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The short-term and long-term effects of cannabis on cognition: recent
advances in the field
Emese Kroon, Lauren Kuhns, Janna Cousijn
PII: S2352-250X(20)30113-5
DOI: https://doi.org/10.1016/j.copsyc.2020.07.005
Reference: COPSYC 1033
To appear in: Current Opinion in Psychology
Please cite this article as: Kroon E, Kuhns L, Cousijn J, The short-term and long-term effects
of cannabis on cognition: recent advances in the field, Current Opinion in Psychology (2020),
doi: https://doi.org/10.1016/j.copsyc.2020.07.005
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1
Title: The short-term and long-term effects of cannabis on cognition: recent advances in the field
Emese Kroon1,2, Lauren Kuhns1,2, Janna Cousijn1,2
1Neuroscience of Addiction (NofA) Lab, Department of Psychology, University of Amsterdam,
Amsterdam, The Netherlands
2The Amsterdam Brain and Cognition Center (ABC), University of Amsterdam, Amsterdam, The
Netherlands
*Correspondence: Emese Kroon, P.O. box 15916, 1001 NK Amsterdam, The Netherlands,
e.kroon@uva.nl
Word count: 1957
Word count abstract: 101
Tables: 1
Figures: -
Abstract
The aim of this review is to discuss the most recent evidence for the short-term and long-term
effects of cannabis on cognition. The evidence that cannabis intoxication is associated with short-
term impairment across several basal cognitive domains, including learning and (episodic) memory,
attentional control, and motor inhibition is increasing. However, evidence regarding the effects of
long-term heavy cannabis use on cognition remains equivocal. Cannabis research suffers from
difficulties in measuring cannabis exposure history, poor control over potential sub-acute effects,
and heterogeneity in cognitive measures and sample composition. Multidisciplinary collaborations
and investment in studies that help overcome these difficulties should be prioritized.
Keywords: cannabis, intoxication, cognition, emotional processing, review
1. Introduction
Recent global changes in cannabis legislation parallel increases in use and decreases in harm
perception [1,2]. Yet, there is still little conclusive evidence on the effects of cannabis use. This
review specifically focuses on the effects of cannabis use on cognition. Cognition encompasses our
thoughts and shapes our behaviour, and refers to distinct but partially overlapping processes such as
learning, memory, attention, inhibition, decision-making, and emotion regulation. Cannabis contains
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over a hundred different cannabinoids including ∆9-tetrahydrocannabinol (THC) and cannabidiol
(CBD; [3]). Although the mechanisms are unclear, cannabinoids like THC and CBD potentially affect
cognition through interactions with the endogenous cannabinoid system in the brain [4]. This system
in-turn regulates many other neurotransmitter systems including the dopamine system often
implicated in substance use disorders (SUD; [5]). Moreover, like in other SUDs, the development of
Cannabis Use Disorder (CUD) may also be related to pre-existing cognitive deficits [6]. Given the
rapidly developing evidence base, we will discuss the most recent evidence for the effects of
cannabis intoxication (short-term) and heavy cannabis use (almost daily use, long-term) on cognition
(Table 1). We thereby start with basal cognitive functions, moving towards more complex cognitive
functions and the role of affective processes therein.
2. Cannabis and cognition: current knowledge and recent advances
2.1 Learning and memory
Cannabis intoxication impairs learning and memory in a dose-dependent manner, although
significant individual differences exist [7–9]. Studies in heavy cannabis users are less consistent, but
learning and immediate recall deficits are most commonly reported in active cannabis users [10]. A
recent longitudinal study [11] in adolescent cannabis users suggests a causal link between cannabis
exposure and immediate, but not delayed recall in an episodic memory task. Furthermore, another
recent study showed that trial-by-trial verbal learning rates were slower in cannabis users compared
to controls, and these learning rates were associated with altered functionality of the
parahippocampal gyrus, thalamus and midbrain regions [12]. While altered feedback processing
may play a role in learning deficits observed in alcohol and other substance users, this may not
necessarily be the case in cannabis users [13]. Furthermore, impairments may not be relegated to
only memory of real experiences. Kloft et al. [14] showed that cannabis intoxication increased
susceptibility to false memory, an effect that appeared most prominent at immediate compared to
delayed recall.
Subacute intoxication effects likely contribute to the described effects in cannabis users. The
effects of cannabis on memory performance and related alterations in brain activity fade with
abstinence [10]. In line with this, working memory performance and functionality of the underlying
brain network was only found to be impaired in individuals with a positive urine screen for THC [15].
