Caffeine sometimes increases the effectiveness of some medications, such as those for headaches.

Birth control pills can extend the half-life of caffeine, requiring greater attention to caffeine consumption.

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.

MAO inhibitor drugs block an enzyme system resulting in increased stores of monoamine neurotransmitters. More common antidepressants such as tricyclic antidepressants and SSRIs block reuptake transporters causing increased levels of norepinephrine or serotonin in synapses. Mood stabilizers include lithium and many anticonvulsants, such as carbamazepine and lamotrigine are also used for mood disorders. This would demonstrate little to zero cross-tolerance with serotonergic or lithium treatment.

Mild physical dependence can result from excessive caffeine intake. Caffeine addiction, or a pathological and compulsive form of use, has not been documented in humans.

Studies have demonstrated that people who take in a minimum of 100 mg of caffeine per day (about the amount in one cup of coffee) can acquire a physical dependence that would trigger withdrawal symptoms that include headaches, muscle pain and stiffness, lethargy, nausea, vomiting, depressed mood, and marked irritability. Professor Roland Griffiths, a professor of neurology at Johns Hopkins in Baltimore strongly believes that caffeine withdrawal should be classified as a psychological disorder. His research suggested that withdrawals began within 12–24 hours after stopping caffeine intake and could last as long as nine days. Continued exposure to caffeine will lead the body to create more adenosine receptors in the central nervous system which makes it more sensitive to the effects of adenosine in two ways. Firstly, it will reduce the stimulatory effects of caffeine by increasing tolerance. Secondly, it will increase the withdrawal symptoms of caffeine as the body will be more sensitive to the effects of adenosine once caffeine intake stops. Caffeine tolerance develops very quickly. Tolerance to the sleep disruption effects of caffeine were seen after consumption of 400 mg of caffeine 3 times a day for 7 days, whereas complete tolerance was observed after consumption of 300 mg taken 3 times a day for 18 days.

These drugs block dopamine receptors and some also block serotonin receptors (such as chlorpromazine, the first antipsychotic used clinically). Having been on one or more antipsychotics for any appreciable amount of time results in dramatically reduced sensitivity to others with similar mechanisms of action. However, an antipsychotic with a substantial disparity in pharmacology (e.g. haloperidol and quetiapine) may retain significant efficacy.

For individuals prescribed anti-anxiety medications such as Alprazolam (Xanax), caffeine can introduce further problems by increasing rates of cytotoxicity and cell death by necrosis. This leads to these medications being essentially ruled out as viable treatments for caffeine-induced anxiety. Due to caffeine’s negative interaction with anti-anxiety medications such as benzodiazepines, treatments for caffeine-induced anxiety disorder tend to focus on abstinence from or a reduction of caffeine intake and behavioral therapy. Some doctors may recommend a continuance of caffeine consumption but with the provision that the patient actively takes note of physiological changes that happen after caffeine intake. The goal of this approach is to help patients better understand the effects of caffeine on the body and to distinguish threatening symptoms from normal reactions.

There is no evidence that any treatment for hangovers is very effective.

- Rehydration: Drinking water before going to bed or during hangover may relieve dehydration-associated symptoms such as thirst, dizziness, dry mouth, and headache.

- Non-steroidal anti-inflammatory drugs such as aspirin or ibuprofen have been proposed as a treatment for the headaches associated with a hangover. There however is no evidence to support a benefit, and there are concerns that taking alcohol and aspirin together may increase the risk of stomach bleeding and liver damage.

- Tolfenamic acid, an inhibitor of prostaglandin synthesis, in a 1983 study reduced headache, nausea, vomiting, irritation but had no effect on tiredness in 30 people.

- Pyritinol: A 1973 study found that large doses (several hundred times the recommended daily intake) of Pyritinol, a synthetic Vitamin B6 analog, can help to reduce hangover symptoms. Possible side effects of pyritinol include hepatitis (liver damage) due to cholestasis and acute pancreatitis.

- Yeast-based extracts: The difference in the change for discomfort, restlessness, and impatience were statistically significant but no significant differences on blood chemistry parameters, blood alcohol or acetaldehyde concentrations have been found, and it did not significantly improve general well-being.

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.

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).

Drugs that may prove more effective and safer than benzodiazepines for insomnia is an area of active research. Nonbenzodiazepine sedative-hypnotic drugs, such as zolpidem (Ambien), zaleplon, zopiclone (Imovane), and eszopiclone (Lunesta), are a class of hypnotic medications that are similar to benzodiazepines in their mechanism of action, and indicated for mild to moderate insomnia. Their effectiveness at improving time to sleeping is slight, and they have similar—though potentially less severe—side effect profiles compared to benzodiazepines.

Suvorexant is FDA approved for insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

Prescribing of nonbenzodiazepines has seen a general increase since their initial release on the US market in 1992, from 2.3% in 1993 among individuals with sleep disorders to 13.7% in 2010.

