A neonatal withdrawal syndrome, sometimes severe, can occur when the mother had taken benzodiazepines, especially during the third trimester. Symptoms include hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress and seizures. The neonatal benzodiazepine withdrawal syndrome has been reported to persist from hours to months after birth.

A withdrawal syndrome is seen in about 20% of pediatric intensive care unit children after infusions with benzodiazepines or opioids. The likelihood of having the syndrome correlates with total infusion duration and dose, although duration is thought to be more important. Treatment for withdrawal usually involves weaning over a 3- to 21-day period if the infusion lasted for more than a week. Symptoms include tremors, agitation, sleeplessness, inconsolable crying, diarrhea and sweating. In total, over fifty withdrawal symptoms are listed in this review article. Environmental measures aimed at easing the symptoms of neonates with severe abstinence syndrome had little impact, but providing a quiet sleep environment helped in mild cases.

The severity and length of the withdrawal syndrome is likely determined by various factors, including rate of tapering, length of use and dosage size, and possible genetic factors. Those who have a prior history of withdrawing from benzodiazepines may have a sensitized or kindled central nervous system leading to worsening cognition and symptomatology, and making each subsequent withdrawal period worse.

Research studies have come to different conclusions on the number of therapeutic dose users who develop a physical dependence and withdrawal syndrome. Estimates by researchers of the number of people affected range 20–100% of patients prescribed benzodiazepines at therapeutic dosages long term are physically dependent and will experience withdrawal symptoms.

Benzodiazepines can be addictive and induce dependence even at low doses, with 23% becoming addicted within 3 months of use. Benzodiazepine addiction is considered a public health problem. Approximately 68.5% of prescriptions of benzodiazepines originate from local health centers, with psychiatry and general hospitals accounting for 10% each. A survey of general practitioners reported that the reason for initiating benzodiazepines was due to an empathy for the patients suffering and a lack of other therapeutic options rather than patients demanding them. However, long-term use was more commonly at the insistence of the patient, it is presumed, because physical dependence or addiction had developed.

Approximately twice as many women as men are prescribed benzodiazepines. It is believed that this is largely because men typically turned to alcohol to cope with stress and women to prescription drugs. Biased perception of women by male doctors may also play a role in increased prescribing rates to women; however, increased anxiety features in women does not account for the wide gap alone between men and women.

A study published in the British Journal of General Practice in July 2017 found that in a sample taken from a survey conducted in 2014–2015 in Bradford a mean of 0.69% of registered patients had been prescribed benzodiazepines for more than a year. This would suggest that there were around 300,000 long-term users of diazepine in the UK.

Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol. Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.

Sending a letter to patients warning of the adverse effects of long-term use of benzodiazepines and recommending dosage reduction has been found to be successful and a cost-effective strategy in reducing benzodiazepine consumption in general practice. Within a year of the letter's going out, there was found to be a 17% fall in the number of benzodiazepines being prescribed, with 5% of patients having totally discontinued benzodiazepines. A study in the Netherlands reported a higher success rate by sending a letter to patients who are benzodiazepine-dependent. The results of the Dutch study reported 11.3% of patients discontinuing benzodiazepines completely within a year.

Complications of benzodiazepine abuse include drug-related deaths due to overdose especially in combination with other depressant drugs such as opioids. Other complications include: blackouts and memory loss, paranoia, violence and criminal behaviour, risk-taking sexual behaviour, foetal and neonatal risks if taken in pregnancy, dependence, withdrawal seizures and psychosis. Injection of the drug carries risk of: thrombophlebitis, deep vein thrombosis, deep and superficial abscesses, pulmonary microembolism, rhabdomyolysis, tissue necrosis, gangrene requiring amputation, hepatitis B and C, as well as blood borne infections such as HIV infection (caused by sharing injecting equipment). Long-term use of benzodiazepines can worsen pre-existing depression and anxiety and may potentially also cause dementia with impairments in recent and remote memory functions.

Use is widespread among amphetamine users, with those that use amphetamines and benzodiazepines having greater levels of mental health problems and social deterioration. Benzodiazepine injectors are almost four times more likely to inject using a shared needle than non-benzodiazepine-using injectors. It has been concluded in various studies that benzodiazepine use causes greater levels of risk and psycho-social dysfunction among drug misusers.

Poly-drug users who also use benzodiazepines appear to engage in more frequent high-risk behaviors. Those who use stimulant and depressant drugs are more likely to report adverse reactions from stimulant use, more likely to be injecting stimulants and more likely to have been treated for a drug problem than those using stimulant but not depressant drugs.

Individuals with a substance abuse history are at an increased risk of misusing benzodiazepines.

Several (primary research) studies, even into the last decade, claimed, that individuals with a history of familial abuse of alcohol or who are siblings or children of alcoholics appeared to respond differently to benzodiazepines than so called "genetically healthy" persons, with males experiencing increased euphoric effects and females having exaggerated responses to the adverse effects of benzodiazepines.

