Substance dependence


Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, which is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.
The International Classification of Diseases classifies substance dependence as a mental and behavioural disorder. In the Diagnostic and Statistical Manual of Mental Disorders , substance abuse and substance dependence were eliminated and replaced with the single diagnosis of substance use disorders. This was done because "the tolerance and withdrawal that previously defined dependence are actually very normal responses to prescribed medications that affect the central nervous system and do not necessarily indicate the presence of an addiction."

Withdrawal

Withdrawal is the body's reaction to abstaining from a substance upon which a person has developed a dependence syndrome. When dependence has developed, cessation of substance-use produces an unpleasant state, which promotes continued drug use through negative reinforcement; i.e., the drug is used to escape or avoid re-entering the associated withdrawal state. The withdrawal state may include physical-somatic symptoms, emotional-motivational symptoms, or both. Chemical and hormonal imbalances may arise if the substance is not re-introduced. Psychological stress may also result if the substance is not re-introduced.
Infants also experience substance withdrawal, known as neonatal abstinence syndrome, which can have severe and life-threatening effects. Addiction to drugs such as alcohol in expectant mothers not only causes NAS, but also an array of other issues which can continually affect the infant throughout their lifetime.

Risk factors

Dependence potential

The dependence potential or dependence liability of a drug varies from substance to substance, and from individual to individual. Dose, frequency, pharmacokinetics of a particular substance, route of administration, and time are critical factors for developing a drug dependence.
An article in The Lancet compared the harm and dependence liability of 20 drugs, using a scale from zero to three for physical dependence, psychological dependence, and pleasure to create a mean score for dependence. Selected results can be seen in the chart below.
DrugMeanPleasurePsychological dependencePhysical dependence
Heroin/Morphine3.003.03.03.0
Cocaine2.393.02.81.3
Tobacco2.212.32.61.8
Barbiturates2.012.02.21.8
Alcohol1.932.31.91.6
Ketamine1.541.91.71.0
Benzodiazepines1.831.72.11.8
Amphetamine1.672.01.91.1
Cannabis1.511.91.70.8
Ecstasy1.131.51.20.7

Capture rates

Capture rates enumerate the percentage of users who reported that they had become dependent to their respective drug at some point.
Drug% of users
Cannabis9%
Caffeine9%
Alcohol15.4%
Cocaine16.7%
Heroin23.1%
Tobacco31.9%

Biomolecular mechanisms

Psychological dependence

Two factors have been identified as playing pivotal roles in psychological dependence: the neuropeptide "corticotropin-releasing factor" and the gene transcription factor "cAMP response element binding protein". The nucleus accumbens 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 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, activates the hypothalamic–pituitary–adrenal 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.

Physical dependence

Upregulation of the signal transduction pathway in the locus coeruleus by has been implicated as the mechanism responsible for certain aspects of opioid-induced physical dependence. The temporal course of withdrawal correlates with LC firing, and administration of α2 agonists into the locus coeruleus leads to a decrease in LC firing and norepinephrine release during withdrawal. A possible mechanism involves upregulation of NMDA receptors, which is supported by the attenuation of withdraw by NMDA receptor antagonists. Physical dependence on opioids has been observed to produce an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which is associated with blunted withdrawal in adult rats, but not neonatal rats While acute administration of opioids decreases AMPA receptor expression and depresses both NMDA and non-NMDA excitatory postsynaptic potentials in the NAC, withdrawal involves a lowered threshold for LTP and an increase in spontaneous firing in the NAc.

Diagnosis

DSM classification

"Substance dependence", as defined in the DSM-IV, can be diagnosed with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence.
DSM-IV substance dependencies include:
Addiction is a complex but treatable condition. It is characterized by compulsive drug craving, seeking, and use that persists even if the user is aware of severe adverse consequences. For some people, addiction becomes chronic, with periodic relapses even after long periods of abstinence. As a chronic, relapsing disease, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. While some with substance issues recover and lead fulfilling lives, others require ongoing additional support. The ultimate goal of addiction treatment is to enable an individual to manage their substance misuse; for some this may mean abstinence. Immediate goals are often to reduce substance abuse, improve the patient's ability to function, and minimize the medical and social complications of substance abuse and their addiction; this is called "harm reduction".
Treatments for addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction, medical complications and the social needs of the individual. Determining the best type of recovery program for an addicted person depends on a number of factors, including: personality, drugs of choice, concept of spirituality or religion, mental or physical illness, and local availability and affordability of programs.
Many different ideas circulate regarding what is considered a successful outcome in the recovery from addiction. Programs that emphasize controlled drinking exist for alcohol addiction. Opiate replacement therapy has been a medical standard of treatment for opioid addiction for many years.
Treatments and attitudes toward addiction vary widely among different countries. In the US and developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments; shifting the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration; reduction in crime committed by drug addicts; and treatment of other comorbid conditions such as AIDS, hepatitis and mental health disorders. These kinds of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favorable outcomes than those in the US because the criteria for measuring success are functional rather than abstinence-based. The supporters of programs with total abstinence from drugs as a goal believe that enabling further drug use means prolonged drug use and risks an increase in addiction and complications from addiction.