Naltrexone is used for the treatment of opioid addiction. It works by blocking the physiological, euphoric, and reinforcing effects of opioids. Non-compliance with naltrexone therapy is a concern with oral formulations because of its daily dosing, and although the alternative intramuscular (IM) injection has better compliance due to its monthly dosing, attempts to override the blocking effect with higher doses and stronger drugs have proven dangerous. Naltrexone monthly IM injections received FDA approval in 2010 for the treatment of opioid dependence in abstinent opioid users.

As of 2012, there is no medication that has been proven effective for treating cannabis use disorder; research is focused on three treatment approaches: agonist substitution, antagonist, and modulation of other neurotransmitter systems. Dronabinol is an agonist that is legally available; in some cases and trials, it reduced symptoms of withdrawal and reduced cannabis use. Entacapone was well-tolerated and decreased cannabis cravings in a trial on a small number of patients. Acetylcysteine (NAC) decreased cannabis use and craving in a trial. Atomoxetine in a small study showed no significant change in cannabis use, and most patients experienced adverse events. Buspirone shows promise as a treatment for dependence; trials show it reducing cravings, irritability and depression. Divalproex in a small study was poorly tolerated and did not show a significant reduction in cannabis use among subjects.

Buprenorphine sublingual preparations are often used to manage opioid dependence (that is, dependence on heroin, oxycodone, hydrocodone, morphine, oxymorphone, fentanyl or other opioids). Preparations were approved for this indication by the United States Food and Drug Administration in October 2002. Some formulations of buprenorphine incorporate the opiate antagonist naloxone during the production of the pill form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration.

Early treatment of acute withdrawal often includes medical detoxification, which can include doses of anxiolytics or narcotics to reduce symptoms of withdrawal. An experimental drug, ibogaine, is also proposed to treat withdrawal and craving.

Neurofeedback therapy has shown statistically significant improvements in numerous researches conducted on alcoholic as well as mixed substance abuse population. In chronic opiate addiction, a surrogate drug such as methadone is sometimes offered as a form of opiate replacement therapy. But treatment approaches universal focus on the individual's ultimate choice to pursue an alternate course of action.

Psychological intervention includes cognitive behavioral therapy (CBT), motivational enhancement therapy (MET), contingency management (CM), supportive-expressive psychotherapy (SEP), family and systems interventions, and twelve-step programs.

Evaluations of Marijuana Anonymous programs, modelled on the 12-step lines of Alcoholics Anonymous and Narcotics Anonymous, have shown small beneficial effects for general drug use reduction. In 2006, the Wisconsin Initiative to Promote Healthy Lifestyles implemented a program that helps primary care physicians identify and address marijuana use problems in patients.

Therapists often classify patients with chemical dependencies as either interested or not interested in changing.

Treatments usually involve planning for specific ways to avoid the addictive stimulus, and therapeutic interventions intended to help a client learn healthier ways to find satisfaction. Clinical leaders in recent years have attempted to tailor intervention approaches to specific influences that affect addictive behavior, using therapeutic interviews in an effort to discover factors that led a person to embrace unhealthy, addictive sources of pleasure or relief from pain.

From the applied behavior analysis literature and the behavioral psychology literature, several evidenced-based intervention programs have emerged (1) behavioral marital therapy (2) community reinforcement approach (3) cue exposure therapy and (4) contingency management strategies. In addition, the same author suggests that social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious.

Behavioral programming is considered critical in helping those with addictions achieve abstinence. From the applied behavior analysis literature and the behavioral psychology literature, several evidence based intervention programs have emerged: (1) behavioral marital therapy; (2) community reinforcement approach; (3) cue exposure therapy; and (4) contingency management strategies. In addition, the same author suggest that Social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious. Community reinforcement has both efficacy and effectiveness data. In addition, behavioral treatment such as community reinforcement and family training (CRAFT) have helped family members to get their loved ones into treatment. Motivational Intervention has also shown to be an effective treatment for substance dependence.

