Review article 605

The acute effects of cannabis on human executive function

Priscilla P. Oomen, Hendrika H. van Hell and Matthijs G. Bossong

Cannabis remains the most frequently used illicit drug overcome the effects of cannabis intoxication on
worldwide. It produces a broad range of acute effects, such performance accuracy. Factors that may account for the
as euphoria, increased heart rate and perceptual alterations. variation in results are the extent to which a paradigm
Over the last few decades, a substantial number of involves attentional processes, differences between
experiments have been conducted to provide insight into studies in administration methods
the acute effects of cannabis on cognition. Here, we and variation in the patients’ history of cannabis use.
systematically review studies that investigated the impact Behavioural Pharmacology 29:605–616 Copyright © 2018
of administration of cannabis or Δ9-tetrahydrocannabinol, Wolters Kluwer Health, Inc. All rights reserved.
the main psychoactive constituent of cannabis, on human Behavioural Pharmacology 2018, 29:605–616
executive function, in particular, on the three principal
domains of inhibition, working memory and reasoning/ Keywords: association, cannabis, endocannabinoid system,
executive function, human, inhibition, reasoning, Δ9-tetrahydrocannabinol,
association. Our findings suggest that cannabis use results working memory
in acute impairment of inhibition, with the strongest effects
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center
after pulmonary administration of higher doses of Δ9- Utrecht, Utrecht, The Netherlands
tetrahydrocannabinol. Results from neuroimaging studies
Correspondence to Matthijs G. Bossong, PhD, Department of Psychiatry,
indicate that these effects are predominantly modulated Brain Center Rudolf Magnus, A01.126, University Medical Center Utrecht,
through neural processes in the inferior frontal gyrus. Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
E-mail: [email protected]
Working memory and reasoning/association are less
clearly affected by cannabis administration, possibly Received 31 May 2018 Accepted as revised 12 August 2018
because of compensational neural mechanisms to

Introduction on microglia, but not neurons (Pertwee, 2006; Cabral

Cannabis is the most frequently used illicit drug, with an et al., 2008). The two most important endocannabinoid
estimate of between 128 and 238 million users worldwide ligands binding to these receptors are anandamide and
(United Nations Office on Drugs and Crime, 2017). 2-arachidonylglycerol, which act as retrograde messen-
Importantly, estimated rates of recent cannabis use are gers. They are synthesized and released postsynaptically
the highest in young adults (17.7% in Europe), and there and bind to presynaptic receptors, thereby regulating the
has been a marked increase in the treatment of cannabis release of both inhibitory and excitatory neuro-
use disorders among young adults in Europe since 2006 transmitters. This signalling works according to an ‘on-
(European Monitoring Centre for Drugs and Drug demand’ principle: endocannabinoids are released when
Addiction, 2017; United Nations Office on Drugs and and where they are needed (Kano et al., 2009; Katona and
Crime, 2017). Freund, 2012).
Although cannabis contains dozens of different cannabi- Consistent with the widespread distribution of CB1
noid compounds, the main psychoactive constituent of receptors, cannabis produces a broad range of acute,
cannabis is Δ9-tetrahydrocannabinol (THC), which pro- dose-dependent psychotropic effects, such as ‘feeling
duces its effects mostly through action on the cannabi- high’, relaxation and euphoria, which are believed to be
noid 1 (CB1) receptor (Ledent et al., 1999; Huestis et al., the main reasons why individuals use cannabis (Green
2001; Bossong and Niesink, 2010). This receptor is part et al., 2004; Mané et al., 2015). In addition, cannabis has
of the endogenous cannabinoid system, which further been shown to acutely induce increased heart rate, per-
consists of CB2 receptors, endogenous ligands and the ceptual alterations, time distortion, infectious laughter,
biochemical machinery for the synthesis, reuptake and talkativeness and intensification of ordinary experiences
metabolism of the endocannabinoids (Kano et al., 2009; such as eating and listening to music (Ashton, 2001; Hall
Katona and Freund, 2012). The CB1 receptor is the most
and Degenhardt, 2009). Most cognitive functions seem to
abundant G-protein-coupled receptor in the central ner-
be reduced during acute cannabis intoxication, with
vous system, whereas CB2 receptors are found primarily
impairments in learning and memory, attention and
executive function among the most consistently
Supplemental Digital Content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of this demonstrated effects (Solowij and Michie, 2007; Crean
article on the journal's website, www.behaviouralpharm.com. et al., 2011; Bossong et al., 2014a, 2014b; Broyd et al., 2016;
0955-8810 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/FBP.0000000000000426

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606 Behavioural Pharmacology 2018, Vol 29 No 7

