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Jamapsychiatry Hines 2020 Oi 200026 1601309834.63439
Jamapsychiatry Hines 2020 Oi 200026 1601309834.63439
Jamapsychiatry Hines 2020 Oi 200026 1601309834.63439
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IMPORTANCE Cannabis use is consistently linked to poorer mental health outcomes, and
there is evidence that use of higher-potency cannabis increases these risks. To date, no
studies have described the association between cannabis potency and concurrent mental
health in a general population sample or addressed confounding using longitudinal data.
OBJECTIVE To explore the association between cannabis potency and substance use and
mental health outcomes, accounting for preceding mental health and frequency of cannabis
use.
DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the Avon Longitudinal
Study of Parents and Children, a UK birth cohort of participants born between April 1, 1991,
and December 31, 1992. Present data on outcomes and exposures were collected between
June 2015 and October 2017 from 1087 participants at 24 years of age who reported recent
cannabis use.
EXPOSURES Self-reported type of cannabis most commonly used in the past year, coded to a
binary exposure of use of high-potency cannabis or lower-potency cannabis.
MAIN OUTCOMES AND MEASURES Outcomes were reported frequency of cannabis use,
reported cannabis use problems, recent use of other illicit drugs, tobacco dependence,
alcohol use disorder, depression, generalized anxiety disorder, and psychotic-like
experiences. The study used secondary data; consequently, the hypotheses were formulated
after data collection.
RESULTS Past-year cannabis use was reported by 1087 participants (580 women; mean [SD]
age at onset of cannabis use, 16.7 [3.0] years). Of these, 141 participants (13.0%) reported the
use of high-potency cannabis. Use of high-potency cannabis was associated with increased
frequency of cannabis use (adjusted odds ratio [AOR], 4.38; 95% CI, 2.89-6.63), cannabis
problems (AOR, 4.08; 95% CI, 1.41-11.81), and increased likelihood of anxiety disorder (AOR,
1.92; 95% CI, 1.11-3.32). Adjustment for frequency of cannabis use attenuated the association
with psychotic experiences (AOR 1.29; 95% CI, 0.67-2.50), tobacco dependence (AOR, 1.42;
95% CI, 0.89-2.27), and other illicit drug use (AOR, 1.29; 95% CI, 0.77-2.17). There was no
evidence of association between the use of high-potency cannabis and alcohol use disorder
or depression.
CONCLUSIONS AND RELEVANCE To our knowledge, this study provides the first general
population evidence suggesting that the use of high-potency cannabis is associated with
mental health and addiction. Limiting the availability of high-potency cannabis may be
associated with a reduction in the number of individuals who develop cannabis use disorders,
the prevention of cannabis use from escalating to a regular behavior, and a reduction in the
risk of mental health disorders.
G
lobally, cannabis is the most commonly used interna-
tionally regulated drug,1 and policy on its use is be- Key Points
coming more liberal worldwide.2 The primary psycho-
Question Does use of high-potency cannabis (compared with use
active component of cannabis is Δ9-tetrahydrocannabinol of low-potency cannabis) increase risks for problems resulting
(THC). The potency (concentration of THC) may be an impor- from cannabis use, common mental disorders, and psychotic
tant factor in the association between cannabis use and men- experiences after controlling for early-life mental health symptoms
tal health. Experimental studies indicate that THC intoxica- and frequency of use?
tion is dose dependent, with higher doses causing greater Findings In this cohort study of 1087 participants who reported
memory impairment and transient psychotic-like symptoms.3 cannabis use in the previous year, after adjusting for frequency of
Policy liberalization has been accompanied by proliferation of cannabis use and early adolescent mental health, use of
high-potency cannabis in legal markets,4,5 and THC concen- high-potency cannabis was associated with a significant increase
trations have increased in markets where cannabis remains in the frequency of cannabis use, likelihood of cannabis problems,
and likelihood of anxiety disorder. Those using high-potency
illegal.6
cannabis had a small increase in the likelihood of psychotic
Cannabis use is consistently linked to poorer mental health experiences; however, this risk was attenuated after adjustment
outcomes,7,8 and there is evidence that higher-potency can- for frequency of cannabis use.
nabis is associated with higher risks. A case-control study of
Meaning Risks for cannabis use problems and anxiety disorders
first-episode psychosis in England found that those who self-
are higher among those reporting use of high-potency cannabis;
reported using higher-potency cannabis were twice as likely provision of public health messaging regarding the importance of
to have a psychotic disorder, compared with participants who reducing both frequency of cannabis use and the potency of the
did not use cannabis.9 When the study was replicated in a mul- drug, as well as limiting the availability of high-potency cannabis,
tinational case-control study of first-episode psychosis across may be effective for reducing these risks.