A number of medications have been approved for the treatment of substance abuse. These include replacement therapies such as buprenorphine and methadone as well as antagonist medications like disulfiram and naltrexone in either short acting, or the newer long acting form. Several other medications, often ones originally used in other contexts, have also been shown to be effective including bupropion and modafinil. Methadone and buprenorphine are sometimes used to treat opiate addiction. These drugs are used as substitutes for other opioids and still cause withdrawal symptoms.

Antipsychotic medications have not been found to be useful. Acamprostate is a glutamatergic NMDA antagonist, which helps with alcohol withdrawal symptoms because alcohol withdrawal is associated with a hyperglutamatergic system.

Psychedelics, such as LSD and psilocin, may have anti-addictive properties.

Residential drug treatment can be broadly divided into two camps: 12-step programs and therapeutic communities. Twelve-step programs are a nonclinical support-group and faith-based approach to treating addiction. Therapy typically involves the use of cognitive-behavioral therapy, an approach that looks at the relationship between thoughts, feelings and behaviors, addressing the root cause of maladaptive behavior. Cognitive-behavioral therapy treats addiction as a behavior rather than a disease, and so is subsequently curable, or rather, unlearnable. Cognitive-behavioral therapy programs recognize that, for some individuals, controlled use is a more realistic possibility.

One of many recovery methods are 12-step recovery programs, with prominent examples including Alcoholics Anonymous, Narcotics Anonymous, Drug Addicts Anonymous and Pills Anonymous. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. Substance-abuse rehabilitation (rehab) centers offer a residential treatment program for some of the more seriously addicted, in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual counseling and group counseling. Frequently, a physician or psychiatrist will prescribe medications in order to help patients cope with the side effects of their addiction. Medications can help immensely with anxiety and insomnia, can treat underlying mental disorders (cf. self-medication hypothesis, Khantzian 1997) such as depression, and can help reduce or eliminate withdrawal symptomology when withdrawing from physiologically addictive drugs. Some examples are using benzodiazepines for alcohol detoxification, which prevents delirium tremens and complications; using a slow taper of benzodiazepines or a taper of phenobarbital, sometimes including another antiepileptic agent such as gabapentin, pregabalin, or valproate, for withdrawal from barbiturates or benzodiazepines; using drugs such as baclofen to reduce cravings and propensity for relapse amongst addicts to any drug, especially effective in stimulant users, and alcoholics (in which it is nearly as effective as benzodiazepines in preventing complications); using clonidine, an alpha-agonist, and loperamide for opioid detoxification, for first-time users or those who wish to attempt an abstinence-based recovery (90% of opioid users relapse to active addiction within eight months or are multiple relapse patients); or replacing an opioid that is interfering with or destructive to a user's life, such as illicitly-obtained heroin, dilaudid, or oxycodone, with an opioid that can be administered legally, reduces or eliminates drug cravings, and does not produce a high, such as methadone or buprenorphine – opioid replacement therapy – which is the gold standard for treatment of opioid dependence in developed countries, reducing the risk and cost to both user and society more effectively than any other treatment modality (for opioid dependence), and shows the best short-term and long-term gains for the user, with the greatest longevity, least risk of fatality, greatest quality of life, and lowest risk of relapse and legal issues including arrest and incarceration.

In a survey of treatment providers from three separate institutions, the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors, measuring the treatment provider's responses on the "Spiritual Belief Scale" (a scale measuring belief in the four spiritual characteristics of AA identified by Ernest Kurtz); the scores were found to explain 41% of the variance in the treatment provider's responses on the "Addiction Belief Scale" (a scale measuring adherence to the disease model or the free-will model of addiction).