Cohen and Weinstein, 2018). In terms of the residual findings on inhibition, 42 studies included measures of
effects of cannabis use, that is, those that persist after acute working memory and 21 studies examined reasoning or
intoxication, meta-analyses found evidence for mild cogni- association (one study can include several assessments).
tive impairments, including executive function, which were A short description of all of the cognitive paradigms used
particularly associated with frequent or heavy cannabis in these studies is provided online in Supplementary
use. Importantly, these effects attenuated with prolonged Table 1 (Supplemental digital content 1, http://links.lww.
abstinence, suggesting recovery from the residual cognitive com/BPHARM/A24). Because papers report the potency
impact of cannabis use (Grant et al., 2003; Schreiner and of the administered drug either as milligrams of Δ9-THC,
Dunn, 2012; Scott et al., 2018). percentage of Δ9-THC or microgram Δ9-THC per kilo-
gram body weight, for all studies, the potency of the drug
Over the last few decades, a substantial number of studies
was converted into milligrams of Δ9-THC. If it was not
have been carried out to provide insight into the acute effects
possible to calculate this from information provided in
of cannabis on human executive function. Here, the term
the paper, it was done on the basis of the characteristics
executive function describes a set of high-level cognitive
of standard cannabis cigarettes supplied by the National
functions that are essential for goal-directed behaviour. They
Institute on Drug Abuse (Chait and Pierri, 1989).
include basic cognitive processes such as inhibitory control,
working memory, reasoning, planning and cognitive flexibility
Acute effects of cannabis on inhibition
(Chan et al., 2008; Diamond, 2013). The network of brain
Neuropsychology
areas that sub serves executive function most prominently
Thirty-three studies reported findings on neuropsycho-
includes the dorsolateral prefrontal cortex and the parietal
logical paradigms that examined inhibition, including a
cortex (Seeley et al., 2007; Sridharan et al., 2008). Importantly,
total of 61 assessments. The characteristics and results
impaired executive function is considered a fundamental
are summarized in Table 1. Forty of the 61 (66%)
cognitive deficit in neurological and psychiatric disorders such
assessments showed impairment of inhibition, whereas
as psychosis, Alzheimer’s disease and attention-deficit and
21 (34%) measures did not show any significant effects.
hyperactivity disorder (Perry and Hodges, 1999; Biederman
None of the five (0%) assessments after intravenous
and Faraone, 2005; Fioravanti et al., 2005).
administration of Δ9-THC showed an impairment of
The aim of the current review is to provide a detailed and up- inhibition. Three of the nine (33%) measures after oral
to-date systematic literature overview of studies that investi- administration showed a significant negative effect on
gated the impact of cannabis or Δ9-THC administration on task performance, whereas 37 of the 47 (79%) assess-
human executive function. To examine the effects of can- ments after pulmonary administration showed impaired
nabis on different aspects of executive function, we focused inhibition. The mean pulmonary dose of Δ9-THC used
on three principal domains: inhibition, working memory and in the assessments that showed impairment was sig-
reasoning/association (Chan et al., 2008; Diamond, 2013). The nificantly higher than the Δ9-THC dose of the measures
results of neuropsychological and functional neuroimaging that did not show an effect on inhibition (21.8 ± 14.9 vs.
studies are reported separately. Methodological and con- 11.1 ± 7.8 mg; P = 0.036). Frequently used measures of
ceptual issues are discussed, and implications of the findings inhibition included the Stop Signal Task (n = 10),
will be considered. Divided Attention Task (n = 8) and Stroop Colour and
Word Test (n = 6). Impairment of inhibition was reported
Literature review in seven assessments with the Stop Signal Task (70%), all
Search strategy of the measures of the Divided Attention Task (100%)
An electronic literature search was performed using and three assessments with the Stroop Colour and Word
the following criteria in the PubMed database: (cannabis Test (50%). Finally, a significant increase in the number
OR THC OR marijuana OR marihuana OR tetra- of false alarms was reported in 10 out of 13 (77%) para-
hydrocannabinol) AND (inhibition OR working memory digms. These results suggest that inhibition is impaired
OR reasoning OR association). Reports in English with after cannabis administration, with the strongest effects
human participants published before April 2018 were after pulmonary administration of higher doses of Δ9-
included. In addition, references of selected papers were THC.
examined to ensure the inclusion of other relevant stu-
dies. Review articles, commentaries and preclinical stu- Neuroimaging
dies were excluded. This review was restricted to the Four functional MRI studies examined the acute effects of
acute effects of Δ9-THC or cannabis on one of the fol- Δ9-THC on brain activity patterns associated with inhibi-
lowing domains of executive function: inhibition, work- tion (Table 1). Ramaekers et al. (2016b) related the effects
ing memory and reasoning/association. of Δ9-THC on performance of the matching familiar figures
test to those on resting-state functional connectivity with
Results the nucleus accumbens. They showed a significant nega-
A total of 75 studies were identified and included in the tive correlation between cognitive impulsivity scores and
current systematic review. Thirty-six studies reported functional connectivity strength between the nucleus

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 Table 1 Human studies investigating the acute effects of cannabis/Δ9-tetrahydrocannabinol on inhibition
References N Sex Age Drug Δ9-THC dose and method Taska Results

Neuropsychology
Cappell et al. (1972) 24 Male/female 21–28 Cannabis 4 mg pulmonary Temporally Controlled Operant Task −
8 mg pulmonary −
16 mg pulmonary −
Carlin et al. (1972) 40 Male 24 (21–32) Cannabis 7.5 mg pulmonary Stroop Colour and Word Task =
15 mg pulmonary −
−
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Chait and Perry (1994) 14 Male/female 25 (21–34) Cannabis 30.6 mg pulmonary Divided Attention Task
Crockett et al. (1976) 81 Male/female 23 (19–31) Cannabis 7.2 mg pulmonary Thematic Apperception Test (sexual content and control) =
13.6 mg pulmonary =
D’Souza et al. (2004) 22 Male/female 29 Δ9-THC 2.5 mg intravenous Hopkins Verbal Learning Test (false positives) =
5 mg intravenous =
2.5 mg intravenous Verbal Fluency Task (perseverations) =
5 mg intravenous =
Desrosiers et al. (2015) 25 Male/female 29 (18–45) Cannabis 54 mg pulmonary Divided Attention Task −
Drew et al. (1972) 24 Male 21 Cannabis 1.75 mg pulmonary Stroop Colour and Word Task =
Henquet et al. (2006)b 74 Male/female 27 (18–56) Cannabis 21 mg pulmonary Stroop Colour and Word Task −
Hooker and Jones (1987) 12 Male 22 (19–26) Cannabis 10.7 mg pulmonary Randt Memory Battery (word list) −
Randt Memory Battery (short story) =
Stroop Colour and Word Task −
Hunault et al. (2009) 24 Male 24 (18–33) Cannabis 29.3 mg pulmonary Divided Attention Task −
49.1 mg pulmonary −
−

