Role in Pathogenesis and Essence of the Early Stage
In the pathogenesis of substance addictions and substance abuse disorders, three consistently developing stages are distinguished: the early stage, the physical dependence stage, and the final stage.
The early stage has several synonyms reflecting its clinical essence: adaptive, psychasthenic, neurasthenic, or the stage of psychological dependence.
The primary characteristic of this period is the formation of a persistent psychological craving for the psychoactive substance (PAS). The patient begins to use the substance as a universal and primary tool for solving any psychoemotional tasks: increasing mental and physical performance, achieving psychological comfort, and eliminating depressive thoughts. Gradually, a specific complex of four pathogenic syndromes forms.
Psychological Dependence Syndrome and Its Pathogenesis
The basis of this syndrome is the emergence of acute psychological discomfort, a sense of dissatisfaction, and depression when the concentration of the substance in the blood drops. These distressing sensations are completely eliminated only when a new portion of the substance enters the body.
The pathogenesis of psychological dependence includes several main components:
- Neurotransmitter depletion: Due to repeated continuous substance use, a gradual decrease in neurotransmitter stores occurs directly within neurons and their terminals.
- Decreased activity of the reward system: An acute deficit of dopamine and other catecholamines develops in the brainstem and limbic system neurons. As a result, the natural maintenance of a comfortable psychoemotional state is disrupted.
- Psychoemotional disturbances: A distressing feeling of resentment, internal discomfort, and a sharp decline in mental and physical energy develop.
- Craving formation: An overwhelming, obsessive need for repeated stimulation of the body by the substance appears.
At this stage, the body attempts to resist. The dopamine deficit is temporarily compensated by the activation of enzymes that synthesize catecholamines: tyrosine 3-monooxygenase (tyrosine hydroxylase), aromatic L-amino acid decarboxylase (dihydroxyphenylalanine decarboxylase), and dopamine beta-hydroxylase. This leads to accelerated metabolism of catecholamines in the nervous system. However, over time, these adaptive mechanisms inevitably become depleted.
Neurasthenic and Psychasthenic Syndromes
The exhaustion of the nervous system manifests through a range of clinical symptoms. Patients exhibit:
- Increased irritability and emotional lability.
- Rapid fatigue during both physical and mental work.
- Noticeable memory impairment and various sleep disturbances.
- Sensory disorders: paresthesias (false sensations of numbness or tingling), as well as hypoesthesia (decreased sensitivity) and hyperesthesia (increased susceptibility to stimuli), may occur.
Tolerance and Adaptation Syndromes
In addition to psychological dependence, two other key syndromes manifest prominently in the early stage:
- Syndrome of progressively increasing tolerance to the substance: The essence of this phenomenon is that the patient requires a continuous increase in the dose of the substance to maintain a familiar comfortable state. Previous amounts no longer produce the expected effect.
- Syndrome of adaptation to the negative effects of the substance: Characterized by the complete blunting and disappearance of the protective unpleasant reactions of the body that previously occurred naturally during initial drug or alcohol use. Nausea and vomiting, pseudo-allergic reactions, severe headaches, and other intoxication symptoms disappear completely. The body stops perceiving the substance as an acute poison, which paves the way for further disease progression.