Very limited evidence indicates that topiramate or pregabalin may be useful in the treatment of alcohol withdrawal syndrome. Limited evidence supports the use of gabapentin or carbamazepine for the treatment of mild or moderate alcohol withdrawal as the sole treatment or as combination therapy with other medications; however, gabapentin does not appear to be effective for treatment of severe alcohol withdrawal and is therefore not recommended for use in this setting. A 2010 Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not supported. Paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and carbamazepine may have advantages for certain symptoms.

There are three medications used to help prevent a return to drinking: disulfiram, naltrexone, and acamprosate. They are used after withdrawal has occurred.

Numerous medications have been investigated for use in cocaine dependence, but , none of them were considered to be effective. Anticonvulsants, such as carbamazepine, gabapentin, lamotrigine, and topiramate, do not appear to be effective as treatment. Limited evidence suggests that antipsychotics are also ineffective for treatment of cocaine dependence. Few studies have examined bupropion (a novel antidepressant) for cocaine dependence; however, trials performed thus far have not shown it to be an effective form of treatment for this purpose.

The National Institute on Drug Abuse (NIDA) of the U.S. National Institutes of Health is researching modafinil, a narcolepsy drug and mild stimulant, as a potential cocaine treatment. Ibogaine has been under investigation as a treatment for cocaine dependency and is used in clinics in Mexico, the Netherlands and Canada, but cannot be used legally in the United States. Other medications that have been investigated for this purpose include acetylcysteine, baclofen, and vanoxerine. Medications, such as phenelzine, have been used to cause an "aversion reaction" when administered with cocaine.

Cognitive behavioral therapy has been found to be more effective for the long-term management of insomnia than sedative hypnotic drugs. No formal withdrawal programs for benzodiazepines exists with local providers in the UK. Meta-analysis of published data on psychological treatments for insomnia show a success rate between 70 and 80%. A large-scale trial utilizing cognitive behavioral therapy in chronic users of sedative hypnotics including nitrazepam, temazepam, and zopiclone found CBT to be a significantly more effective long-term treatment for chronic insomnia than sedative hypnotic drugs. Persisting improvements in sleep quality, sleep onset latency, increased total sleep, improvements in sleep efficiency, significant improvements in vitality, physical and mental health at 3-, 6-, and 12-month follow-ups were found in those receiving CBT. A marked reduction in total sedative hypnotic drug use was found in those receiving CBT, with 33% reporting zero hypnotic drug use. Age has been found not to be a barrier to successful outcome of CBT. It was concluded that CBT for the management of chronic insomnia is a flexible, practical, and cost-effective treatment, and it was also concluded that CBT leads to a reduction of benzodiazepine drug intake in a significant number of patients. Chronic use of hypnotic medications is not recommended due to their adverse effects on health and the risk of dependence. A gradual taper is usual clinical course in getting people off of benzodiazepines, but, even with gradual reduction, a large proportion of people fail to stop taking benzodiazepines. The elderly are particularly sensitive to the adverse effects of hypnotic medications. A clinical trial in elderly people dependent on benzodiazepine hypnotics showed that the addition of CBT to a gradual benzodiazepine reduction program increased the success rate of discontinuing benzodiazepine hypnotic drugs from 38% to 77% and at the 12-month follow-up from 24% to 70%. The paper concluded that CBT is an effective tool for reducing hypnotic use in the elderly and reducing the adverse health effects that are associated with hypnotics such as drug dependence, cognitive impairments, and increased road traffic accidents.

A study of patients undergoing benzodiazepine withdrawal who had a diagnosis of generalized anxiety disorder showed that those having received CBT had a very high success rate of discontinuing benzodiazepines compared to those not having receive CBT. This success rate was maintained at the 12-month follow-up. Furthermore, it was found that, in patients having discontinued benzodiazepines, they no longer met the diagnosis of general anxiety disorder, and that the number of patients no longer meeting the diagnosis of general anxiety disorder was higher in the group having received CBT. Thus, CBT can be an effective tool to add to a gradual benzodiazepine dosage reduction program leading to improved and sustained mental health benefits (Disputed).

Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) have been widely used to help those with cocaine addiction. Cognitive behavioral therapy (CBT) combined with motivational therapy (MT) have proven to be more helpful than 12 step programs in treating cocaine dependency. However, both these approaches have a fairly low success rate. Other non-pharmacological treatments such as acupuncture and hypnosis have been explored, but without conclusive results.

There are eight major evidence-based medications for treating nicotine dependence: bupropion, cytisine (not approved for use in some countries, including the US), nicotine gum, nicotine inhaler, nicotine lozenge/mini-lozenge, nicotine nasal spray, nicotine patch, and varenicline. These medications have been shown to significantly improve long-term (i.e., 6-months post-quit day) abstinence rates, especially when used in combination with psychosocial treatment. The nicotine replacement treatments (i.e., patch, lozenge, gum) are dosed based on how dependent a smoker is—people who smoke more cigarettes or who smoke earlier in the morning use higher doses of nicotine replacement treatments.

Gradually reducing nicotine intake causes less withdrawal than abruptly stopping. Another way to reduce nicotine withdrawal symptoms is to provide the body with an alternative source of nicotine (nicotine replacement therapy) for a temporary period and then taper this new nicotine intake. Other medication used for quitting smoking include bupropion, varenicline, cytisine, nortriptyline, and clonidine. Treatments other than medication, such as increased exercise, can also reduce nicotine withdrawal. Many behavior changes such as avoiding situations where one usually smoked, planning ahead to deal with temptations, and seeking the support of friends and family are effective in helping people quit smoking, but whether this is due to reduced withdrawal is unclear.

There are effective treatments for nicotine dependence, although the majority of the evidence focuses on treatments for cigarette smokers rather than people who use other forms of tobacco (e.g., chew, snus, pipes, hookah, electronic cigarettes). These treatments have been shown to double or even triple a smoker’s chances of quitting successfully.

From the applied behavior analysis literature, behavioral psychology, and from randomized clinical trials, several evidenced based interventions have emerged: behavioral marital therapy, motivational Interviewing, community reinforcement approach, exposure therapy, contingency management They help suppress cravings and mental anxiety, improve focus on treatment and new learning behavioral skills, ease withdrawal symptoms and reduce the chances of relapse.

In children and adolescents, cognitive behavioral therapy (CBT) and family therapy currently has the most research evidence for the treatment of substance abuse problems. Well-established studies also include ecological family-based treatment and group CBT. These treatments can be administered in a variety of different formats, each of which has varying levels of research support Research has shown that what makes group CBT most effective is that it promotes the development of social skills, developmentally appropriate emotional regulatory skills and other interpersonal skills. A few integrated treatment models, which combines parts from various types of treatment, have also been seen as both well-established or probably effective. A study on maternal alcohol and drug use has shown that integrated treatment programs have produced significant results, resulting in higher negative results on toxicology screens. Additionally, brief school-based interventions have been found to be effective in reducing adolescent alcohol and cannabis use and abuse. Motivational interviewing can also be effective in treating substance use disorder in adolescents.

Alcoholics Anonymous and Narcotics Anonymous are one of the most widely known self-help organizations in which members support each other not to use alcohol. Social skills are significantly impaired in people suffering from alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. It has been suggested that social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious, including managing the social environment.

A wide range of drugs whilst not causing a true physical dependence can still cause withdrawal symptoms or rebound effects during dosage reduction or especially abrupt or rapid withdrawal. These can include caffeine, stimulants, steroidal drugs and antiparkinsonian drugs. It is debated if the entire antipsychotic drug class causes true physical dependency, if only a subset does, or if none do, but all, if discontinued too rapidly, cause an acute withdrawal syndrome. When talking about illicit drugs rebound withdrawal is, especially with stimulants, sometimes referred to as "coming down" or "crashing".

