Effects of Cannabis on Neurocognitive Functioning: Recent Advances, Neurodevelopmental Influences, and Sex Differences
TL;DR: The purpose of this review was to provide an update on research of cannabis’ acute and non-acute effects on neurocognition, with a focus on findings since 2007, and suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neuroscience.
Abstract: Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis’ acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning.
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TL;DR: To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.
Abstract: With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.
618 citations
TL;DR: The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood.
Abstract: Aims To examine changes in the evidence on the adverse health effects of cannabis since 1993 Methods A comparison of the evidence in 1993 with the evidence and interpretation of the same health outcomes in 2013 Results Research in the past 20 years has shown that driving while cannabis-impaired approximately doubles car crash risk and that around one in 10 regular cannabis users develop dependence Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs These associations persist after controlling for plausible confounding variables in longitudinal studies This suggests that cannabis use is a contributory cause of these outcomes but some researchers still argue that these relationships are explained by shared causes or risk factors Cannabis smoking probably increases cardiovascular disease risk in middle-aged adults but its effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco Conclusions The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood
484 citations
Cites background from "Effects of Cannabis on Neurocogniti..."
...The increased number of better-controlled studies that have been reported since 1993 (see [57,58] for reviews) have consistently found deficits in verbal learning, memory and attention in regular cannabis users, and these deficits have usually but not always been related to the duration and frequency of cannabis use, the age of initiation and the estimated cumulative dose of THC received [59,60]....
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TL;DR: The current state of knowledge about vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction are reviewed.
Abstract: In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.
303 citations
TL;DR: Results indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use and suggest individual differences in susceptibility to cannabis-associated cognitive dysfunction should be examined.
Abstract: Importance Substantial shifts in perception and policy regarding cannabis have recently occurred, with use of cannabis increasing while its perceived harm decreases. One possible risk of increased cannabis use is poorer cognitive functioning, especially in youth. Objective To provide the first quantitative synthesis of the literature examining cannabis and cognitive functioning in adolescents and young adults (with a mean age of 26 years and younger). Data Sources PubMed, PsycInfo, Academic Search Premier, Scopus, and bibliographies of relevant reviews were searched for peer-reviewed, English-language studies from the date the databases began through May 2017. Study Selection Consensus criteria were used to determine study inclusion through abstract and manuscript review. Data Extraction and Synthesis This study followed Meta-analysis of Observational Studies in Epidemiology guidelines. Effect size estimates were calculated using multivariate mixed-effects models for cognitive functioning outcomes classified into 10 domains. Main Outcomes and Measures Results from neurocognitive tests administered in cross-sectional studies were primary outcomes, and we examined the influence of a priori explanatory variables on variability in effect size. Results Sixty-nine studies of 2152 cannabis users (mean [SD] age, 20.6 [2.8] years; 1472 [68.4%] male) and 6575 comparison participants with minimal cannabis exposure were included (mean [SD] age, 20.8 [3.4]; 3669 [55.8%] male). Results indicated a small overall effect size (presented as meand) for reduced cognitive functioning associated with frequent or heavy cannabis use (d, −0.25; 95% CI, −0.32 to −0.17;P Conclusions and Relevance Associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use. Although other outcomes (eg, psychosis) were not examined in the included studies, results indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use. Reported deficits may reflect residual effects from acute use or withdrawal. Future studies should examine individual differences in susceptibility to cannabis-associated cognitive dysfunction.
252 citations
TL;DR: The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health and there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system.
Abstract: The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid-dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system. Acute THC administration causes increased dopamine release and neuron activity, whereas long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of THC.
234 citations
References
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01 Apr 2003
6,571 citations
TL;DR: This large-scale longitudinal pediatric neuroimaging study confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease.
Abstract: Pediatric neuroimaging studies1,2,3,4,5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.
5,140 citations
"Effects of Cannabis on Neurocogniti..." refers background in this paper
...Similarly, females’ prefrontal cortex gray matter volume peaks 1 to 2 years earlier than in males (Giedd et al. 1999)....
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...Although 90 % of the brain’s total volume has developed by approximately age 6 (Giedd 2004), global cortical development follows an inverted U-shaped trajectory, peaking around 12 to 14 years of age then decreasing in volume and thickness over adolescence (Giedd et al. 1999; Gogtay et al. 2004)....
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TL;DR: The dynamic anatomical sequence of human cortical gray matter development between the age of 4-21 years using quantitative four-dimensional maps and time-lapse sequences reveals that higher-order association cortices mature only after lower-order somatosensory and visual cortices are developed.
Abstract: We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4–21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8–10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse “movies” reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.
4,950 citations
"Effects of Cannabis on Neurocogniti..." refers background in this paper
...Although 90 % of the brain’s total volume has developed by approximately age 6 (Giedd 2004), global cortical development follows an inverted U-shaped trajectory, peaking around 12 to 14 years of age then decreasing in volume and thickness over adolescence (Giedd et al. 1999; Gogtay et al. 2004)....
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...This synaptic pruning of gray-matter density occurs first in more primary sensorimotor areas and last in higher-order association areas like the prefrontal cortex (Giedd 2004; Gogtay et al. 2004)....
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TL;DR: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed, and results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervalued of alternative rein forcers, and deficits in inhibitory control for drug responses.
Abstract: OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to tr...
2,415 citations
"Effects of Cannabis on Neurocogniti..." refers background in this paper
...For example, problems with decision-making, inhibition and/or risk-taking may serve as risk factors for the development of substance use disorders, as found in research on other drugs of abuse (de Wit 2009; Goldstein and Volkow 2002; Schepis et al. 2008), making it more difficult to resist the urge to continue using the drug even when its use is likely to be harmful (Bechara 2005)....
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...…risk-taking may serve as risk factors for the development of substance use disorders, as found in research on other drugs of abuse (de Wit 2009; Goldstein and Volkow 2002; Schepis et al. 2008), making it more difficult to resist the urge to continue using the drug even when its use is likely…...
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TL;DR: Before treatment studies on impulsivity can move forward, measures of impulsivity that capture the core aspects of this behavior need to be refined and tested on the basis of an ideologically neutral model of impulsiveness.
Abstract: OBJECTIVE: The authors discuss the relationship of impulsivity to psychiatric disorders and present selected hypotheses regarding the reasons for these relationships. METHOD: Previous research has shown significantly higher levels of impulsivity among patients with conduct disorder, personality disorders, substance use disorders, and bipolar disorder, compared to other psychiatric patients or healthy comparison subjects. A literature review of the theoretical bases of the relationship between these disorders and impulsivity is presented. Measurements of impulsivity and treatment options are discussed in relation to the physiology of impulsivity and the disorders in which it is a prominent feature. RESULTS: Impulsivity, as defined on the basis of a biopsychosocial approach, is a key feature of several psychiatric disorders. Behavioral and pharmacological interventions that are effective for treating impulsivity should be incorporated into treatment plans for these disorders. CONCLUSIONS: The high comorbidi...
2,277 citations
"Effects of Cannabis on Neurocogniti..." refers result in this paper
...Similar to the findings for decision-making and risk taking, studies examining inhibition, motor impulsivity, and psychomotor control (these domains are invariably linked and generally defined as behavior involving rapid reactions to internal and external stimuli; Moeller et al. 2001) are mixed....
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