Persistent cannabis users show neuropsychological decline from childhood to midlife
Edited by Michael I. Posner, University of Oregon, Eugene, OR, and approved July 30, 2012 (received for review April 23, 2012)
Commentary
September 24, 2012
Abstract
Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.
Author Summary
Table P1.
| Persistence of regular cannabis use | N | % male | Age 7–13 y full-scale IQ | Age 38 y full-scale IQ | Δ IQ effect size* |
|---|---|---|---|---|---|
| Never used | 242 | 38.84 | 99.84 (14.39) | 100.64 (15.25) | 0.05 |
| Used, never regularly | 508 | 50.59 | 102.27 (13.59) | 101.24 (14.81) | −0.07 |
| Used regularly at 1 wave | 47 | 72.34 | 101.42 (14.41) | 98.45 (14.89) | −0.20 |
| Used regularly at 2 waves | 36 | 63.89 | 95.28 (10.74) | 93.26 (11.44) | −0.13 |
| Used regularly at 3+ waves | 41 | 78.05 | 96.00 (16.06) | 90.77 (13.88) | −0.35 |
Means (SDs) are presented on child and adult full-scale IQ as a function of the number of study waves between ages 18 y and 38 y for which study members reported using cannabis on a regular basis (at least 4 d/wk). The last column shows that study members with more persistent cannabis use showed greater IQ decline from childhood to adulthood.
*This coefficient indicates change in IQ from childhood to adulthood, with negative values indicating decreases in IQ. These change scores are in SD units, with values of 0.20, 0.50, and 0.80 reflecting small, medium, and large changes, respectively.
Increasing efforts should be directed toward delaying the onset of cannabis use by young people, particularly given the recent trend of younger ages of cannabis-use initiation in the United States and evidence that fewer adolescents believe that cannabis use is associated with serious health risk (2). In the present study, the most persistent adolescent-onset cannabis users evidenced an average 8-point IQ decline from childhood to adulthood. Quitting, however, may have beneficial effects, preventing additional impairment for adolescent-onset users. Prevention and policy efforts should focus on (i) delivering to the public the message that cannabis use during adolescence can have harmful effects on neuropsychological functioning, (ii) delaying the onset of cannabis use at least until adulthood, and (iii) encouraging cessation of cannabis use particularly for those who began using cannabis in adolescence.
In the present study, we investigated the association between persistent cannabis use—prospectively assessed over 20 y—and neuropsychological functioning in a birth cohort of 1,037 individuals. Study members underwent neuropsychological testing at age 13 y before the onset of cannabis use and again at age 38 y, after some had developed a persistent pattern of cannabis use. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. We answered the following five questions:
i) Do study members with more persistent cannabis use show greater intelligence quotient (IQ) decline? We found that more persistent cannabis users did show greater IQ decline, with the most persistent users (n = 41) losing an average of 5–6 IQ points from age 13 y to 38 y (Table P1).
ii) Is impairment specific to certain neuropsychological domains, or is it global? Persistent cannabis users showed neuropsychological decline across five different areas of mental function (executive functions, memory, processing speed, perceptual reasoning, and verbal comprehension), indicating that decline is global. Furthermore, this decline was still apparent after controlling for years of education and after ruling out multiple other alternative explanations (for example, the decline was not due to persistent dependence on alcohol or other substances).
iii) Does cannabis-associated neuropsychological impairment translate into functional problems in daily life? Ratings of everyday-life functioning by third-party informants showed that persistent cannabis users were more impaired than nonusers.
iv) Are adolescent-onset cannabis users particularly vulnerable? Compared with adult-onset cannabis users, adolescent-onset users experienced marked neuropsychological decline. For example, adolescent-onset cannabis users who used cannabis persistently up to age 38 y (n = 23) lost an average of 8 IQ points from age 13 y to 38 y.
v) What is the effect of cessation of use? Cessation of cannabis use did not fully restore functioning among adolescent-onset cannabis users.
Cannabis, the most widely used illicit drug in the world, is increasingly being recognized for both its toxic and its therapeutic properties (1). Research on the harmful and beneficial effects of cannabis use is important because it can inform decisions regarding the medicinal use and legalization of cannabis, and the results of these decisions will have major public health consequences. As debate surrounding these issues continues in the United States and abroad, new findings concerning the harmful effects of cannabis on neuropsychological functioning are emerging.
This article is a PNAS Direct Submission.
See Commentary on page 15970.
See full research article on page E2657 of www.pnas.org.
Cite this Author Summary as: PNAS 10.1073/pnas.1206820109.
References
1
RM Murray, PD Morrison, C Henquet, M Di Forti, Cannabis, the mind and society: The hash realities. Nat Rev Neurosci 8, 885–895 (2007).
2
LD Johnston, PM O’Malley, JG Bachman, JE Schulenberg, Monitoring the Future National Survey Results on Drug Use, 1975-2010: Secondary School Students (Institute for Social Research, University of Michigan, Ann Arbor, MI), Vol I. (2011).
