Effect of Adolescent Cannabis Use on Brain Functions

Effect of teenager Cannabis Use on star FunctionsCannabis Use During Adolescence A recapitulation of Impacts on Brain Functions and Associated OutcomesRecent suppurate convey seen a dramatic increase in the social acceptability of marijuana usold age in the joined States, with several states having already legalized recreational gist ab wasting disease of the substance and several more projected to do so within the next several years (Leyton, 2016). Concurrently, in that location has been an increase in the amount of juveniles who report using hempen necktie, with recent data indicating that 39% of high school seniors report using hangmans rope within the olden year and 6-7% reporting daily or near daily hempen necktie practise (Johnston & OMalley, 2015). Despite increasing utilization of marihuana products for pain focal point and other ailments (Hwang & Clarke, 2016), some in the scientific community defecate expressed concern about the potential ramifications of recreational legalization of hangmans halter. Chief amongst these concerns is the idea that upstarts willing have very easy access to increasingly potent hempen necktie and synthetic cannabis products (Sobesky & Gorgens, 2016), as a great deal of look has indicated that the wont of cannabis poses several take a chances specific to individuals in the teenaged age range (see Levine, Clemenza, Rynn, & Lieberman, 2017). This paper will summarize the research examining the impact of cannabis usage on the developing girlish brilliance and potential associated outcomes, particularly in the areas of information/executive function, care and picture, psycho maladys, and future substance hold/dependence. The Adolescent Brain To understand the impact of cannabis use on the developing teenager hotshot, it is first-year necessary to understand the changes taking place in the brain during this readingal period. Not surprisingly, the period of adolescence is a era of tremend ous change in the circuitry of the brain. According to Arain et al. (2013), there is a significant amount of neuronal plasticity in the brain during adolescence, meaning the wiring of the brain is extremely adaptable to discipline and experience. Such plasticity, particularly in the prefrontal cortex, lends itself to difficulty thinking rationally and critically, practically leading to the impulsive decision-making that is characteristic of the adolescent years. In addition, the hypothalamic pituitary adrenal (HPA) axis, the system responsible for regulating human responses to stress, also undergoes significant using during the period of adolescence. Within this system, the amount and duration of adrenocorticotropic hormone (ACTH) and glucocorticoids run throughd in response to stress increase significantly as compared to other life periods (Romeo, 2013). before long before puberty, a surge ofsynaptogenesis and neuronal growth occurs in which grey amour in the brain thickenssu bstantially. From this pointthroughout the period of adolescence, the brain is continually rewired throughdendritic pruning and increased myelination of synapses, particularly in theprefrontal cortex (Arain et al., 2013 Lubman, Bonomo, & Yucel, 2007). In addition, white matter increases are seenin the corpus callosum (Arain et al., 2013). taken together, these changes increase the efficiency of communicationwithin the brain, allowing for the eventual select of more complexcognitive functioning, including improved impulse retain, operationalthinking, and working memory board (Hart, 2007 Lubman et al., 2007). In addition to the constant rewiring of braincircuitry that occurs during adolescence, the levels of three neurotransmitters dopamine, serotonin, and melatonin change during the adolescent period(Arain et al., 2013). According to Dahl(2003), dopamine and serotonin levels decrease during adolescence, resulting in aflame dysregulation, image disruptions, and difficulties with impulsecontrol. Melatonin levels, on the otherhand, increase, which in turn increases the amount of sleep that adolescentsneed to be fully re-charged. Given the massive changes that are occurring inthe brain during the period of adolescence, it is a time in which the brain isespecially susceptible to the use of substances, (Lubman et al., 2007) includingcannabis. Cannabis Action in the BrainBefore questioning the specific impacts ofcannabis use on the adolescent brain, it is important to understand howcannabis acts in the brain in general.First, the brain has an endogenous cannabinoid system (endocannabinoidsystem) made up of the ligands anandamide and 2-arachidonoyl glycerol (2-AG)and cannabinoid sensory receptors known as CB1 and CB2 receptors (Moreira & Lutz,2008). CB1 receptors are locatedthroughout the brain, but are