The acute effects of cannabis on human executive function Oomen et al. 607
69.4 mg pulmonary
Ilan et al. (2004) 10 Unknown 27 (23–31) Cannabis 29.3 mg pulmonary Word Presentation Memory Task (false positives) −
Lawn et al. (2016) 17 Male/female 26 (18–70) Cannabis 8 mg pulmonary Effort-related decision-making Task −
MacAvoy and Marks (1975) 32 Male/female 25 Cannabis 2.6 mg pulmonary Central and Peripheral Light Flashes Task =
5.2 mg pulmonary −
McDonald et al. (2003) 37 Male/female 23 (18–45) Δ9-THC 7.5 mg oral Delay Discounting Task =
15 mg oral =
7.5 mg oral Go/No-Go Task =
15 mg oral =
7.5 mg oral Stop Task =
15 mg oral −
Metrik et al. (2012) 136 Male/female 21 (18–30) Cannabis 23.8 mg pulmonary Stroop Colour and Word Task −
Stop Signal Task −
Miller et al. (1977b) 34 Male 21–28 Cannabis 14 mg pulmonary 15 Item Word List Learning (false alarms) =
Miller and Cornett (1978a) 16 Male 21–28 Cannabis 5 mg pulmonary 40 Item Word List Learning (false alarms) −
10 mg pulmonary −
15 mg pulmonary −
Miller et al. (1978b) 12 Male 21–30 Cannabis 10.5 mg pulmonary 30 Item Word List Learning (false alarms) −
Miller et al. (1979) 12 Male 21–30 Cannabis 10 mg pulmonary 15 Item Word List Learning (false alarms) −
Mokrysz et al. (2016) 20 Male 17 (16–17) Cannabis 8 mg pulmonary Stop Signal Task −
25 (24–28) =
Moskowitz (1974) 23 Male 24 (21–32) Cannabis 3.5 mg pulmonary Digit Recall with Signal Detection Task (false alarms) −
7 mg pulmonary −
14 mg pulmonary −
Pfefferbaum et al. (1977) 16 Male 18–35 Δ9-THC 21 mg oral Word Recall Test (false alarms) −
Ramaekers et al. (2009) 24 Male/female 23 Cannabis 34.6 mg pulmonary Stop Signal Task −
Divided Attention Task −
Ramaekers et al. (2011) 21 Male/female 23 (19–38) Cannabis 28 mg pulmonary Stop Signal Task =
Divided Attention Task −
Ramaekers et al. (2016a) 122 Male/female 23 (18–39) Cannabis 21 mg pulmonary Stop Signal Task −
Divided Attention Task −
Ramaekers et al. (2016b) 122 Male/female 23 (18–40) Cannabis 31.5 mg pulmonary Matching familiar figures test −
Ranganathan et al. (2012) 30 Male/female 27 (18–55) Δ9-THC 1.75 mg intravenous Stroop Colour and Word Task =
608 Behavioural Pharmacology 2018, Vol 29 No 7

Results accumbens and the thalamus and striatum. The three other

=
−

−
−
−
−
−
functional MRI studies applied the same Go/No-Go para-
digm. First, in the absence of Δ9-THC-induced effects on
reaction time or inhibition errors, Borgwardt et al. (2008)
Thematic Apperception Test (thought process – sexuality)

showed in 15 patients with minimal cannabis exposure that

oral administration of 10 mg Δ9-THC significantly reduced
activity in the anterior cingulate gyrus, precuneus and right
Ratings of Narrative Quality (degree of intimacy) inferior frontal gyrus, and increased activity in other areas
including the right (para)hippocampal gyrus, the right
superior temporal gyrus and the left posterior cingulate
gyrus. One explanation for these findings is that Δ9-THC
Taska

administration decreased activity in regions known to be

Matching familiar figures test

involved in response inhibition, but that task performance

Divided Attention Task

Divided Attention Task

was kept on par through recruitment of other areas. In an

Decision-Making Test

extension of this study, Atakan et al. (2013) compared brain

Stop Signal Task
Stop Signal Task
Go/No-Go Task

Go/No-Go Task
Go/No-Go Task
Go/No-Go Task

function between patients who did (N = 11) and who did

not (N = 10) experience psychotic effects following oral Δ9-
Please see Supplementary Table 1 (Supplemental digital content 1, http://links.lww.com/BPHARM/A24) for a short description of each cognitive paradigm.

