Abstract
Preclinical studies suggest cannabinoids affect functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the effects of marijuana (MJ) use on HPA axis functioning in humans. Since previous work indicates substances of abuse may dysregulate the HPA axis, it is critical to understand how MJ use affects HPA axis activity. Here, we review studies that (a) examined the effects of acute MJ administration on HPA axis functioning, (b) investigated the impact of stress on HPA axis functioning in MJ users, (c) examined the effect of chronic MJ use on basal cortisol levels, and (d) studied the relationship between MJ use and the cortisol awakening response (CAR). Findings indicate acute MJ administration typically raises cortisol levels, but this increase is blunted in MJ-dependent users relative to controls. Frequent MJ users have blunted adrenocorticotropic hormone and cortisol reactivity in response to acute stress. These findings suggest HPA axis activity may be dysregulated by heavy MJ use. Alternatively, dysregulation of the HPA axis may be a risk marker for heavy MJ use. There is mixed evidence for how MJ use affects basal cortisol levels and the CAR. Future studies should consider MJ use characteristics, method of hormone collection, time when samples are collected, and environmental factors that may influence HPA axis activity in MJ users. By examining existing studies we provide one of the first reviews aimed at synthesizing the literature on HPA axis functioning in MJ users.
Highlights
Marijuana (MJ) is the most commonly used illicit substance worldwide, with ∼147 million past year users [1]
The purpose of this review is to provide a descriptive overview of prior research on the effects of acute MJ administration on HPA axis activity, the impact of stress on HPA axis functioning in MJ users, and the role of chronic MJ use on basal cortisol levels and the cortisol awakening response (CAR)
Preclinical research has indicated that cannabinoids affect functioning of the HPA axis [for review, see Steiner and Wotjak [45]], and it appears that the current findings suggest that overall, acute MJ administration elevates cortisol levels, but to a smaller degree in MJ-dependent users
Summary
Marijuana (MJ) is the most commonly used illicit substance worldwide, with ∼147 million past year users [1]. The purpose of this review is to provide a descriptive overview of prior research on the effects of acute MJ administration on HPA axis activity, the impact of stress on HPA axis functioning in MJ users, and the role of chronic MJ use on basal cortisol levels and the cortisol awakening response (CAR). Several studies have investigated the effects of acute MJ administration on HPA axis response by examining ACTH and/or cortisol levels in a laboratory setting (Table 1). Childs et al [19] found no relationship between acute administration of oral THC and cortisol response The authors suggest their lack of findings could have been the result of collection of salivary rather than serum cortisol, the latter possibly being a more sensitive measure of cortisol. Active MJ users had generally high basal stress hormone levels but reduced responsivity of the HPA axis, potentially due to dysregulation of the stress system
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