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Saturday, January 11, 2025

Biomedical engineering

 

From Wikipedia, the free encyclopedia
Telemedicine system. Federal Center of Neurosurgery in Tyumen, 2013
Hemodialysis, a process of purifying the blood of a person whose kidneys are not working normally

Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare applications (e.g., diagnostic or therapeutic purposes). BME is also traditionally logical sciences to advance health care treatment, including diagnosis, monitoring, and therapy. Also included under the scope of a biomedical engineer is the management of current medical equipment in hospitals while adhering to relevant industry standards. This involves procurement, routine testing, preventive maintenance, and making equipment recommendations, a role also known as a Biomedical Equipment Technician (BMET) or as a clinical engineer.

Biomedical engineering has recently emerged as its own field of study, as compared to many other engineering fields. Such an evolution is common as a new field transitions from being an interdisciplinary specialization among already-established fields to being considered a field in itself. Much of the work in biomedical engineering consists of research and development, spanning a broad array of subfields (see below). Prominent biomedical engineering applications include the development of biocompatible prostheses, various diagnostic and therapeutic medical devices ranging from clinical equipment to micro-implants, imaging technologies such as MRI and EKG/ECG, regenerative tissue growth, and the development of pharmaceutical drugs including biopharmaceuticals.

Bioinformatics

Example of an approximately 40,000 probe spotted oligo microarray with enlarged inset to show detail

Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data. As an interdisciplinary field of science, bioinformatics combines computer science, statistics, mathematics, and engineering to analyze and interpret biological data.

Bioinformatics is considered both an umbrella term for the body of biological studies that use computer programming as part of their methodology, as well as a reference to specific analysis "pipelines" that are repeatedly used, particularly in the field of genomics. Common uses of bioinformatics include the identification of candidate genes and nucleotides (SNPs). Often, such identification is made with the aim of better understanding the genetic basis of disease, unique adaptations, desirable properties (esp. in agricultural species), or differences between populations. In a less formal way, bioinformatics also tries to understand the organizational principles within nucleic acid and protein sequences.

Biomechanics

Data obtained from crash test dummy impacts are integral to the field of biomechanics.

Biomechanics is the study of the structure and function of the mechanical aspects of biological systems, at any level from whole organisms to organs, cells and cell organelles,[4] using the methods of mechanics.[5]

Biomaterials

A biomaterial is any matter, surface, or construct that interacts with living systems. As a science, biomaterials is about fifty years old. The study of biomaterials is called biomaterials science or biomaterials engineering. It has experienced steady and strong growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.

Biomedical optics

Biomedical optics combines the principles of physics, engineering, and biology to study the interaction of biological tissue and light, and how this can be exploited for sensing, imaging, and treatment. It has a wide range of applications, including optical imaging, microscopy, ophthalmoscopy, spectroscopy, and therapy. Examples of biomedical optics techniques and technologies include optical coherence tomography (OCT), fluorescence microscopy, confocal microscopy, and photodynamic therapy (PDT). OCT, for example, uses light to create high-resolution, three-dimensional images of internal structures, such as the retina in the eye or the coronary arteries in the heart. Fluorescence microscopy involves labeling specific molecules with fluorescent dyes and visualizing them using light, providing insights into biological processes and disease mechanisms. More recently, adaptive optics is helping imaging by correcting aberrations in biological tissue, enabling higher resolution imaging and improved accuracy in procedures such as laser surgery and retinal imaging.

Tissue engineering

Tissue engineering, like genetic engineering (see below), is a major segment of biotechnology – which overlaps significantly with BME.

One of the goals of tissue engineering is to create artificial organs (via biological material) for patients that need organ transplants. Biomedical engineers are currently researching methods of creating such organs. Researchers have grown solid jawbones and tracheas from human stem cells towards this end. Several artificial urinary bladders have been grown in laboratories and transplanted successfully into human patients. Bioartificial organs, which use both synthetic and biological component, are also a focus area in research, such as with hepatic assist devices that use liver cells within an artificial bioreactor construct.

Micromass cultures of C3H-10T1/2 cells at varied oxygen tensions stained with Alcian blue

Genetic engineering

Genetic engineering, recombinant DNA technology, genetic modification/manipulation (GM) and gene splicing are terms that apply to the direct manipulation of an organism's genes. Unlike traditional breeding, an indirect method of genetic manipulation, genetic engineering utilizes modern tools such as molecular cloning and transformation to directly alter the structure and characteristics of target genes. Genetic engineering techniques have found success in numerous applications. Some examples include the improvement of crop technology (not a medical application, but see biological systems engineering), the manufacture of synthetic human insulin through the use of modified bacteria, the manufacture of erythropoietin in hamster ovary cells, and the production of new types of experimental mice such as the oncomouse (cancer mouse) for research.

Neural engineering

Neural engineering (also known as neuroengineering) is a discipline that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs. Neural engineering can assist with numerous things, including the future development of prosthetics. For example, cognitive neural prosthetics (CNP) are being heavily researched and would allow for a chip implant to assist people who have prosthetics by providing signals to operate assistive devices.

Pharmaceutical engineering

Pharmaceutical engineering is an interdisciplinary science that includes drug engineering, novel drug delivery and targeting, pharmaceutical technology, unit operations of chemical engineering, and pharmaceutical analysis. It may be deemed as a part of pharmacy due to its focus on the use of technology on chemical agents in providing better medicinal treatment.

Hospital and medical devices

Schematic of silicone membrane oxygenator

This is an extremely broad category—essentially covering all health care products that do not achieve their intended results through predominantly chemical (e.g., pharmaceuticals) or biological (e.g., vaccines) means, and do not involve metabolism.

A medical device is intended for use in:

  • the diagnosis of disease or other conditions
  • in the cure, mitigation, treatment, or prevention of disease.

Some examples include pacemakers, infusion pumps, the heart-lung machine, dialysis machines, artificial organs, implants, artificial limbs, corrective lenses, cochlear implants, ocular prosthetics, facial prosthetics, somato prosthetics, and dental implants.

Biomedical instrumentation amplifier schematic used in monitoring low voltage biological signals, an example of a biomedical engineering application of electronic engineering to electrophysiology

Stereolithography is a practical example of medical modeling being used to create physical objects. Beyond modeling organs and the human body, emerging engineering techniques are also currently used in the research and development of new devices for innovative therapies, treatments, patient monitoring, of complex diseases.