THC administration (10 mg). Δ9-THC showed significantly

stronger effects on inhibition errors in the group of partici-
pants with psychotic symptoms, which was accompanied by
different effects of Δ9-THC between groups on activity in
Δ9-THC dose and method

the left parahippocampal gyrus, the bilateral middle tem-

poral gyrus and the right fusiform gyrus. This effect was
31.5 mg pulmonary

31.5 mg pulmonary

mainly reflected as increased psychosis-related activity in

35 mg pulmonary

21 mg pulmonary

18 mg pulmonary

the right middle temporal gyrus and decreased activity in

Population consisted of patients with a psychotic disorder, relatives of patients with a psychotic disorder and healthy controls.
20 mg oral

10 mg oral
10 mg oral
10 mg oral

the other three areas. These results suggest that acute

5 mg oral

psychotic symptoms are reflected in behavioural changes

and temporal brain activity alterations associated with
response inhibition. Finally, Bhattacharyya et al. (2015)
reported in 36 patients with minimal cannabis exposure that
oral administration of 10 mg Δ9-THC caused acute tran-
Cannabis
Cannabis
Cannabis

Cannabis

Cannabis

Cannabis
Δ -THC

Δ -THC
Δ9-THC
Δ9-THC
Drug

sient psychotic symptoms, inhibition errors and impaired

9

inhibition efficiency. The severity of psychotic symptoms

was directly correlated with inhibition error frequency and
inversely with inhibition efficiency under the influence of
−, significantly reduced task performance; =, no significant effects on task performance.

Δ9-THC. Δ9-THC attenuated left inferior frontal activa-

24 (19–36)

22 (18–40)

23 (18–40)
20 (18–25)

23 (18–32)

20 (21–26)

26 (20–42)

27 (20–42)
Age

tion, which was correlated inversely with the frequency of

23

26

inhibition errors and severity of psychotic symptoms and

positively with inhibition efficiency under its influence.
These results provide experimental evidence that the acute
Population included transiently psychotic and nonpsychotic groups.

effects of Δ9-THC may be related to the modulation of

Male/female

Male/female
Male/female

Male/female

Male/female

inhibitory processing in the inferior frontal gyrus.

Male

Male

Male
Male
Male
Sex

Please refer for a summary of the results to the main text.

Acute effects of cannabis on working memory

Neuropsychology
Forty studies reported findings on neuropsychological
15

24

61

21

15
72
38

17

36

122

paradigms that examined working memory, including a

N

total of 85 assessments. The characteristics and results

are summarized in Table 2. Forty-one of the 85 (48%)
Δ9-THC, tetrahydrocannabinol.

assessments showed impairment of working memory, 43

Bhattacharyya et al. (2015)

Ramaekers et al. (2016b)

(51%) measures did not show any significant effects and

Weil and Zinberg (1969)
Theunissen et al. (2012)

Borgwardt et al. (2008)

Van Wel et al., (2013)
Table 1 (continued)

one (1%) task showed improvement after cannabis. Eight

Atakan et al. (2013)d
Spronk et al. (2016)
Rogers et al. (2007)

of the 12 (67%) assessments after intravenous Δ9-THC

Roth et al. (1975)

Neuroimagingc

administration showed an impairment in working mem-

References

ory. Eight of the 12 (67%) measures after oral adminis-

tration showed reduced task performance, whereas 25 of
the 61 (41%) assessments after pulmonary administration
b

d
c
a

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 Table 2 Human studies investigating the acute effects of cannabis/Δ9-tetrahydrocannabinol on working memory
References N Sex Age Drug Δ9-THC dose and method Taska Results

Neuropsychology
Belgrave et al. (1979) 25 Male/female 22 (18–35) Δ9-THC 22.5 mg oral Boggle Word Construction Test −
Caswell (1975) 24 Male/female 19–31 Cannabis 4.0 mg pulmonary Serial addition/subtraction Task =
9.2 mg pulmonary Serial addition/subtraction Task −
Chait and Perry (1994) 14 Male/female 25 (21–34) Cannabis 30.6 mg pulmonary Digit Span (Backward) =
Curran et al. (2002) 15 Male 24 (18–30) Δ9-THC 7.5 mg oral Serial addition/subtraction Task =
=
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15 mg oral
D’Souza et al. (2004) 22 Male/female 29 Δ9-THC 2.5 mg intravenous Matching to Sample Task (easy task) −
5 mg intravenous −
2.5 mg intravenous Matching to Sample Task (hard task) =
5 mg intravenous =
D'Souza et al. (2008) 28 Male/female 18–55 Δ -THC
9
2 mg intravenous Spatial Working Memory Task (CANTAB) −
Darley et al. (1973) 12 Male Unknown Cannabis 20 mg oral Sternberg Memory Scanning Task −
Desrosiers et al. (2015) 25 Male/female 29 (18–45) Cannabis 54 mg pulmonary Spatial N-Back Task =
Dornbush and Kokkevi (1976) 20 Unknown 44 Cannabis 78 mg pulmonary Digit Span (Backward) =
Cannabis 90 mg pulmonary Digit Span (Backward) =
Cannabis 100 mg pulmonary Digit Span (Backward) =
Cannabis 180 mg pulmonary Digit Span (Backward) =
Cannabis 78 mg pulmonary Serial addition/subtraction Task =
Cannabis 90 mg pulmonary Serial addition/subtraction Task =
Cannabis 100 mg pulmonary Serial addition/subtraction Task =

