Testing the association between tobacco and cannabis use and cognitive functioning: Findings from an observational and Mendelian randomization study

Liam Mahedy; Robyn E Wootton; Steph Suddell; Caroline Skirrow; Matt Field; Jon E Heron; Matt  Hickman; Marcus R Munafo

doi:10.1016/j.drugalcdep.2021.108591

Testing the association between tobacco and cannabis use and cognitive functioning: Findings from an observational and Mendelian randomization study

Liam Mahedy^*, Robyn E Wootton, Steph Suddell, Caroline Skirrow, Matt Field, Jon E Heron, Matt Hickman, Marcus R Munafo

^*Corresponding author for this work

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Abstract

Background: Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation.

Methods: Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13 to 18 in a large UK population cohort (ALSPAC). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship.

Results: We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95%CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95%CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95%CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b=0.18, 95%CI=0.07 to 0.28), and early-onset regular cannabis users (b=0.30, 95%CI=0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95%CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95%CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results.

Conclusion: There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal.

Original language	English
Article number	108591
Number of pages	8
Journal	Drug and Alcohol Dependence
Volume	221
Early online date	12 Feb 2021
DOIs	https://doi.org/10.1016/j.drugalcdep.2021.108591
Publication status	Published - 1 Apr 2021

Bibliographical note

Funding Information:
The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer); a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research. Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MM_UU_00011/7). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-20011) and we acknowledge support from NIHR HPRU in Evaluation. LM is supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC.

Funding Information:
The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1 ). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) ; a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1 ) from the British Heart Foundation , Cancer Research UK , Economic and Social Research Council , Medical Research Council , the Welsh Government and the Wellcome Trust , under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research . Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol ( MM_UU_00011/7 ). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol ( BRC-1215-20011 ) and we acknowledge support from NIHR HPRU in Evaluation . LM is supported by the Elizabeth Blackwell Institute for Health Research , University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z ). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC .

Publisher Copyright:
© 2021 The Authors

Structured keywords

ALSPAC
Tobacco and Alcohol

Keywords

ALSPAC
Cannabis
Tobacco
Cognition
Causal inference

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title = "Testing the association between tobacco and cannabis use and cognitive functioning: Findings from an observational and Mendelian randomization study",

abstract = "Background: Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods: Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13 to 18 in a large UK population cohort (ALSPAC). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship. Results: We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95%CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95%CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95%CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b=0.18, 95%CI=0.07 to 0.28), and early-onset regular cannabis users (b=0.30, 95%CI=0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95%CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95%CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results. Conclusion: There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal.",

keywords = "ALSPAC, Cannabis, Tobacco, Cognition, Causal inference",

author = "Liam Mahedy and Wootton, {Robyn E} and Steph Suddell and Caroline Skirrow and Matt Field and Heron, {Jon E} and Matt Hickman and Munafo, {Marcus R}",

note = "Funding Information: The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer); a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research. Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MM_UU_00011/7). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-20011) and we acknowledge support from NIHR HPRU in Evaluation. LM is supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Funding Information: The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1 ). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) ; a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1 ) from the British Heart Foundation , Cancer Research UK , Economic and Social Research Council , Medical Research Council , the Welsh Government and the Wellcome Trust , under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research . Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol ( MM_UU_00011/7 ). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol ( BRC-1215-20011 ) and we acknowledge support from NIHR HPRU in Evaluation . LM is supported by the Elizabeth Blackwell Institute for Health Research , University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z ). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC . Publisher Copyright: {\textcopyright} 2021 The Authors",

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doi = "10.1016/j.drugalcdep.2021.108591",

language = "English",

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TY - JOUR

T1 - Testing the association between tobacco and cannabis use and cognitive functioning

T2 - Findings from an observational and Mendelian randomization study

AU - Mahedy, Liam

AU - Wootton, Robyn E

AU - Suddell, Steph

AU - Skirrow, Caroline

AU - Field, Matt

AU - Heron, Jon E

AU - Hickman, Matt

AU - Munafo, Marcus R

N1 - Funding Information: The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer); a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research. Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MM_UU_00011/7). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (BRC-1215-20011) and we acknowledge support from NIHR HPRU in Evaluation. LM is supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Funding Information: The work was undertaken with the support of the MRC and Alcohol Research UK (grant number MR/L022206/1 ). We acknowledge also support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) ; a UKCRC Public Health Research Centre of Excellence (joint funding (grant number MR/KO232331/1 ) from the British Heart Foundation , Cancer Research UK , Economic and Social Research Council , Medical Research Council , the Welsh Government and the Wellcome Trust , under the auspices of the UK Clinical Research Collaboration); and the NIHR School of Public Health Research . Support was also provided by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol ( MM_UU_00011/7 ). LM, REW, SS, and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research Centre of Excellence. LM, REW, SS, and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol ( BRC-1215-20011 ) and we acknowledge support from NIHR HPRU in Evaluation . LM is supported by the Elizabeth Blackwell Institute for Health Research , University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (Grant ref: 204813/Z/16/Z ). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC . Publisher Copyright: © 2021 The Authors

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Background: Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods: Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13 to 18 in a large UK population cohort (ALSPAC). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship. Results: We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95%CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95%CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95%CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b=0.18, 95%CI=0.07 to 0.28), and early-onset regular cannabis users (b=0.30, 95%CI=0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95%CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95%CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results. Conclusion: There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal.

AB - Background: Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods: Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13 to 18 in a large UK population cohort (ALSPAC). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship. Results: We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95%CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95%CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95%CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b=0.18, 95%CI=0.07 to 0.28), and early-onset regular cannabis users (b=0.30, 95%CI=0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95%CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95%CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results. Conclusion: There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal.

KW - ALSPAC

KW - Cannabis

KW - Tobacco

KW - Cognition

KW - Causal inference

U2 - 10.1016/j.drugalcdep.2021.108591

DO - 10.1016/j.drugalcdep.2021.108591

M3 - Article (Academic Journal)

C2 - 33618197

SN - 0376-8716

VL - 221

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

M1 - 108591

ER -

Testing the association between tobacco and cannabis use and cognitive functioning: Findings from an observational and Mendelian randomization study

Abstract

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Keywords

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