Whilst all benzodiazepines have abuse potential, certain characteristics increase the potential of particular benzodiazepines for abuse. These characteristics are chiefly practical ones—most especially, availability (often based on popular perception of 'dangerous' versus 'non-dangerous' drugs) through prescribing physicians or illicit distributors. Pharmacological and pharmacokinetic factors are also crucial in determining abuse potentials. A short elimination half-life, high potency and a rapid onset of action are characteristics which increase the abuse potential of benzodiazepines. The following table provides the elimination half-life, relevant potency to other benzodiazepines, speed of onset of action and duration of behavioural effects.

Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death. It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists.

The syndrome may be in part due to persisting physiological adaptations in the central nervous system manifested in the form of continuing but slowly reversible tolerance, disturbances in neurotransmitters and resultant hyperexcitability of neuronal pathways in regards to alcohol. However, data supports neuronal and overwhelming cognitive normalization in regards to chronic amphetamine use and PAWS. Stressful situations arise in early recovery, and the symptoms of post acute withdrawal syndrome produce further distress. It is important to avoid or to deal with the triggers that make post acute withdrawal syndrome worse. The types of symptomatology and impairments in severity, frequency, and duration associated with the condition vary depending on the drug of use.

After long-term use of dopamine agonists, a withdrawal syndrome may occur during dose reduction or discontinuation with the following possible side effects: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years.

About 12% of American adults have had an alcohol dependence problem at some time in their life. In the UK the NHS estimates that around 9% of men and 4% of UK women show signs of alcohol dependence.

A number of groups have been identified as being at greater risk of developing cannabis dependence and include adolescent populations, Aboriginal and Torres Strait Islanders (in Australia) and people suffering from mental health conditions.

A 2012 study from the University of Michigan and the University of Pittsburgh published in the "Journal of the American Medical Association" analyzed information on 7.4 million discharges from 4,121 hospitals in 44 states, to measure trends and costs associated with NAS over the past decade. The study indicated that between 2000 and 2009, the number of mothers using opiates increased from 1.19 to 5.63 per 1,000 hospital births per year. Newborns with NAS were 19% more likely than all other hospital births to have low birthweight and 30% more like to have respiratory complications. Between 2000 and 2009, total hospital charges for NAS cases, adjusted for inflation, are estimated to have increased from $190 million to $720 million.

Neonatal abstinence syndrome in Canada are significant.

Opioid use disorder can develop as a result of self-medication, though this is controversial. Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients.

According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime and the World Health Organization, care providers should not treat opioid use disorder as the result of a weak character or will. Additionally, detoxification alone does not constitute adequate treatment.

Young people are at greater risk of developing cannabis dependency because of the association between early initiation into substance use and subsequent problems such as dependence, and the risks associated with using cannabis at a developmentally vulnerable age. In addition there is evidence that cannabis use during adolescence, at a time when the brain is still developing, may have deleterious effects on neural development and later cognitive functioning.

Drug and alcohol use during pregnancy can lead to many health problems in the baby besides NAS. These may include:

- Birth defects

- Low birth weight

- Premature birth

- Small head circumference

- Sudden infant death syndrome (SIDS)

- Problems with development and behavior

Neonatal abstinence syndrome treatment can last from 1 week to 6 months. Even after medical treatment for NAS is over and babies leave the hospital, they may need continued treatment for weeks or months.

Opioid use disorder is a medical condition characterized by a problematic pattern of opioid use that causes clinically significant impairment or distress. It often includes a strong desire to use opioids, increased tolerance to opioids, and withdrawal syndrome when opioids are abruptly discontinued. Addiction and dependence are components of a substance use disorder and addiction represents the most severe form of the disorder. Opioid dependence can manifest as physical dependence, psychological dependence, or both.

Opioids include substances such as morphine, heroin, codeine and oxycodone. These can be bought illegally or prescribed. The diagnosis of opioid use disorder is often based on criteria by the American Psychiatric Association in the DSM-5. These include a preoccupation with a desire to obtain and take opioids, as well as using more than intended despite social and professional consequences due to these behaviors.

Opioid use disorder can be treated with opioid replacement therapy using methadone or buprenorphine. Being on such treatment reduces the risk of death. Additionally, individuals with opioid use disorder may benefit from twelve-step programs, other peer support, and support from mental health professionals such as individual or group therapy. The medication naltrexone may also be useful to prevent relapse. Naloxone is useful for the treatment of an opioid overdose.

In 2013 opioid use disorders affects about 0.4% of people. About 16 million people have been affected at one point in time. It resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. In the United States in 2015 there were 33,000 deaths due to drug overdose involving opioids. Of those 33,000 deaths, about 15,000 were from prescribed opioids and 13,000 from heroin.

