Psychiatric hospital

From Wikipedia, the free encyclopedia

Traverse City State Hospital, Traverse City, Michigan

Psychiatric hospitals, also known as mental hospitals, mental health units, mental asylums or simply asylums, are hospitals or wards specializing in the treatment of serious mental disorders, such as clinical depression, schizophrenia, and bipolar disorder. Psychiatric hospitals vary widely in their size and grading. Some hospitals may specialize only in short-term or outpatient therapy for low-risk patients. Others may specialize in the temporary or permanent care of residents who, as a result of a psychological disorder, require routine assistance, treatment, or a specialized and controlled environment. Patients are often admitted on a voluntary basis, but people whom psychiatrists believe may pose a significant danger to themselves or others may be subject to involuntary commitment. Psychiatric hospitals may also be referred to as psychiatric wards (or "psych" wards) when they are a subunit of a regular hospital.

Modern psychiatric hospitals evolved from, and eventually replaced the older lunatic asylums. The treatment of inmates in early lunatic asylums was sometimes brutal and focused on containment and restraint. With successive waves of reform, and the introduction of effective evidence-based treatments, most modern psychiatric hospitals provide a primary emphasis on treatment, and attempt where possible to help patients control their own lives in the outside world, with the use of a combination of psychiatric drugs and psychotherapy. An exception is in Japan, where many psychiatric hospitals still use physical restraints on patients, tying them to their beds for days or even months at a time.

A crisis stabilization unit is in effect an emergency department for psychiatry, frequently dealing with suicidal, violent, or otherwise critical individuals. Open units are psychiatric units that are not as secure as crisis stabilization units. Another type of psychiatric hospital is medium term, which provides care lasting several weeks. In the United Kingdom, both crisis admissions and medium term care is usually provided on acute admissions wards. Juvenile or adolescent wards are sections of psychiatric hospitals or psychiatric wards set aside for children or adolescents with mental illness. Long-term care facilities have the goal of treatment and rehabilitation back into society within a short time-frame (two or three years). Another institution for the mentally ill is a community-based halfway house.

History

The York Retreat (c.1796) was built by William Tuke, a pioneer of moral treatment for the mentally ill.

Modern psychiatric hospitals evolved from, and eventually replaced the older lunatic asylums. The development of the modern psychiatric hospital is also the story of the rise of organized, institutional psychiatry.

Hospitals known as bimaristans were built throughout Arab countries beginning around the early 9th century, with the first in Baghdad under the leadership of the Abbasid Caliph Harun al-Rashid. While not devoted solely to patients with psychiatric disorders, they often contained wards for patients exhibiting mania or other psychological distress. Because of cultural taboos against refusing to care for one's family members, mentally ill patients would be surrendered to a bimaristan only if the patient demonstrated violence, incurable chronic illness, or some other extremely debilitating ailment. Psychological wards were typically enclosed by iron bars owing to the aggression of some of the patients.

Western Europe would adopt these views later on with the advances of physicians like Philippe Pinel at the Bicêtre Hospital in France and William Tuke at the York Retreat in England. They advocated the viewing of mental illness as a disorder that required compassionate treatment that would aid in the rehabilitation of the victim. The arrival in the Western world of institutionalisation as a solution to the problem of madness was very much an event of the nineteenth century. The first public mental asylums were established in Britain; the passing of the County Asylums Act 1808 empowered magistrates to build rate-supported asylums in every county to house the many 'pauper lunatics'. Nine counties first applied, the first public asylum opening in 1812 in Nottinghamshire. In 1828, the newly appointed Commissioners in Lunacy were empowered to license and supervise private asylums. The Lunacy Act 1845 made the construction of asylums in every country compulsory with regular inspections on behalf of the Home Secretary. The Act required asylums to have written regulations and to have a resident physician.

At the beginning of the nineteenth century there were a few thousand "sick people" housed in a variety of disparate institutions throughout England, but by 1900 that figure had grown to about 100,000. This growth coincided with the growth of alienism, later known as psychiatry, as a medical specialism. The treatment of inmates in early lunatic asylums was sometimes very brutal and focused on containment and restraint.

In the late 19th and early 20th centuries, terms such as "madness," "lunacy" or "insanity"—all of which assumed a unitary psychosis—were split into numerous "mental diseases," of which catatonia, melancholia and dementia praecox (modern day schizophrenia) were the most common in psychiatric institutions.

In 1961 sociologist Erving Goffman described a theory of the "total institution" and the process by which it takes efforts to maintain predictable and regular behavior on the part of both "guard" and "captor," suggesting that many of the features of such institutions serve the ritual function of ensuring that both classes of people know their function and social role, in other words of "institutionalizing" them. Asylums was a key text in the development of deinstitutionalization.

With successive waves of reform, and the introduction of effective evidence-based treatments, modern psychiatric hospitals provide a primary emphasis on treatment, and attempt where possible to help patients control their own lives in the outside world, with the use of a combination of psychiatric drugs and psychotherapy. These treatments can be involuntary. Involuntary treatments are among the many psychiatric practices which are questioned by the mental patient liberation movement. Most psychiatric hospitals now restrict internet access and any device that can take photos. In the U.S. state of Connecticut, involuntary patients must be examined annually by a court-appointed psychiatrist. Patients may also apply for release at any time and receive a full hearing on the application.

Types

The Republican Vilnius Psychiatric Hospital in Naujoji Vilnia (Parko g. 15), is one of the largest health facilities in Lithuania; built in 1902, official opening on 21 May 1903

There are a number of different types of modern psychiatric hospitals, but all of them house people with mental illnesses of widely variable severity.

Crisis stabilization

Vienna's Narrenturm—German for "fools' tower"—was one of the earliest buildings specifically designed for mentally ill people. It was built in 1784.

The crisis stabilization unit is in effect an emergency department for psychiatry, frequently dealing with suicidal, violent, or otherwise critical individuals.

Open units

Open units are psychiatric units that are not as secure as crisis stabilization units. They are not used for acutely suicidal persons; the focus in these units is to make life as normal as possible for patients while continuing treatment to the point where they can be discharged. However, patients are usually still not allowed to hold their own medications in their rooms, because of the risk of an impulsive overdose. While some open units are physically unlocked, other open units still use locked entrances and exits depending on the type of patients admitted.

Medium-term

Another type of psychiatric hospital is medium term, which provides care lasting several weeks. Most drugs used for psychiatric purposes take several weeks to take effect, and the main purpose of these hospitals is to monitor the patient for the first few weeks of therapy to ensure the treatment is effective.