particularly populous in the front region of thecerebral cortex, the basal ganglia, the cerebellum, the hypothalamus, the former cingulate cortex, and the genu s Hippocampus CB2 receptors are generallyfound throughout the bodys immune system (Hill et al., 2010 Iversen,2004). The endocannabinoid system playsa role in a anatomy of processes, including the regulation of the HPA axisstress response (Hill et al., 2010 Lee & Gorzalka, 2015), neuralplasticity, and learning and memory (Lu et al., 2008). According to Iversen (2004), thepsychoactive component in cannabis is 9-tetrahydrocannabinol (tetrahydrocannabinol). THC, as salutary as increasingly popularsynthetic cannabinoids, act as agonists on CB1 cannabinoid receptors in thebrain. Because CB1 receptors aregenerally presynaptic rather than postsynaptic, cannabinoids control therelease of certain neurotransmitters, including acetylcholine, L-glutamate,-aminobutyric sour (GABA), noradrenaline (norepinephrine), dopamine, and5-hydroxytryptamine (5-HT). The use of exogenous cannabinoids, such as marijuana or synthetic marijuana products,leads to an unnaturally long-lasting activation of CB1 re ceptors, ultimatelyinhibiting the release of the aforementioned neurotransmitters in selectedareas of the brain (Iversen, 2004). Inaddition to its impact on CB1 receptors and associated neurotransmitters, THC alsoappears to trigger the firing of dopaminergic neurons in the ventral tegmentalarea of the brain and the nucleus accumbens areas of the brain that areheavily implicated in the brains reward circuit associated with drug use. This effect is also seen with heroin,cocaine, amphetamines, and nicotine, suggesting that THC may also act on theopioid receptor system within the brain (Iversen, 2004).Impact on Cognition and Executive Function TasksThe literature has focused on severallarger areas of impact regarding cannabis use during adolescence, one of thesebeing the potential impacts on cognition and tasks of executive function. As previously mentioned, the brain undergoesa significant amount of change in the adolescent years, including the frequentre-wiring of neural connection s through neural pruning processes, particularlyin the prefrontal cortex. According toFilbey, McQueeny, DeWitt, and Mishra (2015), cannabis use during adolescencedisrupts this normal pruning process through its modulation ofneurotransmitters and inhibition of microglial processes. This results in abnormal connectivity withinthe brain, including a decrease in white matter volume and integrity (Gruber,Dahlgren, Sagar, Gonenc, & Lukas, 2014 Jacobus et al., 2009). Such changesresult in a number of cognitive impacts, including increased impulsivity,poorer reaction times, and increased errors on executive function tasks (e.g.,planning, organization, self-regulation, etc.) (Becker, Wagner,Gouzoulis-Mayfrank, Spuentrup, & Daumann, 2010 Gruber et al., 2014). Indeed, studies have indicated thatindividuals who begin marijuana use in ahead of time adolescence are at an increasedrisk for developing deficits in attention (Ehrenreich et al., 1999) and visualprocessing (Tapert, Granholm, Leedy, & Brown, 2002), and adjoin adecreased full scale IQ and verbal IQ in big(a)hood (Meier et al., 2012). Memory also appears to be affected by adolescent-onset cannabis use (Tait, Mackinnon, & Christensen, 2011), likely via its impact on the hippocampus a part of the brain heavily implicated in memory functions. Animal research has shown that the hippocampus is affected by cannabis use especially during the period of adolescence. In rats, adolescent pictorial matter to cannabis impacted the microstructure of the hippocampus as well as abnormalities in the way that proteins are expressed in the hippocampus (Quinn et al., 2008). Specifically, it appears that exogenous cannabinoids bind to CB1 receptors and inhibit the release of glutamate, then contributing to deficits in short-term memory (Hart, 2007) and negatively impacting performance on memory-related tasks (see Levine et al., 2017). Some animal studies indicate that lower levels of cannabis use (those most reflective of the actu al amount that adolescents use) are non predictive of long-lasting hippocampal changes. However, because current cannabis products are continuing to increase in potency (Levine et al., 2017), hippocampal changes and subsequent memory problems are topics of concern, especially with regard to adolescent users of cannabis. Working memory also appears to be impactedby cannabis use, particularly in individuals that began using cannabis beforethe age of sixteen. Becker et al. (2010)used functional magnetic resonance imaging to examine performance on a workingmemory task in individuals who began using cannabis before age sixteen(early-onset) as compared to individuals who began using