THEMED ISSUE: CANNABINOIDS REVIEW Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental modelsb ph_721 511..522 (original) (raw)
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Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models
Cannabis is one of the most widely used illicit drugs among adolescents, and most users first experiment with it in adolescence. Adolescence is a critical phase for brain development, characterized by neuronal maturation and rearrangement processes, such as myelination, synaptic pruning and dendritic plasticity. The endocannabinoid system plays an important role in fundamental brain developmental processes such as neuronal cell proliferation, migration and differentiation. Therefore changes in endocannabinoid activity during this specific developmental phase, induced by the psychoactive component of marijuana, D 9 -tetrahydrocannabinol, might lead to subtle but lasting neurobiological changes that can affect brain functions and behaviour. In this review, we outline recent research into the endocannabinoid system focusing on the relationships between adolescent exposure to cannabinoids and increased risk for certain neuropsychiatric diseases such as schizophrenia, as highlighted by both human and animal studies. Particular emphasis will be given to the possible mechanisms by which adolescent cannabis consumption could render a person more susceptible to developing psychoses such as schizophrenia. Adolescent cannabis use and psychosis 512 DT Malone et al British Journal of Pharmacology (2010) 160 511-522 Adolescent cannabis use and psychosis DT Malone et al 513 British Journal of Pharmacology (2010) 160 511-522 Adolescent cannabis use and psychosis DT Malone et al 519 British Journal of Pharmacology (2010) 160 511-522 Adolescent cannabis use and psychosis 522 DT Malone et al British Journal of Pharmacology (2010) 160 511-522
Neurobiological alterations at adult age triggered by adolescent exposure to cannabinoids
Pharmacological Research, 2009
Marijuana is consistently the most widely used illicit drug among teenagers and most users first experiment it in adolescence. Adolescence is the period between childhood and adulthood, encompassing not only reproductive maturation, but also cognitive, emotional and social maturation and is characterized by a brain in transition that differs anatomically and neurochemically from that of the adult. The endocannabinoid system plays an important role in this critical phase for cerebral development, therefore a strong stimulation by the psychoactive component of marijuana, delta-9-tetrahydrocanabinol, that acts through the cannabinoid system, might lead to subtle but lasting neurobiological changes that can affect adult brain functions and behaviour. The literature here summarized, exploiting animal models of cannabis consumption, points to the presence of subtle changes in the adult brain circuits after heavy cannabis consumption in adolescence. These alterations lead to impaired emotional and cognitive performance, enhanced vulnerability for the use of more harmful drugs of abuse, and may represent a risk factor for developing schizophrenia in adulthood. The few studies examining the neurobiological basis of the altered behaviours demonstrate the presence of stable alteration in the endocannabinoid system that can trigger subsequent alteration in synaptic protein and synaptic morphology, thus altering the responsiveness of selected brain areas to different internal and external stimuli. These pre-clinical observations are strengthened by literature in humans where longitudinal studies often support the experimental results. There is an urgent need of multidisciplinary approaches combining behaviour with neurochemical and genetic studies to build a scientific based opinion on the long-lasting consequences of cannabis use in adolescence.
Neuroscience & Biobehavioral Reviews, 2020
Many factors and their interaction are linked to the aetiology of schizophrenia, leading to the development of animal models of multiple risk factors and adverse exposures. Differentiating between separate and combined effects for each factor could better elucidate schizophrenia pathology, and drive development of preventative strategies for high-load risk factors. An epidemiologically valid risk factor commonly associated with schizophrenia is adolescent cannabis use. The aim of this review is to evaluate how early-life adversity from various origins, in combination with adolescent cannabinoid exposure interact, and whether these interactions confer main, synergistic or protective effects in animal models of schizophrenia-like behavioural, cognitive and morphological alterations. Patterns emerge regarding which models show consistent synergistic or protective effects, particularly those models incorporating early-life exposure to maternal deprivation and maternal immune activation, and sex-specific effects are observed. It is evident that more research needs to be conducted to better understand the risks and alterations of interacting factors, with particular interest in sex differences, to better understand the translatability of these preclinical models to humans.
Cannabis and adolescent brain development
Pharmacology & therapeutics, 2015
Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identi...