Juvenile wards

Juvenile wards are sections of psychiatric hospitals or psychiatric wards set aside for children or adolescents with mental illness. However, there are a number of institutions specializing only in the treatment of juveniles, particularly when dealing with drug abuse, self-harm, eating disorders, anxiety, depression or other mental illness.

Long-term care facilities

In the UK long-term care facilities are now being replaced with smaller secure units (some within the hospitals listed above). Modern buildings, modern security and being locally sited to help with reintegration into society once medication has stabilized the condition are often features of such units. An example of this is the Three Bridges Unit, in the grounds of St Bernard's Hospital in West London and the John Munroe Hospital in Staffordshire. However these modern units have the goal of treatment and rehabilitation back into society within a short time-frame (two or three years) and not all patients' treatment can meet this criterion, so the large hospitals mentioned above often retain this role.

These hospitals provide stabilization and rehabilitation for those who are having difficulties such as depression, eating disorders, other mental disorders, and so on.

Halfway houses

One type of institution for the mentally ill is a community-based halfway house. These facilities provide assisted living for patients with mental illnesses for an extended period of time, and often aid in the transition to self-sufficiency. These institutions are considered to be one of the most important parts of a mental health system by many psychiatrists, although some localities lack sufficient funding.

Political imprisonment

In some countries the mental institution may be used in certain cases for the incarceration of political prisoners, as a form of punishment. A notable historical example was the use of punitive psychiatry in the Soviet Union and China.

Secure units

In the UK, criminal courts or the Home Secretary can order the admission of offenders to be detained in hospital under various sections of the Mental Health Act, although the term "criminally insane" is no longer legally or medically recognized. Secure psychiatric units exist in all regions of the UK for this purpose; in addition, there are a small number of Specialist Hospitals which offer care and treatment within conditions of high security. These facilities are run by the National Health Service, which undertake psychiatric assessments and can also provide treatment and accommodation in a safe, hospital environment where patients can be prevented from absconding and there is a reduction in their risk of harm to others and themselves.

These secure hospital facilities are divided into three main categories and are referred to as High, Medium and Low Secure. Although it is a phrase often used by newspapers, there is no such classification as "Maximum Secure". Low Secure units are often incorrectly referred to as "Local Secure" as patients are detained there frequently by local criminal courts for psychiatric assessment before sentencing.

Community hospital utilization

Community hospitals across the United States regularly see mental health discharges. A study of community hospital discharge data from 2003-2011 showed that mental health hospitalizations were increasing for both children (patients aged 0–17 years) and adults (patients aged 18–64). Compared to other hospital utilization, mental health discharges were the slowest increasing hospitalizations for children, but the most rapidly increasing hospitalizations for adults under 64. Some units have been opened to provide "Therapeutically Enhanced Treatment" and so form a subcategory to the three main ones.

The general public are familiar with the names of the High Secure Hospitals due to the frequency that they are mentioned in the news reports about the people who are sent there. Those in England include, Ashworth Hospital in Merseyside; Broadmoor Hospital in Crowthorne, Berkshire and Rampton Secure Hospital in Retford, Nottinghamshire and in Scotland is The State Hospital, Carstairs. Northern Ireland and the Isle of Man have their own Medium and Low Secure units but use the mainland faculties for High Secure, which smaller Channel Islands also transfer their patients to as Out of Area (Off-Island Placements) Referrals under the Mental Health Act 1983. Of the Medium Secure units, there are many more of these in number scattered throughout the UK. As of 2009 there were 27 women only units in England alone. Irish units include those at prisons in Portlaise, Castelrea, and Cork.

Criticism

American psychiatrist Thomas Szasz insisted that psychiatric hospitals are like prisons, not proper hospitals, and that psychiatrists who subject others to coercion function as judges and jailers, not physicians. The French historian Michel Foucault is widely known for his comprehensive critique of the use and abuse of the mental hospital system in Madness and Civilization. He argued that Tuke and Pinel's asylum was a symbolic recreation of the condition of a child under a bourgeois family. It was a microcosm symbolizing the massive structures of bourgeois society and its values: relations of Family–Children (paternal authority), Fault–Punishment (immediate justice), Madness–Disorder (social and moral order).

Erving Goffman coined the term "Total Institution" for mental hospitals and similar places which took over and confined a person's whole life. Goffman placed psychiatric hospitals in the same category as concentration camps, prisons, military organizations, orphanages, and monasteries. In his book Asylums Goffman describes how the institutionalisation process socialises people into the role of a good patient, someone "dull, harmless and inconspicuous"; in turn, it reinforces notions of chronicity in severe mental illness. The Rosenhan experiment of 1973 demonstrated the difficulty of distinguishing sane patients from insane patients.

Franco Basaglia, a leading Italian psychiatrist who inspired and was the architect of the psychiatric reform in Italy, also defined the mental hospital as an oppressive, locked and total institution in which prison-like, punitive rules are applied, in order to gradually eliminate its own contents, and patients, doctors and nurses are all subjected (at different levels) to the same process of institutionalism. American psychiatrist Loren Mosher noticed that the psychiatric institution itself gave him master classes in the art of the "total institution": labeling, unnecessary dependency, the induction and perpetuation of powerlessness, the degradation ceremony, authoritarianism, and the primacy of institutional needs over those of the persons it was ostensibly there to serve-the patients.

The anti-psychiatry movement coming to the fore in the 1960s has opposed many of the practices, conditions, or existence of mental hospitals. The psychiatric consumer/survivor movement has often objected to or campaigned against conditions in mental hospitals or their use, voluntarily or involuntarily. The mental patient liberation movement emphatically opposes involuntary treatment but generally does not have any issue with any psychiatric treatments that are consensual, provided that both parties are free to withdraw consent at any time.

History of psychiatry

From Wikipedia, the free encyclopedia

Ancient

Specialty in psychiatry can be traced in Ancient India. The oldest texts on psychiatry include the ayurvedic text, Charaka Samhita. Some of the first hospitals for curing mental illness were established during the 3rd century BCE.

During the 5th century BCE, mental disorders, especially those with psychotic traits, were considered supernatural in origin, a view which existed throughout ancient Greece and Rome. The beginning of psychiatry as a medical specialty is dated to the middle of the nineteenth century, although one may trace its germination to the late eighteenth century.

