THE INDIVIDUAL

NEUROBIOLOGICAL EFFECTS OF

SUBSTANCE ABUSE ON

ADOLESCENTS:

A Comparative study of Marijuana

and Oxycontin abuse and the

development of Conduct Disorder

related behaviors among rural

adolescents

My signature below certifies that I have complied with the University of

Pennsylvania’s Code of Academic Integrity in completing this paper.

Name: Stephanie Tham Wei Jun

Signature: Date: 12/13/2015

Abstract

As the brain of an adolescent does not reach maturity until past the age of 20, an

adolescent’s tendency to take on reckless behaviors may impede his neurological

development. Antisocial adolescents in particular have impulsive stimulation seeking

behaviors which gives rise to substance abuse. Several studies have supported the view

that alcohol and tobacco abuse is associated with impaired neurological development

which predisposes antisocial behavior. However, with the abuse of prescription and

illicit drugs on the rise especially in rural areas, there is a potential risk of similar

neurodevelopment deficiencies among these adolescents as well. This paper brings to

attention these deficiencies stemming from Oxycodone and Marijuana abuse which

could induce Conduct Disorder related behaviors among rural adolescents. Further, a

comparison between these 2 types of abuse lead to the conclusion that rural Oxycodone

abusers could potentially face a higher risk of developing conduct disorder related

behaviors.

Introduction

Antisocial adolescents have been extensively studied to understand the biological

markers which might indicate if a child is antisocial. Chronic or repetitive antisocial

behaviors entailing aggression, deceit or theft among early adolescents are diagnosed as

conduct disorder based on the Diagnostic and statistical manual of mental disorders

(DSM-V) (Kazdin, 1995). A study conducted revealed that one such marker was low

resting heart rate among antisocial adolescents (Oritz & Raine, 2004). As a low resting

heart rate indicates that antisocial adolescents have lower arousal levels than normal

and tend to be more impulsive stimulation seeking, these adolescents will seek out

more extreme forms of stimulation such as substance abuse instead.

Substance abuse has been both directly and indirectly associated to conduct problems

in an individual depending on the drug abused. For the case of alcohol, maternal alcohol

abuse can give rise to fetal alcohol syndrome which is characterised by central nervous

system dysfunction which contributes to mental retardation and conduct problems

among these offsprings (Hillman, Pauly, & Kerstein, 1989; Streissguth et al., 1991). A

more direct effect of alcohol abuse is seen in conduct disorder adolescents where

alcohol abuse among this group of adolescents lead to the progression of their diagnosis

to adult antisocial personality disorder or worsening of conduct misbehaviors (Finn,

Mazas, Justus, & Steinmetz, 2002; Myers, Stewert, & Brown, 1998).

Similar results were obtained for smokers as well. Maternal smoking leads to a four-

fold increased risk of conduct disorder among their offsprings (Weissman, Warner,

Wickramaratne, & Kandel, 1999). Smoking by adolescents themselves have also been

shown to result in an increase in conduct disorder related behaviors such as

impulsivity, risk taking and novelty seeking characteristics (Turner, Mermelstein, &

Flay, 2004). Thus, these studies hints at the possibility of the reversible relationship

between substance abuse and antisocial adolescents, where substance abuse

predisposes antisocial behavior and vice versa (Mason & Windle, 2002).

In this paper, I would analyse two other forms of substance abuse, namely marijuana

and oxycodone which are the next two most commonly abused drugs after alcohol and

tobacco (Duffy’s Napa Valley Rehab, 2012). In the United States alone, 19.8 million

people aged 12 and above are marijuana abuses while 2.05 million people suffers from

opioid abuse excluding heroine (National Institute of Drug Abuse, 2014). In particular,

this paper would analyse the individual effects of marijuana and oxycodone on

adolescents in terms of changes in their brain function and how their environment

especially characteristics of rural environment might exacerbate substance abuse which

could relate to an increase in conduct disorder related behaviors.