Medical devices are regulated and classified (in the US) as follows (see also Regulation):

  • Class I devices present minimal potential for harm to the user and are often simpler in design than Class II or Class III devices. Devices in this category include tongue depressors, bedpans, elastic bandages, examination gloves, and hand-held surgical instruments, and other similar types of common equipment.
  • Class II devices are subject to special controls in addition to the general controls of Class I devices. Special controls may include special labeling requirements, mandatory performance standards, and postmarket surveillance. Devices in this class are typically non-invasive and include X-ray machines, PACS, powered wheelchairs, infusion pumps, and surgical drapes.
  • Class III devices generally require premarket approval (PMA) or premarket notification (510k), a scientific review to ensure the device's safety and effectiveness, in addition to the general controls of Class I. Examples include replacement heart valves, hip and knee joint implants, silicone gel-filled breast implants, implanted cerebellar stimulators, implantable pacemaker pulse generators and endosseous (intra-bone) implants.

Medical imaging

Medical/biomedical imaging is a major segment of medical devices. This area deals with enabling clinicians to directly or indirectly "view" things not visible in plain sight (such as due to their size, and/or location). This can involve utilizing ultrasound, magnetism, UV, radiology, and other means.

Alternatively, navigation-guided equipment utilizes electromagnetic tracking technology, such as catheter placement into the brain or feeding tube placement systems. For example, ENvizion Medical's ENvue, an electromagnetic navigation system for enteral feeding tube placement. The system uses an external field generator and several EM passive sensors enabling scaling of the display to the patient's body contour, and a real-time view of the feeding tube tip location and direction, which helps the medical staff ensure the correct placement in the GI tract.

A T1-weighted MRI scan of a human head, an example of a biomedical engineering application of electrical engineering to diagnostic imaging. Click here to view an animated sequence of slices.

Imaging technologies are often essential to medical diagnosis, and are typically the most complex equipment found in a hospital including: fluoroscopy, magnetic resonance imaging (MRI), nuclear medicine, positron emission tomography (PET), PET-CT scans, projection radiography such as X-rays and CT scans, tomography, ultrasound, optical microscopy, and electron microscopy.

Medical implants

An implant is a kind of medical device made to replace and act as a missing biological structure (as compared with a transplant, which indicates transplanted biomedical tissue). The surface of implants that contact the body might be made of a biomedical material such as titanium, silicone or apatite depending on what is the most functional. In some cases, implants contain electronics, e.g. artificial pacemakers and cochlear implants. Some implants are bioactive, such as subcutaneous drug delivery devices in the form of implantable pills or drug-eluting stents.

Artificial limbs: The right arm is an example of a prosthesis, and the left arm is an example of myoelectric control.
A prosthetic eye, an example of a biomedical engineering application of mechanical engineering and biocompatible materials to ophthalmology

Bionics

Artificial body part replacements are one of the many applications of bionics. Concerned with the intricate and thorough study of the properties and function of human body systems, bionics may be applied to solve some engineering problems. Careful study of the different functions and processes of the eyes, ears, and other organs paved the way for improved cameras, television, radio transmitters and receivers, and many other tools.

Biomedical sensors

In recent years biomedical sensors based in microwave technology have gained more attention. Different sensors can be manufactured for specific uses in both diagnosing and monitoring disease conditions, for example microwave sensors can be used as a complementary technique to X-ray to monitor lower extremity trauma. The sensor monitor the dielectric properties and can thus notice change in tissue (bone, muscle, fat etc.) under the skin so when measuring at different times during the healing process the response from the sensor will change as the trauma heals.

Clinical engineering

Clinical engineering is the branch of biomedical engineering dealing with the actual implementation of medical equipment and technologies in hospitals or other clinical settings. Major roles of clinical engineers include training and supervising biomedical equipment technicians (BMETs), selecting technological products/services and logistically managing their implementation, working with governmental regulators on inspections/audits, and serving as technological consultants for other hospital staff (e.g. physicians, administrators, I.T., etc.). Clinical engineers also advise and collaborate with medical device producers regarding prospective design improvements based on clinical experiences, as well as monitor the progression of the state of the art so as to redirect procurement patterns accordingly.

Their inherent focus on practical implementation of technology has tended to keep them oriented more towards incremental-level redesigns and reconfigurations, as opposed to revolutionary research & development or ideas that would be many years from clinical adoption; however, there is a growing effort to expand this time-horizon over which clinical engineers can influence the trajectory of biomedical innovation. In their various roles, they form a "bridge" between the primary designers and the end-users, by combining the perspectives of being both close to the point-of-use, while also trained in product and process engineering. Clinical engineering departments will sometimes hire not just biomedical engineers, but also industrial/systems engineers to help address operations research/optimization, human factors, cost analysis, etc. Also, see safety engineering for a discussion of the procedures used to design safe systems. The clinical engineering department is constructed with a manager, supervisor, engineer, and technician. One engineer per eighty beds in the hospital is the ratio. Clinical engineers are also authorized to audit pharmaceutical and associated stores to monitor FDA recalls of invasive items.

Rehabilitation engineering

Ultrasound representation of urinary bladder (black butterfly-like shape) a hyperplastic prostate. An example of practical science and medical science working together.

Rehabilitation engineering is the systematic application of engineering sciences to design, develop, adapt, test, evaluate, apply, and distribute technological solutions to problems confronted by individuals with disabilities. Functional areas addressed through rehabilitation engineering may include mobility, communications, hearing, vision, and cognition, and activities associated with employment, independent living, education, and integration into the community.

While some rehabilitation engineers have master's degrees in rehabilitation engineering, usually a subspecialty of Biomedical engineering, most rehabilitation engineers have an undergraduate or graduate degrees in biomedical engineering, mechanical engineering, or electrical engineering. A Portuguese university provides an undergraduate degree and a master's degree in Rehabilitation Engineering and Accessibility. Qualification to become a Rehab' Engineer in the UK is possible via a University BSc Honours Degree course such as Health Design & Technology Institute, Coventry University.

The rehabilitation process for people with disabilities often entails the design of assistive devices such as Walking aids intended to promote the inclusion of their users into the mainstream of society, commerce, and recreation.

Schematic representation of a normal ECG trace showing sinus rhythm; an example of widely used clinical medical equipment (operates by applying electronic engineering to electrophysiology and medical diagnosis).

Regulatory issues

Regulatory issues have been constantly increased in the last decades to respond to the many incidents caused by devices to patients. For example, from 2008 to 2011, in US, there were 119 FDA recalls of medical devices classified as class I. According to U.S. Food and Drug Administration (FDA), Class I recall is associated to "a situation in which there is a reasonable probability that the use of, or exposure to, a product will cause serious adverse health consequences or death"

A product is safe if patients, users, and third parties do not run unacceptable risks of physical hazards (death, injuries, ...) in its intended use. Protective measures have to be introduced on the devices to reduce residual risks at an acceptable level if compared with the benefit derived from the use of it.