Some of the early manuals about mental disorders were created by the Greeks. In the 4th century BCE, Hippocrates theorized that physiological abnormalities may be the root of mental disorders. In 4th- to 5th-century BCE Greece, Hippocrates wrote that he visited Democritus and found him in his garden cutting open animals. Democritus explained that he was attempting to discover the cause of madness and melancholy. Hippocrates praised his work. Democritus had with him a book on madness and melancholy.

Religious leaders often turned to versions of exorcism to treat mental disorders, often utilizing methods that many consider to be cruel and/or barbaric.

Middle Ages

A number of hospitals known as bimaristans were built throughout Arab countries beginning around the early 9th century, with the first in Baghdad. They sometimes contained wards for mentally ill patients, typically those who exhibited violence or suffered from debilitating chronic illness.

Physicians who wrote on mental disorders and their treatment in the Medieval Islamic period included Muhammad ibn Zakariya al-Razi (Rhazes), the Arab physician Najab ud-din Muhammad, and Abu Ali al-Hussain ibn Abdallah ibn Sina, known in the West as Avicenna.

Specialist hospitals were built in medieval Europe from the 13th century to treat mental disorders but were utilized only as custodial institutions and did not provide any type of treatment.

Early modern period

Plan of the Bethlem Royal Hospital, an early public asylum for the mentally ill.

Founded in the 13th century, Bethlem Royal Hospital in London was one of the oldest lunatic asylums. In the late 17th century, privately run asylums for the insane began to proliferate and expand in size. Already in 1632 it was recorded that Bethlem Royal Hospital, London had "below stairs a parlor, a kitchen, two larders, a long entry throughout the house, and 21 rooms wherein the poor distracted people lie, and above the stairs eight rooms more for servants and the poor to lie in". Inmates who were deemed dangerous or disturbing were chained, but Bethlem was an otherwise open building for its inhabitants to roam around its confines and possibly throughout the general neighborhood in which the hospital was situated. In 1676, Bethlem expanded into newly built premises at Moorfields with a capacity for 100 inmates.

In 1713 the Bethel Hospital Norwich was opened, the first purpose-built asylum in England, founded by Mary Chapman.

In 1621, Oxford University mathematician, astrologer, and scholar Robert Burton published one of the earliest treatises on mental illness, The Anatomy of Melancholy, What it is: With all the Kinds, Causes, Symptomes, Prognostickes, and Several Cures of it. In Three Maine Partitions with their several Sections, Members, and Subsections. Philosophically, Medicinally, Historically, Opened and Cut Up. Burton thought that there was "no greater cause of melancholy than idleness, no better cure than business." Unlike English philosopher of science Francis Bacon, Burton argued that knowledge of the mind, not natural science, is humankind's greatest need.

In 1656, Louis XIV of France created a public system of hospitals for those suffering from mental disorders, but as in England, no real treatment was applied.

Humanitarian reform

Dr. Philippe Pinel at the Salpêtrière, 1795 by Tony Robert-Fleury. Pinel ordering the removal of chains from patients at the Paris Asylum for insane women.

During the Enlightenment attitudes towards the mentally ill began to change. It came to be viewed as a disorder that required compassionate treatment that would aid in the rehabilitation of the victim. In 1758 English physician William Battie wrote his Treatise on Madness on the management of mental disorder. It was a critique aimed particularly at the Bethlem Hospital, where a conservative regime continued to use barbaric custodial treatment. Battie argued for a tailored management of patients entailing cleanliness, good food, fresh air, and distraction from friends and family. He argued that mental disorder originated from dysfunction of the material brain and body rather than the internal workings of the mind.

Thirty years later, then ruling monarch in England George III was known to be suffering from a mental disorder. Following the King's remission in 1789, mental illness came to be seen as something which could be treated and cured. The introduction of moral treatment was initiated independently by the French doctor Philippe Pinel and the English Quaker William Tuke.

In 1792 Pinel became the chief physician at the Bicêtre Hospital. In 1797, Jean-Baptiste Pussin first freed patients of their chains and banned physical punishment, although straitjackets could be used instead.

Patients were allowed to move freely about the hospital grounds, and eventually dark dungeons were replaced with sunny, well-ventilated rooms. Pussin and Pinel's approach was seen as remarkably successful and they later brought similar reforms to a mental hospital in Paris for female patients, La Salpetrière. Pinel's student and successor, Jean Esquirol (1772–1840), went on to help establish 10 new mental hospitals that operated on the same principles. There was an emphasis on the selection and supervision of attendants in order to establish a suitable setting to facilitate psychological work, and particularly on the employment of ex-patients as they were thought most likely to refrain from inhumane treatment while being able to stand up to pleading, menaces, or complaining.

The York Retreat (c.1796) was built by William Tuke, a pioneer of moral treatment for the insane.

William Tuke led the development of a radical new type of institution in northern England, following the death of a fellow Quaker in a local asylum in 1790. In 1796, with the help of fellow Quakers and others, he founded the York Retreat, where eventually about 30 patients lived as part of a small community in a quiet country house and engaged in a combination of rest, talk, and manual work. Rejecting medical theories and techniques, the efforts of the York Retreat centered around minimizing restraints and cultivating rationality and moral strength. The entire Tuke family became known as founders of moral treatment.

William Tuke's grandson, Samuel Tuke, published an influential work in the early 19th century on the methods of the retreat; Pinel's Treatise On Insanity had by then been published, and Samuel Tuke translated his term as "moral treatment". Tuke's Retreat became a model throughout the world for humane and moral treatment of patients suffering from mental disorders. The York Retreat inspired similar institutions in the United States, most notably the Brattleboro Retreat and the Hartford Retreat (now The Institute of Living).

Although Tuke, Pinel and others had tried to do away with physical restraint, it remained widespread into the 19th century. At the Lincoln Asylum in England, Robert Gardiner Hill, with the support of Edward Parker Charlesworth, pioneered a mode of treatment that suited "all types" of patients, so that mechanical restraints and coercion could be dispensed with — a situation he finally achieved in 1838. In 1839 Sergeant John Adams and Dr. John Conolly were impressed by the work of Hill, and introduced the method into their Hanwell Asylum, by then the largest in the country. Hill's system was adapted, since Conolly was unable to supervise each attendant as closely as Hill had done. By September 1839, mechanical restraint was no longer required for any patient.

Phrenology

William A. F. Browne was an influential reformer of the lunatic asylum in the mid-19th century, and an advocate of the new 'science' of phrenology.

