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.

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.

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.

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.

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.

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.

According to the CDC in 2017, in the US, "the age-adjusted drug poisoning death rate involving opioid analgesics increased from 1.4 to 5.4 deaths per 100,000 population between 1999 and 2010, decreased to 5.1 in 2012 and 2013, then increased to 5.9 in 2014, and to 7.0 in 2015. The age-adjusted drug poisoning death rate involving heroin doubled from 0.7 to 1.4 deaths per 100,000 resident population between 1999 and 2011 and then continued to increase to 4.1 in 2015."

In 2012 it was estimated that 9.2 percent of the population over the age of 12 years old had used an illicit drug in the previous month. In 2015, it was estimated the 20.5 million Americans had a substance use disorder. Of these 20.5 million, two million used prescribed pain medications (most of those being opioids) and one-half of a million were using heroin.

In 2015, in the US there were 33,000 deaths due to drug overdose that involved opioid use. Of these, about 15,000 were from prescribed opioids and 13,000 were from heroin use.

Non-medical consumption of opioids peaked around 2010 and then started to decrease between 2011 and 2013.

Among adults, the rate of inpatient hospital stays in the United States related to opioid overuse increased by an average of 5% annually from 1993–2012. The percentage of inpatient stays due to opioid overuse admitted from the emergency department increased from 43% in 1993 to 64% in 2005, but have remained relatively constant since 2005.

The prevalence of opioid use and opioid or opiate dependency varies by age and gender, among a myriad of other factors. Men are at higher risk for opioid use and dependency than women, and men also account for more opioid overdoses than women, although this gap is closing. Women are more likely to be prescribed pain relievers, be given higher doses, use them for longer durations, and may become dependent upon them faster.

Deaths due to opioid use also tend to skew at older ages than deaths from use of other illicit drugs. This does not reflect opioid use as a whole, which includes individuals in younger age demographics. Overdoses from opioids are highest among individuals who are between the ages of 40 and 50, in contrast to heroin overdoses, which are highest among individuals who are between the ages of 20 and 30. 21 to 35-year olds represent 77% of individuals who enter treatment for opioid use disorder, however, the average age of first-time use of prescription painkillers was 21.2 years of age in 2013.

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.

The symptoms of stimulant use disorder include failure to control usage and frequency of use, an intense craving for the drug, increased use over time to obtain the same effects, known as a developed tolerance, and a continued use despite negative repercussions and interference in one’s everyday life and functioning. Furthermore, a disorder is noted when withdrawal symptoms occur because of a decrease in the drug amount and frequency, as well as stopping the use of the drug entirely. These withdrawal symptoms can last for days, weeks, months, and on rare occasions, years, depending on the frequency and dosages used by the individual. These symptoms include, but are not limited to, increased appetite, decreased energy, depression, loss of motivation and interest in once pleasurable activities, anxiety, insomnia, agitation and an intense craving for the drug. Unless intensive medical and psychological treatment is sought after, there is a very high likelihood of relapse among the user.

Risk factors for opioid overdose include opioid dependence, injecting opioids, using high doses of opioids, and use together with alcohol or benzodiazepines. The risk is particularly high following detoxification. Dependence on prescription opioids can occur from their use to treat chronic pain.

Opioid overdoses associated with a conjunction of benzodiazepines and/or alcohol use leads to a contraindicated condition. Other CNS depressants, or "downers", muscle relaxers, pain relievers, anti-convulsants, anxiolytics (anti-anxiety drugs), treatment drugs of a psychoactive or epileptic variety or any other such drug with its active function meant to calm or mitigate neuronal signaling (barbiturates, etc.) can additionally cause a worsened condition with less likelihood of recovery cumulative to each added drug. This includes drugs less immediately classed to a slowing of the metabolism such as with GABAergics like GHB or glutamatergic antagonists like PCP or ketamine.

Alcohol abuse is said to be most common in people aged between 15 and 24 years, according to Moreira 2009. However, this particular study of 7275 college students in England collected no comparative data from other age groups or countries.

Causes of alcohol abuse are complex and are likely the combination of many factors, from coping with stress to childhood development. The US Department of Health & Human Services identifies several factors influencing adolescent alcohol use, such as risk-taking, expectancies, sensitivity and tolerance, personality and psychiatric comorbidity, hereditary factors, and environmental aspects. Studies show that child maltreatment such as neglect, physical, and/or sexual abuse, as well as having parents with alcohol abuse problems, increases the likelihood of that child developing alcohol use disorders later in life. According to Shin, Edwards, Heeren, & Amodeo (2009), underage drinking is more prevalent among teens that experienced multiple types of childhood maltreatment regardless of parental alcohol abuse, putting them at a greater risk for alcohol use disorders. Genetic and environmental factors play a role in the development of alcohol use disorders, depending on age. The influence of genetic risk factors in developing alcohol use disorders increase with age ranging from 28% in adolescence and 58% in adults.