Marijuana and brain function

Chronic marijuana abuse have been shown to result in an increased risk of

neurocognitive impairment. For adolescents who abused marijuana before the age of

17, records have shown that they have smaller whole brain size and reduction in grey

matter when compared to non-abusers (Jacobus, Bava, Cohen-Zion, Mahmood, & Tapert,

2009). Specifically, in marijuana abusers, there is significant volume reduction in the

amygdala in response to heavy marijuana use. (Cousijn et al., 2012). Reduction of grey

matter in these areas are closely related to a lack of empathy which is a characteristic of

adolescents diagnosed with conduct disorder (Sterzer, Stadler, Poustka, & Kleinschmidt,

2007). Thus, Marijuana abuse can result in the reduction of such areas leading to an

increase in lack of empathy.

Morover, marijuana abuse is linked to the increase of white matter volume as well

especially in the prefrontal region (Jacobus et al., 2009; Medina, Nagel, Park, McQueeny,

& Tapert, 2007). This increase in white matter is proven to be a neurobiological basis of

lying where liars have a 22 to 26% increase in their prefrontal white matter as

compared to non-liars (Yang, 2005). Therefore, Marijuana abuse can also lead to

increased pathological lying which is another key characteristic of Conduct Disorder

listed under the DSM-V Conduct Disorder.

The prefrontal cortex itself can undergo various alteration during marijuana abuse

(Jacobus et al., 2009). Such alterations is linked to deficits in planning, emotional

regulation and inhibition of actions. Evidence shows that female adolescent abusers

have a 4% increase in prefrontal cortex volume as compared to controls. In addition,

when the go/no-go task of response inhibition was conducted, Marijuana abusers

showed greater response in the no-go trials which indicated poorer neuropsychological

performance (Squeglia, Jacobus, & Tapert, 2009). This shows increased impulsivity and

lack of emotional management which could lead to greater aggressive behaviour among

adolescent abusers.

Another key brain functioning deficit among marijuana abusers is a volume reduction in

the right posterior cingulate cortex (Jacobus et al., 2009). This region of the brain is

closely linked to moral reasoning and so a reduction in volume indicates that there is a

decrease in moral reasoning capabilities among abusers (De Brito et al., 2008).

Moreover, the posterior cingulate cortex is also essential in allowing an individual to

assess his or her environment (Vogt, Finch, & Olson, 1992). A decrease in volume in this

region might in turn contribute to an increase in recklessness among these individuals.

This under-activation in the posterior cingulate gyrus is also observed in conduct

disorder adolescents which further supports the importance of this region of the brain

in mediating conduct disorder (Rubia et al., 2008). Therefore, it is more likely for

adolescent marijuana abusers to behave impulsively and to commit immoral acts such

as theft more easily.

Oxycodone and brain function

Oxycodone, on the other hand, exhibit its effects mainly in the reward centre of the

brain through the reward potentiating effects of consuming this drug (Wise, 1996). Such

a drug is able to increase the activation of dopaminergic neurons that are responsible

for eliciting a euphoric response in Oxycodone abusers (Hays, 2004). Oxycodone is

likely to exacerbate the abuse of this drug among adolescents as chronic abuse of this

drug will result in brain adaptation. Due to the overwhelming stimulation of neurons by

dopamine, the brain responses and adapts to this chronic stimuli by reducing the

number of dopaminergic receptors. Thus, decreasing the sensitivity of these neurons to

dopamine which indicates that among these abusers, there is a constant need for large

amounts of dopamine to achieve the required basal levels of these transmitters in the

brain (Griffin, 2012). This ultimately enhances the stimulation seeking behaviors among

antisocial adolescents.

Apart from increased stimulation of dopaminergic neurons, the amygdala plays a crucial

role as well in stimulating reward sensations among individuals. The central nucleus of

the amygdala contains a numerous amount of endogenous opioid receptors which is

able to interact with Oxycodone and so increases the reward cue to the brain. This

might enhance reward seeking behaviors among antisocial adolescents as well. This is

exemplified through a study carried out on rats that underwent opioid stimulation in

the central nucleus of the Amygdala. Under such a stimulation, the authors observed an

increased sensitivity and attractiveness of the rats to a particular reward cue. As a

result, the rats were more aggressive and vigorous in their approach in obtaining their

rewards (Mahler & Berridge, 2009). Similarly, antisocial adolescents with conduct

disorder have been shown to make riskier choices after obtaining small rewards. This

indicates that among these adolescents, there exists a shift in their sensitivity for

rewards regardless of the presence of any form of substance abuse (Fairchild et al.,

2009) . If these individuals were to be coupled with the abuse of Oxycodone, they may

experience enhanced decision making with little to no consideration of the risks

involved when obtaining the rewards. Thus, possibly making them more impulsive and

aggressive than they already are in terms of seeking out rewards. As a result, the

amygdala is an essential brain structure in promoting motivational salience among

antisocial Oxycodone abusers.