Scotland's Edinburgh medical school of the eighteenth century developed an interest in mental illness, with influential teachers including William Cullen (1710–1790) and Robert Whytt (1714–1766) emphasising the clinical importance of psychiatric disorders. In 1816, the phrenologist Johann Spurzheim (1776–1832) visited Edinburgh and lectured on his craniological and phrenological concepts; the central concepts of the system were that the brain is the organ of the mind and that human behaviour can be usefully understood in neurological rather than philosophical or religious terms. Phrenologists also laid stress on the modularity of mind.

Some of the medical students, including William A. F. Browne (1805–1885), responded very positively to this materialist conception of the nervous system and, by implication, of mental disorder. George Combe (1788–1858), an Edinburgh solicitor, became an unrivalled exponent of phrenological thinking, and his brother, Andrew Combe (1797–1847), who was later appointed a physician to Queen Victoria, wrote a phrenological treatise entitled Observations on Mental Derangement (1831). They also founded the Edinburgh Phrenological Society in 1820.

Institutionalization

The modern era of institutionalized provision for the care of the mentally ill, began in the early 19th century with a large state-led effort. Public mental asylums were established in Britain after the passing of the 1808 County Asylums Act. This empowered magistrates to build rate-supported asylums in every county to house the many 'pauper lunatics'. Nine counties first applied, and the first public asylum opened in 1812 in Nottinghamshire. Parliamentary Committees were established to investigate abuses at private madhouses like Bethlem Hospital - its officers were eventually dismissed and national attention was focused on the routine use of bars, chains and handcuffs and the filthy conditions the inmates lived in. However, it was not until 1828 that the newly appointed Commissioners in Lunacy were empowered to license and supervise private asylums.

Lord Shaftesbury, a vigorous campaigner for the reform of lunacy law in England, and the Head of the Lunacy Commission for 40 years.

The Lunacy Act 1845 was an important landmark in the treatment of the mentally ill, as it explicitly changed the status of mentally ill people to patients who required treatment. The Act created the Lunacy Commission, headed by Lord Shaftesbury, to focus on lunacy legislation reform. The Commission was made up of eleven Metropolitan Commissioners who were required to carry out the provisions of the Act; the compulsory construction of asylums in every county, with regular inspections on behalf of the Home Secretary. All asylums were required to have written regulations and to have a resident qualified physician. A national body for asylum superintendents - the Medico-Psychological Association - was established in 1866 under the Presidency of William A. F. Browne, although the body appeared in an earlier form in 1841.

In 1838, France enacted a law to regulate both the admissions into asylums and asylum services across the country. Édouard Séguin developed a systematic approach for training individuals with mental deficiencies, and, in 1839, he opened the first school for the severely retarded. His method of treatment was based on the assumption that the mentally deficient did not suffer from disease.

In the United States, the erection of state asylums began with the first law for the creation of one in New York, passed in 1842. The Utica State Hospital was opened approximately in 1850. The creation of this hospital, as of many others, was largely the work of Dorothea Lynde Dix, whose philanthropic efforts extended over many states, and in Europe as far as Constantinople. Many state hospitals in the United States were built in the 1850s and 1860s on the Kirkbride Plan, an architectural style meant to have curative effect.

At the turn of the century, England and France combined had only a few hundred individuals in asylums. By the late 1890s and early 1900s, this number had risen to the hundreds of thousands. However, the idea that mental illness could be ameliorated through institutionalization was soon disappointed. Psychiatrists were pressured by an ever-increasing patient population. The average number of patients in asylums kept on growing. Asylums were quickly becoming almost indistinguishable from custodial institutions, and the reputation of psychiatry in the medical world had hit an extreme low.

Scientific advances

Emil Kraepelin studied and promoted ideas of disease classification for mental disorders.

In the early 1800s, psychiatry made advances in the diagnosis of mental illness by broadening the category of mental disease to include mood disorders, in addition to disease level delusion or irrationality. The term psychiatry (Greek "ψυχιατρική", psychiatrikē) which comes from the Greek "ψυχή" (psychē: "soul or mind") and "ιατρός" (iatros: "healer") was coined by Johann Christian Reil in 1808. Jean-Étienne Dominique Esquirol, a student of Pinel, defined lypemania as an 'affective monomania' (excessive attention to a single thing). This was an early diagnosis of depression.

The 20th century introduced a new psychiatry into the world. Different perspectives of looking at mental disorders began to be introduced. The career of Emil Kraepelin reflects the convergence of different disciplines in psychiatry. Kraepelin initially was very attracted to psychology and ignored the ideas of anatomical psychiatry. Following his appointment to a professorship of psychiatry and his work in a university psychiatric clinic, Kraepelin's interest in pure psychology began to fade and he introduced a plan for a more comprehensive psychiatry. Kraepelin began to study and promote the ideas of disease classification for mental disorders, an idea introduced by Karl Ludwig Kahlbaum. The initial ideas behind biological psychiatry, stating that the different mental disorders were all biological in nature, evolved into a new concept of "nerves" and psychiatry became a rough approximation of neurology and neuropsychiatry. However, Kraepelin was criticized for considering schizophrenia as a biological illness in the absence of any detectable histologic or anatomic abnormalities. While Kraepelin tried to find organic causes of mental illness, he adopted many theses of positivist medicine, but he favoured the precision of nosological classification over the indefiniteness of etiological causation as his basic mode of psychiatric explanation.

Following Sigmund Freud's pioneering work, ideas stemming from psychoanalytic theory also began to take root in psychiatry. The psychoanalytic theory became popular among psychiatrists because it allowed the patients to be treated in private practices instead of warehoused in asylums. By the 1970s the psychoanalytic school of thought had become marginalized within the field.

Otto Loewi's work led to the identification of the first neurotransmitter, acetylcholine.

Biological psychiatry reemerged during this time. Psychopharmacology became an integral part of psychiatry starting with Otto Loewi's discovery of the neuromodulatory properties of acetylcholine; thus identifying it as the first-known neurotransmitter. Neuroimaging was first utilized as a tool for psychiatry in the 1980s. The discovery of chlorpromazine's effectiveness in treating schizophrenia in 1952 revolutionized treatment of the disorder, as did lithium carbonate's ability to stabilize mood highs and lows in bipolar disorder in 1948. Psychotherapy was still utilized, but as a treatment for psychosocial issues. In the 1920s and 1930s, most asylum and academic psychiatrists in Europe believed that manic depressive disorder and schizophrenia were inherited, but in the decades after World War II, the conflation of genetics with Nazi racist ideology thoroughly discredited genetics.

