Sophia Foundation for Medical Research HPA axis Reactivity to Social Stress and Adolescent Cannabis Use: The TRAILS Study Andrea Prince van Leeuwen, Hanneke E. Creemers, Kirstin Greaves-Lord, Frank C. Verhulst, Johan Ormel, Anja C. Huizink Supported by NWO-VIDI Netherlandss (452-06-004 to ACH and APvL).

Hypothalamic–Pituitary–Adrenal (HPA) axis The HPA axis regulates various bodily processes, and is a central component of the body’s neuroendocrine response to stress. HPA axis response to stress The end-product of the HPA axis: cortisol During stressful situations, which is a reflection of stress reactivity of the HPA axis.

Background There is an increasing recognition that HPA axis reactivity is somehow involved in processes that may lead to substance use

Aims We aimed to determine whether HPA stress reactivity during a social stress task is indicative of either lifetime or repeated cannabis use by examining salivary cortisol levels. Because of our interest in the etiology of particularly cannabis use, rather than in the often accompanied use of tobacco, we additionally focused on the differentiation between cannabis users and tobacco smokers. The present study examined: a) If adolescent lifetime cannabis users, lifetime tobacco users, and nonusers of both tobacco and cannabis differ with respect to their HPA axis stress reactivity during a social stress task. b) If adolescent repeated cannabis users, repeated tobacco users, and ever users of either tobacco or cannabis differ with respect to their HPA axis stress reactivity during a social stress task. Based upon previous findings with regard functioning of the HPA axis in relation to cannabis use we hypothesized that lower cortisol stress reactivity is related to cannabis use during adolescence.

TRacking Adolescents’ Individual Lives Survey (TRAILS) 715 (mean age 16.11, 50,9% female) 591 (mean age 16.10, 50.9% male) www.trails.nl

Descriptives Dependent Variables Independent Variables Cannabis Use Lifetime Use: Ever use of cannabis before T3 Repeated Use: Used cannabis at least 5 times in the last year (T3) Tobacco Use Lifetime Use: Ever use of tobacco before T3 Repeated Use: Used tobacco at least 50 times (lifetime) and either daily or weekly use during T3 Independent Variables Axis Stress Reactivity (T3) Confounding Variables Alcohol Use during the Past Month (T3) ES Selection Stratum (T3) ES Time of Day (T3) Assessment of Mood (T3) Use of Oral Contraceptive in Females (T3) Assessment of Depressed Mood (T3) Assessment of Socioeconomic Status (T1)

Multinomial Regression 37% 28% 35% Analysis 1 32% 24% 44% Analysis 2

Multinomial Regressions (Lifetime and Repeated)

Results Lifetime tobacco users could not be differentiated from tobacco abstainers based upon their Maximum Increase, indicating that lower HPA axis stress reactivity was uniquely associated with lifetime cannabis use. When compared to lifetime ever users of tobacco or cannabis, repeated cannabis users had a significantly smaller increase in cortisol-level during the GSST (a lower Maximum Increase; OR = 0.74, CI = 0.53-0.98, p<0.05). Repeated tobacco users did not significantly differ in their Maximum Increase from lifetime tobacco or cannabis users, nor from repeated cannabis users (values). Therefore, lifetime and repeated tobacco users could not be differentiated from abstainers based upon their HPA axis stress reactivity. In contrast, lower HPA axis stress reactivity functioning was associated with cannabis use, lifetime and repeatedly

Discussion Our findings suggest: Particularly adolescents that start using cannabis, rather than those who start smoking tobacco, are characterized by low cortisol stress reactivity. Furthermore, findings suggest that adolescents that repeatedly use cannabis can be differentiated from more experimental users by their lower levels of HPA axis stress reactivity. The findings of our study might be partially explained by the stimulation-seeking hypothesis.

Co-Authors Anja Huizink Kirstin Greaves-Lord Hans Ormel Hanneke Creemers Frank Verhulst

? Andrea Prince van Leeuwen University of Amsterdam Research Institute of Child Development and Education Nieuwe Prinsengracht 130 1018 VZ Amsterdam The Netherlands e-mail:A.L.Prince@uva.nl Tel. + 31 20 5251275