The distribution of naloxone to injection drug users and other opioid drug users decreases the risk of death from overdose. The Centers for Disease Control and Prevention (CDC) estimates that U.S. programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its utilization are estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the U.S. state of North Carolina, and have been replicated in the U.S. military. Nevertheless, scale-up of healthcare-based opioid overdose interventions is limited by providers' insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the US.

Stabilization of the victim's airway, breathing, and circulation (ABCs) is the initial treatment of an overdose. Ventilation is considered when there is a low respiratory rate or when blood gases show the person to be hypoxic. Monitoring of the patient should continue before and throughout the treatment process, with particular attention to temperature, pulse, respiratory rate, blood pressure, urine output, electrocardiography (ECG) and O saturation. Poison control centers and medical toxicologists are available in many areas to provide guidance in overdoses to both physicians and the general public.

Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.

Supportive measures include observation of vital signs, especially Glasgow Coma Scale and airway patency. IV access with fluid administration and maintenance of the airway with intubation and artificial ventilation may be required if respiratory depression or pulmonary aspiration occurs. Supportive measures should be put in place prior to administration of any benzodiazepine antagonist in order to protect the patient from both the withdrawal effects and possible complications arising from the benzodiazepine. A determination of possible deliberate overdose should be considered with appropriate scrutiny, and precautions taken to prevent any attempt by the patient to commit further bodily harm. Hypotension is corrected with fluid replacement, although catecholamines such as norepinephrine or dopamine may be required to increase blood pressure. Bradycardia is treated with atropine or an infusion of norepinephrine to increase coronary blood flow and heart rate.

Tricyclic antidepressants are highly protein bound and have a large volume of distribution; therefore removal of these compounds from the blood with hemodialysis, hemoperfusion or other techniques are unlikely to be of any significant benefit.

The treatment of barbiturate abuse or overdose is generally supportive. The amount of support required depends on the person's symptoms. If the patient is drowsy but awake and can swallow and breathe without difficulty, the treatment can be as simple as monitoring the person closely. If the person is not breathing, it may involve mechanical ventilation until the drug has worn off.

Supportive treatment often includes the following:

- Activated charcoal may be given via nasogastric tube.

- Intravenous administration of saline, naloxone, thiamine, and/or glucose.

- Intubation and bemegride, or a hand-breather where these are not available until the patient can breathe under their own power.

- Observation in the Emergency Department for a number of hours or admission to the hospital for several days of observation if symptoms are severe.

- Advise the patient about drug misuse or refer for psychiatric consult.

Emergency treatment of cocaine-associated hyperthermia consists of administering a benzodiazepine sedation agent, such as diazepam (Valium) or lorazepam (Ativan) to enhance muscle relaxation and decrease sympathetic outflow from the central nervous system. Physical cooling is best accomplished with tepid water misting and cooling with a fan (convection and evaporation), which can be carried out easily in the field or hospital. There is no specific pharmacological antidote for cocaine overdose. The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with a benzodiazepine. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A comprehensive systematic review of all pharmacological treatments of cocaine cardiovascular toxicity revealed benzodiazepines may not always reliably lower heart rate and blood pressure.

Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate. Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered. Alpha-blockers such as phentolamine have been recommended and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate. Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use and titratability. Calcium channel blockers may also be used to treat hypertension and coronary arterial vasoconstriction, but fail to lower tachycardia based on all cocaine-related studies. Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil are preferable, as dihydropyridine agents such as nifedipine have much higher risk of reflex tachycardia.

Agitated patients are best treated with benzodiazepines, but antipsychotics such as haloperidol and olanzapine may also be useful. The alpha-2 agonist dexmedetomidine may also be useful for treatment of agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports. Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports.

The use of beta-blockers for cocaine cardiovascular toxicity has been subject to a relative contraindication by many clinicians for several years despite extremely limited evidence. The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in cocaine-abusing patients, is controversial. This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of the use of all beta-blockers, including specific, non-specific, and mixed. Many clinicians have disregarded this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia. Of the 1,744 total patients identified in the aforementioned systematic review, only 7 adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1). Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the drug, making it unnecessary to aggressively treat any associated tachycardia and hypertension. However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration.

The mixed beta/alpha blocker labetalol has been shown to be safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded. The use of labetalol is approved by a recent AHA/ACC guideline for cocaine and methamphetamine patients with unstable angina/non-STEMI.

Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal which adsorbs the drug in the gastrointestinal tract either by mouth or via a nasogastric tube. Activated charcoal is most useful if given within 1 to 2 hours of ingestion. Other decontamination methods such as stomach pumps, ipecac induced emesis, or whole bowel irrigation are generally not recommended in TCA poisoning. Stomach pumps may be considered within an hour of ingestion but evidence to support the practice is poor.

Barbiturates increase the time that the chloride pore of the GABA receptor is opened for, thereby increasing the efficacy of GABA. This is as opposed to benzodiazepines which increase the frequency that the chloride pore is opened, thereby increasing GABA's potency.

Death can be prevented in individuals who have overdosed on opioids if they receive basic life support and naloxone is administered soon after the overdose occurs. Naloxone is effective at reversing the cause, rather than just the symptoms, of an opioid overdose. A longer-acting variant of naloxone is naltrexone. Naltrexone is primarily used to treat opioid and alcohol dependence.

Programs to provide drug users and their caregivers with naloxone are recommended. In the United States its use is estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the US state of North Carolina, and have been replicated in the US military. Nevertheless, scale-up of healthcare-based opioid overdose interventions are limited by providers’ insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise.

Although opioid overdose accounts for the leading cause of accidental death, it can be prevented in primary care settings. Clear protocols for staff at emergency departments and urgent care centers can reduce opioid prescriptions for individuals presenting in these settings who engage in drug seeking behaviors or who have a history of substance abuse. Providers should routinely screen patients using tools such as the CAGE-AID and the Drug Abuse Screening Test (DAST-10) to screen adults and the CRAFFT to screen adolescents aged 14–18 years. Other “drug seeking” behaviors and physical indications of drug use should be used as clues to perform formal screenings.

Individuals diagnosed with opioid dependence should be prescribed naloxone to prevent overdose and/or should be directed to one of the many intervention/treatment options available, such as needle exchange programs and treatment centers. Brief motivational interviewing can also be performed by the clinician during patient visits and has been shown to improve patient motivation to change their behavior. Despite these opportunities, the dissemination of prevention interventions in the US has been hampered by the lack of coordination and sluggish federal government response.

Prescription monitoring program allow physicians to view individuals' history of prescribed opioids and other controlled substances to prevent risky behaviors, such as doctor shopping and drug diversion. These programs are operational in 49 states and the District of Columbia, and have generally been found to decrease prescribing of opioids.

Regulative policies, such as Florida’s pill mill law, have also been found to decrease opioid prescribing and use, which are both correlated with opioid overdoses. Florida's pill mill law addressed pill mills, or rogue pain management clinics where prescription drugs are inappropriately prescribed and dispensed, and required these clinics to register with the state, have a physician-owner, created inspection requirements, and established prescribing and dispensing requirements and prohibitions for physicians at these clinics.

Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.

One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.

One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.

There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.

Calcitriol, the active metabolite of vitamin D, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes.

In general, the simultaneous use of multiple drugs should be carefully monitored by a qualified individual such as board certified and licensed medical doctor, either an MD or DO Close association between prescribing physicians and pharmacies, along with the computerization of prescriptions and patients' medical histories, aim to avoid the occurrence of dangerous drug interactions. Lists of contraindications for a drug are usually provided with it, either in monographs, package inserts (accompanying prescribed medications), or in warning labels (for OTC drugs). CDI/MDI might also be avoided by physicians requiring their patients to return any unused prescriptions. Patients should ask their doctors and pharmacists if there are any interactions between the drugs they are taking.

On June 30, 2009, an FDA advisory panel recommended that Vicodin and another painkiller, Percocet, be removed from the market because they have allegedly caused over 400 deaths a year. The problem is with paracetamol (acetaminophen/Tylenol for example ) overdose and liver damage. These two drugs, in combination with other drugs like Nyquil and Theraflu, can cause death by multiple drug intake and/or drug overdose. Another solution would be to not include paracetamol with Vicodin or Percocet.

Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes tachyarrhythmias and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, respiratory failure, stroke, cerebral hemorrhage, or heart failure. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in renal failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 5000 deaths occur annually in the US due to cocaine overdose.

The symptoms of sedative/hypnotic toxidrome include ataxia, blurred vision, coma, confusion, delirium, deterioration of central nervous system functions, diplopia, dysesthesias, hallucinations, nystagmus, paresthesias, sedation, slurred speech, and stupor. Apnea is a potential complication. Substances that may cause this toxidrome include anticonvulsants, barbiturates, benzodiazepines, gamma-Hydroxybutyric acid, Methaqualone, and ethanol. While most sedative-hypnotics are anticonvulsant, some such as GHB and methaqualone instead lower the seizure threshold, and so can cause paradoxical seizures in overdose.