Now genetics are once again thought by some prominent researchers to play a large role in mental illness. The genetic and heritable proportion of the cause of five major psychiatric disorders found in family and twin studies is 81% for schizophrenia, 80% for autism spectrum disorder, 75% for bipolar disorder, 75% for attention deficit hyperactivity disorder, and 37% for major depressive disorder. Geneticist Müller-Hill is quoted as saying "Genes are not destiny, they may give an individual a pre-disposition toward a disorder, for example, but that only means they are more likely than others to have it. It (mental illness) is not a certainty.” Molecular biology opened the door for specific genes contributing to mental disorders to be identified.

Deinstitutionalization

Asylums: Essays on the Social Situation of Mental Patients and Other Inmates (1961), written by sociologist Erving Goffman, examined the social situation of mental patients in the hospital. Based on his participant observation field work, the book developed the theory of the "total institution" and the process by which it takes efforts to maintain predictable and regular behavior on the part of both "guard" and "captor". The book suggested that many of the features of such institutions serve the ritual function of ensuring that both classes of people know their function and social role, in other words of "institutionalizing" them. Asylums was a key text in the development of deinstitutionalisation. At the same time, academic psychiatrist and psychoanalyst Thomas Szasz began publishing articles and books that were highly critical of psychiatry and involuntary treatment, including his best-known work The Myth of Mental Illness in 1961.

In 1963, US president John F. Kennedy introduced legislation delegating the National Institute of Mental Health to administer Community Mental Health Centers for those being discharged from state psychiatric hospitals. Later, though, the Community Mental Health Centers focus shifted to providing psychotherapy for those suffering from acute but less serious mental disorders. Ultimately there were no arrangements made for actively following and treating severely mentally ill patients who were being discharged from hospitals. Some of those suffering from mental disorders drifted into homelessness or ended up in prisons and jails. Studies found that 33% of the homeless population and 14% of inmates in prisons and jails were already diagnosed with a mental illness.

In 1973, psychologist David Rosenhan published the Rosenhan experiment, a study with results that led to questions about the validity of psychiatric diagnoses. Critics such as Robert Spitzer placed doubt on the validity and credibility of the study, but did concede that the consistency of psychiatric diagnoses needed improvement.

Psychiatry, like most medical specialties, has a continuing, significant need for research into its diseases, classifications and treatments. Psychiatry adopts biology's fundamental belief that disease and health are different elements of an individual's adaptation to an environment. But psychiatry also recognizes that the environment of the human species is complex and includes physical, cultural, and interpersonal elements. In addition to external factors, the human brain must contain and organize an individual's hopes, fears, desires, fantasies and feelings. Psychiatry's difficult task is to bridge the understanding of these factors so that they can be studied both clinically and physiologically.

Endocannabinoid system

From Wikipedia, the free encyclopedia

 

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the mammalian central nervous system (including the brain) and peripheral nervous system. The endocannabinoid system is involved in regulating a variety of physiological and cognitive processes including fertility, pregnancy, during pre- and postnatal development, appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis. The ECS is also involved in mediating some of the physiological and cognitive effects of voluntary physical exercise in humans and other animals, such as contributing to exercise-induced euphoria as well as modulating locomotor activity and motivational salience for rewards. In humans, the plasma concentration of certain endocannabinoids (i.e., anandamide) have been found to rise during physical activity; since endocannabinoids can effectively penetrate the blood–brain barrier, it has been suggested that anandamide, along with other euphoriant neurochemicals, contributes to the development of exercise-induced euphoria in humans, a state colloquially referred to as a runner's high.

 

Two primary endocannabinoid receptors have been identified: CB1, first cloned in 1990; and CB2, cloned in 1993. CB1 receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), anandamide, as well as its mimetic phytocannabinoid, THC. One other main endocannabinoid is 2-arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD. 2-AG and CBD are involved in the regulation of appetite, immune system functions and pain management.

Basic overview

The endocannabinoid system, broadly speaking, includes:

• The endogenous arachidonate-based lipids, anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG); these are known as "endocannabinoids" and are physiological ligands for the cannabinoid receptors. Endocannabinoids are all eicosanoids.
• The enzymes that synthesize and degrade the endocannabinoids, such as fatty acid amide hydrolase or monoacylglycerol lipase.
• The cannabinoid receptors CB₁ and CB₂, two G protein-coupled receptors that are located in the central and peripheral nervous systems.

The neurons, neural pathways, and other cells where these molecules, enzymes, and one or both cannabinoid receptor types are all colocalized collectively comprise the endocannabinoid system.
The endocannabinoid system has been studied using genetic and pharmacological methods. These studies have revealed that cannabinoids act as neuromodulators for a variety of processes, including motor learning, appetite, and pain sensation, among other cognitive and physical processes. The localization of the CB1 receptor in the endocannabinoid system has a very large degree of overlap with the orexinergic projection system, which mediates many of the same functions, both physical and cognitive. Moreover, CB1 is colocalized on orexin projection neurons in the lateral hypothalamus and many output structures of the orexin system, where the CB1 and orexin receptor 1 (OX1) receptors physically and functionally join together to form the CB1–OX1 receptor heterodimer.

Expression of receptors

Cannabinoid binding sites exist throughout the central and peripheral nervous systems. The two most relevant receptors for cannabinoids are the CB₁ and CB₂ receptors, which are expressed predominantly in the brain and immune system respectively. Density of expression varies based on species and correlates with the efficacy that cannabinoids will have in modulating specific aspects of behavior related to the site of expression. For example, in rodents, the highest concentration of cannabinoid binding sites are in the basal ganglia and cerebellum, regions of the brain involved in the initiation and coordination of movement. In humans, cannabinoid receptors exist in much lower concentration in these regions, which helps explain why cannabinoids possess a greater efficacy in altering rodent motor movements than they do in humans.

A recent analysis of cannabinoid binding in CB₁ and CB₂ receptor knockout mice found cannabinoid responsiveness even when these receptors were not being expressed, indicating that an additional binding receptor may be present in the brain. Binding has been demonstrated by 2-arachidonoylglycerol (2-AG) on the TRPV1 receptor suggesting that this receptor may be a candidate for the established response.

In addition to CB1 and CB2, certain orphan receptors are known to bind endocannabinoids as well, including GPR18, GPR55 (a regulator of neuroimmune function), and GPR119. CB1 has also been noted to form a functional human receptor heterodimer in orexin neurons with OX1, the CB1–OX1 receptor, which mediates feeding behavior and certain physical processes such as cannabinoid-induced pressor responses which are known to occur through signaling in the rostral ventrolateral medulla.