Traditional cigarettes are the most common delivery device for nicotine. However, electronic cigarettes are becoming more popular. Nicotine can also be delivered via other tobacco products such as chewing tobacco, snus, pipe tobacco, hookah, all of which can produce nicotine dependence. The risk for developing dependence is related to how much nicotine is in a product and how fast it can get to the user’s brain. Smoke from products like cigarettes and hookah is absorbed in the lungs and then nicotine gets to the brain in about 6 seconds. Cigarettes and hookah also have large amounts of nicotine in them, and therefore people who use them have a higher risk of developing dependence. Products where nicotine is absorbed into the blood through the mouth (e.g., snus, chewing tobacco), and therefore takes longer to get to the brain, have lower dependence risk. Nicotine replacement medications like the nicotine patch, nicotine lozenges, and nicotine gum have minimal to no dependence risk because they do not contain nearly as much nicotine as tobacco products and they don’t get into the brain very quickly. This is why nicotine replacement medications are safe.

Nicotine binds with nicotinic receptors in the brain and releases a variety of neurotransmitters, including dopamine, which, in turn, produce the pleasurable effects associated with smoking. With repeated exposure to nicotine, the number of binding sites on nicotinic receptors in the brain increases. When these receptors are not occupied by nicotine, they are believed to produce withdrawal symptoms. This upregulation or increase in the number of nicotinic receptors also significantly alters the functioning of the brain reward system. There are genetic risk factors for developing dependence. For instance, genetic markers for a specific type of nicotinic receptor (the α5-α3-β4 nicotine receptors) have been linked to increased risk for dependence. In other words, for smokers with a specific genetic code, exposure to nicotine results in an increased risk for neuroadaptation and the development of nicotine dependence.

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 (physical dependence), emotional-motivational symptoms (psychological dependence), or both. Chemical and hormonal imbalances may arise if the substance is not introduced. Psychological stress may also result if the substance is not re-introduced.

Infants also suffer from substance withdrawal, known as Neonnatal Abstinence Syndrome (NAS) which has severe and life-threatening effects on growing fetus. Addiction to drugs and alcohol in expecting mothers does not only cause NAS but also an array of other issues which can continually affect the infant throughout his/her lifetime. The type of drug which was abused during the months of pregnancy has many different effects on the child which can affect the infant in many ways throughout his/her life.

More than 64,000 Americans died from drug overdoses in 2016. Since 2000, the US drug overdose death rate has gone from 6.2 per 100,000 persons in 2000 to 14.7 per 100,000 in 2014.

The National Center for Health Statistics report that 19,250 people died of accidental poisoning in the U.S. in the year 2004 (8 deaths per 100,000 population).

In 2008 testimony before a Senate subcommittee, Leonard J. Paulozzi, a medical epidemiologist at the Centers for Disease Control and Prevention stated that in 2005 more than 22,000 American lives were lost due to overdoses, and the number is growing rapidly. Paulozzi also testified that all available evidence suggests that unintentional overdose deaths are related to the increasing use of prescription drugs, especially opioid painkillers. However, the vast majority of overdoses are also attributable to alcohol. It is very rare for a victim of an overdose to have consumed just one drug. Most overdoses occur when drugs are ingested in combination with alcohol.

Drug overdose was the leading cause of injury death in 2013. Among people 25 to 64 years old, drug overdose caused more deaths than motor vehicle traffic crashes. There were 43,982 drug overdose deaths in the United States in 2013. Of these, 22,767 (51.8%) were related to prescription drugs.

The 22,767 deaths relating to prescription drug overdose in 2013, 16,235 (71.3%) involved opioid painkillers, and 6,973 (30.6%) involved benzodiazepines. Drug misuse and abuse caused about 2.5 million emergency department (ED) visits in 2011. Of these, more than 1.4 million ED visits were related to prescription drugs. Among those ED visits, 501,207 visits were related to anti-anxiety and insomnia medications, and 420,040 visits were related to opioid analgesics.

Treatments for alcohol dependence can be separated into two groups, those directed towards severely alcohol-dependent people, and those focused for those at risk of becoming dependent on alcohol. Treatment for alcohol dependence often involves utilizing relapse prevention, support groups, psychotherapy, and setting short-term goals. The Twelve-Step Program is also a popular process used by those wishing to recover from alcohol dependence.

The dependence potential 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.

The distribution of naloxone to injection drug users and other opioid drug users decreases the risk of death from overdose. The Centers for Disease Control and Prevention (CDC) estimates that U.S. programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its utilization are estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the U.S. state of North Carolina, and have been replicated in the U.S. military. Nevertheless, scale-up of healthcare-based opioid overdose interventions is limited by providers' insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the US.

Street children in many developing countries are a high risk group for substance misuse, in particular solvent abuse. Drawing on research in Kenya, Cottrell-Boyce argues that "drug use amongst street children is primarily functional – dulling the senses against the hardships of life on the street – but can also provide a link to the support structure of the ‘street family’ peer group as a potent symbol of shared experience."