Marijuana Use and Hypothalamic-Pituitary-Adrenal Axis Functioning in Humans

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.

Emotion Dysregulation Moderates the Association Between Stress and Problematic Cannabis Use

“…While speculative, individuals higher in emotion dysregulation may use cannabis to achieve lower perceived stress, and the HPA axis may play a role in this response. Chronic cannabis use may result in blunted HPA axis reactivity and dampened emotional reactivity to stress at both physiological and psychological levels ( 60 , 61 ), which is in line with the role of the ECS in the HPA axis, mood disorders, and controlling negative affect ( 12 , 19 , 20 , 62 ). While blunted stress and emotional reactivity to stressors could appear beneficial, one must consider that mounting a proper hormonal response to stress is inherently adaptive, as it permits individuals to mobilize energy stores and respond aptly to stressors in the environment ( 63 ).…”

Link between personality and response to THC exposure

“…in human studies, cortisol concentration was also elevated in response to THC administration, which presumably could result in depressive behaviors in sensitive individuals [56]. In our study, Another experiment conducted in the frame of the current study also revealed personalitybased alterations in response to THC.…”

Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta

“…Importantly, acute glucocorticoid elevation results in increased GR expression, however prolonged exposure leads to decreased GR (reviewed in 102 ). As Δ9-THC is reported to increase circulating cortisol/corticosterone levels [103][104][105][106] , we speculate that chronic maternal exposure to Δ9-THC may lead to increased maternal glucocorticoid release and ultimately decreased GR and GLUT1 expression. Future studies are warranted in trophoblast cells to further implicate this direct relationship.…”