Symptoms can sometimes come and go with wave-like reoccurrences or fluctuations in severity of symptoms. Common symptoms include impaired cognition, irritability, depressed mood, and anxiety; all of which may reach severe levels which can lead to relapse.

The protracted withdrawal syndrome from benzodiazepines can produce symptoms identical to generalized anxiety disorder as well as panic disorder. Due to the sometimes prolonged nature and severity of benzodiazepine withdrawal, abrupt withdrawal is not advised.

Common symptoms of post-acute withdrawal syndrome are:

- Psychosocial dysfunction

- Anhedonia

- Depression

- Impaired interpersonal skills

- Obsessive-compulsive behaviour

- Feelings of guilt

- Autonomic disturbances

- Pessimistic thoughts

- Impaired concentration

- Lack of initiative

- Craving

- Inability to think clearly

- Memory problems

- Emotional overreactions or numbness

- Sleep disturbances

- Physical coordination problems

- Stress sensitivity

- Increased sensitivity to pain

- Panic disorder

- Generalized anxiety disorder

- Sleep disturbance (dreams of using, behaviors associated with the life style)

Symptoms occur intermittently, but are not always present. They are made worse by stress or other triggers and may arise at unexpected times and for no apparent reason. They may last for a short while or longer. Any of the following may trigger a temporary return or worsening of the symptoms of post-acute withdrawal syndrome:

- Stressful and/or frustrating situations

- Multitasking

- Feelings of anxiety, fearfulness or anger

- Social conflicts

- Unrealistic expectations of oneself

Disturbances in mental function can persist for several months or years after withdrawal from benzodiazepines. Psychotic depression persisting for more than a year following benzodiazepine withdrawal has been documented in the medical literature. The patient had no prior psychiatric history. The symptoms reported in the patient included, major depressive disorder with psychotic features, including persistent depressed mood, poor concentration, decreased appetite, insomnia, anhedonia, anergia and psychomotor retardation. The patient also experienced paranoid ideation (believing she was being poisoned and persecuted by co-employees), accompanied by sensory hallucinations. Symptoms developed after abrupt withdrawal of chlordiazepoxide and persisted for 14 months. Various psychiatric medications were trialed which were unsuccessful in alleviating the symptomatology. Symptoms were completely relieved by recommending chlordiazepoxide for irritable bowel syndrome 14 months later. Another case report, reported similar phenomenon in a female patient who abruptly reduced her diazepam dosage from 30 mg to 5 mg per day. She developed electric shock sensations, depersonalisation, anxiety, dizziness, left temporal lobe EEG spiking activity, hallucinations, visual perceptual and sensory distortions which persisted for years.

A clinical trial of patients taking the benzodiazepine alprazolam (Xanax) for as little as 8 weeks triggered protracted symptoms of memory deficits which were still present after up to 8 weeks post cessation of alprazolam.

People with discontinuation syndrome have been on an antidepressant for at least four weeks and have recently stopped taking the medication, whether abruptly, after a fast taper, or each time the medication is reduced on a slow taper. Commonly reported symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headaches, sweating) and sleep disturbances (insomnia, nightmares, constant sleepiness). Sensory and movement disturbances have also been reported, including imbalance, tremors, vertigo, dizziness, and electric-shock-like experiences in the brain, often described by sufferers as "brain zaps". Mood disturbances such as dysphoria, anxiety, or agitation are also reported, as are cognitive disturbances such as confusion and hyperarousal.

In cases associated with sudden discontinuation of MAO inhibitors, acute psychosis has been observed. Over fifty symptoms have been reported.

Most cases of discontinuation syndrome last between one and four weeks, are relatively mild, and resolve on their own; in rare cases symptoms can be severe or extended. Paroxetine ("Paxil") and venlafaxine ("Effexor") seem to be particularly difficult to discontinue and prolonged withdrawal syndrome lasting over 18 months have been reported with paroxetine.