cannabis later on the ageof sixteen (later-onset). Results ofthis study indicated that early-onset cannabis users exhibited increasedcortical activity in the parietal lobe as compared to later-onset cannabisusers. The researchers concluded thatthis increased cortical activity indicated decreased cortical ef ficiency inresponse to challenging working memory-related tasks in early-onset, but nonlater-onset, cannabis users (Becker et al., 2010). Such findings are consistent with a number ofstudies indicating that an earlier age of onset of cannabis use is associatedwith greater risk of negative impacts on cognitive functioning during adulthood(Ehrenreich et al., 1999 Fontes et al., 2011 Meier et al., 2012 Pope et al.,2003). Impact on the Development of Anxiety and DepressionSeveral studies indicate a connection among adolescent-onset cannabis use and the development of both disturbance anddepressive disorders (e.g., Brook, Rosen, & Brook, 2001 Degenhardt et al.,2013 Fairman, 2015 Hayatbakhshet al., 2007 Patton et al., 2002 van Laar, van Dorsselaer, Monshouwer, & de Graaf, 2007).Though past researchers have speculated about the directionality of thisrelationship, studies have consistently indicated that adolescent-onsetdepression is not predictive of later cannabis use (e.g., Degenhardt, Hall,& Lynskey, 2003 Moore et al., 2007 Womack, Shaw, Weaver, & Forbes,2016), negating the idea that depressive and/or anxiety symptoms lead to subscribement in cannabis use as a method acting of symptom relief. Instead, such findings promote the idea that cannabisuse during adolescence, in combination with other potential risk factors,increase the risk for the development of anxiety and depressive symptoms inadulthood (Levine et al., 2017). As withthe cognitive changes discussed in the previous section of this paper, it isearly-onset use of cannabis that appears to be riskiest with regard to thedevelopment of future anxiety and depressive symptoms (Hayatbakhsh et al.,2007 Patton et al., 2002). In an interesting study by Spechler et al.(2015), fMRIs were used to examine activity in the amygdalas of adolescent usersof cannabis. The researchers showedparticipants images of both angry and neutral faces, a well-known test ofamygdala activity and a well-regarded index of emotional proc essing. Results of this study indicated that comparedto the control group, adolescent cannabis users exhibited increased amygdalaactivity in response to the images of angry faces whereas the control groupshowed the same amount of amygdala activity when shown images of neutralfaces. Spechler et al. (2015) concludedthat adolescent cannabis use is associated with increased hypersensitivity tonegative affect. However, in this case,the directionality of the relationship is un readable it is possible that thesensitivity of the amygdala pre-dated the cannabis use and the cannabis use wasengaged in due to its anxiolytic effect.Conversely, it is possible that cannabis use led to increasedsensitivity in the amygdala. Either way,it appears that adolescent cannabis users are overly spiritualist to negativeaffect and the potential threat that accompanies it, which may explain theincreased incidence of depressive and anxious symptomatology in thispopulation. There are several potentialneurobiolog ical mechanisms explaining the relationship in the midst of adolescentcannabis use and the development of anxiety and depressive symptoms. One possibility is the impact of exogenouscannabinoids on the HPA axis system. Theendocannabinoid system regulates the responsivity of the HPA axis, which, aspreviously mentioned, undergoes significant development during the adolescentyears (Hill et al., 2010 Lee & Gorzalka, 2015 Romeo, 2013). Studies with both human and rodent subjectshave indicated that the use of exogenous cannabinoids during adolescence hasthe capacity to alter HPA axis stress responses, thus impacting emotionalityand the development of anxiety-related symptoms (Lee & Gorzalka, 2015).Lovelace et al. (2015) discuss anotherneurobiological mechanism that may underlie the relationship between adolescentcannabis use and the development of anxiety and depression. In a rodent study, these researchers examinedmaladaptations in the prefrontal cortex due to cannabis use by looking at presynaptic plasticity at glutamatergic synapses in adolescent rats. The results indicated that exposure toexogenous cannabinoids during adolescence led to over-activation of CB1receptors, which led to permanent changes in synapses in the prefrontalcortex. Overall, mice exposed toexogenous cannabinoids during adolescence showed a loss of presynapticplasticity, which impacts the brains ability to adapt to ever-changing environmentsand thus may contribute to an increased vulnerability of psychopathology duringadulthood (Lovelace