Endocannabinoid synthesis, release, and degradation

During neurotransmission, the pre-synaptic neuron releases neurotransmitters into the synaptic cleft which bind to cognate receptors expressed on the post-synaptic neuron. Based upon the interaction between the transmitter and receptor, neurotransmitters may trigger a variety of effects in the post-synaptic cell, such as excitation, inhibition, or the initiation of second messenger cascades. Based on the cell, these effects may result in the on-site synthesis of endogenous cannabinoids anandamide or 2-AG by a process that is not entirely clear, but results from an elevation in intracellular calcium. Expression appears to be exclusive, so that both types of endocannabinoids are not co-synthesized. This exclusion is based on synthesis-specific channel activation: a recent study found that in the bed nucleus of the stria terminalis, calcium entry through voltage-sensitive calcium channels produced an L-type current resulting in 2-AG production, while activation of mGluR1/5 receptors triggered the synthesis of anandamide.

Evidence suggests that the depolarization-induced influx of calcium into the post-synaptic neuron causes the activation of an enzyme called transacylase. This enzyme is suggested to catalyze the first step of endocannabinoid biosynthesis by converting phosphatidylethanolamine, a membrane-resident phospholipid, into N-acyl-phosphatidylethanolamine (NAPE). Experiments have shown that phospholipase D cleaves NAPE to yield anandamide. This process is mediated by bile acids. In NAPE-phospholipase D (NAPEPLD)-knockout mice, cleavage of NAPE is reduced in low calcium concentrations, but not abolished, suggesting multiple, distinct pathways are involved in anandamide synthesis. The synthesis of 2-AG is less established and warrants further research.

Once released into the extracellular space by a putative endocannabinoid transporter, messengers are vulnerable to glial cell inactivation. Endocannabinoids are taken up by a transporter on the glial cell and degraded by fatty acid amide hydrolase (FAAH), which cleaves anandamide into arachidonic acid and ethanolamine or monoacylglycerol lipase (MAGL), and 2-AG into arachidonic acid and glycerol. While arachidonic acid is a substrate for leukotriene and prostaglandin synthesis, it is unclear whether this degradative byproduct has unique functions in the central nervous system. Emerging data in the field also points to FAAH being expressed in postsynaptic neurons complementary to presynaptic neurons expressing cannabinoid receptors, supporting the conclusion that it is major contributor to the clearance and inactivation of anandamide and 2-AG after endocannabinoid reuptake. A neuropharmacological study demonstrated that an inhibitor of FAAH (URB597) selectively increases anandamide levels in the brain of rodents and primates. Such approaches could lead to the development of new drugs with analgesic, anxiolytic-like and antidepressant-like effects, which are not accompanied by overt signs of abuse liability.

Binding and intracellular effects

Cannabinoid receptors are G-protein coupled receptors located on the pre-synaptic membrane. While there have been some papers that have linked concurrent stimulation of dopamine and CB₁ receptors to an acute rise in cyclic adenosine monophosphate (cAMP) production, it is generally accepted that CB₁ activation via cannabinoids causes a decrease in cAMP concentration by inhibition of adenylyl cyclase and a rise in the concentration of mitogen-activated protein kinase (MAP kinase). The relative potency of different cannabinoids in inhibition of adenylyl cyclase correlates with their varying efficacy in behavioral assays. This inhibition of cAMP is followed by phosphorylation and subsequent activation of not only a suite of MAP kinases (p38/p42/p44), but also the PI3/PKB and MEK/ERK pathway (Galve-Roperh et al., 2002; Davis et al., 2005; Jones et al., 2005; Graham et al., 2006). Results from rat hippocampal gene chip data after acute administration of tetrahydrocannabinol (THC) showed an increase in the expression of transcripts encoding myelin basic protein, endoplasmic proteins, cytochrome oxidase, and two cell adhesion molecules: NCAM, and SC1; decreases in expression were seen in both calmodulin and ribosomal RNAs (Kittler et al., 2000). In addition, CB1 activation has been demonstrated to increase the activity of transcription factors like c-Fos and Krox-24 (Graham et al., 2006).

Binding and neuronal excitability

The molecular mechanisms of CB₁-mediated changes to the membrane voltage have also been studied in detail. Cannabinoids reduce calcium influx by blocking the activity of voltage-dependent N-, P/Q- and L-type calcium channels. In addition to acting on calcium channels, activation of Gi/o and Gs, the two most commonly coupled G-proteins to cannabinoid receptors, has been shown to modulate potassium channel activity. Recent studies have found that CB₁ activation specifically facilitates potassium ion flux through GIRKs, a family of potassium channels. Immunohistochemistry experiments demonstrated that CB₁ is co-localized with GIRK and Kv1.4 potassium channels, suggesting that these two may interact in physiological contexts.

In the central nervous system, CB₁ receptors influence neuronal excitability, reducing the incoming synaptic input. This mechanism, known as presynaptic inhibition, occurs when a postsynaptic neuron releases endocannabinoids in retrograde transmission, which then bind to cannabinoid receptors on the presynaptic terminal. CB₁ receptors then reduce the amount of neurotransmitter released, so that subsequent excitation in the presynaptic neuron results in diminished effects on the postsynaptic neuron. It is likely that presynaptic inhibition uses many of the same ion channel mechanisms listed above, although recent evidence has shown that CB₁ receptors can also regulate neurotransmitter release by a non-ion channel mechanism, i.e. through Gi/o-mediated inhibition of adenylyl cyclase and protein kinase A. Direct effects of CB₁ receptors on membrane excitability have been reported, and strongly impact the firing of cortical neurons.^[42] A series of behavioral experiments demonstrated that NMDAR, an ionotropic glutamate receptor, and the metabotropic glutamate receptors (mGluRs) work in concert with CB₁ to induce analgesia in mice, although the mechanism underlying this effect is unclear.

Functions of the endocannabinoid system

Memory

Mice treated with tetrahydrocannabinol (THC) show suppression of long-term potentiation in the hippocampus, a process that is essential for the formation and storage of long-term memory. These results concur with anecdotal evidence suggesting that smoking cannabis impairs short-term memory. Consistent with this finding, mice without the CB₁ receptor show enhanced memory and long-term potentiation indicating that the endocannabinoid system may play a pivotal role in the extinction of old memories. One study found that the high-dose treatment of rats with the synthetic cannabinoid HU-210 over several weeks resulted in stimulation of neural growth in the rats' hippocampus region, a part of the limbic system playing a part in the formation of declarative and spatial memories, but did not investigate the effects on short-term or long-term memory. Taken together, these findings suggest that the effects of endocannabinoids on the various brain networks involved in learning and memory may vary.