Despite the heterogeneous and potential timebound nature of the observed deficits, cannabis use-
related learning and memory problems could seriously impact daily functioning of heavy cannabis
users, including performance in school or at work. A combination of psychological, neurological, and
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neurobiological research [16] is crucial to further elucidate the apparent complexity of mechanisms
underlying the effects of cannabis on memory.
2.2 Attention
Similar to learning and memory, cannabis intoxication consistently results in a THC-dose-dependent
reduction of the capacity to orient attention towards task-relevant stimuli [17–19]. In heavy
compared to occasional cannabis users, tolerance to the acute effect of cannabis on attentional
control was related to reduced responsiveness of the reward system after intoxication [20]. This
may relate to the general tolerance to cognitive impairments by cannabis intoxication often
observed in heavy users [7,8,17,18,21]. Heavy cannabis users also develop an attentional bias
towards cannabis and related objects that may interfere with other attentional processes [e.g. [22]
but see [23]). Although effect sizes were small, a recent meta-analysis showed evidence for an
attentional bias towards cannabis-related words and pictures in heavy cannabis users [24].
Attentional bias has been linked to the severity of CUD [25] and might reflect an involuntary early
perceptual bias, supported by increased amplitude and earlier peak of the N1 component in
response to distracting cannabis stimuli [26].
2.3 Inhibition
Cannabis use, and drug use in general, has often been associated with poor inhibitory control. With
regards to motor inhibition, cannabis intoxication consistently and dose dependently reduces the
ability to inhibit an ongoing motor response, as measured with the stop-signal task (e.g. [27,28]). In
contrast, inhibition before a response is initiated, as measured with the go/no-go task, may not be
impaired by intoxication [28]. Findings on the effects of heavy cannabis use on motor inhibition are
less consistent [29]. However, aside from potential problems caused by impairments in motor
control due to cannabis intoxication [30], motor inhibition might not well-reflect the daily life
inhibition problems present in most substance users. Indeed, slower proactive inhibitory control-
related processes, such as those measured with the classical Stroop were found to relate to cannabis
craving [23].
2.4 Decision-making
More complex cognitive functions such as decision-making heavily rely on the integrity of the basal
cognitive functions discussed above and deficits in any of those might in turn result in risky decisions
like substance use. The complexity of the processes involved may explain the inconsistent findings
on the effects of cannabis intoxication and heavy use on decision-making [29,31]. Nonetheless,
progress has been made and recent studies provide new insight into how heavy cannabis use and
the context in which decisions are made affect risky decision-making. For example, a recent study on
financial delay discounting (preferring immediate small rewards over delayed bigger rewards)
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observed a positive relationship between increased delay discounting and frequency of cannabis use
[32]. Interestingly, Gilman at al. [33] found that heavy cannabis using adolescents compared to
controls differed on risk taking in the social, safety, and ethical domains, but not the financial
domain. In general, risky decision-making in heavy cannabis users seems associated with increased
sensitivity to immediate gain accompanied by decreased loss sensitivity [34,35].
2.5 The importance of context and emotion
The previously discussed findings highlight the need for a more fine-grained investigation of
cognitive subprocesses and their interactions, as well as the importance of the context in which
cognition is measured. While cannabis use by a popular peer may bias decision-making in an
occasional user, for individuals with a CUD, decision-making may be particularly compromised when
confronted with cannabis-related cues. As with attentional bias, cannabis-related cues may also
activate an approach bias towards cannabis in heavy cannabis users [25]. Moreover, acute stress
may influence cognitive performance. For example, acute stress affects prospective memory
performance in both heavy cannabis users and controls, but the effects are larger in heavy cannabis
users [36]. On the other hand, increased working memory capacity seems to protect heavy cannabis
users from craving under stressful circumstances [37]. Taken together, potential cognitive deficits in
heavy cannabis users may manifest themselves depending on contextual factors.
The impact of cannabis use on emotion processing is an important factor to consider herein.
Although data is limited, cannabis intoxication may negatively affect emotion recognition [38]. This
seems to be most apparent for negative emotions and appears to be related to reduced brain
activity in reward and cognitive control related brain areas when presented with negative faces
[39,40]. A recent study focusing on gender differences identified complex interactions between
gender and cannabis use patterns in relation to the early processing of emotional stimuli (EEG, ERP:
P1 and P3; [41]). This highlights the general importance of assessing gender differences in the effects
of cannabis use. This is a particularly relevant issue in the domain of emotion processing research
because of the high rates of comorbidity between cannabis use and disorders associated with
emotion processing (e.g. anxiety) and the commonly reported gender difference in the prevalence of
these disorders.