Some drugs, like anticonvulsants and antidepressants, describe the drug category and not the mechanism. The individual agents and drug classes in the anticonvulsant drug category act at many different receptors and it is not possible to generalize their potential for physical dependence or incidence or severity of rebound syndrome as a group so they must be looked at individually. Anticonvulsants as a group however are known to cause tolerance to the anti-seizure effect. SSRI drugs, which have an important use as antidepressants, engender a discontinuation syndrome that manifests with physical side effects. E.g., There have been case reports of a discontinuation syndrome with venlafaxine (Effexor).

Flumazenil is being studied as a potential treatment to reduce withdrawal symptoms. As its use may result in seizures this should only be done within hospital in areas experienced with the procedure.

While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use. Some studies found that the abrupt substitution of substitutive pharmacotherapy was actually less effective than gradual dose reduction alone, and only three studies found benefits of adding either melatonin, paroxetine, or trazodone and valproate in conjunction with a gradual dose reduction.

- Antipsychotics are generally ineffective for benzodiazepine withdrawal-related psychosis. Antipsychotics should be avoided during benzodiazepine withdrawal as they tend to aggravate withdrawal symptoms, including convulsions. Some antipsychotic agents may be more risky during withdrawal than others, 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.

- Barbiturates are cross tolerant to benzodiazepines and should be avoided.

- Benzodiazepines or cross tolerant drugs should be avoided after discontinuation, even occasionally. These include the nonbenzodiazepines Z-drugs, which have a similar mechanism of action. This is because tolerance to benzodiazepines has been demonstrated to be still present at four months to two years after withdrawal depending on personal biochemistry. Re-exposures to benzodiazepines typically resulted in a reactivation of the tolerance and benzodiazepine withdrawal syndrome.

- Bupropion, which is used primarily as an antidepressant and smoking cessation aid, is contraindicated in persons experiencing abrupt withdrawal from benzodiazepines or other sedative-hypnotics (e.g. alcohol), due to an increased risk of seizures.

- Buspirone augmentation was not found to increase the discontinuation success rate.

- Caffeine may worsen withdrawal symptoms because of its stimulatory properties. Interestingly, at least one animal study has shown some modulation of the benzodiazepine site by caffeine, which produces a lowering of seizure threshold.

- Carbamazepine, an anticonvulsant, appears to have some beneficial effects in the treatment and management of benzodiazepine withdrawal; however, research is limited and thus the ability of experts to make recommendations on its use for benzodiazepine withdrawal is not possible at present.

- Ethanol, the primary alcohol in alcoholic beverages, even mild to moderate use, has been found to be a significant predictor of withdrawal failure, probably because of its cross tolerance with benzodiazepines.

- Flumazenil has been found to stimulate the reversal of tolerance and the normalization of receptor function. However, further research is needed in the form of randomised trials to demonstrate its role in the treatment of benzodiazepine withdrawal. Flumazenil stimulates the up-regulation and reverses the uncoupling of benzodiazepine receptors to the GABA receptor, thereby reversing tolerance and reducing withdrawal symptoms and relapse rates. Limited research and experience and possible risks involved, the flumazenil detoxification method is controversial and can only be done as an inpatient procedure under medical supervision.

- Fluoroquinolone antibiotics have been noted by Heather Ashton and other authors as increasing the incidence of a CNS toxicity from 1 to 4% in the general population, for benzodiazepine-dependent population or in those undergoing withdrawal from them. This is probably the result of their GABA antagonistic effects as they have been found to competitively displace benzodiazepines from benzodiazepine receptor sites. This antagonism can precipitate acute withdrawal symptoms, that can persist for weeks or months before subsiding. The symptoms include depression, anxiety, psychosis, paranoia, severe insomnia, parathesia, tinnitus, hypersensitivity to light and sound, tremors, status epilepticus, suicidal thoughts and suicide attempt. Fluoroquinolone antibiotics should be contraindicated in patients who are dependent on or in benzodiazepine withdrawal. NSAIDs have some mild GABA antagonistic properties and animal research indicate that some may even displace benzodiazepines from their binding site. However, NSAIDs taken in combination with fluoroquinolones cause a very significant increase in GABA antagonism, GABA toxicity, seizures, and other severe adverse effects.

