Hypothalamic-pituitary-adrenal axis and substance use: so many questions--and we can answer them

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.

Substance use disorders involve a pattern of using drugs more extensively than intended and continuing use despite harmful consequences. This includes legal substances like alcohol and nicotine, as well as illegal drugs. These disorders often involve both physical and psychological dependence, reflecting compulsive use of substances that significantly alter thoughts, feelings, and behaviors, contributing to a major public health issue.
Understanding the concepts of physical dependence,...

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...

Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...

Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not necessarily...

Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...