Psychological dependence
Addiction and dependence glossary | |
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Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms - such as anxiety or anhedonia - upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exposure to certain psychoactive substances or behaviors, which leads to an individual requiring further exposure to avoid withdrawal symptoms, as a result of negative reinforcement. Neuronal counter-adaptation is believed to play a role in generating withdrawal symptoms, which could be mediated through changes in neurotransmitter activity or altered receptor expression. Environmental enrichment and physical activity can attenuate withdrawal symptoms.
Symptoms
Symptoms of psychological dependence include:
Development
Psychological dependence develops through consistent and frequent exposure to drug or behavioral activity. After sufficient exposure to a stimulus capable of inducing psychological dependence (e.g., drug use), an adaptive state develops and results in the onset of withdrawal symptoms that negatively affect cognition upon disengagement.
Psychostimulants, such as amphetamine or cocaine, are an example of a drug class where only emotional and motivational (i.e., cognitive) symptoms are observed in withdrawal, as opposed to somatic withdrawal in cases of physical dependence. Whilst psychological dependence is often associated with effects of drug use, a behavioral dependence-withdrawal syndrome is possible. For example, exercise dependence can develop in amateur and professional athletes whereby marked cognitive withdrawal symptoms - associated with depressive symptoms and increased anxiety - are experienced when abstaining from experience for two weeks or longer.
The mechanism that generates dependence involves a neuronal counter-adaptation, which is localized to areas of the brain responsible for a drug's positive reinforcement. This adaptation occurs as a change in neurotransmitter activity or in receptor expression.
Biomolecular mechanisms
Two factors have been identified as playing pivotal roles in psychological dependence: the neuropeptide "corticotropin-releasing factor" (CRF) and the gene transcription factor "cAMP response element binding protein" (CREB). The nucleus accumbens (NAcc) is one brain structure that has been implicated in the psychological component of drug dependence. In the NAcc, CREB is activated by cyclic adenosine monophosphate (cAMP) immediately after a high and triggers changes in gene expression that affect proteins such as dynorphin; dynorphin peptides reduce dopamine release into the NAcc by temporarily inhibiting the reward pathway. A sustained activation of CREB thus forces a larger dose to be taken to reach the same effect. In addition, it leaves the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for another dose.
In addition to CREB, it is hypothesized that stress mechanisms play a role in dependence. Koob and Kreek have hypothesized that during drug use, CRF activates the hypothalamic–pituitary–adrenal axis (HPA axis) and other stress systems in the extended amygdala. This activation influences the dysregulated emotional state associated with psychological dependence. They found that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid. In rat models, the separate use of CRF inhibitors and CRF receptor antagonists both decreased self-administration of the drug of study. Other studies in this review showed dysregulation of other neuropeptides that affect the HPA axis, including enkephalin which is an endogenous opioid peptide that regulates pain. It also appears that µ-opioid receptors, which enkephalin acts upon, is influential in the reward system and can regulate the expression of stress hormones.
Increased expression of AMPA receptors in nucleus accumbens MSNs is a potential mechanism of aversion produced by drug withdrawal.
Change in neurotransmitter activity
Studies have shown that in rats experiencing ethanol withdrawal, stimulant withdrawal or opioid withdrawal, the nucleus accumbens shows lower levels of serotonin and dopamine than controls. These decreases are associated with depression and anxiety.
In anatomically distinct areas of the rat brain, withdrawal is linked to lower levels of GABA and neuropeptide Y as well as higher levels of dynorphin, corticotropin-releasing factor, and norepinephrine; these fluctuations can contribute to psychological dependence.
Altered receptor expression
Changes in receptor expression have also been linked to various symptoms of drug withdrawal. For example, in a study of rats undergoing nicotine withdrawal there has been observed a down regulation of α6β2*n-icotinic acetylcholine receptors in the mesostriatal dopaminergic pathways.
Methods for reducing dependence
A study examined how rats experienced morphine withdrawal in different surroundings. The rats were either placed in a standard environment (SE) or in an enriched environment (EE). The study concluded that EE reduced depression and anxiety withdrawal symptoms.
Another study tested whether swimming exercises affected the intensity of perceivable psychological symptoms in rodents during morphine withdrawal. It concluded that the anxious and depressive states of the withdrawal were reduced in rats from the exercise group.
Distinction between psychological and physical dependence
Physical dependence | Psychological dependence |
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Alcohols | SSRIs |
Opioids | Hallucinogens |
Barbiturates | Inhalants |
Benzodiazepines | |
Stimulants | |
Cannabis products |
The major differences between psychological dependence and physical dependence are the symptoms they cause. While symptoms of psychological dependence relate to emotional and motivational impairment, physical dependence entails somatic symptoms e.g. increased heart rate, sweating, tremor. The type of dependence experienced after chronic use varies between different substances (see table 1).
Although psychological dependence and physical dependence are distinct entities, they should not be characterized as mutually exclusive. Empirical studies have shown that cravings, which are traditionally associated with psychological dependence, involve a physiological element.