A product is effective if it performs as specified by the manufacturer in the intended use. Effectiveness is achieved through clinical evaluation, compliance to performance standards or demonstrations of substantial equivalence with an already marketed device.

The previous features have to be ensured for all the manufactured items of the medical device. This requires that a quality system shall be in place for all the relevant entities and processes that may impact safety and effectiveness over the whole medical device lifecycle.

The medical device engineering area is among the most heavily regulated fields of engineering, and practicing biomedical engineers must routinely consult and cooperate with regulatory law attorneys and other experts. The Food and Drug Administration (FDA) is the principal healthcare regulatory authority in the United States, having jurisdiction over medical devices, drugs, biologics, and combination products. The paramount objectives driving policy decisions by the FDA are safety and effectiveness of healthcare products that have to be assured through a quality system in place as specified under 21 CFR 829 regulation. In addition, because biomedical engineers often develop devices and technologies for "consumer" use, such as physical therapy devices (which are also "medical" devices), these may also be governed in some respects by the Consumer Product Safety Commission. The greatest hurdles tend to be 510K "clearance" (typically for Class 2 devices) or pre-market "approval" (typically for drugs and class 3 devices).

In the European context, safety effectiveness and quality is ensured through the "Conformity Assessment" which is defined as "the method by which a manufacturer demonstrates that its device complies with the requirements of the European Medical Device Directive". The directive specifies different procedures according to the class of the device ranging from the simple Declaration of Conformity (Annex VII) for Class I devices to EC verification (Annex IV), Production quality assurance (Annex V), Product quality assurance (Annex VI) and Full quality assurance (Annex II). The Medical Device Directive specifies detailed procedures for Certification. In general terms, these procedures include tests and verifications that are to be contained in specific deliveries such as the risk management file, the technical file, and the quality system deliveries. The risk management file is the first deliverable that conditions the following design and manufacturing steps. The risk management stage shall drive the product so that product risks are reduced at an acceptable level with respect to the benefits expected for the patients for the use of the device. The technical file contains all the documentation data and records supporting medical device certification. FDA technical file has similar content although organized in a different structure. The Quality System deliverables usually include procedures that ensure quality throughout all product life cycles. The same standard (ISO EN 13485) is usually applied for quality management systems in the US and worldwide.

Implants, such as artificial hip joints, are generally extensively regulated due to the invasive nature of such devices.

In the European Union, there are certifying entities named "Notified Bodies", accredited by the European Member States. The Notified Bodies must ensure the effectiveness of the certification process for all medical devices apart from the class I devices where a declaration of conformity produced by the manufacturer is sufficient for marketing. Once a product has passed all the steps required by the Medical Device Directive, the device is entitled to bear a CE marking, indicating that the device is believed to be safe and effective when used as intended, and, therefore, it can be marketed within the European Union area.

The different regulatory arrangements sometimes result in particular technologies being developed first for either the U.S. or in Europe depending on the more favorable form of regulation. While nations often strive for substantive harmony to facilitate cross-national distribution, philosophical differences about the optimal extent of regulation can be a hindrance; more restrictive regulations seem appealing on an intuitive level, but critics decry the tradeoff cost in terms of slowing access to life-saving developments.

RoHS II

Directive 2011/65/EU, better known as RoHS 2 is a recast of legislation originally introduced in 2002. The original EU legislation "Restrictions of Certain Hazardous Substances in Electrical and Electronics Devices" (RoHS Directive 2002/95/EC) was replaced and superseded by 2011/65/EU published in July 2011 and commonly known as RoHS 2. RoHS seeks to limit the dangerous substances in circulation in electronics products, in particular toxins and heavy metals, which are subsequently released into the environment when such devices are recycled.

The scope of RoHS 2 is widened to include products previously excluded, such as medical devices and industrial equipment. In addition, manufacturers are now obliged to provide conformity risk assessments and test reports – or explain why they are lacking. For the first time, not only manufacturers but also importers and distributors share a responsibility to ensure Electrical and Electronic Equipment within the scope of RoHS complies with the hazardous substances limits and have a CE mark on their products.

IEC 60601

The new International Standard IEC 60601 for home healthcare electro-medical devices defining the requirements for devices used in the home healthcare environment. IEC 60601-1-11 (2010) must now be incorporated into the design and verification of a wide range of home use and point of care medical devices along with other applicable standards in the IEC 60601 3rd edition series.

The mandatory date for implementation of the EN European version of the standard is June 1, 2013. The US FDA requires the use of the standard on June 30, 2013, while Health Canada recently extended the required date from June 2012 to April 2013. The North American agencies will only require these standards for new device submissions, while the EU will take the more severe approach of requiring all applicable devices being placed on the market to consider the home healthcare standard.

AS/NZS 3551:2012

AS/ANS 3551:2012 is the Australian and New Zealand standards for the management of medical devices. The standard specifies the procedures required to maintain a wide range of medical assets in a clinical setting (e.g. Hospital). The standards are based on the IEC 606101 standards.

The standard covers a wide range of medical equipment management elements including, procurement, acceptance testing, maintenance (electrical safety and preventive maintenance testing) and decommissioning.

Training and certification

Education

Biomedical engineers require considerable knowledge of both engineering and biology, and typically have a Bachelor's (B.Sc., B.S., B.Eng. or B.S.E.) or Master's (M.S., M.Sc., M.S.E., or M.Eng.) or a doctoral (Ph.D., or MD-PhD) degree in BME (Biomedical Engineering) or another branch of engineering with considerable potential for BME overlap. As interest in BME increases, many engineering colleges now have a Biomedical Engineering Department or Program, with offerings ranging from the undergraduate (B.Sc., B.S., B.Eng. or B.S.E.) to doctoral levels. Biomedical engineering has only recently been emerging as its own discipline rather than a cross-disciplinary hybrid specialization of other disciplines; and BME programs at all levels are becoming more widespread, including the Bachelor of Science in Biomedical Engineering which includes enough biological science content that many students use it as a "pre-med" major in preparation for medical school. The number of biomedical engineers is expected to rise as both a cause and effect of improvements in medical technology.

In the U.S., an increasing number of undergraduate programs are also becoming recognized by ABET as accredited bioengineering/biomedical engineering programs. As of 2023, 155 programs are currently accredited by ABET.