3. Field wide difficulties and future directions
Aside from the classic confounders such as polysubstance use and comorbid mental health
problems, as well as a lack of longitudinal data limiting our understanding of the causal relationship
between cannabis and cognition, cannabis research is facing significant difficulties which have been
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brought to attention by the majority of recent reviews on the topic [10,24,42,43]. While overcoming
these difficulties is of utmost importance, clear solutions are still lacking.
First, the vast majority of studies on the long-term effects of heavy cannabis use on
cognition share one confounding factor: the abstinence period. Studies show that THC metabolites
are detectable in the plasma of heavy cannabis users for over a week [44] and even longer
detectability is possible due to THC’s lipophilic characteristics [45]. In line with this, cannabis-use-
dependent neurocognitive impairments can be detected for as long as 28 days after cessation [46].
Hence, studies in current heavy cannabis users struggle to differentiate sub-acute from long-term
effects. Although this confound should be acknowledged and more wide-spread assessment of THC
metabolites is warranted, sub-acute effects should not always be seen as a problem in itself. After
all, the mix of acute, sub-acute, and long-term effects represent what a current heavy cannabis user
is dealing with in daily life. Nevertheless, more knowledge of the potential for recovery after
abstinence and the role of CUD severity in recovery is needed.
Second, problems with quantifying use are often reported and pose a true problem for
comparability across studies. Variable definitions of heavy cannabis use and the lack of standard
cannabis units are recurrent problems. While both problems might reflect semantics, and defining
categories for frequency and heaviness of use might indeed primarily require discussion, developing
a standard unit is extremely complicated. Recently, attempts were made to develop a standard unit
of cannabis [47,48], but the complexity and variability in cannabis products and routes of
administration hampers practicality. Cannabis contains over a hundred different types of
cannabinoids and the THC:CBD ratio differs significantly between region and even between batches
[49]. Poor knowledge about exposure history in most studies complicates research even further. To
improve our knowledge base, accessible and more reliable methods to quantify cannabis use are
needed. However, even then, research in most countries heavily relies on changes in local legislation
to allow for these methods to be used.
Third, there are methodological problems that plague comparability in systematic reviews
and meta-analyses. While increasing the amount of research will increase the power of these types
of reviews, studies are rarely replicated and the variability between measures to assess the same
cognitive construct remains a problem [24,42,43]. An increase in power will not reflect an increase in
knowledge when this heterogeneity problem is not solved. In line with this, it remains important to
be aware of the risks of assuming that similar tasks measure the same construct like is often done
when aggregating results from stop-signal and go/no-go task [50].
Finally, it may be that the effects of heavy cannabis use on cognition are indeed mixed. The
same dose of THC may result in impairments in some, while leading to improvement in others [51].
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These individual differences are likely to depend on a large variety of moderating factors including
THC:CBD ratio, differences in THC metabolization, poly-substance use, severity of cannabis
dependence, age of onset, gender, and mental health. In turn, the combined effects of these factors
might vary with the context under which cannabis is consumed and cognition is assessed.
4. Conclusion
The rapid increase of research into cannabis and its effects on cognition has provided us with
answers as well as questions. While there is increasing evidence that cannabis intoxication
negatively affects basal cognitive functions like episodic memory, attentional control, and motor
inhibition, results on the long-term effects of heavy cannabis use, and potential recovery after
abstinence, remain equivocal for most cognitive domains. Despite a slow start, cannabis research is
breaking ground. Nevertheless, field-wide difficulties in quantification, methods of measuring
cognitive constructs, and the influence of sub-acute effects seriously hamper the road ahead and
require attention now. Multidisciplinary collaboration and investment in studies that solve these
problems should be prioritized.
5. Acknowledgements and funding
This review was supported by grant 1R01 DA042490-01A1 from the National Institute on Drug
Abuse/National Institutes of Health.
EmptyCreditRolesFile
We do not wish to provide an author statement outlining all authors’ individual contributions to this review.
However, the submission system requires me to upload a ‘CRediT roles’ file.
Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
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References
Explanation of annotations: * Of special interest, ** Of outstanding interest
References
[1] UNODC: Cannabis and Hallucinogens. In World Drug Report 2019. 2019: 1–71.
[2] SAMHSA: Key Substance Use and Mental Health Indicators in the United States: Results
from the 2017 National Survey on Drug Use and Health. (HHS Publication No. PEP19-5068,
NSDUH Series H-54). Rockville, MD: Center for Behavioral Health Statistics and Quality,
Substance Abuse and Mental Health Services Administration. 2018.