The use of antipsychotics for insomnia, while common, is not recommended as the evidence does not demonstrate a benefit and the risk of adverse effects is significant. Concerns regarding side effects is greater in the elderly.

Medication is used to relieve fever, seizures, and weight loss or dehydration. When medication is use for opiate withdrawal in newborn babies is deemed necessary, opiates are the treatment of choice; they are slowly tapered down to wean the baby off opiates. Phenobarbital is sometimes used as an alternative but is less effective in suppressing seizures; however, phenobarbital is superior to diazepam for neonatal opiate withdrawal symptoms. In the case of sedative-hypnotic neonatal withdrawal, phenobarbital is the treatment of choice. Clonidine is an emerging add-on therapy.

Opioids such as neonatal morphine solution and methadone are commonly used to treat clinical symptoms of opiate withdrawal, but may prolong neonatal drug exposure and duration of hospitalization. A study demonstrated a shorter wean duration in infants treated with methadone compared to those treated with diluted tincture of opium. When compared to morphine, methadone has a longer half-life in children, which allows for less frequent dosing intervals and steady serum concentrations to prevent neonatal withdrawal symptoms.

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.

Recommendations for foods, drinks and activities to relieve hangover symptoms abound. The ancient Romans, on the authority of Pliny the Elder, favored raw owl's eggs or fried canary, while the "prairie oyster" restorative, introduced at the 1878 Paris World Exposition, calls for raw egg yolk mixed with Worcestershire sauce, Tabasco sauce, salt and pepper. By 1938, the Ritz-Carlton Hotel provided a hangover remedy in the form of a mixture of Coca-Cola and milk (Coca-Cola itself having been invented, by some accounts, as a hangover remedy). Alcoholic writer Ernest Hemingway relied on tomato juice and beer. Other purported hangover cures include cocktails such as Bloody Mary or Black Velvet (consisting of equal parts champagne and stout). A 1957 survey by an American folklorist found widespread belief in the efficacy of heavy fried foods, tomato juice and sexual activity.

Other untested or discredited treatments include:

- Hair of the dog: The belief is that consumption of further alcohol after the onset of a hangover will relieve symptoms, based upon the theory that the hangover represents a form of alcohol withdrawal and that by satiating the body's need for alcohol the symptoms will be relieved. Social drinkers and alcoholics claim that drinking more alcohol gives relief from hangover symptoms, but research shows that the use of alcohol as a hangover cure seems to predict current or future problem drinking and alcohol use disorder, through negative reinforcement and the development of physical dependence. While the practice is popular in tradition and promoted by many sellers of alcoholic beverages, medical opinion holds that the practice merely postpones the symptoms, and courts addiction. Favored choices include Fernet Branca and Bloody Mary.

- Kudzu ("Pueraria montana var. lobata"): The main ingredient in remedies such as kakkonto. A study concluded, "The chronic usage of "Pueraria lobata" at times of high ethanol consumption, such as in hangover remedies, may predispose subjects to an increased risk of acetaldehyde-related neoplasm and pathology. ... Pueraria lobata appears to be an inappropriate herb for use in herbal hangover remedies as it is an inhibitor of ALDH2."

- Artichoke: Research shows that artichoke extract does not prevent the signs and symptoms of alcohol-induced hangover.

- Sauna or steam-bath: Medical opinion holds this may be dangerous, as the combination of alcohol and hyperthermia increases the likelihood of dangerous cardiac arrhythmias.

- Oxygen: There have been anecdotal reports from those with easy access to a breathing oxygen supply – medical staff, and military pilots — that oxygen can also reduce the symptoms of hangovers sometimes caused by alcohol consumption. The theory is that the increased oxygen flow resulting from oxygen therapy improves the metabolic rate, and thus increases the speed at which toxins are broken down. However, one source states that (in an aviation context) oxygen has no effect on physical impairment caused by hangover.

- Fructose and glucose: Glucose and fructose significantly inhibit the metabolic changes produced by alcohol intoxication, nevertheless they have no significant effect on hangover severity.

- Vitamin B: No effects on alcohol metabolism, peak blood alcohol and glucose concentrations have been found and psychomotor function is not significantly improved when using Vitamin B supplements.

- Caffeinated drinks: No significant correlation between caffeine use and hangover severity has been found.

Currently, stimulants are used medicinally to treat certain types of asthma, the common cold, depression, obesity and a wide variety of physical pain and ailments. Most commonly, stimulants such as Adderall and Ritalin are prescribed for both children and adults diagnosed with attention deficit hyperactivity disorder (ADHD). Additionally, stimulant medications are available such as Provigil which are given to individuals diagnosed with narcolepsy.

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.