In Canada and Australia, accredited graduate programs in biomedical engineering are common. For example, McMaster University offers an M.A.Sc, an MD/PhD, and a PhD in Biomedical engineering. The first Canadian undergraduate BME program was offered at University of Guelph as a four-year B.Eng. program. The Polytechnique in Montreal is also offering a bachelors's degree in biomedical engineering as is Flinders University.

As with many degrees, the reputation and ranking of a program may factor into the desirability of a degree holder for either employment or graduate admission. The reputation of many undergraduate degrees is also linked to the institution's graduate or research programs, which have some tangible factors for rating, such as research funding and volume, publications and citations. With BME specifically, the ranking of a university's hospital and medical school can also be a significant factor in the perceived prestige of its BME department/program.

Graduate education is a particularly important aspect in BME. While many engineering fields (such as mechanical or electrical engineering) do not need graduate-level training to obtain an entry-level job in their field, the majority of BME positions do prefer or even require them. Since most BME-related professions involve scientific research, such as in pharmaceutical and medical device development, graduate education is almost a requirement (as undergraduate degrees typically do not involve sufficient research training and experience). This can be either a Masters or Doctoral level degree; while in certain specialties a Ph.D. is notably more common than in others, it is hardly ever the majority (except in academia). In fact, the perceived need for some kind of graduate credential is so strong that some undergraduate BME programs will actively discourage students from majoring in BME without an expressed intention to also obtain a master's degree or apply to medical school afterwards.

Graduate programs in BME, like in other scientific fields, are highly varied, and particular programs may emphasize certain aspects within the field. They may also feature extensive collaborative efforts with programs in other fields (such as the university's Medical School or other engineering divisions), owing again to the interdisciplinary nature of BME. M.S. and Ph.D. programs will typically require applicants to have an undergraduate degree in BME, or another engineering discipline (plus certain life science coursework), or life science (plus certain engineering coursework).

Education in BME also varies greatly around the world. By virtue of its extensive biotechnology sector, its numerous major universities, and relatively few internal barriers, the U.S. has progressed a great deal in its development of BME education and training opportunities. Europe, which also has a large biotechnology sector and an impressive education system, has encountered trouble in creating uniform standards as the European community attempts to supplant some of the national jurisdictional barriers that still exist. Recently, initiatives such as BIOMEDEA have sprung up to develop BME-related education and professional standards. Other countries, such as Australia, are recognizing and moving to correct deficiencies in their BME education. Also, as high technology endeavors are usually marks of developed nations, some areas of the world are prone to slower development in education, including in BME.

Licensure/certification

As with other learned professions, each state has certain (fairly similar) requirements for becoming licensed as a registered Professional Engineer (PE), but, in US, in industry such a license is not required to be an employee as an engineer in the majority of situations (due to an exception known as the industrial exemption, which effectively applies to the vast majority of American engineers). The US model has generally been only to require the practicing engineers offering engineering services that impact the public welfare, safety, safeguarding of life, health, or property to be licensed, while engineers working in private industry without a direct offering of engineering services to the public or other businesses, education, and government need not be licensed. This is notably not the case in many other countries, where a license is as legally necessary to practice engineering as it is for law or medicine.

Biomedical engineering is regulated in some countries, such as Australia, but registration is typically only recommended and not required.

In the UK, mechanical engineers working in the areas of Medical Engineering, Bioengineering or Biomedical engineering can gain Chartered Engineer status through the Institution of Mechanical Engineers. The Institution also runs the Engineering in Medicine and Health Division. The Institute of Physics and Engineering in Medicine (IPEM) has a panel for the accreditation of MSc courses in Biomedical Engineering and Chartered Engineering status can also be sought through IPEM.

The Fundamentals of Engineering exam – the first (and more general) of two licensure examinations for most U.S. jurisdictions—does now cover biology (although technically not BME). For the second exam, called the Principles and Practices, Part 2, or the Professional Engineering exam, candidates may select a particular engineering discipline's content to be tested on; there is currently not an option for BME with this, meaning that any biomedical engineers seeking a license must prepare to take this examination in another category (which does not affect the actual license, since most jurisdictions do not recognize discipline specialties anyway). However, the Biomedical Engineering Society (BMES) is, as of 2009, exploring the possibility of seeking to implement a BME-specific version of this exam to facilitate biomedical engineers pursuing licensure.

Beyond governmental registration, certain private-sector professional/industrial organizations also offer certifications with varying degrees of prominence. One such example is the Certified Clinical Engineer (CCE) certification for Clinical engineers.

Career prospects

In 2012 there were about 19,400 biomedical engineers employed in the US, and the field was predicted to grow by 5% (faster than average) from 2012 to 2022. Biomedical engineering has the highest percentage of female engineers compared to other common engineering professions. Now as of 2023, there are 19,700 jobs for this degree, the average pay for a person in this field is around $100,730.00 and making around $48.43 an hour. There is also expected to be a 7% increase in jobs from here 2023 to 2033 (even faster than the last average).

Notable figures

Anxiolytic

From Wikipedia, the free encyclopedia

An anxiolytic (/ˌæŋksiəˈlɪtɪk, ˌæŋksi-/; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.

Nature of anxiety

Anxiety is a naturally-occurring emotion and response. When anxiety levels exceed the tolerability of a person, anxiety disorders may occur. People with anxiety disorders can exhibit fear responses, such as defensive behaviors, high levels of alertness, and negative emotions. Those with anxiety disorders may have concurrent psychological disorders, such as depression. Anxiety disorders are classified using six possible clinical assessments:

Type Description
Generalized anxiety disorders (GAD) The anxiety symptoms are usually persistent and constant. Patients of this disorder could experience excessive anxiety for a long duration, commonly over six months and the symptoms could occur without any specific triggers.
Panic disorder This disorder specifically refers to the suffering from panic attacks and also the fear of repetitive attacks. Commonly found in agoraphobia patients (the fear of difficulty in leaving a confined venue). Panic attacks are sudden upsurges in anxiety level usually with unexplained reasons.
Social phobia This refers to the fear of staging in social situations where one experiences public observation among people or performs in front of the public. The fears are often unexplained and persistent. The fear could also be attributed to the possible humiliation in front of others due to poor performance or awkward social interactions.
Specific phobias Persistent fear towards a specific object, either tangible or intangible. This leads to undeniable avoidance or thought of escape from the object or endurance of the object in immense levels of anxiety.
Post-traumatic stress disorder (PTSD) PTSDs develop due to experience of severe trauma or life-threatening events. Specific symptoms include flashbacks to traumatic events triggered during similar situations, as well as avoidance of these situations. The fear of re-experiencing the event is also associated with feelings of helplessness or horror.
Obsessive–compulsive disorder (OCD) Person with OCD would experience compulsive impulses of removing an obsession. One common example is the obsession with impurities or contamination. The person would have compulsion or urge in sterilizing the environment to remove the contamination. Another example is the obsession with orderliness. The person would manipulate the surroundings including visual presentations to ease their obsession.