A 2009 Advisory Committee to the FDA found that online anecdotal reports of discontinuation syndrome related to duloxetine ("Cymbalta") included severe symptoms and exceeded prevalence of both paroxetine ("Paxil") and venlafaxine ("Effexor") reports by over 250% (although acknowledged this may have been influenced by duloxetine being a much newer drug). It also found that the safety information provided by the manufacturer not only neglected important information about managing discontinuation syndrome, but also explicitly advised against opening capsules, a practice required to gradually taper dosage.

Typically the severity of the symptoms experienced will depend on the amount and duration of prior alcohol consumption, as well as the number and severity of previous withdrawals. Even the most severe of these symptoms can occur in as little as 2 hours after cessation; therefore, the overall unpredictability necessitates either pre-planned hospitalization, treatment coordinated with a doctor, or at the very least rapid access to medical care, and a supporting system of friends or family should be introduced prior to addressing detoxification. In many cases, however, symptoms follow a reasonably predictable time frame as exampled below:

Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea or vomiting occur. Other comparable symptoms may also exist in this period. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations (with awareness of reality), tremor, agitation, and similar ailments.

At 24 to 48 hours following the last ethanol ingestion, the possibility of seizures should be anticipated. Meanwhile, none of the earlier withdrawal symptoms will have abated. Seizures carry the risk of death for the alcoholic.

Although, most often, the patient's condition begins to improve past the 48-hour mark, it can sometimes continue to increase in severity to delirium tremens, characterized by hallucinations that are indistinguishable from reality, severe confusion, more seizures, high blood pressure and fever which can persist anywhere from 4 to 12 days.

Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as sleep disturbances and anxiety to severe and life-threatening symptoms such as delirium, hallucinations, and autonomic instability.

Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, tonic-clonic seizures, and autonomic instability.

The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified:

- Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear.

- Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures.

- Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations. This usually occurs 24 to 72 hours after alcohol cessation. Delirium tremens is the most severe form of withdrawal and occurs in 5 to 20% of patients experiencing detoxification and 1/3 of patients experiencing withdrawal seizures.

Physical dependence can manifest itself in the appearance of both physical and psychological symptoms which are caused by physiological adaptions in the central nervous system and the brain due to chronic exposure to a substance. Symptoms which may be experienced during withdrawal or reduction in dosage include increased heart rate and/or blood pressure, sweating, and tremors. More serious withdrawal symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care. Sedative hypnotic drugs such as alcohol, benzodiazepines, and barbiturates are the only commonly available substances that can be fatal in withdrawal due to their propensity to induce withdrawal convulsions. Abrupt withdrawal from other drugs, such as opioids can cause an extremely physiologically and psychologically painful withdrawal that is very rarely fatal in patients of general good health and with medical treatment, but is more often fatal in patients with weakened cardiovascular systems; toxicity is generally caused by the often-extreme increases in heart rate and blood pressure (which can be treated with clonidine), or due to arrhythmia due to electrolyte imbalance caused by the inability to eat, and constant diarrhea and vomiting (which can be treated with loperamide and ondansetron respectively) associated with acute opioid withdrawal, especially in longer-acting substances where the diarrhea and emesis can continue unabated for weeks, although life-threatening complications are extremely rare, and nearly non-existent with proper medical management.

Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms that emerge when a person who has taken benzodiazepines, either medically or recreationally, and has developed a physical dependence undergoes dosage reduction or discontinuation. Development of physical dependence and/or addiction and the resulting withdrawal symptoms, some of which may last for years, may result from either drug-seeking behaviors or from taking the medication as prescribed. Benzodiazepine withdrawal is characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, sweating, difficulty with concentration, confusion and cognitive difficulty, memory problems, dry retching and nausea, weight loss, palpitations, headache, muscular pain and stiffness, a host of perceptual changes, hallucinations, seizures, psychosis, and suicide (see "Signs and Symptoms" section below for full list). Further, these symptoms are notable for the manner in which they wax and wane and vary in severity from day to day or week by week instead of steadily decreasing in a straightforward monotonic manner.

