Adverse effect (medicine) In medicine, an adverse effect is a harmful and undesired effect that results from a therapy like medication, chemotherapy, surgery or other intervention. An adverse effect may be called an "adverse reaction"[1] or "side-effect" (when it is less important than the therapeutic effect). It may result from an human error (mistakes) by the patient, from abuse (of substances), or caused by medical errors such as incorrect prescribing of drugs or surgical procedures. Unsuitable or incorrect drug dosage, or medical procedures can come with adverse effects and other risk. Drug-on-drug interactions, where one drug changes how another drug works, are common when people are taking multiple drugs (such as in recreational drug use) or on multi-drug treatment. Some adverse effects happen only at the beginning or a change of a treatment. Medical error was the third most common cause of death in the United States in 2019.[2] Reporting systems In many countries, adverse effects have to be reported and researched in clinical trials and included into the patient information accompanying medical devices and drugs for sale to the public. This is called pharmacovigilance. An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. Adverse effects of medical treatment resulted in 142,000 deaths in 2013 up from 94,000 deaths in 1990 globally. The harmful outcome is usually indicated by some result such as morbidity, mortality, alteration in body weight, levels of enzymes, loss of function, or as a pathological change detected at the microscopic, macroscopic or physiological level. It may also be indicated by symptoms reported by a patient. Adverse effects may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures, such as drug interactions. Adverse effects can occur as a collateral or side effect of many interventions, but they are particularly important in pharmacology, due to its wider, and sometimes uncontrollable, use by way of self-medication. Thus, responsible drug use becomes an important issue here. Adverse effects, like therapeutic effects of drugs, are a function of dosage or drug levels at the target organs, so they may be avoided or decreased by means of careful and precise pharmacokinetics, the change of drug levels in the organism in function of time after administration. Adverse effects may also be caused by drug interaction. This often occurs when patients fail to inform their physician and pharmacist of all the medications they are taking, including herbal and dietary supplements. The new medication may interact agonistically or antagonistically (potentiate or decrease the intended therapeutic effect), causing significant morbidity and mortality around the world. Drug-drug and food-drug interactions may occur, and so-called "natural drugs" used in alternative medicine can have dangerous adverse effects. For example, extracts of St John's wort (Hypericum perforatum), a phytotherapic used for treating mild depression are known to cause an increase in the cytochrome P450 enzymes responsible for the metabolism and elimination of many drugs, so patients taking it are likely to experience a reduction in blood levels of drugs they are taking for other purposes, such as cancer chemotherapeutic drugs, protease inhibitors for HIV and hormonal contraceptives. The scientific field of activity associated with drug safety is increasingly government-regulated, and is of major concern for the public, as well as to drug manufacturers. The distinction between adverse and nonadverse effects is a major undertaking when a new drug is developed and tested before marketing it. This is done in toxicity studies to determine the nonadverse effect level (NOAEL). These studies are used to define the dosage to be used in human testing (phase I), as well as to calculate the maximum admissible daily intake. Imperfections in clinical trials, such as insufficient number of patients or short duration, sometimes lead to public health disasters, such as those of fenfluramine (the so-called fen-phen episode), thalidomide and, more recently, of cerivastatin (Baycol, Lipobay) and rofecoxib (Vioxx), where drastic adverse effects were observed, such as teratogenesis, pulmonary hypertension, stroke, heart disease, neuropathy, and a significant number of deaths, causing the forced or voluntary withdrawal of the drug from the market. Most drugs have a large list of nonsevere or mild adverse effects which do not rule out continued usage. These effects, which have a widely variable incidence according to individual sensitivity, include nausea, dizziness, diarrhea, malaise, vomiting, headache, dermatitis, dry mouth, etc. These can be considered a form of pseudo-allergic reaction, as not all users experience these effects; many users experience none at all. The Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D) warns that people with dementia are

The legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids-often used as adjuvants to standard medicines-may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Growing evidence indicates that dysregulation of ECS may contribute to brain dysfunction, psychopathology, neurodevelopmental problems, neurodegenerative diseases, neuroinflammation, among other physiological functions [ 9 , 10 ]. The last decade has also seen a significant increase in scientific literature addressing the effects of cannabis and cannabinoids for recreational and medicinal purposes [ 11 – 13 ]. To guide policies regarding access and oversight for cannabis for recreational of medicinal purposes it is crucial to summarize the literature on the risks for recreational use and its therapeutic benefits. In this review we summarize (1) mental, physical, and social risks of cannabis when used as recreational drug and (2) the efficacy and safety of cannabis-based medicines. Methods This work aims to update a large systematic literature research on “benefits and risks of cannabinoids” commissioned by the German Ministry of Health [ 14 – 18 ]. For this reason, we conducted a selective literature research in PubMed and the Cochrane Central Register of Clinical Trials. The search period was from 10.5.2016 to 10.5.2023. PubMed was searched with combinations of the mesh terms “Cannabis” or “Cannabinoid” or “Marijuana” or “Medical Marihuana” or “Medical cannabis” or “Pharmaceutical cannabis”. Overdosing and unintentional cannabis use may cause short term psychiatric, gastrointestinal, and cardiovascular problems in children, teens, and adults [ 22 , 23 ]. These unpleasant symptoms generally subside without the need for medical assistance but can require medical assistance in more severe cases. Motoric incoordination Acute cannabis consumption has consistently been associated with a modest increase in the risk of traffic accidents, with odd ratios Only one RCT has compared cannabinoids to a guideline medication (ondansetron) for CINV prevention [ 95 ] and none compared them to new generation drugs (5-HT3- or NK1 antagonists or neuroleptics) [ 94 ]. In cancer anorexia cachexia syndrome patients’ cannabinoid treatment did not significantly improve appetite, oral intake, or anorexia-related quality of life [ 96 ]. Epilepsy CBD has recently been approved as Antiseizure medications for children and adults. A meta-analysis [ 97 ] shows that CBD is moderately efficacious both as standalone and adjunct therapy with clobazam for controlling refractory epilepsy in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. Eye disease Effects of CBD-based cannabinoids are heterogeneous. THC-based effects on intraocular pressure are short-timed and reduced by the development of tolerance. Safe and effective drugs are already available on the market [ 98 ]. Mental disorders To date, only very few studies tested the effects of medicinal cannabinoids to improve symptoms of mental disorders, e.g. CBD is not intoxicating and has fewer safety concerns than THC, but there is the potential for liver toxicity, drug-drug interactions, and there is poor regulatory oversight of CBD products [ 105 ]. THC and/or CBD increase SSRI concentrations in adolescents, and coadministration of CBD and SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue [ 106 ]. A systematic review recently estimated the prevalence of cannabis use disorders in people who use medicinal cannabis is estimated at 25% (CI: 18–33%) [ 107 ]. This risk could be higher in people with chronic non-cancer pain, mental health or substance use disorders [ 107 ].

as a recreational drug inducing a brief "high". It is known for its disassociative effects. When abused chronically, it may cause neurological damage Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas or nitrous, among others, is a chemical compound, an oxide of nitrogen with the formula N2O. At room temperature, it is a colourless non-flammable gas, and has a slightly sweet scent and flavour. At elevated temperatures, nitrous oxide is a powerful oxidiser similar to molecular oxygen. Nitrous oxide has signif Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas or nitrous, among others, is a chemical compound, an oxide of nitrogen with the formula N2O. At room temperature, it is a colourless non-flammable gas, and has a slightly sweet scent and flavour. At elevated temperatures, nitrous oxide is a powerful oxidiser similar to molecular oxygen. Nitrous oxide has significant medical uses, especially in surgery and dentistry, for its anaesthetic and pain-reducing effects, and it is on the World Health Organization's List of Essential Medicines. Its colloquial name, "laughing gas", coined by Humphry Davy, describes the euphoric effects upon inhaling it, which make it attractive as a recreational drug inducing a brief "high". It is known for its disassociative effects. When abused chronically, it may cause neurological damage through inactivation of vitamin B12. It is also used as an oxidiser in rocket propellants and motor racing fuels, and as a frothing gas for whipped cream. Nitrous oxide is also an atmospheric pollutant, with a concentration of 333 parts per billion (ppb) in 2020, increasing at 1 ppb annually. It is a major scavenger of stratospheric ozone, with an impact comparable to that of CFCs. About 40% of human-caused emissions are from agriculture, as nitrogen fertilisers are digested into nitrous oxide by soil micro-organisms. As the third most important greenhouse gas, nitrous oxide Its colloquial name, "laughing gas", coined by Humphry Davy, describes the euphoric effects upon inhaling it, which make it attractive as a recreational drug inducing a brief "high". It is known for its disassociative effects. When abused chronically, it may cause neurological damage through inactivation of vitamin B12. It is also used as an oxidiser in rocket propellants and motor racing fuels, and as a frothing gas for whipped cream. Nitrous oxide is also an atmospheric pollutant, with a concentration of 333 parts per billion (ppb) in 2020, increasing at 1 ppb annually. It is a major scavenger of stratospheric ozone, with an impact comparable to that of CFCs. In that publication, Davy notes the analgesic effect of nitrous oxide at page 465 and its potential to be used for surgical operations at page 556. Davy coined the name "laughing gas" for nitrous oxide. Despite Davy's discovery that inhalation of nitrous oxide could relieve a conscious person from pain, another 44 years elapsed before doctors attempted to use it for anaesthesia. The use of nitrous oxide as a recreational drug at "laughing gas parties", primarily arranged for the British upper class, became an immediate success beginning in 1799. Widespread recreational use of the drug throughout the UK was featured in the 2017 Vice documentary Inside The Laughing Gas Black Market, in which journalist Matt Shea met with dealers of the drug who stole it from hospitals. A significant issue cited in London's press is the effect of nitrous oxide canister littering, which is highly visible and causes significant complaints from communities. Prior to 8 November 2023 in the UK, nitrous oxide was subject to the Psychoactive Substances Act 2016, making it illegal to produce, supply, import or export nitrous oxide for recreational use. The updated law prohibited possession of nitrous oxide, classifying it as a Class C drug under the Misuse of Drugs Act 1971. While nitrous oxide is understood by most recreational users to give a "safe high", many are unaware that excessive consumption may cause neurological harm which, if left untreated, can cause permanent neurological damage. In Australia, recreational use became a public health concern following a rise in reports of neurotoxicity and emergency room admissions. In the state of South Australia, legislation was passed in 2020 to restrict canister sales. The National Institute for Occupational Safety and Health recommends that workers' exposure to nitrous oxide should be controlled during the administration of anaesthetic gas in medical, dental and veterinary operators. It set a recommended exposure limit (REL) of 25 ppm (46 mg/m3) to escaped anaesthetic. Exposure to nitrous oxide causes short-term impairment of cognition, audiovisual acuity, and manual dexterity, as well as spatial and temporal disorientation, putting the user at risk of accidental injury. Nitrous oxide is neurotoxic, and medium or long-term habitual consumption of significant quantities can cause neurological harm with the potential for permanent damage if left untreated. In August 2015, the Council of the London Borough of Lambeth (UK) banned the use of the drug for recreational purposes, making offenders liable to an on-the-spot fine of up to £1,000. In September 2023, the UK Government announced that nitrous oxide would be made illegal by the end of the year as a class C drug, with possession potentially carrying up to a two-year prison sentence or an unlimited fine. Possession of nitrous oxide is legal under United States federal law and is not subject to DEA purview. It is, however, regulated by the Food and Drug Administration under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of human consumption without a proper medical license. Many states have laws regulating the possession, sale and distribution of nitrous oxide. Such laws usually