Different types of anxiety disorders will share some general symptoms while having their own distinctive symptoms. This explains why people with different types of anxiety disorders will respond differently to different classes of anti-anxiety medications.

Etiology

The etiology of anxiety disorder remains unknown. There are several contributing factors that are still yet to be proved to cause anxiety disorders. These factors include childhood anxiety, drug induction by central stimulant drugs, metabolic diseases or having depressive disorder.

Medications

Anti-anxiety medication is any drug that can be taken or prescribed for the treatment of anxiety disorders, which may be mediated by neurotransmitters like norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA) in the central nervous system. Anti-anxiety medication can be classified into six types according to their different mechanisms: antidepressants, benzodiazepines, azapirones, antiepileptics, antipsychotics, and beta blockers.

Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). SSRIs are used in all types of anxiety disorders while SNRIs are used for generalized anxiety disorder (GAD). Both of them are considered as first-line anti-anxiety medications. TCAs are second-line treatment as they cause more significant adverse effects when compared to the first-line treatment. Benzodiazepines are effective in emergent and short-term treatment of anxiety disorders due to their fast onset but carry the risk of dependence. Buspirone is indicated for GAD, which has much slower onset but with the advantage of less sedating and withdrawal effects.

History

The first monoamine oxidase inhibitor (MAOI), iproniazid, was discovered accidentally when developing the new antitubercular drug isoniazid. The drug was found to induce euphoria and improve the patient's appetite and sleep quality.

The first tricyclic antidepressant, imipramine, was originally developed and studied to be an antihistamine alongside other first-generation antihistamines of the time, such as promethazine. TCAs can increase the level of norepinephrine and serotonin by inhibiting their reuptake transport proteins. The majority of TCAs exert greater effect on norepinephrine, which leads to side effects like drowsiness and memory loss. 

In order to be more effective on serotonin agonism and avoid anticholinergic and antihistaminergic side effects, selective serotonin reuptake inhibitors (SSRI) were researched and introduced to treat anxiety disorders. The first SSRI, fluoxetine (Prozac), was discovered in 1974 and approved by FDA in 1987. After that, other SSRIs like sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro) have entered the market.

The first serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine (Effexor), entered the market in 1993. SNRIs can target serotonin and norepinephrine transporters while avoiding imposing significant effects on other adrenergic (α1, α2, and β), histamine (H1), muscarinic, dopamine, or postsynaptic serotonin receptors.

Classifications

There are six groups of anti-anxiety medications available that have been proven to be clinically significant in treatment of anxiety disorders. The groups of medications are as follows.

Drug Class Examples
Antidepressants (e.g., SSRIs, SNRIs) SSRIs e.g., fluoxetine, sertraline; SNRIs e.g., venlafaxine; MAOIs; TCAs
Benzodiazepines Lorazepam, diazepam, alprazolam
Azapirones Buspirone, gepirone, tandospirone
Antiepileptics Gabapentin, pregabalin, tiagabine and valproate
Antipsychotics Olanzapine, risperidone
Beta-adrenoceptor antagonists Propranolol, atenolol

Antidepressants

Medications that are indicated for both anxiety disorders and depression. Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are new generations of antidepressants. They have a much lower adverse effect profile than older antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Therefore, SSRIs and SNRIs are now the first-line agent in treating long term anxiety disorders, given their applications and significance in all six types of disorders.

Benzodiazepines

Benzodiazepines are used for acute anxiety and could be added along with current use of SSRIs to stabilize a treatment. Long-term use in treatment plans is not recommended. Different kinds of benzodiazepine will vary in its pharmacological profile, including its strength of effect and time taken for metabolism. The choice of the benzodiazepine will depend on the corresponding profiles.

Benzodiazepines are used for emergent or short-term management. They are not recommended as the first-line anti-anxiety drugs, but they can be used in combination with SSRIs/SNRIs during the initial treatment stage. Indications include panic disorder, sleep disorders, seizures, acute behavioral disturbance, muscle spasm and premedication and sedation for procedures.

Azapirones

Buspirone can be useful in GAD but not particularly effective in treating phobias, panic disorder or social anxiety disorders. It is a safer option for long-term use as it does not cause dependence like benzodiazepines.

Antiepileptics

Antiepileptics are rarely prescribed as an off-label treatment for anxiety disorders and post-traumatic stress disorders. There have been some suggestions that they may help with anxiety symptoms but there is generally a lack of research on its use.

One antiepileptic, pregabalin, has been found to be better at treating GAD than a placebo, and comparable effects to benzodiazepines. It has also been shown be potentially efficient in treating social anxiety disorder. Gabapentin has been prescribed off-label for anxiety despite a lack of research evidence supporting such use, although some studies have indicated that it may relieve anxiety symptoms. The potential anxiolytic effect of tiagabine has been observed in some pre-clinical trials, but its effectiveness has not yet been proved. Similarly, there is a lack of research on valproate for the treatment of anxiety disorders.

Antipsychotics

Olanzapine and risperidone are atypical antipsychotics which are also effective in GAD and PTSD treatment. However, there is a higher chance of experiencing adverse effects than the other anti-anxiety medications.

Beta-adrenoceptor antagonists

Propranolol is originally used for high blood pressure and heart diseases. It can also be used to treat anxiety with symptoms like tremor or increased heart rate. They work on the nervous system and alleviate the symptoms as a relief. Propranolol is also commonly used for public speaking when one is nervous.

Mechanism of action

SSRIs and SNRIs

Both selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) are reuptake inhibitors of a class of nerve signal transduction chemical called neurotransmitters. Serotonin and norepinephrine are neurotransmitters that are related to nervous control in mood regulation. The level of these neurotransmitters is regulated by the nerve through reuptake to avoid accumulation of the neurotransmitter at the endings of nerve fibers. By reuptaking the neurotransmitter, the level of neuronal activity will go back down and be ready to go back up upon excitation from a new nerve signal. However the neurotransmitter level of patients with anxiety disorders is usually low or the patients’ nerve fibers are insensitive to the neurotransmitters. SSRIs and SNRIs will then block the channel of reuptake and increase the level of the neurotransmitter. The nerve fibers will inhibit further production of neurotransmitters upon the increase. However the prolonged increase will eventually desensitize the nerve about the change in level. Therefore, the action of both SSRIs and SNRIs will take 4–6 weeks to exert their full effect.