It is a potentially serious condition, and is complex and often protracted in time course. Long-term use, defined as daily use for at least three months, is not desirable because of the associated increased risk of dependence, dose escalation, loss of efficacy, increased risk of accidents and falls, particularly for the elderly, as well as cognitive, neurological, and intellectual impairments. Use of short-acting hypnotics, while being effective at initiating sleep, worsen the second half of sleep due to withdrawal effects. Nevertheless, long-term users of benzodiazepines should not be forced to withdraw against their will.

Benzodiazepine withdrawal can be severe and can provoke life-threatening withdrawal symptoms, such as seizures, particularly with abrupt or overly rapid dosage reduction from high doses or long time users. A severe withdrawal response can nevertheless occur despite gradual dose reduction, or from relatively low doses in short time users, even after a single large dose in animal models. A minority of individuals will experience a protracted withdrawal syndrome whose symptoms may persist at a sub-acute level for months, or years after cessation of benzodiazepines. The likelihood of developing a protracted withdrawal syndrome can be minimized by a slow, gradual reduction in dosage.

Chronic exposure to benzodiazepines causes neural adaptations that counteract the drug's effects, leading to tolerance and dependence. Despite taking a constant therapeutic dose, long-term use of benzodiazepines may lead to the emergence of withdrawal-like symptoms, particularly between doses. When the drug is discontinued or the dosage reduced, withdrawal symptoms may appear and remain until the body reverses the physiological adaptations. These rebound symptoms may be identical to the symptoms for which the drug was initially taken, or may be part of discontinuation symptoms. In severe cases, the withdrawal reaction may exacerbate or resemble serious psychiatric and medical conditions, such as mania, schizophrenia, and, especially at high doses, seizure disorders. Failure to recognize discontinuation symptoms can lead to false evidence for the need to take benzodiazepines, which in turn leads to withdrawal failure and reinstatement of benzodiazepines, often to higher doses.

Awareness of the withdrawal reactions, individualized taper strategies according to withdrawal severity, the addition of alternative strategies such as reassurance and referral to benzodiazepine withdrawal support groups, all increase the success rate of withdrawal.

Antidepressant discontinuation syndrome is a condition that can occur following the interruption, dose reduction, or discontinuation of antidepressant drugs, including selective serotonin re-uptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). The symptoms can include flu-like symptoms and disturbances in sleep, senses, movement, mood, and thinking. In most cases symptoms are mild, short-lived, and resolve without treatment. More severe cases may be successfully treated by reintroduction of the drug, provided reintroduction is done in a timely fashion. Symptoms, including tardive akathisia, and Post SSRI Sexual Dysfunction (PSSD) may persist for months to years, yet may spontaneously resolve after prolonged presence.

Protracted withdrawal syndrome refers to symptoms persisting for months or even years. A significant minority of people withdrawing from benzodiazepines, perhaps 10 to 15%, experience a protracted withdrawal syndrome which can sometimes be severe. Symptoms may include tinnitus, psychosis, cognitive deficits, gastrointestinal complaints, insomnia, paraesthesia (tingling and numbness), pain (usually in limbs and extremities), muscle pain, weakness, tension, painful tremor, shaking attacks, jerks, dizziness and blepharospasm and may occur even without a pre-existing history of these symptoms. Tinnitus occurring during dose reduction or discontinuation of benzodiazepines is alleviated by recommencement of benzodiazepines. Dizziness is often reported as being the withdrawal symptom that lasts the longest.

A study testing neuropsychological factors found psychophysiological markers differing from normals, and concluded that protracted withdrawal syndrome was a genuine iatrogenic condition caused by the long-term use. The causes of persisting symptoms are a combination of pharmacological factors such as persisting drug induced receptor changes, psychological factors both caused by the drug and separate from the drug and possibly in some cases, particularly high dose users, structural brain damage or structural neuronal damage. Symptoms continue to improve over time, often to the point where people eventually resume their normal lives, even after years of incapacity.