[3] Chandra S, Radwan MM, Majumdar CG, Church JC, Freeman TP, ElSohly MA: New trends in
cannabis potency in USA and Europe during the last decade (2008–2017). Eur Arch
Psychiatry Clin Neurosci 2019, 269: 5–15. https://doi.org/10.1007/s00406-019-00983-5.
[4] Russo EB: Beyond Cannabis: Plants and the Endocannabinoid System. Trends Pharmacol Sci
2016, 37: 594–605. https://doi.org/10.1016/j.tips.2016.04.005.
[5] Covey DP, Mateo Y, Sulzer D, Cheer JF, Lovinger DM: Endocannabinoid modulation of
dopamine neurotransmission. Neuropharmacology 2017, 124: 52–61.
https://doi.org/10.1016/j.neuropharm.2017.04.033.
[6] Bickel WK, Mellis AM, Snider SE, Athamneh LN, Stein JS, Pope DA: 21st century
neurobehavioral theories of decision making in addiction: Review and evaluation.
Pharmacol Biochem Behav 2018, 164: 4–21. https://doi.org/10.1016/j.pbb.2017.09.009.
[7] Schoeler T, Bhattacharyya S: The effect of cannabis use on memory function: an update.
Subst Abuse Rehabil 2013, 4: 11–27. https://doi.org/10.2147/SAR.S25869.
[8] Ranganathan M, D’Souza DC: The acute effects of cannabinoids on memory in humans: a
review. Psychopharmacology (Berl) 2006, 188: 425–444. https://doi.org/10.1007/s00213-
006-0508-y.
[9] Petker T, Owens MM, Amlung MT, Oshri A, Sweet LH, Mackillop J: Cannabis involvement and
neuropsychological performance: Findings from the human connectome project. J.
Psychiatry Neurosci 2019, 44: 414–422. https://doi.org/10.1503/jpn.180115.
* A study assessing associations between cannabis use (recent use, lifetime use, cannabis use disorder, and
onset of use) and neuropsychological performance (eight different domains) in a large group of young adults
(N=1121; part of human connectome project). Results show that positive THC screening was associated with
worse episodic memory and reduced processing speed. On the other hand, positive CUD status was associated
with lower fluid intelligence.
[10] Blest-Hopley G, Giampietro V, Bhattacharyya S: A systematic review of human neuroimaging
evidence of memory-related functional alterations associated with cannabis use
complemented with preclinical and human evidence of memory performance alterations.
Brain Sci 2020, 10: 102. https://doi.org/10.3390/brainsci10020102.
**An extensive systematic review of the evidence for a relationship between memory and cannabis use,
including human neuroimaging studies, preclinical behavioural studies, and human behavioural studies. An
informative distinction between the evidence for the effects on adolescents and adults is made and problems in
the literature are extensively discussed.
[11] Duperrouzel JC, Hawes SW, Lopez-Quintero C, Pacheco-Colón I, Coxe S, Hayes T, Gonzalez R:
Adolescent cannabis use and its associations with decision-making and episodic memory:
Preliminary results from a longitudinal study. Neuropsychology 2019, 33: 701–710.
https://doi.org/10.1037/neu0000538.
*A longitudinal study presenting preliminary results on the association between adolescent cannabis use (N =
401) and decision-making, as well as episodic memory. Results show that there were cross-sectional
Journal Pre-proof
8
associations between cannabis use and poorer decision-making and episodic memory. These decision-making
deficits were not predictive of use at 1-year-follow-up, suggesting decision-making deficits as measured with
this paradigm might not relate to escalation of use. However, an increase in cannabis use at follow-up was
found to be associated with decreased immediate recall over that period.
[12] Blest-Hopley G, O’Neill A, Wilson R, Giampietro V, Bhattacharyya S: Disrupted
parahippocampal and midbrain function underlie slower verbal learning in adolescent-
onset regular cannabis use. Psychopharmacology (Berl) 2019, 1-17.
https://doi.org/10.1007/s00213-019-05407-9.
* A fMRI study focussed on the brain correlates of verbal learning in cannabis users (N = 42). Trial-by-trial
analysis of the verbal learning task showed that cannabis users had slower verbal learning rates than non-using
controls, which in turn was found to be associated with disrupted brain activity in the midbrain,
parahippocampal gyrus and thalamus. These results point towards the importance of studying learning
processes, not only learning outcomes.
[13] Aloi J, Blair KS, Crum KI, Bashford-Largo J, Zhang R, Lukoff J, Carollo E, White SF, Hwang S,
Filbey FM, et al.: Alcohol Use Disorder, But Not Cannabis Use Disorder, Symptomatology in
Adolescents Is Associated With Reduced Differential Responsiveness to Reward Versus
Punishment Feedback During Instrumental Learning. Biol Psychiatry Cogn Neurosci
Neuroimaging 2020, 5: 610-618. https://doi.org/10.1016/j.bpsc.2020.02.003.