- Gabapentin can relieve most of the discomfort of benzodiazepine withdrawal; including anxiety, insomnia, irritability, tremor and muscle spasms. However, gabapentin may give rise to its own withdrawal syndrome upon discontinuation if taken continuously for long periods.

- Imidazenil has received some research for management of benzodiazepine withdrawal, but is not currently used in withdrawal.

- Imipramine was found to statistically increase the discontinuation success rate.

- Melatonin augmentation was found to statistically increase the discontinuation success rate for people with insomnia.

- Phenibut may help with the anxiety, insomnia and muscle tension brought on by benzodiazepine discontinuation. However, there is a commonly known 'rebound' effect felt with Phenibut that may be exacerbated for people in withdrawal, it is also not recommended to be taken for more than 3 consecutive days to avoid developing a dependency.

- Phenobarbital, (a barbiturate), is used at "detox" or other inpatient facilities to prevent seizures during rapid withdrawal or cold turkey. The phenobarbital is followed by a one- to two-week taper, although a slow taper from phenobarbital is preferred. In a comparison study, a rapid taper using benzodiazepines was found to be superior to a phenobarbital rapid taper.

- Pregabalin may help reduce the severity of benzodiazepine withdrawal symptoms, and reduce the risk of relapse.

- Progesterone has been found to be ineffective for managing benzodiazepine withdrawal.

- Propranolol was not found to increase the discontinuation success rate.

- SSRI antidepressants have been found to have little value in the treatment of benzodiazepine withdrawal.

- Tramadol has been found to lower the seizure threshold and should be avoided during benzodiazepine withdrawal.

- Trazodone was not found to increase the discontinuation success rate.

Management of benzodiazepine dependence involves considering the person's age, comorbidity and the pharmacological pathways of benzodiazepines. Psychological interventions may provide a small but significant additional benefit over gradual dose reduction alone at post-cessation and at follow-up. The psychological interventions studied were relaxation training, cognitive-behavioral treatment of insomnia, and self-monitoring of consumption and symptoms, goal-setting, management of withdrawal and coping with anxiety.

With sufficient motivation and the proper approach, almost anyone can successfully withdraw from benzodiazepines. However, a prolonged and severe syndrome can lead to collapsed marriages, business failures, bankruptcy, committal to a hospital, and the most serious adverse effect, suicide. As such, long-term users should not be forced to discontinue against their will. Over-rapid withdrawal, lack of explanation, and failure to reassure individuals that they are experiencing temporary withdrawal symptoms led some people to experience increased panic and fears they are going mad, with some people developing a condition similar to post-traumatic stress disorder as a result. A slow withdrawal regimen, coupled with reassurance from family, friends, and peers improves the outcome.

Behavioral addiction and substance abuse disorders are treated similarly; treatment options include exposure and response prevention. No medications have been approved for the treatment of behavioral addictions. Studies have shown promise in the use of glutamatergic altering drugs to treat addictions other than exercise. Exercise addictions comorbid in patients with an eating disorder may be treated through psychotherapy involving education, behavioral interventions, and a strengthened family support structure. In treating the eating disorder, obsessions and compulsions produced by obscured body image ideals will also be treated, this includes exercise addiction.

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.

The condition gradually improves over a period of time which can range from six months to several years in more severe cases.

Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

Acamprosate has been found to be effective in alleviating some of the post acute withdrawal symptoms of alcohol withdrawal. Carbamazepine or trazodone may also be effective in the treatment of post acute withdrawal syndrome in regards to alcohol use. Cognitive behavioral therapy can also help the post acute withdrawal syndrome especially when cravings are a prominent feature.