A slow withdrawal rate significantly reduces the risk of a protracted and/or severe withdrawal state. Protracted withdrawal symptoms can be punctuated by periods of good days and bad days. When symptoms increase periodically during protracted withdrawal, physiological changes may be present, including dilated pupils as well as an increase in blood pressure and heart rate. The change in symptoms has been proposed to be due to changes in receptor sensitivity for GABA during the process of tolerance reversal. A meta-analysis found cognitive impairments due to benzodiazepine use show improvements after six months of withdrawal, but the remaining cognitive impairments may be permanent or may require more than six months to reverse.

Protracted symptoms continue to fade over a period of many months or several years. There is no known cure for protracted benzodiazepine withdrawal syndrome except time, however, the medication flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

The signs and symptoms of benzodiazepine dependence include feeling unable to cope without the drug, unsuccessful

attempts to cut down or stop benzodiazepine use, tolerance to the effects of benzodiazepines, and withdrawal symptoms when not taking the drug. Some withdrawal symptoms that may appear include anxiety, depressed mood, depersonalisation, derealisation, sleep disturbance, hypersensitivity to touch and pain, tremor, shakiness, muscular aches, pains, twitches, and headache. Benzodiazepine dependence and withdrawal have been associated with suicide and self-harming behaviors, especially in young people. The Department of Health substance misuse guidelines recommend monitoring for mood disorder in those dependent on or withdrawing from benzodiazepines.

Benzodiazepine dependence is a frequent complication for those prescribed for or using for longer than four weeks, with physical dependence and withdrawal symptoms being the most common problem, but also occasionally drug-seeking behavior. Withdrawal symptoms include anxiety, perceptual disturbances, distortion of all the senses, dysphoria, and, in rare cases, psychosis and epileptic seizures.

Physical dependence is a physical condition caused by chronic use of a tolerance forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids, and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

Long-term use and benzodiazepine dependence is a serious problem in the elderly. Failure to treat benzodiazepine dependence in the elderly can cause serious medical complications. The elderly have less cognitive reserve and are more sensitive to the short (e.g., in between dose withdrawal) and protracted withdrawal effects of benzodiazepines, as well as the side-effects both from short-term and long-term use. This can lead to excessive contact with their doctor. Research has found that withdrawing elderly people from benzodiazepines leads to a significant reduction in doctor visits per year, it is presumed, due to an elimination of drug side-effects and withdrawal effects.

Tobacco and alcohol are the most common substances that elderly people get a dependence on or misuse. The next-most-common substance that elderly people develop a drug dependence to or misuse is benzodiazepines. Drug-induced cognitive problems can have serious consequences for elderly people and can lead to confusional states and "pseudo-dementia". About 10% of elderly patients referred to memory clinics actually have a drug-induced cause that most often is benzodiazepines. Benzodiazepines have also been linked to an increased risk of road traffic accidents and falls in the elderly. The long-term effects of benzodiazepines are still not fully understood in the elderly or any age group. Long-term benzodiazepine use is associated with attentional and visuospatial functional impairments. Withdrawal from benzodiazepines can lead to improved alertness and decreased forgetfulness in the elderly. Withdrawal led to statistical significant improvements in memory function and performance related skills in those having withdrawn successfully from benzodiazepines, whereas those having remained on benzodiazepines experienced worsening symptoms. People having withdrawn from benzodiazepines also felt their sleep was more refreshing, making statements such as ""I feel sharper when I wake up"" or ""I feel better, more awake"", or ""It used to take me an hour to fully wake up."" This suggests that benzodiazepines may actually make insomnia worse in the elderly.

A withdrawal syndrome, also called a discontinuation syndrome is a set of symptoms occurring in discontinuation or dosage reduction of some types of medications. The risk of a discontinuation syndrome occurring increases with dosage and length of use.