11 sites in Europe and Brazil, the incidence of psychosis across
sites was positively correlated with the prevalence of high- disordered use of other substances, common mental disor-
potency cannabis use in the site-specific control samples.10 In ders, and psychotic experiences (PEs) by comparing those who
a self-selecting sample of people who use internationally regu- use high-potency cannabis with those who use lower po-
lated drugs, the use of high-potency strains of cannabis was tency cannabis; and (3) determine the extent to which such as-
associated with self-report of lifetime depression11 and can- sociations are explained by adolescent mental health at 12 to
nabis dependence.12 These findings indicate that the avail- 13 years of age, age at onset of cannabis use, and current fre-
ability of high-potency cannabis may increase risks of poorer quency of cannabis use.
mental health, addiction, and need for treatment among those
who are using the drug.
The strength of association between the use of cannabis
and mental health outcomes is increased when cannabis use
Methods
is frequent; consequently, increased frequency of use may con- Study Population
found the association between cannabis potency and mental ALSPAC is a UK population-based birth cohort, the methods
health outcomes.12 Understanding the extent to which harms of which have previously been outlined13,14 (see eAppendix 1
of high-potency cannabis are due to the THC content of the in the Supplement for full details). The sample for the pre-
drug, and the extent to which these harms may be accounted sent analyses comprised the 1087 participants who reported
for by increased frequency of use, is important for informing on their past-year cannabis use while attending the ALSPAC
policy decisions around taxation and limits on drug potency. clinic between June 2015 and October 2017 at a mean (SD) age
To our knowledge, to date, no studies of the association of 24.0 (0.8) years (Figure 1). Data on the 2085 individuals who
between cannabis potency and mental health have been con- participated in the assessment at 24 years of age but were ex-
ducted in a general population sample. General population cluded based on reporting no recent cannabis use are avail-
studies can provide a valid estimate of the association be- able in eTable 3 in the Supplement (see also eAppendix 1 in the
tween mental health outcomes and cannabis potency at the Supplement for further details on all the measures de-
population level, which may be crucial for informing policy scribed). Ethical approval for the study was obtained from the
makers and clinical service providers. We use data from the ALSPAC Ethics and Law Committee and the local Research Eth-
Avon Longitudinal Study of Parents and Children (ALSPAC), a ics Committees. Written informed consent for the use of data
large general population birth cohort where contemporane- collected via questionnaires and clinics was obtained from par-
ous data were collected when participants were 24 years of age ticipants following the recommendations of the ALSPAC Eth-
on cannabis potency, cannabis use frequency, and validated ics and Law Committee at the time.
measures of mental health outcomes, and prospective mea-
sures of adolescent mental health were collected from partici- Exposure
pants up to 24 years of age. Those who reported past-year cannabis use were asked “What
The aims of our study were to (1) describe the use of dif- type of cannabis have you most commonly used or taken in
ferent potencies of cannabis among a population of UK ado- the last 12 months?” and were able to select from the follow-
lescents; (2) explore the association between cannabis po- ing options: “herbal cannabis/marijuana,” “skunk/other stron-
tency and problems resulting from cannabis use, use and ger types of herbal cannabis,” “hashish/resin/solid,” “other,”
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Cannabis use, %a
Characteristic High potency (n = 141) Lower potency (n = 946) P valueb
Regular cannabis use 56.8 17.6 ≤.001
Cannabis use problems 10.1 0.8 ≤.001
Use of other illicit drugs 82.9 66.5 ≤.001
Tobacco dependence 37.0 15.1 ≤.001
Alcohol use disorder 15.1 10.0 ≤.001
Major depression (moderate or severe symptoms) 11.7 9.7 ≤.001
Generalized anxiety disorder 19.1 11.6 ≤.001
Psychotic-like experiences 12.4 7.1 ≤.001
Male sex 71.6 43.4 ≤.001
Low maternal educational level 19.2 13.1 ≤.001
Lower parental occupational class 32.2 29.2 ≤.001 Abbreviations: MFQ, Mood and
Feelings Questionnaire; NA, not
Black or minority ethnic group 5.3 5.3 .94 applicable; PEs, psychotic
Age at onset of cannabis use, mean (95% CI), y 14.7 (14.3-15.1) 16.9 (16.8-17.2) NA experiences.
a
MFQ score at 13 y, mean (95% CI) 5.6 (4.65-6.49) 5.6 (5.26-5.95) NA All numbers estimated from
imputed proportions.
