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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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 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."

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.

The impact of alcohol on weight-gain is contentious: some studies find no effect, others find decreased or increased effect on weight gain.

Alcohol use increases the risk of chronic gastritis (stomach inflammation); it is one cause of cirrhosis, hepatitis, and pancreatitis in both its chronic and acute forms.

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).

ICD–10 criteria for dependence include experience of at least three of the following during the past year:

- a strong desire to take steroids

- difficulty in controlling use

- withdrawal syndrome when use is reduced

- evidence of tolerance

- neglect of other interests and persistent use despite harmful consequences

However, the following ICD-10-CM Index entries contain back-references to ICD-10-CM F55.3:

- Abuse

- hormones F55.5

- steroids F55.5

- drug NEC (non-dependent) F19.10

- hormones F55.5

- steroids F55.5

- non-psychoactive substance NEC F55.8

- hormones F55.5

- steroids F55.5

ICD-10 goes on to state that “although it is usually clear that the patient has a strong motivation to take the substance, there is no development of dependence or withdrawal symptoms as in the case of the psychoactive substances.”

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.

A study concluded, "Mild to moderate alcohol consumption is associated with a lower prevalence of the metabolic syndrome, with a favorable influence on lipids, waist circumference, and fasting insulin. This association was strongest among whites and among beer and wine drinkers." This is also true for Asians. A J-curve association between alcohol intake and metabolic syndrome was found: "The results of the present study suggest that the metabolic syndrome is negatively associated with light alcohol consumption (1–15 g alcohol/d) in Korean adults". However, "odds ratios for the metabolic syndrome and its components tended to increase with increasing alcohol consumption."

Comorbidity of addictive disorders and other psychiatric disorders, i.e., dual disorders, is very common and a large body of literature has accumulated demonstrating that mental disorders are strongly associated with substance use disorders. The 2011 USA National Survey on Drug Use and Health found that 17.5% of adults with a mental illness had a co-occurring substance use disorder; this works out to 7.98 million people. Estimates of co-occurring disorders in Canada are even higher, with an estimated 40-60% of adults with a severe and persistent mental illness experiencing a substance use disorder in their lifetime.

A study by Kessler et al. in the United States attempting to assess the prevalence of dual diagnosis found that 47% of clients with schizophrenia had a substance misuse disorder at some time in their life, and the chances of developing a substance misuse disorder was significantly higher among patients suffering from a psychotic illness than in those without a psychotic illness.

Another study looked at the extent of substance misuse in a group of 187 chronically mentally ill patients living in the community. According to the clinician's ratings, around a third of the sample used alcohol, street drugs, or both during the six months before evaluation.

Further UK studies have shown slightly more moderate rates of substance misuse among mentally ill individuals. One study found that individuals suffering from schizophrenia showed just a 7% prevalence of problematic drug use in the year prior to being interviewed and 21% reported problematic use some time before that.

Wright and colleagues identified individuals with psychotic illnesses who had been in contact with services in the London borough of Croydon over the previous 6 months. Cases of alcohol or substance misuse and dependence were identified through standardized interviews with clients and keyworkers. Results showed that prevalence rates of dual diagnosis were 33% for the use of any substance, 20% for alcohol misuse only and 5% for drug misuse only. A lifetime history of any illicit drug use was observed in 35% of the sample.

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.

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.

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.