[14] Kloft L, Otgaar H, Blokland A, Monds LA, Toennes SW, Loftus EF, Ramaekers JG: Cannabis
increases susceptibility to false memory. Proc Natl Acad Sci U S A 2020,117: 4585–4589.
https://doi.org/10.1073/pnas.1920162117.
*A double-blind, randomized, placebo-controlled study (N=64) assessing the effects of THC on false memory.
Result show that cannabis intoxication increased false memory formation and that these effects were most
prominent in the acute-intoxication phase.
[15] Owens MM, McNally S, Petker T, Amlung MT, Balodis IM, Sweet LH, MacKillop J: Urinary
tetrahydrocannabinol is associated with poorer working memory performance and
alterations in associated brain activity. Neuropsychopharmacology 2019, 44: 613–619.
https://doi.org/10.1038/s41386-018-0240-4.
* A fMRI study assessing the association between cannabis use and working memory (WM) performance and
WM related brain activity in a large group of young adults (N = 1038; part of human connectome project).
Results show that positive THC screening was associated with worse WM performance and that reduced brain
activity in WM-related regions in combination with increased activity in WM-unrelated regions mediated this
relationship. Moreover, both WM performance and related brain activity were not associated with history of
cannabis use, suggesting short-term rather than long-term effects of cannabis on WM.
[16] Prini P, Zamberletti E, Manenti C, Gabaglio M, Parolaro D, Rubino T: Neurobiological
mechanisms underlying cannabis-induced memory impairment. Eur Neuropsychopharmacol
2020, In Press. https://doi.org/10.1016/j.euroneuro.2020.02.002.
**A review on cannabis-induced memory impairment in which animal models are discussed to explain
potential neurobiological mechanisms underlying these impairments.
[17] Theunissen EL, Kauert GF, Toennes SW, Moeller MR, Sambeth A, Blanchard MM, Ramaekers
JG: Neurophysiological functioning of occasional and heavy cannabis users during THC
intoxication. Psychopharmacology (Berl) 2012, 220: 341–350.
https://doi.org/10.1007/s00213-011-2479-x.
[18] Ramaekers JG, Kauert G, Theunissen EL, Toennes SW, Moeller MR: Neurocognitive
performance during acute THC intoxication in heavy and occasional cannabis users. J
Psychopharmacol 2009, 23: 266–277. https://doi.org/10.1177/0269881108092393.
[19] D’Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J:
Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent
Journal Pre-proof
9
Users of Cannabis. Neuropsychopharmacology 2008, 33: 2505–2516.
https://doi.org/10.1038/sj.npp.1301643.
[20] Mason NL, Theunissen EL, Hutten NRPW, Tse DHY, Toennes SW, Jansen JFA, Stiers P,
Ramaekers JG: Reduced responsiveness of the reward system is associated with tolerance
to cannabis impairment in chronic users. Addict Biol 2019, e12870.
https://doi.org/10.1111/adb.12870.
*A double-blind, randomized, placebo-controlled, cross-over study (N = 24) in which the acute effects of THC on
behavioural (sustained attention and subjective high) and brain-related outcomes (7T fMRI and spectroscopy)
were assessed. Results show THC-induced alterations in the reward circuit in occasional cannabis users,
associated with increased subjective high and reduced sustained attention. However, these alterations were
absent in heavy cannabis users, suggesting tolerance related reduced responsiveness of the reward system in
heavy cannabis users.
[21] Schwope DM, Bosker WM, Ramaekers JG, Gorelick DA, Huestis MA: Psychomotor
Performance, Subjective and Physiological Effects and Whole Blood 9-
Tetrahydrocannabinol Concentrations in Heavy, Chronic Cannabis Smokers Following Acute
Smoked Cannabis. J Anal Toxicol 2012, 36: 405–412. https://doi.org/10.1093/jat/bks044.
[22] Alcorn JL, Marks KR, Stoops WW, Rush CR, Lile JA: Attentional bias to cannabis cues in
cannabis users but not cocaine users. Addict Behav 2019, 88: 129–136.
https://doi.org/10.1016/j.addbeh.2018.08.023.
[23] Van Kampen AD, Cousijn J, Engel C, Rinck M, Dijkstra BAG: Addictive Behaviors Attentional
bias , craving and cannabis use in an inpatient sample of adolescents and young adults
diagnosed with cannabis use disorder: The moderating role of cognitive control. Addict
Behav 2020, 100: 106126. https://doi.org/10.1016/j.addbeh.2019.106126.