No. PEs at 12 y, mean (95% CI) 0.33 (0.18-0.48) 0.20 (0.16-0.24) NA b
Determined by χ2 test.
(1) adjusting for sex and childhood socioeconomic position; (2) puted data sets using the Rubin rules, and assessment of Monte
additional adjustment for age at onset of cannabis use for mod- Carlo variability confirmed this as a suitable number of
els of substance use outcomes, depression symptom score at imputations.24
13 years of age for models of major depressive disorder and gen-
eralized anxiety disorder outcomes, and PEs at 12 years of age
for the model with PE as the outcome (time points selected to
ensure mental health symptoms preceded onset of cannabis
Results
use); and (3) adjusted as in model 2, with inclusion of a cat- Of the 1087 participants reporting past-year cannabis use at
egorical measure of cannabis use frequency. This measure al- 24 years of age, 12.8% (number estimated from imputed
lowed estimation of the extent to which preexisting symp- proportions) reported the use of high-potency cannabis
toms of mental health disorders and the frequency of cannabis (Table 1). Use of lower-potency forms of cannabis was
use explained any association between the use of high- reported by 87.2% (number estimated from imputed pro-
potency cannabis and substance use and mental health out- portions) of those who used cannabis in the past year (see
comes. Results are presented as odds ratios (ORs) with 95% CIs. eTable 3 in the Supplement for data on this and on all analy-
Propensity score models were applied to complete case data sis variables). Use of high-potency cannabis was more com-
as a sensitivity test (eAppendix 2 and eTables 1 and 2 in the mon than use of lower-potency cannabis in those who were
Supplement). male (71.6% vs 43.3%) and those who reported regular can-
nabis use (56.8% vs 17.6%), recent cannabis use problems
Missing Data and Imputation (10.1% vs 0.8%), recent use of other illicit drugs (82.9% vs
As outcomes and exposures were collected at the same point, 66.5%), tobacco dependence (37.0% vs 15.1%), AUD (15.1%
most missing data were in the covariates assessed at earlier ages vs 10.0%), depression (11.7% vs 9.7%), generalized anxiety
(eAppendix 1 and eTable 3 in the Supplement). Missing data disorder (19.1% vs 11.6%), and PE (12.4% vs 7.1%) (Table 1).
in all analysis variables (exposures, outcomes, and covari-
ates) were addressed through multiple imputation using Cannabis Use Outcomes
chained equations, which uses a series of univariate regres- There was an unadjusted association between the use of
sion models to impute each incomplete variable sequen- high-potency cannabis and frequency of cannabis use at 24
tially. Each model included all other analysis variables, along years of age (OR, 6.21; 95% CI, 4.24-9.11) (Table 2). This
with the following auxiliary variables: race/ethnicity, experi- association was attenuated by adjustment for sociodemo-
encing bullying up to 16 years of age, parental separation up graphic factors and by the age at onset of cannabis use, but
to 16 years of age, parental mental health problems up to 16 those reporting use of high-potency cannabis remained
years of age, parental substance use up to 16 years of age, Mood more than 4 times as likely to report using cannabis at least
and Feelings Questionnaire score at 16 and 18 years of age, num- weekly compared with those reporting use of lower-potency
ber of self-reported psychotic-like experiences at 14 years of forms of cannabis (adjusted OR [AOR], 4.38; 95% CI, 2.89-
age, and conduct disorder symptoms up to 13 years of age. 6.63). There was also an unadjusted association between
Estimates were obtained by pooling results across 40 im- the use of high-potency cannabis and reporting recent can-
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Table 2. Logistic Regression Analysis of the Association Between High-Potency Cannabis and Substance Use and Mental Health Outcomesa
Adjusted for
childhood Adjusted for Adjusted for
sociodemographic prospective mental frequency of
Univariable OR factors, health measures, cannabis use,
Outcome variable (95% CI) P value AOR (95% CI) P value AOR (95% CI) P value AOR (95% CI) P value