Long-term consequences of adolescent cannabinoid exposure in adult psychopathology
Frontiers in Neuroscience, 2014
Marijuana is the most widely used illicit drug among adolescents and young adults. Unique cognitive, emotional, and social changes occur during this critical period of development from childhood into adulthood. The adolescent brain is in a state of transition and differs from the adult brain with respect to both anatomy (e.g., neuronal connections and morphology) and neurochemistry (e.g., dopamine, GABA, and glutamate). These changes are thought to support the emergence of adult cerebral processes and behaviors. The endocannabinoid system plays an important role in development by acting on synaptic plasticity, neuronal cell proliferation, migration, and differentiation. Delta-9-tetrahydrocanabinol (THC), the principal psychoactive component in marijuana, acts as a partial agonist of the cannabinoid type 1 receptor (CB1R). Thus, over-activation of the endocannabinoid system by chronic exposure to CB1R agonists (e.g., THC, CP-55,940, and WIN55,212-2) during adolescence can dramatically alter brain maturation and cause long-lasting neurobiological changes that ultimately affect the function and behavior of the adult brain. Indeed, emerging evidence from both human and animal studies demonstrates that early-onset marijuana use has long-lasting consequences on cognition; moreover, in humans, this use is associated with a twofold increase in the risk of developing a psychotic disorder. Here, we review the relationship between cannabinoid exposure during adolescence and the increased risk of neuropsychiatric disorders, focusing on both clinical and animal studies.
Cerebral cortex (New York, N.Y. : 1991), 2016
Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociatio...
University of Toronto Medical Journal, 2019
Adolescence represents one of the most crucial periods of human brain development. This unique neurodevelopmental window involves a complex interplay of synaptic re-modelling, the establishing of cortical and sub-cortical emotional processing and cognitive neural circuits along with a greater propensity for engaging in risky behaviours and experimentation with illicit drugs. A growing body of both clinical and pre-clinical evidence has demonstrated that exposure to cannabis, and more specifically, Δ-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, can strongly increase the likelihood of developing serious neuropsychiatric disorders in later life. Adolescent THC exposure is linked to long-term cognitive impairments, emotional dysregulation, mood disorders and increased vulnerability to schizophrenia. The interplay between adolescent THC exposure and mental health risks have been linked to a wide array of underlying neurobiological pathologies, including st...
International Journal of Molecular Sciences, 2021
Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these can...
Long lasting consequences of cannabis exposure in adolescence
Molecular and Cellular Endocrinology, 2008
Despite the increasing use of cannabis among adolescents, there are little and often contradictory studies on the long-term neurobiological consequences of cannabis consumption in juveniles. Adolescence is a critical phase for cerebral development, where the endocannabinoid system plays an important role influencing the release and action of different neurotransmitters. Therefore, a strong stimulation by the psychoactive component of marijuana, delta-9-tetrahydrocanabinol (THC), might lead to subtle but lasting neurobiological changes that can affect adult brain functions and behaviour.
Cannabis and the developing brain: Insights from behavior
European Journal of Pharmacology, 2008
The isolation and identification, in 1964, of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, opened the door to a whole new field of medical research. The exploration of the therapeutic potential of THC and other natural and synthetic cannabinoid compounds was paralleled by the discovery of the endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, which offered exciting new insights into brain function. Besides its well-known involvement in specific brain functions, such as control of movement, memory and emotions, the endocannabinoid system plays an important role in fundamental developmental processes such as cell proliferation, migration and differentiation. For this reason, changes in its activity during stages of high neuronal plasticity, such as the perinatal and the adolescent period, can have long-lasting neurobehavioral consequences. Here, we summarize human and animal studies examining the behavioral and neurobiological effects of in utero and adolescent exposure to cannabis. Since cannabis preparations are widely used and abused by young people, including pregnant women, understanding how cannabinoid compounds affect the developing brain, leading to neurobehavioral alterations or neuropsychiatric disorders later in life, is a serious health issue. In addition, since the endocannabinoid system is emerging as a novel therapeutic target for the treatment of several neuropsychiatric diseases, a detailed investigation of possible adverse effects of cannabinoid compounds on the central nervous system (CNS) of immature individuals is warranted.