[24] O’Neill A, Bachi B, Bhattacharyya S: Attentional bias towards cannabis cues in cannabis
users: A systematic review and meta-analysis. Drug Alcohol Depend 2020, 206: 107719.
https://doi.org/10.1016/j.drugalcdep.2019.107719.
** A systematic review and meta-analysis on attentional bias in cannabis users. While study heterogeneity is a
problem and effect sizes are small, there is evidence that cannabis users show an attentional bias for cannabis
words as well as pictures. Interestingly, effect sizes are bigger in studies where stimuli are presented for shorter
periods of time, suggesting that attentional bias might be a predominantly fast and automatic process.
[25] Cousijn J, Watson P, Koenders L, Vingerhoets WAM, Goudriaan AE, Wiers RW: Cannabis
dependence, cognitive control and attentional bias for cannabis words. Addict Behav 2013,
38: 2825–2832. https://doi.org/10.1016/j.addbeh.2013.08.011.
[26] Ruglass LM, Shevorykin A, Dambreville N, Melara RD: Neural and behavioral correlates of
attentional bias to cannabis cues among adults with cannabis use disorders. Psychol Addict
Behav 2019, 33: 69–80. https://doi.org/10.1037/adb0000423.
* An EEG study (N = 40) investigating the neural mechanisms underlying attentional bias. Results show that
individuals with a cannabis use disorder had poorer inhibition a nd selective attention than controls, and
attentional bias for cannabis cues seems to be related to altered early perceptual processing.
[27] Metrik J, Kahler CW, Reynolds B, McGeary JE, Monti PM, Haney M, de Wit H, Rohsenow DJ:
Balanced placebo design with marijuana: pharmacological and expectancy effects on
impulsivity and risk taking. Psychopharmacology (Berl) 2012, 223: 489–99.
https://doi.org/10.1007/s00213-012-2740-y.
[28] McDonald J, Schleifer L, Richards JB, de Wit H: Effects of THC on Behavioral Measures of
Impulsivity in Humans. Neuropsychopharmacology 2003, 28: 1356–1365.
https://doi.org/10.1038/sj.npp.1300176.
[29] Broyd SJ, van Hell HH, Beale C, Yücel M, Solowij N: Acute and Chronic Effects of
Cannabinoids on Human Cognition—A Systematic Review. Biol Psychiatry 2016, 79: 557–
567. https://doi.org/10.1016/j.biopsych.2015.12.002.
[30] Boggs DL, Cortes-Briones JA, Surti T, Luddy C, Ranganathan M, Cahill JD, Sewell AR, D’Souza
Journal Pre-proof
10
DC, Skosnik PD: The dose-dependent psychomotor effects of intravenous delta-9-
tetrahydrocannabinol (Δ9-THC) in humans. J Psychopharmacol 2018, 32: 1308–1318.
https://doi.org/10.1177/0269881118799953.
[31] Kroon E, Kuhns L, Hoch E, Cousijn J: Heavy cannabis use, dependence and the brain: a
clinical perspective. Addiction 2020, 115: 559-572. https://doi.org/10.1111/add.14776.
[32] Sofis MJ, Budney AJ, Stanger C, Knapp AA, JBorodovsky JT: Greater delay discounting and
cannabis coping motives are associated with more frequent cannabis use in a large sample
of adult cannabis users. Drug Alcohol Depend 2020, 207: 107820.
https://doi.org/10.1016/j.drugalcdep.2019.107820.
[33] Gilman JM, Calderon V, Curran MT, Evins AE: Young adult cannabis users report greater
propensity for risk-taking only in non-monetary domains. Drug Alcohol Depend 2015, 147:
26–31. https://doi.org/10.1016/j.drugalcdep.2014.12.020.
[34] Fridberg DJ, Queller S, Ahn WY, Kim W, Bishara AJ, Busemeyer JR, Porrino L, Stout JC:
Cognitive mechanisms underlying risky decision-making in chronic cannabis users. J Math
Psychol 2010, 54: 28–38. https://doi.org/10.1016/j.jmp.2009.10.002.
[35] Wesley MJ, Hanlon CA, Porrino LJ: Poor decision-making by chronic marijuana users is
associated with decreased functional responsiveness to negative consequences. Psychiatry
Res - Neuroimaging 2011, 191: 51–59. https://doi.org/10.1016/j.pscychresns.2010.10.002.