Regular cannabis use 6.21 (4.24-9.11) ≤.001 5.81 (3.90-8.65) ≤.001 4.38 (2.89-6.63)b ≤.001 NA NA
Recent cannabis use 13.17 (5.41-32.04) ≤.001 13.52 (5.28-34.60) ≤.001 8.45 (3.04-23.50)b ≤.001 4.08 (1.41-11.81) .009
problems
Recent use of other 2.47 (1.53-3.97) ≤.001 2.19 (1.35-3.56) .002 1.50 (0.91-2.49)b .11 1.29 (0.77-2.17) .34
illicit drugs
Tobacco dependence 3.31 (2.23-4.92) ≤.001 3.30 (2.18-4.99) ≤.001 2.05 (1.31-3.19)b .002 1.42 (0.89-2.27) .14
Alcohol use disorder 1.60 (0.94-2.73) .08 1.49 (0.86-2.56) .15 0.99 (0.56-1.76)b .97 0.90 (0.49-1.64) .73
Major depression 1.24 (0.70-2.18) .46 1.61 (0.89-2.93) .12 1.54 (0.84-2.82)c .16 1.28 (0.68-2.32) .44
(moderate or severe
symptoms)
Generalized anxiety 1.77 (1.09-2.86) .02 2.35 (1.41-3.92) ≤.001 2.28 (1.36-3.83)c .002 1.92 (1.11-3.32) .02
disorder
Psychotic-like 1.81 (1.01-3.24) .047 2.03 (1.10-3.73) .02 1.86 (1.00-3.46)d .05 1.29 (0.67-2.50) .45
experiences
c
Abbreviations: AOR, adjusted odds ratio; NA, not applicable; OR, odds ratio. Depression symptom score at 13 years of age.
a d
All results estimated from imputed data. Multivariable model adjustment is Number of psychotic experiences at 12 years of age.
incremental.
b
Age at onset of cannabis use.
nabis problems (OR, 13.17; 95% CI, 5.41-32.04). This associa- Participants reporting the use of high-potency cannabis
tion was attenuated by adjustment for age at onset of can- were almost twice as likely to report frequent or distressing
nabis use and frequency of cannabis use, but people PEs (OR, 1.81; 95% CI, 1.01-3.24) (not occurring directly after
reporting the use of high-potency cannabis were still more drug use) (Table 2). However, evidence of association was
than 4 times as likely to report having recently experienced weakened after adjustment for frequency of cannabis use
problems associated with their cannabis use (AOR, 4.08; (AOR, 1.29; 95% CI, 0.67-2.50) (Table 2 and Figure 2).
95% CI, 1.41-11.81) (Table 2 and Figure 2).
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jamapsychiatry.com (Reprinted) JAMA Psychiatry October 2020 Volume 77, Number 10 1049
of cannabis potency. Characteristics of those who did not re- the selection of high-potency strains. The present study sug-
port cannabis use at 24 years of age are in eTable 4 in the gests that risks for cannabis use problems and anxiety disor-
Supplement. ders are further increased among those reporting the use of
high-potency cannabis, even after accounting for sociodemo-
graphic factors, adolescent mental health, and frequency of
cannabis use. Providing public health messaging regarding the
Conclusions importance of reducing both the frequency of cannabis use and
The use of high-potency cannabis may occur as part of a pro- the potency of the drug, as well as limiting the availability of
file of other illicit drug use and substance dependency, likely high-potency cannabis, may be effective for reducing the harms
owing to shared risk factors underlying these behaviors and associated with cannabis use.
ARTICLE INFORMATION (MR/M006727/1). The work was undertaken with 4. Cascini F, Aiello C, Di Tanna G. Increasing
Accepted for Publication: March 23, 2020. the support of The Centre for the Development and delta-9-tetrahydrocannabinol (Δ-9-THC) content in
Evaluation of Complex Interventions for Public herbal cannabis over time: systematic review and
Published Online: May 27, 2020. Health Improvement (DECIPHer), a UK Clinical meta-analysis. Curr Drug Abuse Rev. 2012;5(1):32-
doi:10.1001/jamapsychiatry.2020.1035 Research Collaboration Public Health Research 40. doi:10.2174/1874473711205010032
Open Access: This is an open access article Centre of Excellence. Joint funding (MR/ 5. Potter DJ, Hammond K, Tuffnell S, Walker C, Di
distributed under the terms of the CC-BY License. KO232331/1) was provided by the British Heart Forti M. Potency of Δ9-tetrahydrocannabinol and
© 2020 Hines LA et al. JAMA Psychiatry. Foundation, Cancer Research UK, Economic and other cannabinoids in cannabis in England in 2016:
Author Affiliations: Population Health Science, Social Research Council, Medical Research Council, implications for public health and pharmacology.