Role in hippocampal neurogenesis

In the adult brain, the endocannabinoid system facilitates the neurogenesis of hippocampal granule cells. In the subgranular zone of the dentate gyrus, multipotent neural progenitors (NP) give rise to daughter cells that, over the course of several weeks, mature into granule cells whose axons project to and synapse onto dendrites on the CA3 region. NPs in the hippocampus have been shown to possess fatty acid amide hydrolase (FAAH) and express CB₁ and utilize 2-AG. Intriguingly, CB₁ activation by endogenous or exogenous cannabinoids promote NP proliferation and differentiation; this activation is absent in CB₁ knockouts and abolished in the presence of antagonist.

Induction of synaptic depression

The inhibitory effects of cannabinoid receptor stimulation on neurotransmitter release have caused this system to be connected to various forms of depressant plasticity. A recent study conducted with the bed nucleus of the stria terminalis found that the endurance of the depressant effects was mediated by two different signaling pathways based on the type of receptor activated. 2-AG was found to act on presynaptic CB₁ receptors to mediate retrograde short-term depression (STD) following activation of L-type calcium currents, while anandamide was synthesized after mGluR5 activation and triggered autocrine signalling onto postsynapic TRPV1 receptors that induced long-term depression (LTD). Similar post-synaptic receptor dependencies were found in the striatum, but here both effects relied on presynaptic CB₁ receptors. These findings provide the brain a direct mechanism to selectively inhibit neuronal excitability over variable time scales. By selectively internalizing different receptors, the brain may limit the production of specific endocannabinoids to favor a time scale in accordance with its needs.

Appetite

Evidence for the role of the endocannabinoid system in food-seeking behavior comes from a variety of cannabinoid studies. Emerging data suggests that THC acts via CB₁ receptors in the hypothalamic nuclei to directly increase appetite. It is thought that hypothalamic neurons tonically produce endocannabinoids that work to tightly regulate hunger. The amount of endocannabinoids produced is inversely correlated with the amount of leptin in the blood. For example, mice without leptin not only become massively obese but express abnormally high levels of hypothalamic endocannabinoids as a compensatory mechanism. Similarly, when these mice were treated with an endocannabinoid inverse agonists, such as rimonabant, food intake was reduced. When the CB₁ receptor is knocked out in mice, these animals tend to be leaner and less hungry than wild-type mice. A related study examined the effect of THC on the hedonic (pleasure) value of food and found enhanced dopamine release in the nucleus accumbens and increased pleasure-related behavior after administration of a sucrose solution. A related study found that endocannabinoids affect taste perception in taste cells In taste cells, endocannabinoids were shown to selectively enhance the strength of neural signaling for sweet tastes, whereas leptin decreased the strength of this same response. While there is need for more research, these results suggest that cannabinoid activity in the hypothalamus and nucleus accumbens is related to appetitive, food-seeking behavior.

Energy balance and metabolism

The endocannabinoid system has been shown to have a homeostatic role by controlling several metabolic functions, such as energy storage and nutrient transport. It acts on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. It has also been implied in modulating insulin sensitivity. Through all of this, the endocannabinoid system may play a role in clinical conditions, such as obesity, diabetes, and atherosclerosis, which may also give it a cardiovascular role.

Stress response

While the secretion of glucocorticoids in response to stressful stimuli is an adaptive response necessary for an organism to respond appropriately to a stressor, persistent secretion may be harmful. The endocannabinoid system has been implicated in the habituation of the hypothalamic-pituitary-adrenal axis (HPA axis) to repeated exposure to restraint stress. Studies have demonstrated differential synthesis of anandamide and 2-AG during tonic stress. A decrease of anandamide was found along the axis that contributed to basal hypersecretion of corticosterone; in contrast, an increase of 2-AG was found in the amygdala after repeated stress, which was negatively correlated to magnitude of the corticosterone response. All effects were abolished by the CB₁ antagonist AM251, supporting the conclusion that these effects were cannabinoid-receptor dependent. These findings show that anandamide and 2-AG divergently regulate the HPA axis response to stress: while habituation of the stress-induced HPA axis via 2-AG prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the HPA axis to novel stimuli.

Exploration, social behavior, and anxiety

These contrasting effects reveal the importance of the endocannabinoid system in regulating anxiety-dependent behavior. Results suggest that glutamatergic cannabinoid receptors are not only responsible for mediating aggression, but produce an anxiolytic-like function by inhibiting excessive arousal: excessive excitation produces anxiety that limited the mice from exploring both animate and inanimate objects. In contrast, GABAergic neurons appear to control an anxiogenic-like function by limiting inhibitory transmitter release. Taken together, these two sets of neurons appear to help regulate the organism's overall sense of arousal during novel situations.

Immune function

Evidence suggests that endocannabinoids may function as both neuromodulators and immunomodulators in the immune system. Here, they seem to serve an autoprotective role to ameliorate muscle spasms, inflammation, and other symptoms of multiple sclerosis and skeletal muscle spasms. Functionally, the activation of cannabinoid receptors has been demonstrated to play a role in the activation of GTPases in macrophages, neutrophils, and BM cells. These receptors have also been implicated in the proper migration of B cells into the marginal zone (MZ) and the regulation of healthy IgM levels. Some disorders seem to trigger an upregulation of cannabinoid receptors selectively in cells or tissues related to symptom relief and inhibition of disease progression, such as in that rodent neuropathic pain model, where receptors are increased in the spinal cord microglia, dorsal root ganglion, and thalamic neurons.

Multiple sclerosis

Historical records from ancient China and Greece suggest that preparations of Cannabis indica were commonly prescribed to ameliorate multiple sclerosis-like symptoms such as tremors and muscle pain. Modern research has confirmed these effects in a study on diseased mice, wherein both endogenous and exogenous agonists showed ameliorating effects on tremor and spasticity. It remains to be seen whether pharmaceutical preparations such as dronabinol have the same effects in humans. Due to increasing use of medical Cannabis and rising incidence of multiple sclerosis patients who self-medicate with the drug, there has been much interest in exploiting the endocannabinoid system in the cerebellum to provide a legal and effective relief. In mouse models of multiple sclerosis, there is a profound reduction and reorganization of CB₁ receptors in the cerebellum. Serial sections of cerebellar tissue subjected to immunohistochemistry revealed that this aberrant expression occurred during the relapse phase but returned to normal during the remitting phase of the disease. Other studies suggest that CB₁ agonists promote the survival of oligodendrocytes in vitro in the absence of growth and trophic factors; in addition, these agonist have been shown to promote mRNA expression of myelin lipid protein. (Kittler et al., 2000; Mollna-Holgado et al., 2002). Taken together, these studies point to the exciting possibility that cannabinoid treatment may not only be able to attenuate the symptoms of multiple sclerosis but also improve oligodendrocyte function (reviewed in Pertwee, 2001; Mollna-Holgado et al., 2002). 2-AG stimulates proliferation of a microglial cell line by a CB₂ receptor dependent mechanism, and the number of microglial cells is increased in multiple sclerosis.

