Are the adverse consequences of cannabis use age-dependent?

Multiple Sclerosis, Cannabinoids, and Cognition

Byline: Amresh. Shrivastava, Megan. Johnston, Ming. Tsuang This review considers the effects of cannabis on cognitive functioning, in both short and long term. Although the general impression supported by many studies is that cannabis causes cognitive decline, particularly with long-term usage, some research suggests that this may not be the case. Nevertheless, certain specific neuropsychological parameters have been found to be affected. Most commonly and consistently reported are response time, prolongation of word viewing time, basic oculomotor deficit, residual verbal memory and executive functioning. The pathways to cognitive dysfunction are given particular focus, including the role of the central nervous system (CNS) cannabinoid system. Finally, the psychiatric effects of cannabis are considered in light of the idea that cognitive function may be the common denominator in the association between cannabis and psychotic disorders. Effect of Cannabis on Cognition Cannabis is one of the most commonly abused illicit drugs. The World Health Organization [sup][1] reports that almost 3% of the world's adult population abuses cannabis, with many more individuals reporting less frequent use. Adolescents in particular consume high levels of cannabis, starting generally between 12 and 16 years of age. This is an important factor from a psychiatric and developmental point of view. [sup][2] Cannabis use is of important consideration in light of its recognized acute and long-term health effects. [sup][1],[3] Active compounds of cannabis, called cannabidols, have 64 active isomers, each having different effects on human health and behavior. Only one metabolite, tetrahydrocannabinol (THC), is reported to be an active metabolite responsive for its effects. [sup][4] Studies show that it induces both psychical and physical dependencies, [sup][5] but the perception of withdrawal is weak on account of its slow elimination. [sup][6] There is a widely held belief that cannabis is inert to the brain, [sup][7] and although the psychological consequences are quite evident, the population at large seems unconvinced. There is much debate about the nature of cannabis dependence, as it is considered non-addicting due to the absence of a withdrawal state. This presumption has also been proved wrong. [sup][6] The general impression supported by many studies is that cannabis causes cognitive decline, particularly with long-term usage. Majority of studies have suggested a significant cognitive decline in cannabis abusers compared to non-abusers and healthy controls. [sup][8],[9],[10] A report by Bartholomew et al. [sup][11] suggested that cannabis use has a detrimental effect on prospective memory ability in young adults but users may not be aware of these deficits. Cannabis is known to produce substantial acute effects on human cognition and visuomotor skills. Many recent studies additionally revealed rather long-lasting effects on basic oculomotor control, especially after chronic use. [sup][12] Even so, it is still unknown to what extent these deficits play a role in everyday tasks that strongly rely on an efficient saccade system, such as reading. Cannabis has a negative impact on cognition; however, the current body of research literature does not provide evidence of significant, long-term effects due to cannabis use. Several acute effects are noted and some are suggestive of negative mental health consequences. [sup][13] Evidence from both animal and human studies suggests that the severity of the effects of cannabis use on cognitive development is dependent on the age when cannabis use begins. [sup][14] One possible explanation is that those who begin cannabis use early in adolescence are more likely to become heavily dependent. It is plausible that chronic cannabis abuse will then interfere with educational and vocational training. From a more biological perspective, however, use of cannabis during critical developmental periods in the still maturing brain may induce persistent alterations in brain structure and brain function. …