Amphetamine dependence refers to a state of psychological dependence on a drug in the amphetamine class. In individuals with substance use disorder (problematic use or abuse with dependence), psychotherapy is currently the best treatment option as no pharmacological treatment has been approved. Tolerance is expected to develop with regular substituted amphetamine use. When substituted amphetamines are abused, drug tolerance develops rapidly.

Severe withdrawal associated with dependence from recreational substituted amphetamine use can be difficult for a user to cope with. Long-term use of certain substituted amphetamines, particularly methamphetamine, can reduce dopamine activity in the brain. Psychostimulants that increase dopamine and mimic the effects of substituted amphetamines, but with lower abuse liability, could theoretically be used as replacement therapy in amphetamine dependence. However, the few studies that used amphetamine, bupropion, methylphenidate and modafinil as a replacement therapy did not result in less methamphetamine use or craving.

In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an "amphetamine use disorder" resulted in an estimated 3,788 deaths worldwide (3,425–4,145 deaths, 95% confidence).

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.

The National Institute on Drug Abuse (NIDA) says that "even though anabolic steroids do not cause the same high as other drugs, steroids are reinforcing and can lead to addiction. Studies have shown that animals will self-administer steroids when given the opportunity, just as they do with other addictive drugs. People may persist in abusing steroids despite physical problems and negative effects on social relationships, reflecting these drugs’ addictive potential. Also, steroid abusers typically spend large amounts of time and money obtaining the drug; another indication of addiction. Individuals who abuse steroids can experience withdrawal symptoms when they stop taking them, including mood swings, fatigue, restlessness, loss of appetite, insomnia, reduced sex drive, and steroid cravings, all of which may contribute to continued abuse. One of the most dangerous withdrawal symptoms is depression. When depression is persistent, it can sometimes lead to suicidal thoughts. Research has found that some steroid abusers turn to other drugs such as opioids to counteract the negative effects of steroids."

Male anabolic-androgenic steroid abusers often have a troubled social background.

The cause of alcohol abuse is complex. Alcohol abuse is related to economic and biological origins and is associated with adverse health consequences. Peer pressure influences individuals to abuse alcohol; however, most of the influence of peers is due to inaccurate perceptions of the risks of alcohol abuse. According to Gelder, Mayou and Geddes (2005) easy accessibility of alcohol is one of the reasons people engage in alcohol abuse as this substance is easily obtained in shops. Another influencing factor among adolescents and college students are the perceptions of social norms for drinking; people will often drink more to keep up with their peers, as they believe their peers drink more than they actually do. They might also expect to drink more given the context (e.g. sporting event, fraternity party, etc.). This perception of norms results in higher alcohol consumption than is normal.

Alcohol abuse is also associated with acculturation, because social and cultural factors such as an ethnic group’s norms and attitudes can influence alcohol abuse.

There are many potential complications that can arise due to substance abuse such as severe physiological damage, psychological changes and social changes that are often not desirable.

Physiological damage is often the most obvious, observed as an abnormal condition affecting the body of an organism: For instance, there are several known alcohol-induced diseases (e.g. alcoholic hepatitis, alcoholic liver disease, alcoholic cardiomyopathy.) Substance abuse is also often associated with premature ageing, fertility complications, brain damage and a higher risk of infectious diseases due to a weakened immune system.

Long term abuse has been linked to personality changes such as depression, paranoia, anxiety which can be related to psychological disorders. It is often reported that substance abuse coincides with personality disorders, such as borderline personality disorder. It has also now been linked to severe brain damage leading to an inability to control behaviours, which could explain why many people who abuse substances go on to develop addictions.

Substance abuse is often regarded as negative in society and therefore those who engage in such behaviours can often be subject to social discrimination. The use of many drugs can lead to criminal convictions, whether the drug itself is illegal or abusers use unlawful methods to fund their substances. It is also more likely that someone will partake in criminal or anti-social behaviour when they are under the influence of a drug.

Examples (and ICD-10 code) include:

- F10.0 alcohol intoxication

- F11.0 opioid intoxication

- F12.0 cannabinoid intoxication

- F13.0 sedative and hypnotic intoxication (see benzodiazepine overdose and barbiturate overdose)

- F14.0 cocaine intoxication

- F15.0 caffeine intoxication

- F16.0 hallucinogen intoxication (See for example Lysergic acid diethylamide effects)

- F17.0 tobacco intoxication

The term contact high is sometimes used to describe intoxication without direct administration, either by second-hand smoke as with cannabis, or by placebo in the presence of others who are high.

Substance-related disorders were originally subcategorized into "substance use disorders" (SUD) and "substance-induced disorders" (SID). Though DSM-IV makes a firm distinction between the two, SIDs often occur in the context of SUDs.

People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.

In Europe, the rate of problem gambling is typically 0.5 to 3 percent. The "British Gambling Prevalence Survey 2007", conducted by the United Kingdom Gambling Commission, found approximately 0.6 percent of the adult population had problem gambling issues—the same percentage as in 1999. The highest prevalence of problem gambling was found among those who participated in spread betting (14.7%), fixed odds betting terminals (11.2%) and betting exchanges (9.8%). In Norway, a December 2007 study showed the amount of present problem gamblers was 0.7 percent.