- Alcohol withdrawal syndrome, symptoms seen when an individual reduces or stops alcohol consumption after periods of excessive alcohol intake

- Antidepressant discontinuation syndrome, a syndrome that can occur following the interruption, dose reduction, or discontinuation of SSRI or SNRI medications

- Antipsychotic withdrawal syndrome or dopamine supersensitivity psychosis, symptoms seen when an individual reduces or suddenly stops antipsychotics

- Benzodiazepine withdrawal syndrome, symptoms that appear when a long term user stops taking benzodiazepines or reduces the dosage

- Cannabis withdrawal, a form of withdrawal associated with the substance cannabis

- Drug withdrawal

- Neonatal withdrawal, a withdrawal syndrome of infants, caused by administration of drugs or the prenatal exposure to a substance

- Nicotine withdrawal, the effects felt by a person who is nicotine dependent and suddenly stops or significantly reduces his or her nicotine intake

- Opioid withdrawal, symptoms seen cessation or rapid reduction of intake of opioid class drugs

Include the following:

- Depression

- Shaking

- Feeling unreal

- Appetite loss

- Muscle twitching

- Memory loss

- Motor impairment

- Nausea

- Muscle pains

- Dizziness

- Apparent movement of still objects

- Feeling faint

- Noise sensitivity

- Light sensitivity

- Peculiar taste

- Pins and needles

- Touch sensitivity

- Sore eyes

- Hallucinations

- Smell sensitivity

All sedative-hypnotics, e.g. alcohol, barbiturates, benzodiazepines and the nonbenzodiazepine Z-drugs have a similar mechanism of action, working on the GABA receptor complex and are cross tolerant with each other and also have abuse potential. Use of prescription sedative-hypnotics; for example the nonbenzodiazepine Z-drugs often leads to a relapse back into substance misuse with one author stating this occurs in over a quarter of those who have achieved abstinence.

Research data indicates that steroids affect the serotonin and dopamine neurotransmitter systems of the brain. In an animal study, male rats developed a conditioned place preference to testosterone injections into the nucleus accumbens, an effect blocked by dopamine antagonists, which suggests that androgen reinforcement is mediated by the brain. Moreover, testosterone appears to act through the mesolimbic dopamine system, a common substrate for drugs of abuse. Nonetheless, androgen reinforcement is not comparable to that of cocaine, nicotine, or heroin. Instead, testosterone resembles other mild reinforcers, such as caffeine, or benzodiazepines. The potential for androgen addiction remains to be determined.

Anabolic steroids are not psychoactive and cannot be detected by stimuli devices like a pupilometer which makes them hard to spot as a source of neuropsychological imbalaces in some AAS users.

The main symptoms of delirium tremens are nightmares, agitation, global confusion, disorientation, visual and auditory hallucinations, tactile hallucinations, fever, high blood pressure, heavy sweating, and other signs of autonomic hyperactivity (fast heart rate and high blood pressure). These symptoms may appear suddenly, but typically develop two to three days after the stopping of heavy drinking, being worst on the fourth or fifth day. Also, these "symptoms are characteristically worse at night". In general, DT is considered the most severe manifestation of alcohol withdrawal and occurs 3–10 days following the last drink. Other common symptoms include intense perceptual disturbance such as visions of insects, snakes, or rats. These may be hallucinations, or illusions related to the environment, e.g., patterns on the wallpaper or in the peripheral vision that the patient falsely perceives as a resemblance to the morphology of an insect, and are also associated with tactile hallucinations such as sensations of something crawling on the subject—a phenomenon known as formication. Delirium tremens usually includes extremely intense feelings of "impending doom". Severe anxiety and feelings of imminent death are common DT symptoms.

DT can sometimes be associated with severe, uncontrollable tremors of the extremities and secondary symptoms such as anxiety, panic attacks and paranoia. Confusion is often noticeable to onlookers as those with DT will have trouble forming simple sentences or making basic logical calculations.

