and choice reaction time tasks, were administered at each wave. The Spot-the-Word test was used to assess premorbid verbal ability. Self-reported cannabis use in the past year (no use, < weekly use,  weekly use) was assessed at each wave.

Findings

Participants who used cannabis  weekly had worse immediate recall (b = −0.68, p = 0.014) and showed a trend toward worse delayed recall (b = −0.55, p = 0.062) compared to non-users after adjusting for correlates of cannabis use and premorbid verbal ability. These effects were due to between-person differences. There were no significant within-person associations between cannabis use and recall, nor was there evidence of greater cognitive decline in cannabis users with age.

Conclusions

Mid-life cannabis users had poorer verbal recall than non-users, but this was not related to their current level of cannabis use, and cannabis use was not associated with accelerated cognitive decline.

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.

References (62)

  • J. Schaefer et al.

    The global cognitive impairment in schizophrenia: consistent over decades and around the world

    Schizophr. Res.

    (2013)
  • L.K. Sheridan et al.

    Normative symbol digit modalities test performance in a community-based sample

    Arch. Clin. Neuropsychol.

    (2006)
  • S.G. Shollenbarger et al.

    Impact of cannabis use on prefrontal and parietal cortex gyrification and surface area in adolescents and emerging adults

    Dev. Cogn. Neurosci.

    (2015)
  • N. Solowij

    Do cognitive impairments recover following cessation of cannabis use?

    Life Sci.

    (1995)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders

    (2013)
  • K.J. Anstey et al.

    Cohort profile: the PATH through life project

    Int. J. Epidemiol.

    (2012)
  • K.J. Anstey et al.

    Development of a new method for assessing global risk of Alzheimer's disease for use in population health approaches to prevention

    Prev. Sci.

    (2013)
  • K.J. Anstey et al.

    Cognitive development over 8 years in midlife and its association with cardiovascular risk factors

    Neuropsychology

    (2014)
  • T.F. Babor et al.

    The Alcohol Use Disorders Identification Test

    (2001)
  • A. Baddeley et al.

    The spot-the-word test: a robust estimate of verbal intelligence based on lexical decision

    Br. J. Clin. Psychol.

    (1993)
  • R.I. Block et al.

    Effects of chronic marijuana use on human cognition

    Psychopharmacology (Berl.)

    (1993)
  • E. Bora et al.

    Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis?

    Schizophr. Bull.

    (2014)
  • L.M. Borgelt et al.

    The pharmacologic and clinical effects of medical cannabis

    Pharmacotherapy

    (2013)
  • C.R. Bowie et al.

    Cognitive deficits and functional outcome in schizophrenia

    Neuropsychiatr. Dis. Treat.

    (2006)
  • A.S. Carlin et al.

    The effect of long-term chronic marijuana use on neuropsychological functioning

    Int. J. Addict.

    (1977)
  • N.A. Crane et al.

    Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences

    Neuropsychol. Rev.

    (2013)
  • R.J. Croft et al.

    The relative contributions of ecstasy and cannabis to cognitive impairment

    Psychopharmacology (Berl.)

    (2001)
  • R.I. Dafters et al.

    Contribution of cannabis and MDMA (ecstasy) to cognitive changes in long-term polydrug users

    Psychopharmacology (Berl.)

    (2004)
  • L. Degenhardt et al.

    The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study

    PLoS One

    (2013)
  • D.C. Delis et al.

    CVLT, California Verbal Learning Test: Adult Version

    (1987)
  • D.M. Dougherty et al.

    Impulsivity, attention, memory, and decision-making among adolescent marijuana users

    Psychopharmacology (Berl.)

    (2013)
  • Cited by (32)

    • Impact of cannabis on memory: From in utero to adulthood

      2023, Cannabis Use, Neurobiology, Psychology, and Treatment
    • Residual effects of cannabis-use on neuropsychological functioning

      2021, Cognitive Development
      Citation Excerpt :

      The varying evidence on neurocognitive effects of cannabis might partially be explained by cross-sectional study designs and therefore lack of control for pre-existing group differences (Gonzalez, Pacheco-Colon, Duperrouzel, & Hawes, 2017). Recently, some longitudinal studies have been conducted but most of them focus on adult cannabis users (e.g., Grant, Chamberlain, Schreiber, & Odlaug, 2012; McHale & Hunt, 2008; McKetin, Parasu, Cherbuin, Eramudugolla, & Anstey, 2016; Meier et al., 2012; Tait, Mackinnon, & Christensen, 2011). All in all, the nature of non-acute effects of cannabis on neurocognition in adolescents remains unclear (Crane et al., 2013; Figueiredo, Tolomeo, Steele, & Baldacchino, 2020; Gonzalez et al., 2017).

    • Acute effects of partial CB<inf>1</inf> receptor agonists on cognition – A meta-analysis of human studies

      2021, Progress in Neuro-Psychopharmacology and Biological Psychiatry
      Citation Excerpt :

      Cognitive deficits that result from administration of partial CB1 receptor agonists in humans do not appear to be unequivocal across all cognitive domains. A recent systematic review (Broyd et al., 2016) showed that verbal learning and memory – often measured using word list learning tasks that evaluate immediate and delayed recall – were particularly disrupted by acute and chronic cannabinoid consumption (Auer et al., 2016; D'Souza et al., 2008a; D'Souza et al., 2008b; Fried et al., 2005; Hanson et al., 2010; McKetin et al., 2016; Messinis et al., 2006; Ranganathan et al., 2012; Tait et al., 2011; Theunissen et al., 2015; Wesnes et al., 2010). Recovery of verbal learning and memory with abstinence has been observed in some studies (Hanson et al., 2010; Lyons et al., 2004; Medina et al., 2007; Roten et al., 2015; Tait et al., 2011; Thames et al., 2014), but not others (Lyons et al., 2004; Medina et al., 2007; Winward et al., 2014).

    • Adolescent cannabis use, cognition, brain health and educational outcomes: A review of the evidence

      2020, European Neuropsychopharmacology
      Citation Excerpt :

      The only significant difference they found was improved immediate memory recall in former heavy cannabis users, which persisted after controlling for education and sex. McKetin et al. (2016) reported a follow up of 1897 Australians first assessed at 40–46 years of age and followed for four (94%) and eight years (87%). They assessed the same cognitive domains as Tait et al. (2011) above.

    • The implications of late-life cannabis use on brain health: A mapping review and implications for future research

      2020, Ageing Research Reviews
      Citation Excerpt :

      Since these studies cannot provide information about cannabis exposure in late-life, we did not include them in this review. However, one cohort study of almost 2000 participants who were followed-up for up to 8 years (McKetin et al., 2016) (Table 2) assessed current use (while data on past use in both current users and non-users was not documented). The study found differences in verbal recall between current cannabis users and non-users, yet no differences in rates of cognitive decline were observed between the groups.

    View all citing articles on Scopus
    View full text