Over the past 20 years epidemiological studies have left us better informed about the adverse effects of regular cannabis use in young adulthood on mental health and psychosocial outcomes [1]. The Christchurch Health and Development Study (CHDS) of David Fergusson and colleagues has made an especially valuable contribution to this literature, as indicated by the summary of its key findings on the mental health and psychosocial outcomes of cannabis use in the current issue. The CHDS followed the life course of a birth cohort of 1000 New Zealanders, 80 % of whom had used cannabis by their mid-20s. Nearly a third used cannabis regularly enough, and for long enough, to enable assessment of associations between common adverse psychosocial and mental health outcomes and regular cannabis use. The study also collected detailed information on the personal and social situations of the cohort that enabled the researchers to assess whether the associations they observed between daily cannabis use and adverse outcomes could be explained by pre-existing differences between those who had and had not used cannabis regularly. This study has consistently found associations between daily cannabis use and poor mental health and psychosocial outcomes. Daily cannabis users had poorer educational attainment in adolescence and poorer employment outcomes in young adulthood, were more likely to use other illicit drugs, and were more likely to report more symptoms of psychosis, depression and suicide. Many of these risks increased with the intensity of cannabis use, and these associations persisted after statistical adjustment for plausible confounding factors. Many of these results have been replicated in the Dunedin birth cohort (e.g. [2]), and in longitudinal studies in other countries such as Australia (e.g. [3]), Germany [4] and the Netherlands [5]. Fergusson and colleagues show that the adverse health effects of cannabis are most concentrated among daily users (nearly 20 % of those who ever used the drug). This pattern was most common among young people who began using cannabis in their mid-teens and continued to use daily throughout young adulthood. Not all cannabis users experienced harm: many adolescent users did not use cannabis regularly enough or for long enough to do so; and a substantial proportion of adult cannabis users, the majority of whom reported using cannabis less than daily, did not report any harms related to their cannabis use. The cannabis policy debate has been presented in many countries as a forced choice between two packages of belief: (1) that cannabis use does not harm users, and so it should be legalized to avoid users acquiring criminal records; and (2) that cannabis use can harm some users, and so we should continue to prohibit its use [1]. This framing has often hindered a fair appraisal of the adverse health effects of cannabis. Evidence on the harms of cannabis use cannot decide cannabis policy [6]. The policy choice will depend upon societal beliefs about the priority that should be given to competing social values, such as, preserving individual freedom and protecting human health and well-being. It will also depend on political views on the extent to which the state should use criminal law to prevent adults from & Wayne Hall w.hall@uq.edu.au

Persistent and Long-Term Neuropsychiatric Implications of Cannabis Use in Adolescents

Cannabis is the most widely used illicit substance and one of the most commonly used psychoactive substances in the world, preceded only by alcohol, tobacco and caffeine. Recent changes in legislation regarding cannabis use in Canada and potential upcoming changes worldwide may have a further impact on the prevalence of cannabis use. Thus, it is critical to understand the risks and potential adverse health effects of acute and long-term cannabis use. Current literature is lacking in many areas surrounding cannabis use, and for the most part is unable to provide clear associations once confounding variables are considered. Here we provide a general overview of the history of cannabis, the physical and mental health consequences, and the risks to specific groups. A scoping search of published articles in PubMed from the start date (1946) until 2018. Current evidence supports an association between cannabis use and mild respiratory and cardiac effects, but no clear increased risk of cancer. Psychiatric disorders, including schizophrenia and anxiety, show associations with cannabis use; however, a causal effect of cannabis use is unclear. While no evidence for increased risk in pregnancy has been found, risk is still undetermined. Youth may be at a greater risk as earlier initiation of use increases the risk of adverse health effects. Overall, evidence for direct and long-term adverse effects of cannabis use is minimal and additional longitudinal studies will be required to better delineate unidentified effects.

First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups. We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use. Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5). FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.

Orbitofrontal Cortex and Neuromaturation: A Gateway to Risk?

Cannabis and Brain Health: What Is Next for Developmental Cohort Studies?

Background: Cannabis use has been linked to anxiety and mood disorders (AMD) in clinical cases, but little research on this relationship has been reported at the epidemiological level. Objectives: We examined the relationship between self-reported frequency of cannabis use and risk for AMD in the general Ontario adult population. Methods: Data were based on the CAMH Monitor survey of Ontario adults from 2001 to 2006 (n = 14,531). AMD was assessed with the 12-item version of the General Health Questionnaire (GHQ12). Frequency of cannabis use within the past year was grouped into five categories: No use (abstainer), less than once a month but at least once a year, less than once a week but at least once a month, less than daily but at least once a week, almost every day to more than once a day. Logistic regression analysis of AMD and cannabis use was implemented while controlling for demographics and alcohol problems. Results: AMD was most common among heavy cannabis users (used almost every day or more) (18.1%) and lowest for abstainers (8.7%). Compared to abstainers, the risk of AMD was significantly greater for infrequent cannabis users (OR = 1.43) and heavy cannabis users (OR = 2.04) but not for those in between. Conclusion: These data provide epidemiological evidence for a link between both light and heavy cannabis use and AMD. Scientific Significance: Recognizing the comorbidity of heavy cannabis use and AMD should facilitate improved treatment efforts. Our results also suggest the possibility that, for some individuals, AMD may occur at relatively low levels of cannabis use.

Cannabinoid Hyperemesis Syndrome Is Associated With High Disease Burden: An Internet-Based Survey.

Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use. To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US. This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015). Young adults (aged 22-36 years) with magnetic resonance imaging (MRI), urine toxicology, and cannabis use data were included in the analysis. Data were analyzed from January 31 to July 30, 2024. History of heavy cannabis use was assessed using the Semi-Structured Assessment for the Genetics of Alcoholism, with variables for lifetime history and diagnosis of cannabis dependence. Individuals were grouped as heavy lifetime cannabis users if they had greater than 1000 uses, as moderate users if they had 10 to 999 uses, and as nonusers if they had fewer than 10 uses. Participants provided urine samples on the day of scanning to assess recent use. Diagnosis of cannabis dependence (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was also included. Brain activation was assessed during each of the 7 tasks administered during the functional MRI session (working memory, reward, emotion, language, motor, relational assessment, and theory of mind). Mean activation from regions associated with the primary contrast for each task was used. The primary analysis was a linear mixed-effects regression model (one model per task) examining the association of lifetime cannabis and recent cannabis use on the mean brain activation value. The sample comprised 1003 adults (mean [SD] age, 28.7 [3.7] years; 470 men [46.9%] and 533 women [53.1%]). A total of 63 participants were Asian (6.3%), 137 were Black (13.7%), and 762 were White (76.0%). For lifetime history criteria, 88 participants (8.8%) were classified as heavy cannabis users, 179 (17.8%) as moderate users, and 736 (73.4%) as nonusers. Heavy lifetime use (Cohen d = -0.28 [95% CI, -0.50 to -0.06]; false discovery rate corrected P = .02) was associated with lower activation on the working memory task. Regions associated with a history of heavy use included the anterior insula, medial prefrontal cortex, and dorsolateral prefrontal cortex. Recent cannabis use was associated with poorer performance and lower brain activation in the working memory and motor tasks, but the associations between recent use and brain activation did not survive false discovery rate correction. No other tasks were associated with lifetime history of heavy use, recent use, or dependence diagnosis. In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long lasting.

The major adverse acute psychological effects of cannabis use are as follows: ♦ Anxiety, dysphoria, panic, and paranoia, especially in naive users ♦ Impairment of attention, memory, and psychomotor performance while intoxicated ♦ An increased risk of accident if an intoxicated person attempts to drive a vehicle. The major psychological effects of daily heavy cannabis use over many years remain contested but probably include the following: ♦ A cannabis-dependence syndrome ♦ Subtle forms of cognitive impairment that affect attention and memory and which persist while the user remains chronically intoxicated ♦ Impaired educational achievement in adolescents with a history of poor school performance, whose achievement may be limited by the cognitive impairments produced by chronic intoxication with cannabis ♦ Among those who initiate cannabis use in the early teens, a higher risk of progressing to heavy cannabis and other illicit drug use, and becoming dependent on cannabis.

To conduct a comprehensive search of the peer-reviewed literature to assess risk of cannabis-related mortality. Systematic peer-reviewed literature searches were conducted in Medline, EMBASE and PsycINFO to identify data on mortality associated with cannabis use. Search strings for cannabis and mortality were used. Searches were limited to human subjects and the publication timeframe of January 1990 to January 2008. Reference lists of review articles and of specific studies deemed important by colleagues were searched to identify additional studies. A list of the selected articles was emailed to experts in the field asking for comment on completeness. There is insufficient evidence, particularly because of the low number of studies, to assess whether the all-cause mortality rate is elevated among cannabis users in the general population. Case-control studies suggest that some adverse health outcomes may be elevated among heavy cannabis users, namely, fatal motor vehicle accidents, and possibly respiratory and brain cancers. The evidence is as yet unclear as to whether regular cannabis use increases the risk of suicide. There is a need for long-term cohort studies that follow cannabis using individuals into old age, when the likelihood of any detrimental effects of cannabis use are more likely to emerge among those who persist in using cannabis into middle age and older. Case-control studies of cannabis use and various causes of mortality are also needed.