Another key area that links Oxycodone abuse to reward seeking behaviors is the

hyperactivity of the striatum as marked by increased striatum dopamine levels.

Oxycodone abuse has also been shown to increase hyperactivity of the striatum only in

adolescents as compared to adult mice (Zhang et al., 2009). This translates into the

possibility that adolescents who abuse Oxycodone are more likely to experience this

brain function abnormality. Moreover, for the case of conduct disorder adolescents, they

have been observed to have increased striatal activation regardless of the presence of a

reward. This implies that these adolescents are constantly seeking for rewards without

taking into consideration any negative consequence which might arise from their

actions (Gatzke-Kopp et al., 2009). Thus, antisocial adolescents who are Oxycodone

abusers will experience heightened stimulation seeking behaviors which predisposes

conduct disorder.

Impacts of Rural Areas

In many aspects, adolescents living in the rural areas are less well off than their urban

counterparts. For instance, it is known that rural adolescents have lower Intellectual

Quota (IQ) due to the lack of psychosocial stimulation achieved through education in

these areas (Walker, Grantham-McGregor, Powell, & Chang, 2000; Hawk, 2011).

Moreover, due to the lower levels of education available in rural areas, adolescents in

these areas will be less knowlegable about the use of illicit drugs and these families tend

to have negative family relations which often results in parental neglect. These social

factors would no doubt increase the number of rural adolescents abusing marijuana

(Ramirez et al., 2004). Another disparity between rural and urban areas is income. On

average urban households earn about 32% more than rural households in terms of their

yearly income (Hawk, 2011). These factors contribute to the lack of awareness of rural

adolescents to the dangers of substance abuse. Thus, it is not surprising for adolescent

abusers of marijuana and Oxycodone to stem from rural areas (Havens, Young, &

Havens, 2011; Lambert, Gale, & Hartley, 2008).

For the case of Oxycodone, the demographics of rural areas do play a vital role in

mediating abuse of this drug as well. As about 70% of the poor living in rural areas rely

heavily on agriculture as their source of income (World Bank, 2014), this labour

intensive workload increases the demand for painkillers such as Oxycodone in these

areas compared to urban areas. Thus, increasing the ease of access of rural antisocial

adolescents to such drugs especially since a major source of Oxycodone for adolescents

is the legitimate prescription of Oxycodone to their parents. This is supported by

increased prescription and marketing of Oxycodone to rural people in areas such as

Appalachian Kentucky (Keyes, Cerdá, Brady, Havens, & Galea, 2014). Furthermore, rural

areas have higher rates of conduct disorder compared to urban areas. In the Smoky

Mountain Study conducted in Appalachia, about 20% of their sample met the DSM-V CD

criteria (Costello, Farmer, Angold, Burns, & Erkanli, 1997). Compared to the U.S.

baseline of 9.5% of adolescents diagnosed with conduct disorder, Appalachia has a

baseline of 6.5% which is relatively high (Nock, et al., 2013). Therefore, the high rate of

conduct disorder coupled with high rates of Oxycodone abuse may result in increased

aggression and violence in rural areas.

Another key characteristic of the rural environment is that social networks among the

people are stronger than those in the urban areas. This is due to the fact that a larger

emphasis is placed on community within rural areas which result in these individuals to

be more likely to engage socially with those living around them (Keyes et al., 2014). This

close network might promote quicker diffusion of Oxycodone prescription among

adolescents, leading to higher rates of Oxycodone abuse among rural areas which will in

turn promote conduct disorder among these adolescents.

Higher stress levels in rural areas attributes to higher rates of conduct disorder as well.

With reference to the neurological impact of Oxycodone on the central nucleus of the

amygdala among abusers, stress increases corticotropin-releasing factors in the central

nucleus of the amygdala which increases anxiety among substance abusers (Mahler &

Berridge, 2009). The onset of stress can in turn increase the impulsiveness of

adolescents and elicit Oxycodone or marijuana craving among them. One such source of

this stress is financial stress due to the higher rates of unemployment in rural areas.

