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.

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.

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.

A study consisting of 1,081 U.S. residents who had first used cocaine within the previous 24 months was conducted. It was found that the risk of becoming dependent on cocaine within two years of first use was 5–6%. The risk of becoming dependent within 10 years of first use increased to 15–16%. These were the aggregate rates for all types of use considered, such as smoking, snorting, and injecting. Among recent-onset users individual rates of dependency were higher for smoking (3.4 times) and much higher for injecting. Women were 3.3 times more likely to become dependent, compared with men. Users who started at ages 12 or 13 were four times as likely to become dependent compared to those who started between ages 18 and 20.

However, a study of non-deviant users in Amsterdam found a "relative absence of destructive and compulsive use patterns over a ten year period" and concluded that cocaine users can and do exercise control. "Our respondents applied two basic types of controls to themselves: 1) restricting use to certain situations and to emotional states in which cocaine's effects would be most positive, and 2) limiting mode of ingestion to snorting of modest amounts of cocaine, staying below 2.5 grams a week for some, and below 0.5 grams a week for most. Nevertheless, those whose use level exceeded 2.5 grams a week all returned to lower levels".

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.

Most daily cigarette smokers have at least one of the above withdrawal symptoms when they try to stop. Withdrawal can occur in less-frequent users, however heavier users and those with a past or current psychiatric disorder tend to have more severe withdrawal. Genetics also influence the severity of withdrawal.

In the United States, cocaine use results in about 5,000–6,000 deaths annually.

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.

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.

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.

There are approximately 976 million smokers in the world. Estimates are that half of smokers (and one-third of former smokers) are dependent based on DSM criteria, regardless of age, gender or country of origin, but this could be higher if different definitions of dependence were used. Recent data suggest that, in the United States, the rates of daily smoking and the number of cigarettes smoked per day are declining, suggesting a reduction in population-wide dependence among current smokers. However, there are different groups of people who are more likely to smoke than the average population, such as those with low education or low socio-economic status and those with mental illness. There is also evidence that among smokers, some subgroups may be more dependent than other groups. Men smoke at higher rates than do women and score higher on dependence indices; however, women may be less likely to be successful in quitting, suggesting that women may be more dependent by that criterion. Higher nicotine dependence has also been linked with mental illness, including anxiety and depression.

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.

As demonstrated by the chart below, numerous studies have examined factors which mediate substance abuse or dependence. In these examples, the predictor variables lead to the mediator which in turn leads to the outcome, which is always substance abuse or dependence. For example, research has found that being raised in a single-parent home can lead to increased exposure to stress and that increased exposure to stress, not being raised in a single-parent home, leads to substance abuse or dependence. The following are some, but by no means all, of the possible mediators of substance abuse.

As demonstrated by the chart below, numerous studies have examined factors which moderate substance abuse or dependence. In these examples, the moderator variable impacts the level to which the strength of the relationship varies between a given predictor variable and the outcome of substance abuse or dependence. For example, there is a significant relationship between psychobehavioral risk factors, such as tolerance of deviance, rebelliousness, achievement, perceived drug risk, familism, family church attendance and other factors, and substance abuse and dependence. That relationship is moderated by familism which means that the strength of the relationship is increased or decreased based on the level of familism present in a given individual.

Examples of mediators and moderators can be found in several empirical studies. For example, Pilgrim et al.’s hypothesized mediation model posited that school success and time spent with friends mediated the relationship between parental involvement and risk-taking behavior with substance use (2006). More specifically, the relationship between parental involvement and risk-taking behavior is explained via the interaction with third variables, school success and time spent with friends. In this example, increased parental involvement led to increased school success and decreased time with friends, both of which were associated with decreased drug use. Another example of mediation involved risk-taking behaviors. As risk-taking behaviors increased, school success decreased and time with friends increased, both of which were associated with increased drug use.

A second example of a mediating variable is depression. In a study by Lo and Cheng (2007), depression was found to mediate the relationship between childhood maltreatment and subsequent substance abuse in adulthood. In other words, childhood physical abuse is associated with increased depression, which in turn, in associated with increased drug and alcohol use in young adulthood. More specifically, depression helps to explain how childhood abuse is related to subsequent substance abuse in young adulthood.