[36] Cuttler C, Spradlin A, Nusbaum AT, Whitney P, Hinson JM, McLaughlin RJ: Joint effects of
stress and chronic cannabis use on prospective memory. Psychopharmacology (Berl) 2019,
236: 1973–1983. https://doi.org/10.1007/s00213-019-5184-9.
[37] Miranda R, Wemm SE, Treloar Padovano H, Carpenter RW, Emery NN, Gray JC, Mereish EH:
Weaker Memory Performance Exacerbates Stress-Induced Cannabis Craving in Youths’
Daily Lives. Clin Psychol Sci 2019, 7: 1094–1108.
https://doi.org/10.1177/2167702619841976.
* A study assessing the association between working memory (WM), (cue-induced) craving and stress (N = 85),
with results indicating that good WM might protect against increased craving under stressful circumstances.
[38] Hindocha C, Freeman TP, Schafer G, Gardener C, Das RK, Morgan CJA, Curran HV: Acute
effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial
emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis
users. Eur Neuropsychopharmacol 2015, 25: 325–334.
https://doi.org/10.1016/j.euroneuro.2014.11.014.
[39] Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M,
Surguladze SA, O’Carrol C, Atakan Z, et al.: Distinct Effects of Δ9-Tetrahydrocannabinol and
Cannabidiol on Neural Activation During Emotional Processing. Arch Gen Psychiatry 2009,
66: 95-105. https://doi.org/10.1001/archgenpsychiatry.2008.519.
[40] Bossong MG, van Hell HH, Jager G, Kahn RS, Ramsey NF, Jansma JM: The endocannabinoid
system and emotional processing: A pharmacological fMRI study with ∆9-
tetrahydrocannabinol. Eur Neuropsychopharmacol 2013, 23: 1687–1697.
https://doi.org/10.1016/j.euroneuro.2013.06.009
[41] Troup LJ, Andrzejewski JA, Torrence RD: The effects of sex and residual cannabis use on
emotion processing: An event-related potential study. Exp Clin Psychopharmacol 2109, 27:
318–325. https://doi.org/10.1037/pha0000265.
* An EEG study assessing the relationship between residual cannabis use, gender, and emotional processing (N
= 144). Results show complex gender interactions that highlight the importance of assessing gender differences
in the effects of cannabis on in particular emotion processing.
[42] Figueiredo PR, Tolomeo S, Steele JD, Baldacchino A: Neurocognitive consequences of chronic
cannabis use: a systematic review and meta-analysis. Neurosci Biobehav Rev 2020, 108:
358–369. https://doi.org/10.1016/j.neubiorev.2019.10.014.
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11
** A systematic review and meta-analysis assessing the evidence for the association between chronic cannabis
use and neurocognitive functioning, finding small associations between chronic cannabis use and performance
in a variety of cognitive domains, but not motor impulsivity. Problems with the heterogeneity in measures used
to assess the same cognitive domain are discussed.
[43] Fatima H, Howlett AC, Whitlow CT: Reward, control & decision-making in cannabis use
disorder: Insights from functional MRI. Br J Radiol 2019, 92: 20190165.
https://doi.org/10.1259/bjr.20190165.
[44] Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Herning WI, Cadet JL, Huestis MA:
Implications of Plasma 9-Tetrahydrocannabinol, 11-Hydroxy-THC, and 11-nor-9-Carboxy-
THC Concentrations in Chronic Cannabis Smokers. J Anal Toxicol 2009, 33: 469–477.
https://doi.org/10.1093/jat/33.8.469.
[45] Sharma P, Murthy P, Bharath MMS: Chemistry, metabolism, and toxicology of cannabis:
clinical implications. Iran J Psychiatry 2012, 7: 149–56.
[46] Bolla KI, Brown K, Eldreth D, Tate K, Cadet JL: Dose-related neurocognitive effects of
marijuana use. Neurology 2002, 59: 1337–1343.
https://doi.org/10.1212/01.WNL.0000031422.66442.49
[47] Casajuana Kögel C, Balcells-Olivero MM, López-Pelayo H, Miquel L, Teixidó L, Colom J, Nutt
DJ, Rehm J, Gual A: The Standard Joint Unit. Drug Alcohol Depend 2017, 176: 109–116.
https://doi.org/10.1016/j.drugalcdep.2017.03.010.
[48] Freeman TP, Lorenzetti V: ‘Standard THC units’: a proposal to standardize dose across all
cannabis products and methods of administration. Addiction 2019, 115: 1207-1216.
https://doi.org/10.1111/add.14842.
**A recent effort introducing the ‘Standard THC unit’ as a potential standardized measure of THC dose.
Advantages include that it has the potential to be used across multiple products and administration methods.