The acute effects of cannabis on human executive function Oomen et al. 609
Cannabis 180 mg pulmonary Serial addition/subtraction Task −
Englund et al. (2013) 48 Male/female 26 (21–50) Δ9-THC 1.5 mg intravenous Digit Span (Backward) −
Englund et al. (2016) 10 Male 24 (21–35) Δ9-THC 1 mg intravenous Digit Span (Backward) =
Evans et al. (1976) 11 Male 21–30 Cannabis 3.5 mg pulmonary Delayed Auditory Feedback Device =
Fant et al. (1998) 10 Male 27 (24–31) Cannabis 15.6 mg pulmonary Digit Recall Task =
25.1 mg pulmonary =
15.6 mg pulmonary Serial addition/subtraction Task =
25.1 mg pulmonary =
Foltin et al. (1993) 12 Male 21–45 Cannabis 13–27 mg pulmonary Sternberg Memory Scanning Task =
Freeman et al. (2015)b 121 Male/female 30 (21–50) Δ9-THC 1.5 mg intravenous WAIS 3 Digit Span and Letter Number Test −
Greenwald and Stitzer (2000) 13 Male/female 21 (19–27) Cannabis 30 mg pulmonary – 3 puffs Digit Span (Backward) =
30 mg pulmonary – 9 puffs =
30 mg pulmonary – 18 puffs =
Hart et al. (2001) 11 Male/female 25 (21–35) Cannabis 15.3 mg pulmonary Alphabet Task =
33.2 mg pulmonary =
15.3 mg pulmonary Digit Span (Backward) =
33.2 mg pulmonary =
15.3 mg pulmonary Mental Calculation Task =
33.2 mg pulmonary −
15.3 mg pulmonary Story Recognition Task =
33.2 mg pulmonary −
Heishman et al. (1989) 12 Male 31 (23–43) Cannabis 12 mg pulmonary Digit Span (Backward) =
21 mg pulmonary −
Hooker and Jones (1987) 12 Male 22 (19–26) Cannabis 10.7 mg pulmonary Digit Span (Backward) =
Hunault et al. (2009) 24 Male 24 (18–33) Cannabis 29.3 mg pulmonary Sternberg Working Memory Scanning Task −
49.1 mg pulmonary −
69.4 mg pulmonary −
Ilan et al. (2004) 10 Male/female 27 (23–31) Cannabis 29.3 mg pulmonary Spatial N-Back Task (low load) =
Spatial N-Back Task (high load) −
Word Presentation Memory Task (number colours correct) =
Word Presentation Memory Task (number words correct) =
Ilan et al. (2005) 24 Male/female 26 (21–45) Cannabis 15.3 mg pulmonary Spatial N-Back Task −
30.6 mg pulmonary Spatial N-Back Task −
 610 Behavioural Pharmacology 2018, Vol 29 No 7
Table 2 (continued)

References N Sex Age Drug Δ9-THC dose and method Taska Results

Kiplinger et al. (1971) 15 Unknown Unknown Cannabis 0.4 mg pulmonary Delayed Auditory Feedback Device =
0.9 mg pulmonary −
1.75 mg pulmonary −
3.5 mg pulmonary −
Klonoff et al. (1973) 81 Male/female Unknown Cannabis 7.2 mg pulmonary Picture Recognition Test =
13.6 mg pulmonary −
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Lane et al. (2005) 5 Male/female 21–34 Cannabis 9.4 mg pulmonary Delayed Match to Sample Task −
33 mg pulmonary −
Leweke et al. (1998) 19 Male 27 (24–37) Δ -THC
9
10 mg oral Visual Continuous Word Recognition Task −
Makela et al. (2006) 7 Female 22 Δ9-THC 5 mg oral Spatial Working Memory Task +
12 Male −
Manno et al. (1971) 12 Male 20–30 Cannabis 2.5 mg pulmonary Delayed Auditory Feedback Device −
5 mg pulmonary −
Mcdonald et al. (2003) 37 Male/female 23 (18–45) Δ -THC
9
7.5 mg oral Digit Span (Backward) −
Δ9-THC 15 mg oral −
Miller et al. (1977a) 40 Male 21–28 Cannabis 10.5 mg pulmonary Cued Recall of Story Test −
Miller et al. (1977b) 34 Male 21–28 Cannabis 14 mg pulmonary 15-Item word List – Word list Learning – Input Serial Position Effect −
Miller et al. (1979) 12 Male 21–30 Cannabis 10 mg pulmonary 15-Item word List – Word list Learning – Input Serial Position Effect −
Mokrysz et al. (2016) 20 Male 17 (16–17) Cannabis 8 mg pulmonary Spatial N-Back Task =
25 (24–28) −
Morrison et al. (2009) 22 Male 28 (21–50) Δ9-THC 2.5 mg intravenous Digit Span (Backward) −
Morrison et al. (2011) 20 Male/female 26 (21–50) Δ9-THC 1.25 mg intravenous Spatial N-Back Task −
Pearl et al. (1973) 12 Male 26 (21–33) Cannabis 4.5 mg pulmonary Conceptual Clustering Memory Test −
8.7 mg pulmonary −
4.5 mg pulmonary Word Anagram Solution Task =
8.7 mg pulmonary =
Peeke et al. (1976) 14 Male 21–30 Cannabis 18 mg pulmonary Matching to Sample Test =
Ranganathan et al. (2012) 30 Male/female 27 (18–55) Δ9-THC 1.75 mg intravenous Spatial Working Memory Task (CANTAB) =
Tunbridge et al. (2015)b 78 Male/female 32 (21–50) Δ9-THC 1.5 mg intravenous Digit Span (Backward) −
Wesnes et al. (2010) 24 Male 29 Δ9-THC (nabilone) 3 mg oral Numeric Working Memory Task −
2 mg oral −
1 mg oral =
Neuroimagingc
Böcker et al. (2010) 16 Male 18–45 Cannabis 29.3 mg pulmonary Sternberg Working Memory Scanning Task
49.1 mg pulmonary
69.4 mg pulmonary
Bossong et al. (2012) 17 Male 21 (18–27) Δ9-THC 9 mg pulmonary Sternberg Item-Recognition Paradigm
Ilan et al. (2004) 10 Male/female 27 (23–31) Cannabis 29.3 mg pulmonary Spatial N-Back Task (low load)
Spatial N-Back Task (high load)
Word Presentation Memory Task (number colours correct)
Word Presentation Memory Task (number words correct)
Ilan et al. (2005) 24 Male/female 26 (21–45) Cannabis 15.3 mg pulmonary Spatial N-Back Task
30.6 mg pulmonary Spatial N-Back Task

