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Review
. 2015 Sep:153:55-78.
doi: 10.1016/j.pharmthera.2015.06.003. Epub 2015 Jun 3.

Emergence of sex differences in the development of substance use and abuse during adolescence

Cynthia Kuhn  1
Affiliations
Review

Emergence of sex differences in the development of substance use and abuse during adolescence

Cynthia Kuhn. Pharmacol Ther. 2015 Sep.

Abstract

Substance use and abuse begin during adolescence. Male and female adolescent humans initiate use at comparable rates, but males increase use faster. In adulthood, more men than women use and abuse addictive drugs. However, some women progress more rapidly from initiation of use to entry into treatment. In animal models, adolescent males and females consume addictive drugs similarly. However, reproductively mature females acquire self-administration faster, and in some models, escalate use more. Sex/gender differences exist in neurobiologic factors mediating both reinforcement (dopamine, opioids) and aversiveness (CRF, dynorphin), as well as intrinsic factors (personality, psychiatric co-morbidities) and extrinsic factors (history of abuse, environment especially peers and family) which influence the progression from initial use to abuse. Many of these important differences emerge during adolescence, and are moderated by sexual differentiation of the brain. Estradiol effects which enhance both dopaminergic and CRF-mediated processes contribute to the female vulnerability to substance use and abuse. Testosterone enhances impulsivity and sensation seeking in both males and females. Several protective factors in females also influence initiation and progression of substance use including hormonal changes of pregnancy as well as greater capacity for self-regulation and lower peak levels of impulsivity/sensation seeking. Same sex peers represent a risk factor more for males than females during adolescence, while romantic partners increase risk for women during this developmental epoch. In summary, biologic factors, psychiatric co-morbidities as well as personality and environment present sex/gender-specific risks as adolescents begin to initiate substance use.

Keywords: Addiction; Adolescence; Impulsivity; Self-regulation; Sex; Substance abuse.

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Conflict of interest statement

There are no other sources of funding or conflicts of interest.

Figures

Figure 1
Figure 1
Factors In Addiction
Figure 2
Figure 2
Neurobiology Factors in Addiction
Figure 3
Figure 3
Factors Influencing Initiation of Substance Use during Adolescence
Figure 4
Figure 4
The triadic model of executive function (adapted from (Richards et al., 2012)
Figure 5
Figure 5
Trajectory of accumbens, amygdala and cortical development (modified from (Mills et al., 2014)
Figure 6
Figure 6
The modified triadic model of executive function
Figure 7
Figure 7
Sexual differentiation of brain and behaviour.
See this image and copyright information in PMC

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