Disadvantages for research as well as implementation include the limitations that are put on analysing
cannabis samples in jurisdictions where cannabis is not fully legal.
[49] UNODC: Analysis of drug markets. In World Drug Report 2018, 2018: 1–72.
[50] Littman R, Takács Á: Do all inhibitions act alike? A study of go/no-go and stop-signal
paradigms. PLoS One 2017, 12: 1–20. https://doi.org/10.1371/journal.pone.0186774.
[51] Cousijn J, Núñez AE, Filbey FM: Time to acknowledge the mixed effects of cannabis on
health: a summary and critical review of the NASEM 2017 report on the health effects of
cannabis and cannabinoids. Addiction 2018, 113: 958–966.
https://doi.org/10.1111/add.14084.
[52] Crean RD, Crane NA, Mason BJ: An Evidence-Based Review of Acute and Long-Term Effects
of Cannabis Use on Executive Cognitive Functions. J Addict Med 2011, 5: 1–8.
https://doi.org/10.1097/ADM.0b013e31820c23fa.
[53] Zhang MWB, Ying J, Wing T, Song G, Fung DSS, Smith HE: Cognitive Biases in Cannabis,
Opioid, and Stimulant Disorders: A Systematic Review. Front Psychiatry 2018, 9: 376.
https://doi.org/10.3389/fpsyt.2018.00376.
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Table 1. Summary of current evidence for short-term and long-term effects of cannabis on cognition
This table is an adaptation and update of the table presented in Kroon et al. (2019) [31], focussing on the existing knowledge and most recent evidence for short-term and long-term effects of cannabis on cognition.
The short-term effects column includes results from intoxication studies, while the long-term effects column includes evidence for the effects of longer periods of heavy (near daily) cannabis use on cognition.
Short-term effects
Long-term effects
Suggested Reading
Domain
Evidence
Potential moderators
Evidence
Potential moderators
Reviews
Recent Evidence
Learning &
Memory
Sufficient evidence that THC/cannabis
impairs (non)-verbal learning and episodic
memory. Limited evidence for
impairment of other types of learning and
memory.
Dose ↑
Early onset ↑
Heavy history ↓
Low THC:CBD ratio ↓
Sufficient evidence for impairments in
current heavy users.
Insufficient evidence for lasting effects after
abstinence. Indications of (partial) recovery.
Sub-acute THC/cannabis effects ↑
Early onset ↑
Heavy history ↑
Comorbid mental health issues↑
[7,8,10,16]
[11–14,36,37]
Working
Memory
Inconsistent evidence that THC/cannabis
impairs working memory.
-
Inconsistent evidence for long-term working
memory deficits in current heavy users.
Limited evidence for recovery after
abstinence.
Sub-acute THC/cannabis effects ↑
Heavy history ↑
Early onset ↑
Task complexity ↑
[7,8,10]
[15]
Attentional
Control
Sufficient evidence that THC/cannabis
impairs attentional control.
Dose ↑
Heavy history ↓
Sufficient evidence for impairments in
sustained and divided attention in current
heavy users.
Insufficient evidence for lasting effects after
abstinence. Indications of (partial) recovery.
Sub-acute THC/cannabis effects ↑
Early onset ↑
Heavy history ↑
[29,42,52]
[9]
Motor
Inhibition
Sufficient evidence that THC/cannabis
impairs inhibition of ongoing responses
(stop-signal task).
Inconsistent results with other inhibition
tasks.
Dose ↑
Limited and inconsistent evidence for
impairments in current heavy users.
-
[29,42,52]
[9]
Cognitive
Biases
Limited evidence for cannabis-related
approach bias and attentional bias.
-
Sufficient evidence for attentional bias, but
insufficient evidence for approach bias in
current heavy users.
No evidence to support or refute lasting
effects after abstinence.
Heavy history ↑
CUD severity ↑
THC ↑
Craving ↑
[24,53]
[22,23,26]
Emotion
Processing
Consistent, but limited evidence that
THC/cannabis impairs emotion
recognition, particularly for negative
emotions.
Low THC:CBD ratio ↓
Limited evidence for impaired emotion
identification/recognition in current heavy
users.
No evidence to support or refute lasting
effects after abstinence.
-
-
[41]
Decision
Making
Insufficient evidence that THC/cannabis
impairs decision-making.
-
Insufficient and inconsistent evidence for
impairments in current heavy users.
Cognitive subdomain
[29,43,53]
[11]
THC = ∆9-tetrahydrocannabinol; CBD = cannabidiol
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