et al., 2015). In an interesting rodent study conductedby Rubino et al. (2008), researchers found that exposure to THC duringadolescence was associated with decreased density and function of CB1 receptorsin the ventral tegmental area, the nucleus accumbens, and the amygdala. These areas of the brain are implicated inemotional processing and reward and are thus implicated in the development ofdepressive symptomatology. The behaviorof the rats in this study also mirrored depressive symptomatology. Specifically, rats exposed to THC duringadolescence exhibited both behavioural despair (which the researchers definedas time the rats were immobile) and anhedonia (as measured through decreasedconsumption of sucrose). interpreted together,it appears that several neurobiological mechanisms are at play in theconnection between adolescent cannabis use and the development of anxiety anddepressive symptoms. Impact on the Development of Psychotic DisordersA substantial body of literature has indicated a connection between the use of cannabis during adolescence and the later development of psychotic person disorders (e.g., van Os et al., 2002 Henquet et al., 2005 Stefanis et al., 2004). This is especially true for individuals who are already genetically predisposed to develop psychotic disorders (Henquet et al., 2005) though the connection has also been found in individuals that do not have this genetic predisposition (van Os et al., 2002). As with the impact on cognition and on anxiety/depressive symptoms, it appears that early-onset cannabis use (Arseneault et al., 2002 Moore et al., 2007) as well as heavier (i.e. daily or near-daily) use pose the greatest risk for the later development of a psychotic disorder (Moore et al., 2007 van Os et al., 2002).Rubino and Parolaro (2014) discuss the possible neurobiological mechanisms behind the connection between adolescent cannabis use and the development of psychotic disorders. In general, it appears that the use of exogenous cannabinoids during adolescence disrupts the maturational processes occurring in the brain during this time, especially in the hippocampus and the prefrontal cortex two areas of the brain that are implicated in the psychotic disorder schizophrenia, in particular. The endocannabinoid system itself undergoes a significant amount of change during the adolescent years thus, exogenous cannabinoid exposure during this time period has the potential to alter the long-term functionality of CB1 receptors, which then impacts the activity of several neurotransmitters implicated in psychotic symptomatology, especially dopamine (Rubino & Parolaro, 2014). Additionally, being exposed to cannabis during the adolescent period has been shown to disrupt prepulse inhibition (the ability to accurately perceive and process stimuli) and down-regulate GABAergic activity in the prefrontal cortex both symptoms commonly seen in individuals with schizophrenia (Morales-Muoz et al., 2014 Zamberletti et al., 2014). As previously mentioned, individuals who have a genetically predisposed vulnerability to develop psychotic disorders are at an especially high risk to do so if they engage in cannabis use during adolescence (Henquet et al., 2005). For example, individuals who have a specific variant of the gene for catechol-O-methyltransferase (COMT), which breaks down dopamine the neurotransmitter implicated in schizophrenia are at a much higher risk for developing the disor der if they used cannabis during adolescence as compared to individuals who do not have that specific variant of the gene for COMT (Caspi et al., 2005). Another gene that influences the relationship between adolescent cannabis use and psychosis is the ATK1 gene, which affects dopamine breakdown in the striatum. According to DiForti et al. (2012), cannabis users with a certain variant of the ATK1 gene were seven times more likely to develop psychosis as compared to individuals with this gene variant who did not use cannabis. Clearly, in individuals that already possess these specific genetic variants, cannabis use during adolescence can be the trigger that leads to the expression of these genes and the development of psychotic symptoms and/or disorders. In addition, adults with psychotic disorders who used cannabis during adolescence are at a greater risk for recur of psychotic symptoms, poorer adherence to treatment, and increased rates of hospitalization related to their diagnosi s (Hunt, Bergen, & Bashir, 2002 Lewis, Tarrier, & Drake, 2005 Wade et al., 2006). Impact on the Future Development of Substance Use DisordersSeveral studies have indicated a link between adolescent cannabis use and the later development of a substance use disorder. Again, this relationship is especially strong for individuals that engage in cannabis use in early adolescence