Acknowledgments
We thank the Dunedin Study members, their families, the Dunedin Multidisciplinary Health and Development Research Unit staff, and study founder Phil Silva. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council. This research received support from UK Medical Research Council Grants G0100527 and MR/K00381X/1, US National Institute on Aging Grant AG032282, US National Institute of Mental Health Grant MH077874, and US National Institute on Drug Abuse Grant P30 DA023026. Additional support was provided by the Jacobs Foundation.
Supporting Information
Supporting Information (PDF)
Supporting Information
- Download
- 438.57 KB
st01.docx
- Download
- 17.13 KB
st02.docx
- Download
- 44.46 KB
st03.docx
- Download
- 30.08 KB
References
1
RM Murray, PD Morrison, C Henquet, M Di Forti, Cannabis, the mind and society: The hash realities. Nat Rev Neurosci 8, 885–895 (2007).
2
N Solowij, R Battisti, The chronic effects of cannabis on memory in humans: A review. Curr Drug Abuse Rev 1, 81–98 (2008).
3
N Solowij, et al., Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA; Marijuana Treatment Project Research Group 287, 1123–1131 (2002).
4
HG Pope, D Yurgelun-Todd, The residual cognitive effects of heavy marijuana use in college students. JAMA 275, 521–527 (1996).
5
JM Fletcher, et al., Cognitive correlates of long-term cannabis use in Costa Rican men. Arch Gen Psychiatry 53, 1051–1057 (1996).
6
KI Bolla, K Brown, D Eldreth, K Tate, JL Cadet, Dose-related neurocognitive effects of marijuana use. Neurology 59, 1337–1343 (2002).
7
N Solowij Cannabis and Cognitive Functioning (Cambridge Univ Press, Cambridge, UK, 1998).
8
HG Pope, et al., Early-onset cannabis use and cognitive deficits: What is the nature of the association? Drug Alcohol Depend 69, 303–310 (2003).
9
HG Pope, AJ Gruber, JI Hudson, MA Huestis, D Yurgelun-Todd, Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58, 909–915 (2001).
10
SA Gruber, KA Sagar, MK Dahlgren, M Racine, SE Lukas, Age of onset of marijuana use and executive function. Psychol Addict Behav, 2011).
11
MA Harvey, JD Sellman, RJ Porter, CM Frampton, The relationship between non-acute adolescent cannabis use and cognition. Drug Alcohol Rev 26, 309–319 (2007).
12
KL Medina, et al., Neuropsychological functioning in adolescent marijuana users: Subtle deficits detectable after a month of abstinence. J Int Neuropsychol Soc 13, 807–820 (2007).
13
N Solowij, et al., Verbal learning and memory in adolescent cannabis users, alcohol users and non-users. Psychopharmacology (Berl) 216, 131–144 (2011).
14
H Ehrenreich, et al., Specific attentional dysfunction in adults following early start of cannabis use. Psychopharmacology (Berl) 142, 295–301 (1999).
15
MA Fontes, et al., Cannabis use before age 15 and subsequent executive functioning. Br J Psychiatry 198, 442–447 (2011).
16
L Messinis, A Kyprianidou, S Malefaki, P Papathanasopoulos, Neuropsychological deficits in long-term frequent cannabis users. Neurology 66, 737–739 (2006).
17
PR Giancola, RE Tarter, Executive cognitive functioning and risk for substance abuse. Psychol Sci 10, 203–205 (1999).
18
RE Tarter, et al., Neurobehavioral disinhibition in childhood predicts early age at onset of substance use disorder. Am J Psychiatry 160, 1078–1085 (2003).
19
KD Ersche, et al., Abnormal brain structure implicated in stimulant drug addiction. Science 335, 601–604 (2012).
20
A Verdejo-García, AJ Lawrence, L Clark, Impulsivity as a vulnerability marker for substance-use disorders: Review of findings from high-risk research, problem gamblers and genetic association studies. Neurosci Biobehav Rev 32, 777–810 (2008).
21
PA Fried, B Watkinson, R Gray, Neurocognitive consequences of marihuana—a comparison with pre-drug performance. Neurotoxicol Teratol 27, 231–239 (2005).
22
CN Brinch, TA Galloway, Schooling in adolescence raises IQ scores. Proc Natl Acad Sci USA 109, 425–430 (2011).
23
LJ Horwood, et al., Cannabis use and educational achievement: Findings from three Australasian cohort studies. Drug Alcohol Depend 110, 247–253 (2010).
24
M Schneider, M Koch, Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28, 1760–1769 (2003).
25
N Solowij, N Pesa, [Cognitive abnormalities and cannabis use]. Rev Bras Psiquiatr 32, S31–S40 (2010).
26
W Wilson, et al., Brain morphological changes and early marijuana use: A magnetic resonance and positron emission tomography study. J Addict Dis 19, 1–22 (2000).
27
M O’Shea, ME Singh, IS McGregor, PE Mallet, Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol 18, 502–508 (2004).
28
T Rubino, et al., Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus 19, 763–772 (2009).
29
M Ashtari, et al., Medial temporal structures and memory functions in adolescents with heavy cannabis use. J Psychiatr Res 45, 1055–1066 (2011).