Δ9-THC, tetrahydrocannabinol.
a
Please see Supplementary Table 1 (Supplemental digital content 1, http://links.lww.com/BPHARM/A24) for a short description of each cognitive paradigm.
b
Population included participants who were vulnerable to paranoia.
c
Please refer for a summary of the results to the main text.
−, significantly reduced task performance; =, no significant effects on task performance; +, significantly improved task performance.
 The acute effects of cannabis on human executive function Oomen et al. 611

showed impaired working memory. The mean pulmon- and results are summarized in Table 3. Sixteen of the 43
ary dose of Δ9-THC used in the assessments that showed (37%) assessments showed impairment of reasoning or
impairment was not significantly different from the Δ9- association, whereas 27 (63%) measures did not show any
THC dose of the measures that did not show an effect on significant effects. The only study with intravenous Δ9-
working memory (25.0 ± 36.3 vs. 35.7 ± 37.9 mg; P = 0.275). THC administration showed a significantly effect on the
Frequently used measures of working memory included Logical Reasoning Task. Four out of 10 (40%) assess-
the Digit Span (Backward) (n = 19), the Serial Addition/ ments after oral administration showed a significant
Subtraction Task (n = 10) and the Spatial N-Back Task reduction in task performance, whereas 11 of the 32
(n = 8). Impairment in working memory was reported in (34%) measures after pulmonary administration showed
six assessments with the Digit Span (Backward) (32%), impaired reasoning or association. The mean pulmonary
two measures of the Serial Addition/Subtraction Task dose of Δ9-THC used in the assessments that showed
(20%) and five assessments with the Spatial N-Back Task impairment was not significantly different from the Δ9-
(63%). These results suggest that working memory is THC dose of the measures that did not show an effect on
moderately affected after cannabis administration, with reasoning or association (13.8 ± 6.0 vs. 14.0 ± 9.2 mg;
only half of the measures showing significant impairments. P = 0.952). Frequently used tasks measuring reasoning or
association included the Logical Reasoning Task (n = 6)
Neuroimaging and the Halstead Category Test (n =5). Impaired task
Four studies have been published that examined the performance was reported in two assessments with the
impact of cannabis on brain activity related to executive Halstead Category Test (20%) and two assessments with
function (Table 2). Two studies by Ilan and colleagues with the Logical Reasoning Task (33%). Response times were
a spatial N-back working memory task showed increased significantly increased in two measures of the Logical
reaction times and decreased performance accuracy after Reasoning Task (33%). These results suggest that rea-
Δ9-THC administration, particularly for the two-back con- soning and association are mildly affected after cannabis
dition, which was accompanied by reduced alpha band administration.
EEG reactivity in response to increased task difficulty (Ilan
et al., 2004, 2005). Using a Sternberg item recognition Discussion
paradigm with four conditions (2–5 digits), Böcker et al. The current review provides a systematic literature
(2010) showed a linear increase in reaction times and overview of studies that investigated the impact of can-
decrease in performance accuracy as a function of both nabis administration on human executive function, in
memory load and the administered dose of Δ9-THC. This particular on inhibition, working memory, and reasoning
decline in working memory accuracy was significantly cor- and association. Our findings suggest that cannabis
related with the Δ9-THC-induced decrease in resting-state acutely impairs inhibition, with the strongest effects after
EEG theta power measured after task performance. Finally, pulmonary administration of higher doses of Δ9-THC.
Bossong et al. (2012) studied the acute effects of Δ9-THC Results from neuroimaging studies indicate that these
inhalation (6 mg) in seventeen recreational cannabis users effects are predominantly modulated by neural activity in
who performed a parametric Sternberg item recognition the inferior frontal gyrus. Working memory and reasoning
paradigm with five difficulty levels. During the placebo and association are less clearly affected by cannabis
condition, brain activity increased linearly with increasing administration, possibly because of compensational
working memory load. Δ9-THC administration enhanced neural mechanisms to overcome the effects of Δ9-THC
activity for low working memory loads, and reduced the intoxication on performance accuracy.
linear relationship between working memory load and
Our findings are in line with the results of other recent
activity in a network of working memory-related brain
systematic reviews on the acute and chronic effects of
regions and in the left dorsolateral prefrontal cortex, the
cannabinoids on human cognition (Crean et al., 2011; Broyd
inferior temporal gyrus, the inferior parietal gyrus and the
et al., 2016; Cohen and Weinstein, 2018). Consistent with
cerebellum in particular. In addition, performance accuracy
our findings, Broyd et al. (2016) conclude on the basis of
after Δ9-THC was only reduced for moderately high
studies carried out in the decade before publication of their
working memory loads. These results suggest that patients
thorough systematic review paper that there is moderate
show enhanced brain activity during working memory tasks
evidence for acute impairment of inhibition, but mixed
that they perform at the normal level, possibly reflecting a
results on the acute impact of cannabis on working memory
compensational neural mechanism to overcome the effects
and reasoning and association. Both the reviews of Crean
of Δ9-THC intoxication on performance accuracy.
et al. (2011) and Cohen and Weinstein (2018) report general
impairment in executive functions associated with cannabis
Acute effects of cannabis on reasoning/association
use, including attention, inhibition, working memory and
Neuropsychology
cognitive flexibility.
Twenty-one studies reported findings on neuropsycho-
logical paradigms that examined reasoning or association, One possible factor that may have influenced the find-
including a total of 43 assessments. The characteristics ings of studies that investigated acute effects of cannabis