and who engage in heavy (i.e., daily or near-daily) use (Fergusson, Boden, & Horwood, 2006 Hall & Lynskey, 2005 Stuart & Green, 2008). Past researchers have speculated upon various explanations for this trend, including the so-called gateway hypothesis. In general, the gateway hypothesis assumes that individuals who use harder drugs such as heroin and cocaine almost always started their use of substances with using cannabis, and that this link is explicitly causal (Van Gundy & Rebellon, 2010). This hypothesis is based on research findings indicating that the use of cannabis during adolescence often predates the u se of other illicit substances, including heroin, methamphetamines, and cocaine (Fergusson et al., 2006). Though the causality of this link has been repeatedly questioned in the literature (e.g., Morral, McCaffrey, & Paddock, 2002 Van Gundy & Rebellon, 2010), many researchers have attempted to explain the mechanisms behind the early use of cannabis and the later use of other substances and/or development of a substance use disorder. There are countless potential psychosocial explanations for this connection (e.g., peer pressure, propensity toward risk-taking behaviors, availability of substances, etc.) however, for the purposes of this paper, the potential neurobiological mechanisms behind the connection will be discussed.The major possible neurobiological mechanism behind the connection between early cannabis use and the later development of a substance use disorder has to do with the effect of cannabis on the brains opioidergic system. A great deal of animal research has indicate d that the endocannabinoid system and the opioidergic system are intricately linked. For example, Pickel, Chan, Kash, Rodriguez, and Mackie (2004) and Rodriguez, Mackie, and Pickel (2001) found that CB1 receptors and opioid receptors are found on the same neurons in both the striatum and the ventral tegmental area, and Cossu et al. (2001) and Ledent et al. (1999) found that animals without CB1 receptor genes do not self-administer opioids. Drawing upon this clear connection betweenthe endocannabinoid and opioidergic brain systems, Ellgren, Spano, and Hurd(2007) investigated the hypothesis that cannabis exposure during adolescencechanges opioid-related neural functions and leads to increased likelihood of lateropioid use. Findings of this researchconfirmed that rats exposed to THC during the adolescent periodself-administered greater amounts of heroin compared to the control group. Moreover, findings indicated that ratsexposed to THC in adolescence showed a persistent disturbance in the activityof enkephalin, which is the endogenous opioid neuropeptide associated withreward behaviors and sybaritic states. Findingsalso indicated that THC exposure led to changes in the functions of opioidreceptors such that heroin use was more reinforcing (via dopamine release) forrats exposed to THC during adolescence as compared to the control group. Taken together, these results indicate thatcannabis use during adolescence leads to a greater vulnerability to the reinforcingeffects of opioids during adulthood, potentially leading to a greater risk fordependence and likelihood of relapse of substance use disorders. ConclusionDespite the increasing popularity of cannabis use, both for medicinal and recreational purposes (Hwang & Clarke, 2016 Leyton, 2016), it is important to consider the resulting increased availability of cannabis to individuals during the sensitive period of adolescence. Given the profound changes occurring in the brain during adolescence (Arain et al., 2013 Dahl, 2003 Hart, 2007 Lubman et al., 2007), teenagers are particularly susceptible to the influence of substances, which may lead to lasting changes in the brains functioning. Such changes are associated with poor outcomes in several areas, including deficits in performance on executive function tasks (Becker et al., 2010 Ehrenreich et al., 1999 Fontes et al., 2011 Gruber et al., 2014 Meier et al., 2012 Pope et al., 2003 Tapert et al., 2002), an increased risk for the development of anxiety and/or depressive symptoms (Brook et al., 2001 Degenhardt et al., 2013 Fairman, 2015 Hayatbakhsh et al., 2007 Patton et al., 2002 van Laar, van Dorsselaer, Monshouwer, & de Graaf, 2007), an increased risk for the development of a psychotic disorder (Arseneault et al., 2002 Caspi et al., 2005 DiForti et al., 2012 Henquet et al., 2005 Moore et al., 2007 Rubino & Parolaro, 2014 Stefanis et al., 2004 van Os et al., 2002), and an increased risk for future substance use/dependence (Fergusson et al., 2 006 Hall & Lynskey, 2005 Stuart & Green, 2008). Such considerations may have important implications for policy development related to the legalization of cannabis. 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