DT should be distinguished from alcoholic hallucinosis, the latter of which occurs in approximately 20% of hospitalized alcoholics and does not carry a significant mortality. In contrast, DT occurs in 5–10% of alcoholics and carries up to 15% mortality with treatment and up to 35% mortality without treatment. DT is characterized by the presence of altered sensorium; that is, a complete hallucination without any recognition of the real world. DT has extreme autonomic hyperactivity (high pulse, blood pressure, and rate of breathing), and 35-60% of patients have a fever. Some patients experience seizures.

Sedative-hypnotics such as alcohol, benzodiazepines, and the barbiturates are known for the severe physical dependence that they are capable of inducing which can result in severe withdrawal effects. This severe neuroadaptation is even more profound in high dose drug users and misusers. A high degree of tolerance often occurs in chronic benzodiazepine abusers due to the typically high doses they consume which can lead to a severe benzodiazepine dependence. The benzodiazepine withdrawal syndrome seen in chronic high dose benzodiazepine abusers is similar to that seen in therapeutic low dose users but of a more severe nature. Extreme antisocial behaviors in obtaining continued supplies and severe drug-seeking behavior when withdrawals occur. The severity of the benzodiazepine withdrawal syndrome has been described by one benzodiazepine drug misuser who stated that I'd rather withdraw off heroin any day. If I was withdrawing from benzos you could offer me a gram of heroin or just 20mg of diazepam and I'd take the diazepam every time – I've never been so frightened in my life. Those who use benzodiazepines intermittently are less likely to develop a dependence and withdrawal symptoms upon dose reduction or cessation of benzodiazepines than those who use benzodiazepines on a daily basis.

Misuse of benzodiazepines is widespread amongst drug misusers; however, many of these people will not require withdrawal management as their use is often restricted to binges or occasional misuse. Benzodiazepine dependence when it occurs requires withdrawal treatment. There is little evidence of benefit from long-term substitution therapy of benzodiazepines, and conversely, there is growing evidence of the harm of long-term use of benzodiazepines, especially higher doses. Therefore, gradual reduction is recommended, titrated against withdrawal symptoms. For withdrawal purposes, stabilisation with a long-acting agent such as diazepam is recommended before commencing withdrawal. Chlordiazepoxide (Librium), a long-acting benzodiazepine, is gaining attention as an alternative to diazepam in substance abusers dependent on benzodiazepines due to its decreased abuse potential. In individuals dependent on benzodiazepines who have been using benzodiazepines long-term, taper regimens of 6–12 months have been recommended and found to be more successful. More rapid detoxifications e.g. of a month are not recommended as they lead to more severe withdrawal symptoms.

Tolerance leads to a reduction in GABA receptors and function; when benzodiazepines are reduced or stopped this leads to an unmasking of these compensatory changes in the nervous system with the appearance of physical and mental withdrawal effects such as anxiety, insomnia, autonomic hyperactivity and possibly seizures.

Cocaine increases alertness, feelings of well-being, euphoria, energy, competence, sociability, and sexuality. Common side effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause insomnia, anorexia, tachycardia, hallucinations, and paranoid delusions. Possible lethal side effects include rapid heartbeat, abnormal heart rhythms, tremors, convulsions, markedly increased core temperature, renal failure, heart attack, stroke and heart failure.

Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), which can eventually lead to its complete disappearance.

Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.

Barbiturate dependence develops with regular use of barbiturates. This in turn may lead to a need for increasing doses of the drug to get the original desired pharmacological or therapeutic effect. Barbiturate use can lead to both addiction and physical dependence, and as such they have a high potential for abuse. Management of barbiturate dependence involves considering the affected person's age, comorbidity and the pharmacological pathways of barbiturates. Psychological addiction to barbiturates can develop quickly. The GABA receptor, one of barbiturates' main sites of action, is thought to play a pivotal role in the development of tolerance to and dependence on barbiturates, as well as the euphoric "high" that results from their abuse. The mechanism by which barbiturate tolerance develops is believed to be different from that of ethanol or benzodiazepines, even though these drugs have been shown to exhibit cross-tolerance with each other. The management of a physical dependence on barbiturates is stabilisation on the long-acting barbiturate phenobarbital followed by a gradual titration down of dose. The slowly eliminated phenobarbital lessens the severity of the withdrawal syndrome and reduces the chances of serious barbiturate withdrawal effects such as seizures. Antipsychotics are not recommended for barbiturate withdrawal (or other CNS depressant withdrawal states) especially clozapine, olanzapine or low potency phenothiazines e.g. chlorpromazine as they lower the seizure threshold and can worsen withdrawal effects; if used extreme caution is required.