30
GCK Chan, TR Hinds, S Impey, DR Storm, Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. J Neurosci 18, 5322–5332 (1998).
31
M Schneider, E Schömig, FM Leweke, Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict Biol 13, 345–357 (2008).
32
KL Hanson, et al., Longitudinal study of cognition among adolescent marijuana users over three weeks of abstinence. Addict Behav 35, 970–976 (2010).
33
G Jager, NF Ramsey, Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: An overview of animal and human research. Curr Drug Abuse Rev 1, 114–123 (2008).
34
AC Scallet, Neurotoxicology of cannabis and THC: A review of chronic exposure studies in animals. Pharmacol Biochem Behav 40, 671–676 (1991).
35
G Jager, RI Block, M Luijten, NF Ramsey, Cannabis use and memory brain function in adolescent boys: A cross-sectional multicenter functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry 49, 561–572, 572, e1–e3 (2010).
36
PE Meehl, High school yearbooks: A reply to Schwarz. J Abnorm Psychol 77, 143–148 (1971).
37
JN Giedd, et al., Brain development during childhood and adolescence: A longitudinal MRI study. Nat Neurosci 2, 861–863 (1999).
38
T Paus, Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci 9, 60–68 (2005).
39
TE Moffitt, et al., How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment. Psychol Med 40, 899–909 (2010).
40
J McLaren, W Swift, P Dillon, S Allsop, Cannabis potency and contamination: A review of the literature. Addiction 103, 1100–1109 (2008).
41
W Hall, W Swift, The THC content of cannabis in Australia: Evidence and implications. Aust N Z J Public Health 24, 503–508 (2000).
42
LD Johnston, PM O’Malley, JG Bachman, JE Schulenberg, Monitoring the Future National Survey Results on Drug Use, 1975-2010: Secondary School Students (Institute for Social Research, University of Michigan, Ann Arbor, MI), Vol I. (2011).
43
LN Robins, JE Helzer, J Croughan, KS Ratcliff, National Institute of Mental Health Diagnostic Interview Schedule. Its history, characteristics, and validity. Arch Gen Psychiatry 38, 381–389 (1981).
44
LN Robins, L Cottler, KK Bucholz, W Compton Diagnostic Interview Schedule for DSM-IV (Washington Univ School of Medicine, St Louis, MO, 1995).
45
; American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 3rd Ed, Revised, Washington, DC, 1987).
46
; American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 4th Ed, Washington, DC, 1994).
47
D Wechsler Manual for the Wechsler Intelligence Scale for Children—Revised (Psychological Corporation, New York, 1974).
48
D Wechsler Wechsler Adult Intelligence Scale (Pearson Assessment, 4th Ed, San Antonio, TX, 2008).
49
D Wechsler Wechsler Memory Scale (Psychological Corporation, 3rd Ed, San Antonio, TX, 1997).
50
; Army Individual Test Battery Manual and Directions for Scoring (War Department, Adjutant General’s Office, Washington, DC, 1944).
51
BJ Sahakian, AM Owen, Computerized assessment in neuropsychiatry using CANTAB: Discussion paper. J R Soc Med 85, 399–402 (1992).
52
MD Lezak Neuropsychological Assessment (Oxford Univ Press, 4th Ed, New York, 2004).
53
A Reichenberg, et al., Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: A 30-year study. Am J Psychiatry 167, 160–169 (2010).
54
J Cohen, A power primer. Psychol Bull 112, 155–159 (1992).
Information & Authors
Information
Published in
Classifications
Submission history
Published online: August 27, 2012
Published in issue: October 2, 2012
Keywords
Acknowledgments
We thank the Dunedin Study members, their families, the Dunedin Multidisciplinary Health and Development Research Unit staff, and study founder Phil Silva. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council. This research received support from UK Medical Research Council Grants G0100527 and MR/K00381X/1, US National Institute on Aging Grant AG032282, US National Institute of Mental Health Grant MH077874, and US National Institute on Drug Abuse Grant P30 DA023026. Additional support was provided by the Jacobs Foundation.
Notes
This article is a PNAS Direct Submission.
See Commentary on page 15970.
See full research article on page E2657 of www.pnas.org.
This article is a PNAS Direct Submission.
See Commentary on page 15970.
See Author Summary on page 15980 (volume 109, number 40).
Authors
Competing Interests
The authors declare no conflict of interest.
Metrics & Citations
Metrics
Altmetrics
Citations
Cite this article
Persistent cannabis users show neuropsychological decline from childhood to midlife, Proc. Natl. Acad. Sci. U.S.A.
109 (40) E2657-E2664,
https://doi.org/10.1073/pnas.1206820109
(2012).
Copied!
Copying failed.
Export the article citation data by selecting a format from the list below and clicking Export.
Cited by
Loading...
View Options
View options
PDF format
Download this article as a PDF file
DOWNLOAD PDFLogin options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginRecommend to a librarian
Recommend PNAS to a LibrarianPurchase options
Purchase this article to access the full text.