A third example of a mediating variable is an increase of externalizing symptoms. King and Chassin (2008) conducted research examining the relationship between stressful life events and drug dependence in young adulthood. Their findings identified problematic externalizing behavior on subsequent substance dependency. In other words, stressful life events are associated with externalizing symptoms, such as aggression or hostility, which can lead to peer alienation or acceptance by socially deviant peers, which could lead to increased drug use. The relationship between stressful life events and subsequent drug dependence however exists via the presence of the mediation effects of externalizing behaviors.

An example of a moderating variable is level of cognitive distortion. An individual with high levels of cognitive distortion might react adversely to potentially innocuous events, and may have increased difficulty reacting to them in an adaptive manner (Shoal & Giancola, 2005). In their study, Shoal and Giancola investigated the moderating effects of cognitive distortion on adolescent substance use. Individuals with low levels of cognitive distortion may be more apt to choose more adaptive methods of coping with social problems, thereby potentially reducing the risk of drug use. Individuals with high levels of cognitive distortions, because of their increased misperceptions and misattributions, are at increased risk for social difficulties. Individuals may be more likely to react aggressively or inappropriately, potentially alienating themselves from their peers, thereby putting them at greater risk for delinquent behaviors, including substance use and abuse. In this study, social problems are a significant risk factor for drug use when moderated by high levels of cognitive distortions.

Discontinuing benzodiazepines or antidepressants abruptly due to concerns of teratogenic effects of the medications has a high risk of causing serious complications, so is not recommended. For example, abrupt withdrawal of benzodiazepines or antidepressants has a high risk of causing extreme withdrawal symptoms, including suicidal ideation and a severe rebound effect of the return of the underlying disorder if present. This can lead to hospitalisation and potentially, suicide. One study reported one-third of mothers who suddenly discontinued or very rapidly tapered their medications became acutely suicidal due to 'unbearable symptoms'. One woman had a medical abortion, as she felt she could no longer cope, and another woman used alcohol in a bid to combat the withdrawal symptoms from benzodiazepines. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines. The study reported physicians generally are not aware of the severe consequences of abrupt withdrawal of psychotropic medications such as benzodiazepines or antidepressants.

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 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.

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.

Treatment for physical dependence depends upon the drug being withdrawn and often includes administration of another drug, especially for substances that can be dangerous when abruptly discontinued or when previous attempts have failed. Physical dependence is usually managed by a slow dose reduction over a period of weeks, months or sometimes longer depending on the drug, dose and the individual. A physical dependence on alcohol is often managed with a cross tolerant drug, such as long acting benzodiazepines to manage the alcohol withdrawal symptoms.

Some medical systems, including those of at least 15 states of the United States, refer to an Addiction Severity Index to assess the severity of problems related to substance use. According to DARA Thailand, the index assesses potential problems in seven categories: medical, employment/support, alcohol, other drug use, legal, family/social, and psychiatric.

There are efforts to decrease the number of opioids prescribed in an effort to decrease opioid use disorder and deaths related to opioid use.

The long-term abuse of stimulants ultimately causes very serious medical issues, including but not limited to, addiction. Addiction, which is a disease that causes high rates of relapse, can be defined as a chronic disease that is characterized as a compulsive drug seeking behavior in which the user will stop at nothing to obtain the drug. Long time users of stimulants have noted changes in the body such as brain function, chemistry and molecular or cellular adaptations.

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."

In order to maintain high-quality performance, some musicians take chemical substances. Some musicians take drugs or alcohol to deal with the stress of performing. As a group they have a higher rate of substance abuse. The most common chemical substance which is abused by pop musicians is cocaine, because of its neurological effects. Stimulants like cocaine increase alertness and cause feelings of euphoria, and can therefore make the performer feel as though they in some ways ‘own the stage’. One way in which substance abuse is harmful for a performer (musicians especially) is if the substance being abused is aspirated. The lungs are an important organ used by singers, and addiction to cigarettes may seriously harm the quality of their performance. Smoking causes harm to alveoli, which are responsible for absorbing oxygen.

Even in small doses, stimulants cause a decrease in appetite, an increase in physical activity and alertness, convulsions, an elevated body temperature, increased respiration, irregular heart beat and increased blood pressure; some of which can cause sudden death depending upon the medical history of the user, even among first time users.