## Neurocognitive Consequences of Chronic CannabisUse : A Systematic Review and Meta-Analysis

Pedro Rafael Figueiredo, Serenella Tolomeo, J. Douglas Steele, Alexander Baldacchino

Neuroscience and Biobehavioral Reviews, 2019

Doi : 10.1016/j.neubiorev.2019.10.014

“Une méta-analyse échoue à mettre en évidence une “toxicité” de l’usage du cannabis à long terme, sur les fonctions neuropsychologiques cognitives”

Highlights

 A meta-analysis was conducted to assess the neuropsychological impact of cannabis.
 A limited association was found between chronic cannabis use and neurocognitive deficits.
 Memory and chronic cannabis smoking were linked.

ABSTRACT

Cannabis is currently the most used illicit substance in the world with a global widespread distribution. Although its acute neurocognitive effects on human behaviour have been reported, there is a lack of robust analysis investigating the link, if any, between chronic cannabis use and neurocognitive function. A systematic review of the literature was conducted in order to identify relevant studies published from 2010 to 2019. A meta-analysis was performed on 13 selected studies testing performance of chronic cannabis users compared with non-users in six different neurocognitive domains. There was a low cross-sectional association between neurocognitive impairments and chronic cannabis use in cognitive impulsivity, cognitive flexibility, attention, short-term memory and longterm memory. No association was found between chronic cannabis use and motor impulsivity. By analysing a specific target population with strict inclusion criteria, these findings provide inconclusive evidence that there are cognitive impairments associated with chronic cannabis use. Future research is needed to determine if the findings of this meta-analysis are biased by the methodological limitations encountered.

KEYWORDS : Cannabis; Chronic cannabis use; Neuropsychologie; Impulsivity;
Memory; Intelligence; Attention; Cognitive Flexibility; Meta-Analysis.

### 1. Introduction

Cannabis is the most widely cultivated, trafficked and used illicit drug, with an estimated 147 million people (2.5% of the world population) consuming it (WHO, 2019). It contains several chemical compounds, including cannabinoids, terpenoids, flavonoids and alkaloids. The cannabinoids are the most psychoactive constituent with more than 100 different ingredients described in the literature (Andre et al., 2016, Bonini et al., 2018, Curran et al., 2016). So far, most of the research has focused on the two most prominent cannabinoids: Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), describing a range of opposing effects of these substances on human brain receptors during the acute phase of consumption (Atakan, 2012, Curran et al., 2016, Englund et al., 2013). It is argued that Δ9-THC is linked with impaired learning, psychosis-like events and anxiety, whereas CBD enhances learning and has anti-psychotic and anxiolytic properties (Curran et al., 2016, D’Souza et al., 2004, Das et al., 2013, Leweke et al., 2012, McGuire et al., 2018).

Currently, there is also increasing evidence that acute cannabis use is associated with other neuro-cognitive impairments in decision-making, such as speed of processing, sustained attention, verbal fluency and executive functioning (Bartholomew et al., 2010, Becker et al., 2014, Gonzalez et al., 2012, Grant et al., 2012, Griffith-Lendering et al., 2012, Huestegge et al., 2010, Lorenzetti et al., 2019, Nusbaum et al., 2017). However, studies investigating persistent neurocognitive impairments, if any, due to chronic cannabis exposure are comparatively scarce inhibiting definitive conclusions (Broyd et al., 2016, Crean et al., 2011, Schreiner and Dunn, 2012). Previous reviews have reported that chronic use of cannabis impacts on cognitive functioning in several domains in adolescents and young adults (i.e. episodic memory, sustained attention, decision making, psychomotor speed, executive functioning, new learning) (Broyd et al., 2016, Curran et al., 2016, Ganzer et al., 2016, Lisdahl et al., 2014, Lubman et al., 2015). A meta-analysis performed by Grant and colleagues (2003) reported no substantial effect (d, -0.16) of long-term cannabis consumption on neurocognitive functioning (Grant et al., 2003). Similarly, another meta-analysis published by Schreiner and Dunn (2012) indicated a small neurocognitive impairment effect (d, -0.29) due to chronic cannabis use that persists after acute intoxication particularly on learning and memory, attention and motor functioning (Schreiner and Dunn, 2012). The same authors argued for no significant effect on neurocognitive performance after a period of abstinence of at least 25 days (Schreiner and Dunn, 2012). A recent meta-analysis by Scott and colleagues (2018) also concluded a small effect size (d, -0.25) for neurocognitive impairments in frequent and/or heavy cannabis users, with the largest effects in learning and memory, executive functioning, speed of processing, and attention (Scott et al., 2018).

Although prior meta-analysis provided a quantitative association between chronic cannabis use and neurocognitive impairments, caution is required in interpreting these results. This is mainly due to methodological limitations in the heterogenicity of the studied population and the neurocognitive tasks used, the operational definition of “chronic use” and the lack of clear specification of the abstinence period, if any, prior to testing.

We aimed to further analyse the potential association between chronic cannabis use and neurocognitive impairments by addressing some of the previous methodological limitations in previous reviews focusing on individuals with an age of 18 years or older. Stricter inclusion criteria and a clearly delineated specific period of non-use for each group before the day of testing was used. Furthermore, following similar studies in the field of nicotine (Conti et al., 2019) and opioids (Baldacchino et al., 2012, Baldacchino et al., 2017), standardised differential tasks were used to quantify cognitive impairments.

(…)

1-s2.0-S0149763419307328-main