Benzodiazepine

Benzodiazepines bind selectively to the GABA receptor, which is the receptor protein found in the nervous system and is in control of the nervous response. Benzodiazepine will increase the entry of chloride ions into the cells by improving the binding between GABA and GABA receptors and then the better opening of the channel for chloride ion passage. The high level of chloride ion inside the nerve cells makes the nerve more difficult to depolarize and inhibit further nerve signal transduction. The excitability of the nerves then reduces and the nervous system slows down. Therefore, the drug can alleviate symptoms of anxiety disorder and make the person less nervous.

Clinical use

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are a class of medications used in the treatment of depression, anxiety disorders, OCD and some personality disorders. SSRIs are the first-line anti-anxiety medications. Serotonin is one of the crucial neurotransmitters in mood enhancement, and increasing serotonin level produces an anti-anxiety effect. SSRIs increase the serotonin level in the brain by inhibiting serotonin uptake pumps on serotonergic systems, without interactions with other receptors and ion channels. SSRIs are beneficial in both acute response and long-term maintenance treatment for both depression and anxiety disorder.

SSRIs can increase anxiety initially due to negative feedback through the serotonergic autoreceptors; for this reason a concurrent benzodiazepine can be used until the anxiolytic effect of the SSRI occurs.

The SSRIs paroxetine and escitalopram are USFDA approved to treat generalized anxiety disorder.

Therapeutic use

Drug Indication Common side effect
Citalopram
  • Depressive illness
  • Panic disorder
  • Acute angle closure glaucoma
  • Apathy (caused by decrease in dopamine release)
  • Flatulence
  • Drowsiness
  • Hypersalivation
  • Migraine
  • Rhinitis
Escitalopram

(active enantiomer of citalopram)

  • Depressive illness
  • Generalized anxiety disorder
  • Obsessive-compulsive disorder
  • Panic disorder
  • Social anxiety disorder
Fluoxetine
  • Chills
  • Feeling abnormal
  • Postmenopausal hemorrhage
  • Uterine disorder
  • Vasodilation
  • Blurred vision

Adverse effect

The common early side effects of SSRIs include nausea and loose stool, which can be solved by discontinuing the treatment. Headache, dizziness, insomnia are the common early side effects as well.

Sexual dysfunction, anorgasmia, erectile dysfunction, and reduced libido are common adverse side effects of SSRIs. Sometimes they may persist after the cessation of treatment.

Withdrawal symptoms like dizziness, headache and flu-like symptoms (fatigue/myalgia/loose stool) may occur if SSRI is stopped suddenly. The brain is incapable of upregulating the receptors to sufficient levels especially after discontinuation of the drugs with short half life like paroxetine. Both fluoxetine and its active metabolite have a long half life therefore it causes the least withdrawal symptoms.

Serotonin–norepinephrine reuptake inhibitors

Serotonin–norepinephrine reuptake inhibitor (SNRIs) include venlafaxine and duloxetine drugs. Venlafaxine, in extended release form, and duloxetine, are indicated for the treatment of GAD. SNRIs are as effective as SSRIs in the treatment of anxiety disorders.

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) have anxiolytic effects; however, side effects are often more troubling or severe and overdose is dangerous. They are considered effective, but have generally been replaced by antidepressants that cause different adverse effects. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.

Therapeutic use

Drugs Indication Common side effect
Imipramine
  • Nocturnal enuresis for children above six years old
  • Severe depression
  • Antihistamine side effects like sedation, weight gain
  • Anticholinergic side effects like blurred vision, dry mouth, constipation
Clomipramine
  • Depressive illness
  • Phobic and obsessional states
  • Adjunctive treatment of cataplexy associated with narcolepsy

Contraindication

TCAs may cause drug poisoning in patients with hypotension, cardiovascular diseases and arrhythmias.

Tetracyclic antidepressants

Mirtazapine has demonstrated anxiolytic effect comparable to SSRIs while rarely causing or exacerbating anxiety. Mirtazapine's anxiety reduction tends to occur significantly faster than SSRIs.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are first-generation antidepressants effective for anxiety treatment but their dietary restrictions, adverse effect profile and availability of newer medications have limited their use. MAOIs include phenelzine, isocarboxazid and tranylcypromine. Pirlindole is a reversible MAOI that lacks dietary restriction.

Barbiturates

Barbiturates are powerful anxiolytics but the risk of abuse and addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable for the short-term treatment of severe insomnia, though only after benzodiazepines or non-benzodiazepines have failed.

Benzodiazepines

Benzodiazepines are prescribed to quell panic attacks. Benzodiazepines are also prescribed in tandem with an antidepressant for the latent period of efficacy associated with many ADs for anxiety disorder. There is risk of benzodiazepine withdrawal and rebound syndrome if BZDs are rapidly discontinued. Tolerance and dependence may occur. The risk of abuse in this class of medication is smaller than in that of barbiturates. Cognitive and behavioral adverse effects are possible.

Benzodiazepines include: alprazolam (Xanax), bromazepam, chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), oxazepam, temazepam, and Triazolam.

Therapeutic use

Drug Indication Common Side effect
Lorazepam
  • Decreased alertness
  • Ataxia, confusion (more in elderly)
Diazepam
  • Muscle spasm of varied aetiology
  • Anxiety
  • Acute drug-induced dystonic reactions
  • Sedation for minor surgical and medical procedures
  • Abnormal appetite
  • Concentration impairment
  • Gastrointestinal disorder
  • Movement disorder
  • Muscle spasm
  • Vomiting
Alprazolam
  • Short term use in anxiety
  • As all benzodiazepines

Adverse effect

Benzodiazepines lead to central nervous system depression, resulting in common adverse effects like drowsiness, oversedation, light-headedness. Memory impairment can be a common adverse effect especially in elderly, hypersalivation, ataxia, slurred speech, psychomotor effects.

Sympatholytics

Sympatholytics are a group of anti-hypertensives which inhibit activity of the sympathetic nervous system. Beta blockers reduce anxiety by decreasing heart rate and preventing shaking. Beta blockers include propranolol, oxprenolol, and metoprolol. The alpha-1 antagonist prazosin could be effective for PTSD. The alpha-2 agonists clonidine and guanfacine have demonstrated both anxiolytic and anxiogenic effects.