Due to this, individuals living in the rural areas might feel more stressed than their

urban counterparts. This translates into higher levels of stress among the adolescents

which places them in a high risk group in terms of exposure to any form of substance

abuse.

With reference to Table 1, it is observed that rural Appalachia has higher

unemployment rates as compared to the rest of the United States regardless of marital

status which indicates higher levels of stress among rural areas. In these financially

distressed families, studies have shown that there is increased parental hostility

towards their children. As a result, these adolescents are more likely to be more

rebellious and have behaviorial problems which includes getting involved in substance

abuse (Lichter & Campbell, 2005).

Comparison of risk between marijuana and Oxycodone abusers

Although the rates of marijuana and Oxycodone abuse are both high in rural areas, the

risk in which adolescents may develop conduct disorder might differ between these two

drugs.

Based on Table 2, it is observed that the mean age onset of marijuana and Oxycodone

abuse differs by about 5 years. For the case of marijuana, the age onset is an average of

14 years while the mean for Oxycodone is 19 years. Based on this sole comparison of

age of first use, marijuana adolescent abusers are seen to have a higher risk of

developing conduct disorder. As the brain only becomes fully developed in the early

20s, the harmful neurobiological effects as aforementioned will be greater among

marijuana abusers than those of Oxycodone (Health, 2011). Thus, the risk of developing

conduct disorder seems to be higher among marijuana abusers in rural areas.

However, with Oxycodone being more legally recognised and easier to purchase as

compared to marijuana, Oxycodone abuses do have a higher risk as compared to

marijuana abusers in rural areas in developing conduct disorder despite the later age

onset of abuse (Warren, Smalley, & Barefoot, 2015). Furthermore, the purchase of illicit

drugs off the street are more closely monitored by law enforcement officials and an

increase rates of arrests is observed for abuse of illicit drugs than prescription drugs

such as Oxycodone (Room, 2010). In another study, it is observed that adolescents’

perception of harm differs between these two drugs. Adolescents perceive marijuana to

be more harmful than Oxycodone. This is coupled with the idea that Oxycodone is more

socially acceptable since it is commonly used as a painkiller and its route of

administration does not necessarily have to be through socially stigmatised routes such

as snorting or injecting (Keyes et al., 2014). Therefore, in terms of ease of access and

social perception of Oxycodone, adolescents are more likely to abuse Oxycodone in

rural areas which increases their risk of developing conduct disorder as compared to

marijuana.

Conclusion

Overall, marijuana and Oxycodone abuse are highly potent to adolescents neurologically

as their brains are still in midst of development and are more sensitive towards the

harmful effects of substance abuse. This would in turn promote conduct disorder

related behaviors among these adolescents and the risk as discussed above is higher for

oxycodone abusers living in the rural areas. However, with the increased awareness of

health implications of Oxycodone abuse, governments are exhibiting greater control in

the availability of Oxycodone. For instance, the Canadian government has banned the

sale of Oxycodone in their health markets. However, this does not serve as an effective

deterrent for opioid abuse as opioid consumption in Canada is found to be even higher

than that of the U.S despite the ban (Paperny, 2013). This implies that people are

seeking alternative sources of opioids such as heroin instead (Cicero & Ellis, 2015).

Thus, it may be possible in future for heroin opioid abuse to takeover Oxycodone abuse

which could have detrimental implications on adolescents especially antisocial

adolescents and the risk of developing conduct disorder as well.

Future considerations involving alternative measures to reduce Oxycodone abuse aside

from prohibiting the sales of this drug should be conducted in order to effectively tackle

this issue. One such possibility would be the implementation of better monitoring

programmes such as the geographic information systems which can offer real time post-

marking surveillance on opioids prescribed (Ilhan et al., 2009). This could potentially

provide more accurate surveillance of opioid usage. Therefore, future studies should be

conducted on potential surveillance methods to be implemented in rural areas with a

more streamlined focus on antisocial adolescents who pose a larger risk of developing

conduct disorder in the presence of substance abuse.

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Tables

Table 1. Comparison of rates of unemployment between rural Appalachia and Urban

U.S. (Lichter & Campbell, 2005)

Table 2. Comparison of age onset of marijuana and Oxycodone abuse between rural and

urban areas (Leukefeld et al., 2002)