Bristol Medical School, University of Bristol, Bristol, the Welsh Government, and the Wellcome Trust, Drug Test Anal. 2018;10(4):628-635. doi:10.1002/
United Kingdom (Hines, Zammit, Hickman, under the auspices of the UK Clinical Research dta.2368
MacLeod, Heron); Addiction and Mental Health Collaboration. Collection of data used in this study
was funded by the Medical Research Council grant 6. Freeman TP, Groshkova T, Cunningham A,
Group, Department of Psychology, University of Sedefov R, Griffiths P, Lynskey MT. Increasing
Bath, Bath, United Kingdom (Freeman); Institute of MR/M006727/1. Dr Cannon is supported by a
European Research Council Consolidator Award potency and price of cannabis in Europe, 2006-16.
Psychiatry, Psychology & Neuroscience, National Addiction. 2019;114(6):1015-1023. doi:10.1111/add.
Addiction Centre, London, United Kingdom (iHEAR 724809). This study also received funding
from the National Institute for Health Research 14525
(Freeman); Clinical Psychopharmacology Unit,
University College London, London, United (NIHR) School of Public Health Research. Dr Hines 7. Moore THM, Zammit S, Lingford-Hughes A, et al.
Kingdom (Freeman); Addiction Group, Department is supported by a Wellcome Trust Sir Henry Cannabis use and risk of psychotic or affective
of Psychological Sciences, University of Liverpool, Wellcome Postdoctoral Fellowship. The Medical mental health outcomes: a systematic review. Lancet.
Liverpool, United Kingdom (Gage); Medical Research Council and Alcohol Research UK (MR/ 2007;370(9584):319-328. doi:10.1016/S0140-6736
Research Council Centre for Neuropsychiatric L022206/1) supports Dr Heron. Dr Zammit is (07)61162-3
Genetics and Genomics, Cardiff University, Cardiff, supported by the NIHR Biomedical Research Centre 8. Gobbi G, Atkin T, Zytynski T, et al. Association of
United Kingdom (Zammit); Department of at University Hospitals Bristol NHS Foundation cannabis use in adolescence and risk of depression,
Psychiatry, Royal College of Surgeons in Ireland, Trust and the University of Bristol. The Society for anxiety, and suicidality in young adulthood:
Dublin, Ireland (Cannon); Experimental Psychology, the Study of Addiction supports Dr Freeman. a systematic review and meta-analysis. JAMA
University of Bristol School of Psychological Role of the Funder/Sponsor: The funding sources Psychiatry. 2019;76(4):426-434. doi:10.1001/
Science, Bristol, United Kingdom (Munafo). had no role in the design and conduct of the study; jamapsychiatry.2018.4500
Author Contributions: Drs Hines and Heron had collection, management, analysis, and 9. Di Forti M, Marconi A, Carra E, et al. Proportion
full access to all of the data in the study and take interpretation of the data; preparation, review, or of patients in south London with first-episode
responsibility for the integrity of the data and the approval of the manuscript; and decision to submit psychosis attributable to use of high potency
accuracy of the data analysis. the manuscript for publication. cannabis: a case-control study. Lancet Psychiatry.
Concept and design: Hines, Zammit, Hickman, Additional Contributions: We thank all the families 2015;2(3):233-238. doi:10.1016/S2215-0366(14)
Cannon, Munafo, Heron. who took part in this study, the midwives for their 00117-5
Acquisition, analysis, or interpretation of data: help in recruiting them, and the whole Avon 10. Di Forti M, Quattrone D, Freeman TP, et al;
Hines, Freeman, Gage, Zammit, Hickman, Longitudinal Study of Parents and Children team, EU-GEI WP2 Group. The contribution of cannabis
Macleod, Heron. which includes interviewers, computer and use to variation in the incidence of psychotic
Drafting of the manuscript: Hines, Gage, laboratory technicians, clerical workers, research disorder across Europe (EU-GEI): a multicentre
Zammit, Munafo. scientists, volunteers, managers, receptionists, case-control study. Lancet Psychiatry. 2019;6(5):
Critical revision of the manuscript for important and nurses. 427-436. doi:10.1016/S2215-0366(19)30048-3
intellectual content: All authors.
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