Miscellaneous

Buspirone

Buspirone (Buspar) is a 5-HT1A receptor agonist used to treated generalized anxiety disorder. If an individual has only recently stopped taking benzodiazepines, buspirone will be less effective.

Pregabalin

Pregabalin (Lyrica) produces anxiolytic effect after one week of use comparable to lorazepam, alprazolam, and venlafaxine with more consistent psychic and somatic anxiety reduction. Unlike BZDs, it does not disrupt sleep architecture nor does it cause cognitive or psychomotor impairment.

Hydroxyzine

Hydroxyzine (Atarax) is an antihistamine originally approved for clinical use by the FDA in 1956. Hydroxyzine has a calming effect which helps ameliorate anxiety. Hydroxyzine efficacy is comparable to benzodiazepines in the treatment of generalized anxiety disorder.

Phenibut

Phenibut (Anvifen, Fenibut, Noofen) is an anxiolytic used in Russia. Phenibut is a GABAB receptor agonist, as well as an antagonist at α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin. The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.

Temgicoluril

Temgicoluril (Mebicar) is an anxiolytic produced in Latvia and used in Eastern Europe. Temgicoluril has an effect on the structure of limbic-reticular activity, particularly on the hypothalamus, as well as on all four basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity. Temgicoluril decreases noradrenaline, increases serotonin, and exerts no effect on dopamine.

Fabomotizole

Fabomotizole (Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. Its mechanism of action is poorly-defined, with GABAergic, NGF and BDNF release promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma receptor agonism thought to have some involvement.

Bromantane

Bromantane is a stimulant drug with anxiolytic properties developed in Russia during the late 1980s. Bromantane acts mainly by facilitating the biosynthesis of dopamine, through indirect genomic upregulation of relevant enzymes (tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD)).

Emoxypine

Emoxypine is an antioxidant that is also a purported anxiolytic. Its chemical structure resembles that of pyridoxine, a form of vitamin B6.

Menthyl isovalerate

Menthyl isovalerate is a flavoring food additive marketed as a sedative and anxiolytic drug in Russia under the name Validol.

Racetams

Some racetam based drugs such as aniracetam can have an antianxiety effect.

Alpidem

Alpidem is a nonbenzodiazepine anxiolytic with similar anxiolytic effectiveness as benzodiazepines but reduced sedation and cognitive, memory, and motor impairment. It was marketed briefly in France but was withdrawn from the market due to liver toxicity.

Etifoxine

Etifoxine has similar anxiolytic effects as benzodiazepine drugs, but does not produce the same levels of sedation and ataxia. Further, etifoxine does not affect memory and vigilance, and does not induce rebound anxiety, drug dependence, or withdrawal symptoms.

Alcohol

Alcohol is sometimes used as an anxiolytic by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.

Alternatives to medication

Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder, while exposure therapy is the recommended treatment for anxiety related phobias. Healthcare providers can guide those with anxiety disorder by referring them to self-help resources. Sometimes medication is combined with psychotherapy but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.

If CBT is found ineffective, both the Canadian and American medical associations then suggest the use of medication.

Euphoria

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Euphoria
Playing can induce an intense state of happiness and contentment, like this girl playing in the snow.

Euphoria (/juːˈfɔːriə/ yoo-FOR-ee-ə) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and dancing, can induce a state of euphoria. Euphoria is also a symptom of certain neurological or neuropsychiatric disorders, such as mania. Romantic love and components of the human sexual response cycle are also associated with the induction of euphoria. Certain drugs, many of which are addictive, can cause euphoria, which at least partially motivates their recreational use.

Hedonic hotspots – i.e., the pleasure centers of the brain – are functionally linked. Activation of one hotspot results in the recruitment of the others. Inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense euphoria.

History

The word "euphoria" is derived from the Ancient Greek terms εὐφορία: εὖ eu meaning "well" and φέρω pherō meaning "to bear". It is semantically opposite to dysphoria.

A 1706 English dictionary defines euphoria as "the well bearing of the Operation of a Medicine, i.e., when the patient finds himself eas'd or reliev'd by it".

During the 1860s, the English physician Thomas Laycock described euphoria as the feeling of bodily well-being and hopefulness; he noted its misplaced presentation in the final stage of some terminal illnesses and attributed such euphoria to neurological dysfunction. Sigmund Freud's 1884 monograph Über Coca described (his own) consumption of cocaine producing "the normal euphoria of a healthy person", while about 1890 the German neuropsychiatrist Carl Wernicke lectured about the "abnormal euphoria" in patients with mania.

A 1903 article in The Boston Daily Globe refers to euphoria as "pleasant excitement" and "the sense of ease and well-being". In 1920 Popular Science magazine described euphoria as "a high sounding name" meaning "feeling fit": normally making life worth living, motivating drug use, and ill formed in certain mental illnesses. Robert S. Woodworth's 1921 textbook Psychology: A study of mental life, describes euphoria as an organic state which is the opposite of fatigue, and "means about the same as feeling good."

In 1940, The Journal of Psychology defined euphoria as a "state of general well being ... and pleasantly toned feeling." A decade later, finding ordinary feelings of well being difficult to evaluate, American addiction researcher Harris Isbell redefined euphoria as behavioral changes and objective signs typical of morphine. However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable but an effect which "enhance[s] the value of a major analgesic." The 1977 edition of A Concise Encyclopaedia of Psychiatry called euphoria "a mood of contentment and well-being," with pathologic associations when used in a psychiatric context. As a sign of cerebral disease, it was described as bland and out of context, representing an inability to experience negative emotion.

In the 21st century, euphoria is generally defined as a state of great happiness, well-being and excitement, which may be normal, or abnormal and inappropriate when associated with psychoactive drugs, manic states, or brain disease or injury.

Neuropsychology

Hedonic hotspots are functionally interrelated neural substrates/structures that (intrinsically or extrinsically) generate the feelings of pleasure. Activation of one hedonic hotspot involves the stimulation of the others. Inhibition of one hedonic hotspot blunts the activation the other ones. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is probably necessary for generating the sensation of euphoria.

Types

Many different types of stimuli can induce euphoria, including psychoactive drugs, natural rewards, and social activities. Affective disorders such as unipolar mania or bipolar disorder can involve euphoria as a symptom.

Exercise-induced

Continuous exercise can produce a transient state of euphoria – an emotional state involving the experience of pleasure and feelings of profound contentment, elation, and well-being – which is colloquially known as a "runner's high" in distance running or a "rower's high" in rowing.