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 612 Behavioural Pharmacology 2018, Vol 29 No 7
Table 3 Human studies investigating the acute effects of cannabis/Δ9-tetrahydrocannabinol on reasoning and association
References N Sex Age Drug Δ9-THC dose and method Taska Results

Abel (1971) 49 Male/female Unknown Cannabis Dose unknown, pulmonary Picture Arrangement Test =
Block and Wittenborn (1985) 36 Male 24 Cannabis 10 mg pulmonary Associative Processing Test (response rate) −
Block and Wittenborn (1985) 48 Male 23 Cannabis 10 mg pulmonary Associative Processing Test (category fluency) =
Block and Wittenborn (1984) 36 Male 24 Cannabis 10 mg pulmonary Categorization Task =
Block et al. (1992) 48 Male 21 (18–42) Cannabis 19 mg pulmonary Concept Formation Task =
Free and Constrained Associations Task −
Copyright r 2018 Wolters Kluwer Health, Inc. All rights reserved.

Iowa Test of Educational Development −

Carlin et al. (1972) 40 Male 24 (21–32) Cannabis 7.5 mg pulmonary Alternate Use Task =
15 mg pulmonary =
7.5 mg pulmonary Association IV =
15 mg pulmonary −
Chait and Perry (1994) 30 Male/female 25 (21–34) Cannabis 30.6 mg pulmonary Baddeley/Logical Reasoning Task =
Chesher et al. (1976) 12 Male/female 21 Δ9-THC 10 mg oral Numerical Reasoning Task =
Chesher et al. (1977) 15 Male/female 18–32 Δ9-THC 15 mg oral Numerical Reasoning Task −
Crockett et al. (1976) 81 Male/female 23 (19–31) Cannabis 7.2 mg pulmonary Thematic Apperception Test (multiplicity of meaning/abstraction) −
13.6 mg pulmonary =
Curran et al. (2002) 15 Male 24 (18–30) Δ9-THC 7.5 mg oral Baddeley/Logical Reasoning Task −
15 mg oral −
Fant et al. (1998) 10 Male 27 (24–31) Cannabis 15.6 mg pulmonary Baddeley/Logical Reasoning Task =
25.1 mg pulmonary −
Hart et al. (2001) 18 Male/female 25 (21–35) Cannabis 15.3 mg pulmonary Analogy Task =
33.2 mg pulmonary =
15.3 mg pulmonary Object-Match Task =
33.2 mg pulmonary =
Klonoff et al. (1973) 81 Male/female Unknown Cannabis 7.2 mg pulmonary Halstead Category Test −
13.6 mg pulmonary −
Morrison et al. (2009) 22 Male 28 (21–50) Δ9-THC 2.5 mg intravenous Baddeley/Logical Reasoning Task −
Pearl et al. (1973) 12 Male 26 (21–33) Cannabis 4.5 mg pulmonary Hidden Word Test =
8.7 mg pulmonary =
4.5 mg pulmonary Letter Series Test =
8.7 mg pulmonary −
4.5 mg pulmonary Water-Jar Test =
8.7 mg pulmonary =
4.5 mg pulmonary Word Grouping Test =
8.7 mg pulmonary −
Peeke et al. (1976) 14 Male 21–30 Cannabis 18 mg pulmonary Contingent Categorization Task =
Peters et al. (1976) 20 Male/female 21–34 Δ9-THC 14 mg oral Halstead Category Test =
28 mg oral =
42 mg oral =
Roth et al. (1975) 72 Male 20 (18–25) Cannabis 20 mg oral Thematic Apperception Test (thought process – non-narrativeness/ −
inconsistency/inexplicitness/novelty/timelessness)
Thematic Apperception Test (thought process – unrelatedness/ =
imaginary/inconclusiveness/repetitiveness)
Tinklenberg et al. (1978) 16 Male 18–35 Δ9-THC 21 mg oral Object Description Test =
Weil and Zinberg (1969) 17 Male 20 (21–26) Cannabis 18 mg pulmonary Ratings of Narrative Quality (coherence/thought completion/unity/time- −
orientation)

