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Drug addiction is widely considered a pathological state. The disorder of addiction involves the progression of acute drug use to the development of drug-seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally rewarding stimuli. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) has categorized three stages of addiction: preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect. These stages are characterized, respectively, everywhere by constant cravings and preoccupation with obtaining the substance; using more of the substance than necessary to experience the intoxicating effects; and experiencing tolerance, withdrawal symptoms, and decreased motivation for normal life activities. By the American Society of Addiction Medicine definition, drug addiction differs from drug dependence and drug tolerance.

It is, both among scientists and other writers, quite usual to allow the concept of drug addiction to include persons who are not drug abusers according to the definition of the American Society of Addiction Medicine. The term drug addiction is then used as a category which may include the same persons who under the DSM-IV can be given the diagnosis of substance dependence or substance abuse. (See also DSM-IV Codes)

Drugs causing addiction

Drugs known to cause addiction include illegal drugs as well as prescription or over-the-counter drugs, according to the definition of the American Society of Addiction Medicine.

• Stimulants:
  • Amphetamine and Methamphetamine
  • Caffeine
  • Cocaine
  • Nicotine

• Sedatives and Hypnotics:
  • Alcohol
  • Barbiturates
  • Benzodiazepines, particularly alprazolam, clonazepam, temazepam, and nimetazepam
  • Methaqualone and the related quinazolinone sedative-hypnotics

• Opiate and Opioid analgesics
  • Morphine and Codeine, the two naturally-occurring opiate analgesics
  • Semi-synthetic opiates, such as Heroin (Diacetylmorphine), Oxycodone, Hydrocodone, and Hydromorphone
  • Fully synthetic opioids, such as Fentanyl and its analogs, Meperidine/Pethidine, and Methadone

• Hallucinogens
  • LSD
  • Psilocybin

Addictive drugs also include a large number of substrates that are currently considered to have no medical value and are not available over the counter or by prescription.

An article in The Lancet compared the harm and addiction of 20 drugs, using a scale from 0 to 3 for physical addiction, psychological addiction, and pleasure to create a mean score for addiction. Caffeine was not included in the study. The results can be seen in the chart above.

Addictive potency

The addictive potency of drugs varies from substance to substance, and from individual to individual

Drugs such as codeine or alcohol, for instance, typically require many more exposures to addict their users than drugs such as heroin or cocaine. Likewise, a person who is psychologically or genetically predisposed to addiction is much more likely to suffer from it.

Although dependency on hallucinogens like LSD ("acid") and psilocybin (key hallucinogen in "magic mushrooms") is listed as Substance-Related Disorder in the DSM-IV, most psychologists do not classify them as addictive drugs.

Prevalence

The most common drug addictions are to legal substances such as:

• Caffeine
• Nicotine in the form of tobacco, particularly cigarettes
• Alcohol
• Sugar

The physiological basis of drug addiction

Researchers have conducted numerous investigations using animal models and functional brain imaging on humans in order to define the mechanisms underlying drug addiction in the brain. This intriguing topic incorporates several areas of the brain and synaptic changes, or neuroplasticity, which occurs in these areas.

Acute effects

Acute (or recreational) drug use causes the release and prolonged action of dopamine and serotonin within the reward circuit. Different types of drugs produce these effects by different methods. Dopamine (DA) appears to harbor the largest effect and its action is characterized. DA binds to the D1 receptor, triggering a signaling cascade within the cell. cAMP-dependent protein kinase (PKA) phosphorylates cAMP response element binding protein (CREB), a transcription factor, which induces the synthesis of certain genes including C-Fos.

Reward circuit

When examining the biological basis of drug addiction, one must first understand the pathways in which drugs act and how drugs can alter those pathways. The reward circuit, also referred to as the mesolimbic system, is characterized by the interaction of several areas of the brain.

• The ventral tegmental area (VTA) consists of dopaminergic neurons which respond to glutamate. These cells respond when stimuli indicative of a reward are present. The VTA supports learning and sensitization development and releases dopamine (DA) into the forebrain. These neurons also project and release DA into the nucleus accubems, through the mesolimbic pathway. Virtually all drugs causing drug addiction increase the dopamine release in the mesolimbic pathway, in addition to their specific effects.
• The nucleus accumbens (NAcc) consists mainly of medium-spiny projection neurons (MSNs), which are GABA neurons. The NAcc is associated with acquiring and eliciting conditioned behaviors and involved in the increased sensitivity to drugs as addiction progresses.
• The prefrontal cortex, more specifically the anterior cingulate and orbitofrontal cortices, is important for the integration of information which contributes to whether a behavior will be elicited. It appears to be the area in which motivation originates and the salience of stimuli are determined.
• The basolateral amygdala projects into the NAcc and is thought to be important for motivation as well.
• More evidence is pointing towards the role of the hippocampus in drug addiction because of its importance in learning and memory. Much of this evidence stems from investigations manipulating cells in the hippocampus alters dopamine levels in NAcc and firing rates of VTA dopaminergic cells.

Stress response

In addition to the reward circuit, it is hypothesized that stress mechanisms also play a role in addiction. Koob and Kreek have hypothesized that during drug use corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal axis (HPA) and other stress systems in the extended amygdala. This activation influences the dysregulated emotional state associated with drug addiction. They have found that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid (CSF). In rat models, the separate use of CRF antagonists and CRF receptor antagonists both decreased self-administration of the drug of study. Other studies in this review showed a dysregulation in other hormones associated with the HPA axis, including enkephalin which is an endogenous opioid peptides that regulates pain. It also appears that the µ-opioid receptor system, which enkephalin acts on, is influential in the reward system and can regulate the expression of stress hormones.

Behavior

Understanding how learning and behavior work in the reward circuit can help understand the action of addictive drugs. Drug addiction is characterized by strong, drug seeking behaviors in which the addict persistently craves and seeks out drugs, despite the knowledge of harmful consequences. Addictive drugs produce a reward, which is the euphoric feeling resulting from sustained DA concentrations in the synaptic cleft of neurons in the brain. Operant conditioning is exhibited in drug addicts as well as laboratory mice, rats, and primates; they are able to associate an action or behavior, in this case seeking out the drug, with a reward, which is the effect of the drug. Evidence shows that this behavior is most likely a result of the synaptic changes which have occurred due to repeated drug exposure. The drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the NAc. This idea is supported with data from experiments showing the drug seeking behavior can be prevented following the inhibition of AMPA glutamate receptors and glutamate release in the NAc.

Allostasis

Allostasis is the process of achieving stability through changes in behavior as well as physiological features. As a person progresses into drug addiction, he or she appears to enter a new allostatic state, defined as divergence from normal levels of change which persist in a chronic state. Addiction to drugs can cause damage to your brain and body as you enter the pathological state; the cost stemming from damage is known as allostatic load. The dysregulation of allostasis gradually occurs as the reward from the drug decreases and the ability to overcome the depressed state following drug use begins to decrease as well. The resulting all