From the ICD-9 database:

- A chronic disease in which a person craves drinks that contain alcohol and is unable to control his or her drinking. A person with this disease also needs to drink greater amounts to get the same effect and has withdrawal symptoms after stopping alcohol use. Alcoholism affects physical and mental health, and can cause problems with family, friends, and work.

- A disorder characterized by a pathological pattern of alcohol use that causes a serious impairment in social or occupational functioning.

- A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (morse & flavin for the joint commission of the national council on alcoholism and drug dependence and the american society of addiction medicine to study the definition and criteria for the diagnosis of alcoholism: in jama 1992;268:1012-4)

- For most adults, moderate alcohol use is probably not harmful. However, about 18 million adult Americans are alcoholics or have alcohol problems. Alcoholism is a disease with four main features:

- craving - a strong need to drink

- loss of control - not being able to stop drinking once you've started

- physical dependence - withdrawal symptoms, such as nausea, sweating, or shakiness when you don't drink

- tolerance - the need to drink greater amounts of alcohol to feel the same effect

- Temporary mental disturbance marked by muscle incoordination and paresis as the result of excessive alcohol ingestion.

The Diagnostic Statistical Manual IV (DSM IV) and the International Classification of Diseases, Volume 10 (ICD 10) differ in the way they regard Anabolic-Androgenic Steroids' (AAS) potential for producing dependence.

DSM IV regards AAS as potentially dependence producing. ICD 10 however regards them as non-dependence producing. Anabolic steroids are not physically addictive but users can develop a psychological dependence on the physical result.

Both alcoholic hallucinosis and DTs have been thought of as different manifestations of the same physiological process in the body during alcohol withdrawal. Alcoholic hallucinosis is a much less serious diagnosis than delirium tremens. Delirium tremens (DTs) do not appear suddenly, unlike alcoholic hallucinosis. DTs also take approximately 48 to 72 hours to appear after the heavy drinking stops. A tremor develops in the hands and can also affect the head and body. A common symptom of delirium tremens is that people become severely uncoordinated. The biggest difference between alcoholic hallucinosis and delirium tremens is that alcoholic hallucinosis have a much better prognosis than DTs. Moreover, delirium tremens can be fatal when untreated.

Substance dependence also known as drug dependence is an adaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use. 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, is now known to be a critical component and common factor in the development of virtually all forms of behavioral addiction and drug addictions, but not dependence.

Within the framework of the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM-IV"), substance dependence is redefined as a drug addiction, and can be diagnosed without the occurrence of a withdrawal syndrome. It is now described accordingly: "When an individual persists in use of alcohol or other drugs despite problems related to use of the substance, substance dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance Abuse are considered Substance Use Disorders."

LSD use by the mother produces symptoms. Since polydrug abuse often accompanies the use of LSD the symptoms may be masked. Abnormal feeding, tremors and hypertonia can be seen in the infant. Withdrawal symptoms manifest as hypertonia, tremors, poor feeding, and abnormal feeding patterns.

An infant withdrawing from methadone can have sleeping difficulties, seizures and a higher risk of dying from Sudden infant death syndrome. Methadone withdrawal occurs after 7–14 days. If a child is premature they have a lower risk of severe symptoms. Those born < 35 weeks’ after gestation have lower CNS abstinence scores than term infants. It may be because preterm infants may have been exposed to less of the drug, possess an immature nervous system and lower adipose tissue.