Δ9-THC, tetrahydrocannabinol.
a
Please see Supplementary Table 1 (Supplemental digital content 1, http://links.lww.com/BPHARM/A24) for a short description of each cognitive paradigm.
−, significantly reduced task performance; =, no significant effects on task performance.
 The acute effects of cannabis on human executive function Oomen et al. 613

on executive function is attention. Reduced subjective be important in the effects of cannabis (Iseger and
measures of attention or alertness are commonly reported Bossong, 2015; Colizzi and Bhattacharyya, 2017). For
after cannabis or Δ9-THC administration (van Hell et al., example, in a series of naturalistic studies, Morgan and
2011; Bossong et al., 2012, 2013; Jansma et al., 2013). colleagues showed that the use of cannabis with high
Significant decreases in alertness may be associated with CBD/Δ9-THC ratios was associated with fewer psychotic
the acute cannabis effects on executive function that we symptoms and better cognitive function (Morgan and
report in this systematic review. First, the strongest Curran, 2008; Morgan et al., 2010, 2012). However, when
effects of cannabis were found on tasks that examined Ilan et al. (2005) administered cannabis with varying
inhibition, good performance of which also relies on concentrations of CBD and Δ9-THC, performance on the
attentional processes. This is further supported by the spatial N-back was significantly impaired after cannabis,
fact that, in particular, performance on the Divided but this was not affected by the concentrations of either
Attention Task was reduced after cannabis administra- of the cannabinoids. Future studies may consider exam-
tion. Second, from the working memory paradigms, the ining the acute effects of cannabis with different CBD/
most impaired performance was on the spatial N-back Δ9-THC ratios on human cognition. Second, studies
task, which typically requires more attentional control applied different methods of administration with varying
than other working memory tasks such as for example doses of Δ9-THC, resulting in different pharmacokinetic
digit span or subtraction tasks (Kane et al., 2007). Third, and pharmacodynamic effects (Grotenhermen, 2003).
reductions in activity during response inhibition were Generally, oral consumption leads to slower absorption
particularly shown in the inferior frontal gyrus (Borgwardt and lower bioavailability of Δ9-THC, and a delay in the
et al., 2008; Bhattacharyya et al., 2015), which has been onset of acute behavioural effects compared with inha-
implicated in attentional processes (Corbetta and lation (Agurell et al., 1986; Grotenhermen, 2003). Third,
Shulman, 2002; Corbetta et al., 2008). Finally, decreases variation in the patients’ history of cannabis use between
in alertness after cannabis may have led to an increase in studies may have affected the findings as frequent can-
effort to keep task performance on par, which may be nabis use may result in blunted responses to acute effects
associated with the reported increased brain activity of cannabis (Colizzi and Bhattacharyya, 2018). Some of
during response inhibition (Borgwardt et al., 2008) and the studies included in this review addressed this issue.
during the processing of lower working memory loads For example, the impact of cannabis administration on
(Bossong et al., 2012). the performance of several executive function tasks has
A potential neurobiological mechanism underlying the been shown to be stronger in nonregular users than in
acute effects of cannabis as discussed in this review may regular users, including the Spatial Working Memory task
be found in the regulatory role of the endocannabinoid (D’Souza et al., 2008), the Stop Signal Task (Ramaekers
system in neurotransmitter release. The endocannabi- et al., 2009; Theunissen et al., 2012) and the Divided
noid system is a retrograde messenger system that reg- Attention Task (Ramaekers et al., 2009; Theunissen et al.,
ulates both excitatory glutamate and inhibitory GABA 2012; Desrosiers et al., 2015). Finally, because in
neurotransmission according to an ‘on-demand’ principle: approximately half of the studies included in the current
endocannabinoids are released when and where they are review only men were allowed to participate, findings
needed (Kano et al., 2009; Katona and Freund, 2012). may be confounded by possible sex differences in the
This endocannabinoid-mediated regulation of synaptic acute effects of cannabis on executive function. Although
transmission is a widespread phenomenon in the brain sex differences have been consistently reported in
and is considered to play an important role in higher brain cannabis-induced effects related to cannabis abuse and
functions, including executive function (Pattij et al., 2008; dependence (more evident in males) or anxiety,
Kano et al., 2009; Katona and Freund, 2012). It has been depression and psychosis (more evident in females)
shown that it can be disrupted by the administration of (Fattore and Fratta, 2010; Ketcherside et al., 2016), little
both Δ9-THC (Mato et al., 2004) and synthetic cannabi- is known about the impact of sex on the acute cognitive
noids (e.g. Wilson and Nicoll, 2001; for reviews, see Kano effects of cannabis. Only two of the included studies
et al., 2009; Katona and Freund, 2012). addressed this issue. McDonald et al. (2003) did not find
differences between males and females in the acute
Studies discussed in this review show important differ- effects of Δ9-THC on inhibitory control tasks including
ences in characteristics, which may account for the var- the Stop Signal task, the Go/No-Go task and the Delay
iation in results. First, in some experiments, participants Discounting Task. In contrast, Makela et al. (2006)
were administered cannabis, whereas in other studies, showed significant improvement in working memory
pure Δ9-THC was administered. Although Δ9-THC is performance after Δ9-THC in female participants only.
the main psychoactive ingredient, cannabis contains at More research on sex differences in the acute effects of
least 80 cannabinoid compounds, and therefore, the acute
cannabis on cognition is warranted.
effects of Δ9-THC and cannabis might be slightly dif-
ferent. In particular, the ratio between Δ9-THC and Impaired executive function is considered a fundamental
another cannabinoid compound, cannabidiol (CBD), may cognitive deficit in neurological and psychiatric disorders

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614 Behavioural Pharmacology 2018, Vol 29 No 7

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