Music-induced

Euphoria can occur as a result of dancing to music, music-making, and listening to emotionally arousing music. Neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure. Pleasurable emotionally arousing music strongly increases dopamine neurotransmission in the dopaminergic pathways that project to the striatum (i.e., the mesolimbic pathway and nigrostriatal pathway). Approximately 5% of the population experiences a phenomenon termed "musical anhedonia", in which individuals do not experience pleasure from listening to emotionally arousing music despite having the ability to perceive the intended emotion that is conveyed in passages of music.

A clinical study from January 2019 that assessed the effect of a dopamine precursor (levodopa), dopamine antagonist (risperidone), and a placebo on reward responses to music – including the degree of pleasure experienced during musical chills, as measured by changes in electrodermal activity as well as subjective ratings – found that the manipulation of dopamine neurotransmission bidirectionally regulates pleasure cognition (specifically, the hedonic impact of music) in human subjects. This research suggests that increased dopamine neurotransmission acts as a sine qua non condition for pleasurable hedonic reactions to music in humans.

Sex-induced

The various stages of copulation may also be described as inducing euphoria in some people. Various analysts have described either the entire sexual act, the moments leading to orgasm, or the orgasm itself as the pinnacle of human pleasure or euphoria.

Drug-induced

A large dose of methamphetamine causes a drug-induced euphoria.

A euphoriant is a type of psychoactive drug which tends to induce euphoria. Most euphoriants are addictive drugs due to their reinforcing properties and ability to activate the brain's reward system.

Stimulants

Dopaminergic stimulants like amphetamine, methamphetamine, cocaine, MDMA, and methylphenidate are euphoriants. Nicotine is a parasympathetic stimulant that acts as a mild euphoriant in some people. Xanthines such as caffeine and theobromine may also be considered mild euphoriants by some.

Chewing areca nut (seeds from the Areca catechu palm) with slaked lime (calcium hydroxide) – a common practice in South- and Southeast Asia – produces stimulant effects and euphoria. The major psychoactive ingredients – arecoline (a muscarinic receptor partial agonist) and arecaidine (a GABA reuptake inhibitor) – are responsible for the euphoric effect.

Depressants

Certain depressants can produce euphoria; some of those drugs in this class include alcohol in moderate doses, γ-hydroxybutyric acid (GHB), and ketamine.

Some barbiturates and benzodiazepines may cause euphoria. Euphoriant effects are determined by the drug's speed of onset, increasing dose, and with intravenous administration. Barbiturates more likely to cause euphoria include amobarbital, secobarbital and pentobarbital. Benzodiazepines more likely to cause euphoria are flunitrazepam, alprazolam and clonazepam. Benzodiazepines also tend to enhance opioid-induced euphoria.

Pregabalin induces dose-dependent euphoria. Occurring in a small percentage of individuals at recommended doses, euphoria is increasingly frequent at supratherapeutic doses (or with intravenous- or nasal administration). At doses five times the maximum recommended, intense euphoria is reported. Another GABA analogue, gabapentin, may induce euphoria. Characterized as opioid-like but less intense, it may occur at supratherapeutic doses, or in combination with other drugs, such as opioids or alcohol. Ethosuximide and perampanel can also produce euphoria at therapeutic doses.

Opioids

μ-Opioid receptor agonists are a set of euphoriants that include drugs such as heroin, morphine, codeine, oxycodone, and fentanyl. By contrast, κ-opioid receptor agonists, like the endogenous neuropeptide dynorphin, are known to cause dysphoria, a mood state opposite to euphoria that involves feelings of profound discontent.

Cannabinoids

Cannabinoid receptor 1 agonists are a group of euphoriants that includes certain plant-based cannabinoids (e.g., THC from the cannabis plant), endogenous cannabinoids (e.g., anandamide), and synthetic cannabinoids.

Inhalants

Certain gases, like nitrous oxide (N2O, aka "laughing gas"), can induce euphoria when inhaled.

Psychedelics

Traditional psychedelic drugs, such as LSD and psilocybin are capable of inducing euphoria despite lacking addictive qualities. The Global Drug Survey has revealed that out of 22,000 participant reports, MDMA, LSD, and psilocybin mushrooms were ranked most positively on the Net Pleasure Index of all recreational drugs included in the study.

Glucocorticoids

Acute exogenous glucocorticoid administration is known to produce euphoria, but this effect is not observed with long-term exposure.

List of euphoriants by mechanism of action

The following is a full list of euphoriant or rewarding/reinforcing drugs:

Fasting–induced

Fasting has been associated with improved mood, well-being, and sometimes euphoria. Various mechanisms have been proposed and possible applications in treating depression considered.

Neuropsychiatric

Mania

Euphoria is also strongly associated with both hypomania and mania, mental states characterized by a pathological heightening of mood, which may be either euphoric or irritable, in addition to other symptoms, such as pressured speech, flight of ideas, and grandiosity.

Although hypomania and mania are syndromes with multiple etiologies (that is, ones that may arise from any number of conditions), they are most commonly seen in bipolar disorder, a psychiatric illness characterized by alternating periods of mania and depression.

Epilepsy

Euphoria may occur during auras of seizures typically originating in the temporal lobe, but affecting the anterior insular cortex. This euphoria is symptomatic of a rare syndrome called ecstatic seizures, often also involving mystical experiences. Euphoria (or more commonly dysphoria) may also occur in periods between epileptic seizures. This condition, interictal dysphoric disorder, is considered an atypical affective disorder. Persons who experience feelings of depression or anxiety between or before seizures occasionally experience euphoria afterwards.

Migraine

Some persons experience euphoria in the prodrome – hours to days before the onset – of a migraine headache. Similarly, a euphoric state occurs in some persons following the migraine episode.

Multiple sclerosis

Euphoria sometimes occurs in persons with multiple sclerosis as the illness progresses. This euphoria is part of a syndrome originally called euphoria sclerotica, which typically includes disinhibition and other symptoms of cognitive and behavioral dysfunction.

Gender euphoria

Gender euphoria is satisfaction or enjoyment felt by a person due to consistency between their gender identity and gendered features associated with a gender different to the sex they were assigned at birth. It is considered to be the positive counterpart of gender dysphoria. Related euphorias have also been recorded in studies of alignments between sexual identity and social recognition such as support in schools for lesbian and gay people, and experiences of intersex variation and their diagnoses such as receiving a diagnosis of congenital adrenal hyperplasia which explained physical differences for example.

Computational theory of mind

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Computational_theory_of_mind In phil...