Treatment depends on the drug involved, the infant's overall health, abstinence scores and whether the baby was born full-term or premature. Clinicians will watch the newborn carefully for up to a week after birth for signs of withdrawal, feeding problems, and weight gain. Babies who vomit or who are very dehydrated may need to get fluids through a vein (IV).

Some babies with severe symptoms need medicines such as methadone and morphine to treat withdrawal symptoms. These babies may need to stay in the hospital for weeks or months after birth. The goal of treatment is to prescribe the infant a drug similar to the one the mother used during pregnancy and slowly decrease the dose over time. This helps wean the baby off the drug and relieves some withdrawal symptoms.

If the symptoms are severe, especially if other drugs were used, a second medicine such as phenobarbital or clonidine may be added. Breastfeeding may also be helpful if the mother is in a methadone or buprenorphine treatment program without other drug use.

Babies with this condition often have severe diaper rash or other areas of skin breakdown. This requires treatment with special ointment or cream. Babies may also have problems with feeding or slow growth. These problems may require higher-calorie feedings that provide greater nutrition and smaller portions given more often. Objectives of management are to minimize negative outcomes and promote normal development.

When consumed in moderation, caffeine can have many beneficial effects. However, over the course of several years, chronic caffeine consumption can produce various long-term health deficits in individuals, "including permanent changes in brain excitability". As previously stated, long-term effects are most often seen in adolescents who regularly consume excess amounts of caffeine. This can effect their neuroendocrine functions and increase the risk of anxiety-disorder development.

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.

Caffeine is a commonplace central nervous system stimulant drug which occurs in nature as part of the coffee, tea, yerba mate and other plants. It is also an additive in many consumer products, most notably beverages advertised as energy drinks. Caffeine is also added to sodas such as Coca-Cola and Pepsi, where, on the ingredients listing, it is designated as a flavoring agent, due to pure caffeine powder having a bitter flavour.

Caffeine's mechanism of action is somewhat different from that of cocaine and the substituted amphetamines; caffeine blocks adenosine receptors A and A2A. Adenosine is a by-product of cellular activity, and stimulation of adenosine receptors produces feelings of tiredness and the need to sleep. Caffeine's ability to block these receptors means the levels of the body's natural stimulants, dopamine and norepinephrine, continue at higher levels.

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.

Meth mouth is very difficult to treat unless the patient stops using methamphetamine; persistent drug use makes changes in hygiene or nutrition practices unlikely. Many drug users lack access to dental treatment, and few are willing to participate in such a course of action, often because of poverty. Those who are willing to seek dental treatment often resist discussing their drug use. Providing dental treatment to individuals who use methamphetamine can also be dangerous, because the potential combination of local anesthetic and methamphetamine can cause serious heart problems. There is also an increased risk of serious side effects if opioid medications are used in the patient's treatment.

Treatment of meth mouth usually attempts to increase salivary flow, halt tooth decay, and encourage behavioral changes. Toothpaste with fluoride is very important to the restoration of dental health. Only prescription fluoride rinses can adequately treat the condition. Sialogogues, drugs that increase the amount of saliva in the mouth, can be used to treat dry mouth and protect against dental health problems. Pilocarpine and cevimeline are sialogogues approved by the Food and Drug Administration (FDA) to treat low salivation caused by Sjogren's syndrome and may have the potential to effectively treat dry mouth caused by methamphetamine use.

Education about oral hygiene for long-term methamphetamine users is sometimes required. Changes in diet are often necessary for recovering drug users that are receiving dental treatment, and the use of sugar-free gum may be beneficial. The consumption of water and the avoidance of beverages with a diuretic (dehydrating) effect can also help patients with meth mouth.

Caffeine is the most widely used alerting drug in the world and has been shown to improve alertness in simulated night work. Caffeine and naps before a night shift reduces sleepiness during the shift. Modafinil and armodafinil are non-amphetamine alerting drugs originally developed for the treatment of narcolepsy that have been approved by the FDA (the US Food and Drug Administration) for excessive sleepiness associated with SWSD.

Sobriety is the condition of not having any measurable levels, or effects from mood-altering drugs. According to WHO "Lexicon of alcohol and drug terms..." sobriety is continued abstinence from psychoactive drug use. Sobriety is also considered to be the natural state of a human being given at a birth. In a treatment setting, sobriety is the achieved goal of independence from consuming or craving mind-altering substances. As such, sustained abstinence is a prerequisite for sobriety. Early in abstinence, residual effects of mind-altering substances can preclude sobriety. These effects are labeled "PAWS", or "post acute withdrawal syndrome". Someone who abstains, but has a latent desire to resume use, is not considered truly sober. An abstainer may be subconsciously motivated to resume drug use, but for a variety of reasons, abstains (e.g. such as a medical or legal concern precluding use). Sobriety has more specific meanings within specific contexts, such as the culture of Alcoholics Anonymous, other 12 step programs, law enforcement, and some schools of psychology. In some cases, sobriety implies achieving "life balance".