During the latter part of the 20th century, the number of poisonings from salicylates declined, mainly because of the increased popularity of other over-the-counter analgesics such as paracetamol (acetaminophen). Fifty-two deaths involving single-ingredient aspirin were reported in the United States in 2000; however, in all but three of these cases, the reason for the ingestion of lethal doses was intentional—predominantly suicidal.

In a study comparing the central nervous depression due to supra-therapeutic doses of Triazolam (Benzodiazepine), Pentobarbital (Barbiturate) and GHB it appeared as if GHB had the strongest dose-effect function. Since, GHB had a high correlation between its dose and its central nervous system depression it has a high risk of accidental overdose. In the case of accidental overdose of GHB, patients could become drowsy, fall asleep and may enter a coma. Although GHB had higher sedative effects at high doses as compared to Triazolam and Pentobarbital, it had less amnestic effects as compared to Triazolam and Pentobarbital. Arousal of subjects in the GHB group sometimes even required a painful stimulus; this was not seen in the Triazolam or the Pentobarbital group. Fortunately, during this heavy sedation with GHB the subjects maintained normal respiration and blood pressure. This is often not the case with opioids as they will cause respiratory depression.

The symptoms of a sympathomimetic toxidrome include anxiety, delusions, diaphoresis, hyperreflexia, mydriasis, paranoia, piloerection, and seizures. Complications include hypertension, and tachycardia. Substances that may cause this toxidrome include salbutamol, amphetamines, cocaine, ephedrine (Ma Huang), methamphetamine, phenylpropanolamine (PPA's), and pseudoephedrine. It may appear very similar to the anticholinergic toxidrome, but is distinguished by hyperactive bowel sounds and sweating.

If there is evidence of overdose or it is suspected, the patient should be given gastric lavage, activated charcoal, or both; this could make the difference between life and death in a close situation. It can however aggravate the patient which should be taken into account.

The first line treatments are diazepam and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, alprazolam and propranolol; alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition.

Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down.

CNS depression is treated within a hospital setting by maintaining breathing and circulation. Individuals with reduced breathing may be given supplemental oxygen, while individuals who are not breathing can be ventilated with bag valve mask ventilation or by mechanical ventilation with a respirator. Sympathomimetic drugs may be used to attempt to stimulate cardiac output in order to maintain circulation. CNS Depression caused by certain drugs may respond to treatment with an antidote.

There are two antidotes that are frequently used in the hospital setting and these are Naloxone and Flumazenil. Naloxone is an opioid antagonist and reverses the central nervous depressive effects seen in opioid overdose. In the setting of a colonoscopy, Naloxone is rarely administered but when it is administered, its half life is shorter than some common opioid agonists. Therefore, the patient may still exhibit central nervous system depression after Naloxone has been cleared. Typically, Naloxone is administered in short intervals with relatively small doses in order to prevent the occurrence of withdrawal, pain, and sympathetic nervous system activation. Flumazenil is a benzodiazepine antagonists and blocks the binding of benzodiazepines to GABAa. Similarly to Naloxone, Flumazenil has a short half life, and this needs to be taken into account because the patient may exhibit central nervous depression after the antidote has been cleared. Benzodiazepines are used in the treatment of seizures and subsequently, the administration of Flumazenil may result in seizures. Therefore, slow administration of Flumazenil is necessary to prevent the occurrence of a seizure. These agents are rarely used in the setting of a colonoscopy as 98.8% of colonoscopies use sedatives but only 0.8% of them result in the administration of one of these antidotes. Even if they are rarely used in colonoscopies they are important in preventing the patient from entering a coma or developing respiratory depression when sedatives are not properly dosed. Outside of the colonoscopy setting, these agents are used for other procedures and in the case of drug overdose.

Intravenous fluids containing dextrose such as D5W are recommended to keep a urinary output between 2 and 3 ml/kg/h.

Sodium bicarbonate is given in a significant aspirin overdose (salicylate level greater than 35 mg/dl 6 hours after ingestion) regardless of the serum pH, as it enhances elimination of aspirin in the urine. It is given until a urine pH between 7.5 and 8.0 is achieved.

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

Kim Janda has been working for years on a vaccination that would treat cocaine use disorders by limiting its rewarding effects.

Transcranial magnetic stimulation (TMS) is being studied as a treatment for cocaine addiction. So far studies have been undertaken by Medical University of South Carolina (MUSC), National Institute on Drug Abuse (NIDA), and Mexican National Institute of Psychiatry.