Female reproduction

The developing embryo expresses cannabinoid receptors early in development that are responsive to anandamide secreted in the uterus. This signaling is important in regulating the timing of embryonic implantation and uterine receptivity. In mice, it has been shown that anandamide modulates the probability of implantation to the uterine wall. For example, in humans, the likelihood of miscarriage increases if uterine anandamide levels are too high or low. These results suggest that intake of exogenous cannabinoids (e.g. cannabis) can decrease the likelihood for pregnancy for women with high anandamide levels, and alternatively, it can increase the likelihood for pregnancy in women whose anandamide levels were too low.

Autonomic nervous system

Peripheral expression of cannabinoid receptors led researchers to investigate the role of cannabinoids in the autonomic nervous system. Research found that the CB₁ receptor is expressed presynaptically by motor neurons that innervate visceral organs. Cannabinoid-mediated inhibition of electric potentials results in a reduction in noradrenaline release from sympathetic nervous system nerves. Other studies have found similar effects in endocannabinoid regulation of intestinal motility, including the innervation of smooth muscles associated with the digestive, urinary, and reproductive systems.

Analgesia

At the spinal cord, cannabinoids suppress noxious-stimulus-evoked responses of neurons in the dorsal horn, possibly by modulating descending noradrenaline input from the brainstem. As many of these fibers are primarily GABAergic, cannabinoid stimulation in the spinal column results in disinhibition that should increase noradrenaline release and attenuation of noxious-stimuli-processing in the periphery and dorsal root ganglion.

The endocannabinoid most researched in pain is palmitoylethanolamide. Palmitoylethanolamide is a fatty amine related to anandamide, but saturated and although initially it was thought that palmitoylethanolamide would bind to the CB1 and the CB2 receptor, later it was found that the most important receptors are the PPAR-alpha receptor, the TRPV receptor and the GPR55 receptor. Palmitoylethanolamide has been evaluated for its analgesic actions in a great variety of pain indications and found to be safe and effective. Basically these data are proof of concept for endocannabinoids and related fatty amines to be therapeutically useful analgesics; palmitoylethanolamide is available under the brand names Normast and PeaPure as nutraceuticals.
Endocannabinoids are involved in placebo induced analgesia responses.

Thermoregulation

Anandamide and N-arachidonoyl dopamine (NADA) have been shown to act on temperature-sensing TRPV1 channels, which are involved in thermoregulation. TRPV1 is activated by the exogenous ligand capsaicin, the active component of chili peppers, which is structurally similar to endocannabinoids. NADA activates the TRPV1 channel with an EC₅₀ of approximately of 50 nM.  The high potency makes it the putative endogenous TRPV1 agonist. Anandamide has also been found to activate TRPV1 on sensory neuron terminals, and subsequently cause vasodilation. TRPV1 may also be activated by methanandamide and arachidonyl-2'-chloroethylamide (ACEA).

Sleep

Increased endocannabinoid signaling within the central nervous system promotes sleep-inducing effects. Intercerebroventricular administration of anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep. Administration of anandamide into the basal forebrain of rats has also been shown to increase levels of adenosine, which plays a role in promoting sleep and suppressing arousal. REM sleep deprivation in rats has been demonstrated to increase CB1 receptor expression in the central nervous system. Furthermore, anandamide levels possess a circadian rhythm in the rat, with levels being higher in the light phase of the day, which is when rats are usually asleep or less active, since they are nocturnal.

Physical exercise

Anandamide is an endogenous cannabinoid neurotransmitter that binds to cannabinoid receptors. It has been shown that aerobic exercise causes an increase in plasma anandamide levels, where the magnitude of this increase is highest at moderate exercise intensity (i.e., exercising at ~70–80% maximum heart rate). Increases in plasma anandamide levels are associated with psychoactive effects because anandamide is able to cross the blood–brain barrier and act within the central nervous system. Thus, because anandamide is a euphoriant and aerobic exercise is associated with euphoric effects, it has been proposed that anandamide partly mediates the short-term mood-lifting effects of exercise (e.g., the euphoria of a runner's high) via exercise-induced increases in its synthesis.

In mice it was demonstrated that certain features of a runner's high depend on cannabinoid receptors. Pharmacological or genetic disruption of cannabinoid signaling via cannabinoid receptors prevents the analgesic and anxiety-reducing effects of running.

Experimental use of CB1 -/- phenotype

Neuroscientists often utilize transgenic CB₁ knockout mice to discern novel roles for the endocannabinoid system. While CB₁ knockout mice are healthy and live into adulthood, there are significant differences between CB₁ knockout and wild-type mice. When subjected to a high-fat diet, CB₁ knockout mice tend to be about sixty percent leaner and slightly less hungry than wildtype. Compared to wildtype, CB₁ knockout mice exhibit severe deficits in motor learning, memory retrieval, and increased difficulty in completing the Morris water maze. There is also evidence indicating that these knockout animals have an increased incidence and severity of stroke and seizure.

Endocannabinoids in plants

The endocannabinoid system is by molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicative of biosynthetic plasticity and potential physiological roles of endocannabinoid-like lipids in plants, and detection of arachidonic acid (AA) indicates chemotaxonomic connections between monophyletic groups with common ancestor dates to around 500 million years ago (silurian; devonian). The phylogenetic distribution of these lipids may be a consequence of interactions/adaptations to the surrounding conditions such as chemical plant-pollinator interactions, communication and defense mechanisms. The two novel EC-like molecules derived from the eicosatetraenoic acid juniperonic acid, an omega-3 structural isomer of AA, namely juniperoyl ethanolamide and 2-juniperoyl glycerol (1/2-AG) in gymnosperms, lycophytes and few monilophytes, show AA is an evolutionarily conserved signalling molecule that acts in plants in response to stress similar to that in animal systems.