Cannabis acutely impairs cognitive performance so it is possible that chronic use may cause longer-lasting cognitive impairment. This possibility seemed to be supported by clinical observations in the USA during the early 1970s (e.g. Kolansky and Moore, 1971) that young adults who had used cannabis weekly or more often had poor attention span, poor concentration, and confusion (Kolansky and Moore, 1971). More recently, long-term cannabis users seeking help to stop using cannabis report impaired memory and thinking (Stephens et al, 2000). The difficulty with these reports has been in ruling out the possibilities that these cognitive impairments preceded cannabis use or that they were due to other drug use. Cross-cultural studies One research strategy in searching for any cognitive effect of cannabis has been to assess the cognitive performance of heavy cannabis users in cultures with a tradition of such use. An early report by Soueif (1971) illustrates the problems with this strategy. Soueif studied Egyptian male prisoners of whom 850 were hashish smokers and 839 controls. The hashish users performed more poorly than the controls on 10 out of 16 measures of cognitive performance (Soueif, 1971) but the two groups differed in other ways that may have affected cognitive performance, namely, the hashish users were less well-educated and more likely to use opiates and alcohol than the controls (Carlin, 1986). In the late 1960s three cross-cultural studies were conducted in Jamaica (Rubin and Comitas, 1975), Greece (Kokkevi and Dornbush, 1977) and Costa Rica (Satz et al., 1976) to assess the effects of chronic cannabis use on cognitive functioning. It was assumed that any cognitive effects of chronic daily cannabis use would be apparent in users with a long history of heavy cannabis use, a pattern that was common in these cultures. These cross-cultural studies users provide equivocal evidence of subtle cognitive impairment among long-term cannabis users. Some studies failed to find any differences (e.g. Rubin and Comitas, 1975) and the others found modest cognitive impairment in persons with a long history of heavy cannabis use (Page et al., 1988).

Event Abstract Back to Event Impaired verbal learning and reduced medial temporal volumes in long-term heavy cannabis users Murat Yücel1, 2*, M. Solowij3, 4, S. Whittle1, 2, C. Respondek3, Alex Fornito2, C. Pantelis2 and D. I. Lubman1 1 ORYGEN Research Centre, Australia 2 The University of Melbourne and Melbourne Health , Australia 3 University of Wollongong , Australia 4 Schizophrenia Research Institute, Australia Background: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term impact on the human brain. Our aim was to determine whether long-term and heavy cannabis use is associated with verbal learning deficits and gross anatomical abnormalities in two cannabinoid receptor rich regions of the brain, the hippocampus and amygdala. Method: A cross-sectional design using high-resolution (3-Tesla) structural magnetic resonance imaging (MRI) was utilised. Participants were recruited from the general community and scanned at a hospital research facility. Fifteen carefully selected long-term (>10 years duration) and heavy (>5 joints per day) cannabis-using males (mean age 39.8 years; 19.7 years of regular use) with no history of polydrug abuse or neurological/mental disorder, and 16 matched non-using healthy volunteers (mean age 36.4 years). Volumetric measures of hippocampus and amygdala, combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured. Results: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P=0.001) with a relatively (and significantly; P=0.018) greater magnitude of reduction in the former (12.0% in hippocampus vs 7.1% in amygdala). Left hippocampal volume was inversely associated with cumulative dose of cannabis use over the previous 10 years (P=0.014), as well as subthreshold positive psychotic symptoms (P<0.001). Positive symptom scores were also associated with cumulative dose of cannabis used (P= 0.048). While cannabis users performed significantly worse than controls on verbal learning (P= 0.0005), this did not correlate with regional brain volumes in either group. Conclusions: Our results provide new evidence of dose-related structural abnormalities in the hippocampus and amygdala of long-term heavy cannabis users, and corroborate similar findings within the animal literature. These findings indicate that heavy daily cannabis use over protracted periods exerts harmful effects on brain tissue and mental health. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Turkey, 1 Sep - 5 Sep, 2008. Presentation Type: Oral Presentation Topic: Memory & Learning Citation: Yücel M, Solowij M, Whittle S, Respondek C, Fornito A, Pantelis C and Lubman DI (2008). Impaired verbal learning and reduced medial temporal volumes in long-term heavy cannabis users. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.259 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Dec 2008; Published Online: 09 Dec 2008. * Correspondence: Murat Yücel, ORYGEN Research Centre, Melbourne, VIC., Australia, murat.yucel@monash.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Murat Yücel M. Solowij S. Whittle C. Respondek Alex Fornito C. Pantelis D. I Lubman Google Murat Yücel M. Solowij S. Whittle C. Respondek Alex Fornito C. Pantelis D. I Lubman Google Scholar Murat Yücel M. Solowij S. Whittle C. Respondek Alex Fornito C. Pantelis D. I Lubman PubMed Murat Yücel M. Solowij S. Whittle C. Respondek Alex Fornito C. Pantelis D. I Lubman Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.