disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
drug withdrawal – symptoms that occur upon cessation of repeated drug use
psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
sensitization – an amplified response to a stimulus resulting from repeated exposure to it
substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
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.[5][6][7][8][9]Environmental enrichment and physical activity can attenuate withdrawal symptoms.[10][11]
Psychological dependence develops through consistent and frequent exposure to drug or behavioral activity.[12] 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.[4]
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.[4] 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.[13]
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.[5]
Biomolecular mechanisms
This section is
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.[14]
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
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.[10]
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.[11]
Distinction between psychological and physical dependence
Table 1: List of different drugs and which type of dependence they induce[17]
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).[17]
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
. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
. Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe. Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
. The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. ... Addictive drugs are both rewarding and reinforcing. ... Familiar pharmacologic terms such as tolerance, dependence, and sensitization are useful in describing some of the time-dependent processes that underlie addiction. ... Dependence is defined as an adaptive state that develops in response to repeated drug administration, and is unmasked during withdrawal, which occurs when drug taking stops. Dependence from long-term drug use may have both a somatic component, manifested by physical symptoms, and an emotional–motivation component, manifested by dysphoria. While physical dependence and withdrawal occur with some drugs of abuse (opiates, ethanol), these phenomena are not useful in the diagnosis of addiction because they do not occur with other drugs of abuse (cocaine, amphetamine) and can occur with many drugs that are not abused (propranolol, clonidine).
The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2000), which makes distinctions between drug use, abuse, and substance dependence, is flawed. First, diagnosis of drug use versus abuse can be arbitrary and reflect cultural norms, not medical phenomena. Second, the term substance dependence implies that dependence is the primary pharmacologic phenomenon underlying addiction, which is likely not true, as tolerance, sensitization, and learning and memory also play central roles. It is ironic and unfortunate that the Manual avoids use of the term addiction, which provides the best description of the clinical syndrome.
. Results showed a consistent pattern for adverse effects of exercise withdrawal on these mental health measures, particularly depressive symptoms and anxiety. For the studies reviewed, depressive symptoms consistently occurred following the cessation of exercise. Depressive symptoms includes a variety of complaints, including fatigue, tension, confusion, lower self-esteem, insomnia, and irritability [25,27,28,36]. However, the severity of these symptoms did not reach the level of a clinical diagnosis. Exercise deprivation also consistently resulted in an increase in general anxiety (state anxiety) [24,26,32,33], but no information was provided regarding anxiety disorders based on clinical diagnostic criteria. Regarding general mood symptoms and general well-being, results indicated consistent negative changes in both general mood and wellbeing [21,22,24–28,31–37]. The most frequently reported feelings were guilt, irritability, anger, confusion, restlessness, tension, frustration, stress, and sluggishness (loss of vigor).
^AJ Giannini, RQ Quinones, DM Martin. Role of beta-endorphin and cAMP in addiction and mania. Society for Neuroscience Abstracts. 15:149, 1998.