mediated through elevations in norepinephrine, dopamine, and serotonin leading to euphoria and increased alertness. Classic hallucinogens are serotonin agonists that result in both somatic and neuropsychiatric effects. In the acute setting, monitoring for autonomic instability may be warranted though the management is largely supportive. Anesthetics, inhalants, and other drugs of abuse can lead to non-specific neurological syndromes such as sympathetic hyperactivity, psychomotor agitation, and impaired awareness as well as more distinct complications such as decreased pain perception (PCP, ketamine) and myelopathy (nitrous oxide). Synopsis. Substance use disorders – and their associated neurological complications – are frequently encountered by neurologists as well as emergency room physicians, internists, psychiatrists, and medical intensivists. Prominent neurological sequelae of drug abuse, such as seizure and stroke, are common, and often result in patients receiving medical attention. However, less overt neurologic manifestations, such as dysautonomia and perceptual disturbances, may be initially misattributed to primary medical or psychiatric illness, respectively. This chapter focuses on the epidemiology, pharmacology, and complications associated with commonly-used recreational drugs including opioids, alcohol, marijuana, cocaine, and hallucinogens. PCP, ketamine, and nitrous oxide are also briefly discussed. The neurological aspects of acute intoxication as well as associated withdrawal syndromes are reviewed alongside management strategies. Clinics Care Points. Diagnosing the opioid-associated amnestic syndrome requires timely toxicological screening and brain imaging; the window of detection for fentanyl and other opioids may last for several days, while that for the detection of characteristic hippocampal damage on MRI may last for approximately one week. Naltrexone is indicated for both opioid addiction and alcohol dependence. Tetrahydracannabinol (THC)

Volatile substances of abuse. Substances that are inhaled for the purpose of recreational self-intoxication include aliphatic hydrocarbons, alkyl halides, alkyl nitrites, aromatic hydrocarbons, ethers, and ketones. All have the ability to cause asphyxia, arrhythmias, cardiovascular depression, neurologic dysfunction, and mucosal, pulmonary, and skin irritation following acute exposure and permanent neurologic damage with chronic exposure. The acute effects of alkyl halides and alkyl nitrites also include carbon monoxide poisoning and hepatorenal toxicity, and methemoglobinemia, respectively. Chronic exposure to aromatic hydrocarbons and ketones can result in liver, kidney, and bone marrow injury; myopathy, rhabdomyolysis, metabolic acidosis, and electrolyte abnormalities are further complications of chronic aromatic hydrocarbon inhalation. Published in Emergency medicine clinics of North America (1990)

from any part of plants for medicinal purposes. The medicinal uses of plants are for both … well as to most drugs of abuse. Recreational and Medicinal Uses Responses vary according to … Some of these accidents or events can cause permanent nerve and brain damage to the injured