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Cannabinoid Receptor
Definição
Os receptores canabinoides, localizados por todo o corpo, fazem parte do sistema endocanabinoide, que está envolvido em uma variedade de processos fisiológicos, incluindo apetite, sensação de dor, humor e memória.
Os receptores canabinóides são de uma classe de receptores de membrana celular na superfamília de receptores acoplados à proteína G. Como é típico dos receptores acoplados à proteína G, os receptores canabinóides contêm sete domínios transmembranares. Os receptores canabinóides são ativados por três grupos principais de ligantes: endocanabinóides, produzidos pelo corpo mamilar; [carece de fontes?] Canabinóides vegetais (como o tetraidrocanabinol, produzido pela planta cannabis); e canabinóides sintéticos (como HU-210). Todos os endocanabinóides e fitocanabinóides (canabinóides vegetais) são lipofílicos, como os compostos solúveis em gordura.
Atualmente, existem dois subtipos conhecidos de receptores de canabinóides, denominados CB1 e CB2. O receptor CB1 é expresso principalmente no cérebro (sistema nervoso central ou "SNC"), mas também nos pulmões, fígado e rins. O receptor CB2 é expresso principalmente no sistema imunológico e em células hematopoiéticas; no entanto, pesquisas posteriores descobriram a existência desses receptores também em partes do cérebro. Evidências crescentes sugerem que existem novos receptores de canabinoides, ou seja, não CB1 e não CB2, que são expressos em células endoteliais e no SNC. Em 2007, foi descrita a ligação de vários canabinóides ao receptor acoplado à proteína G GPR55 no cérebro.
As sequências de proteínas dos receptores CB1 e CB2 são cerca de 44% semelhantes. Quando apenas as regiões transmembranares dos receptores são consideradas, a similaridade de aminoácidos entre os dois subtipos de receptores é de aproximadamente 68%. Além disso, foram identificadas pequenas variações em cada receptor. Os canabinoides ligam-se reversivelmente e estereo-seletivamente aos receptores de canabinoides. Foram desenvolvidos canabinóides seletivos de subtipo que, teoricamente, podem ter vantagens para o tratamento de certas doenças, como a obesidade.
Parece que os receptores canabinóides são exclusivos do filo Chordata e, como tal, têm uma distribuição filogenética bastante restrita no reino animal. No entanto, as enzimas envolvidas na biossíntese / inativação de endocanabinoides e na sinalização de endocanabinoides em geral (envolvendo outros alvos além dos receptores do tipo CB1 / 2) ocorrem em todo o reino animal. Embora os receptores canabinoides sejam exclusivos dos Cordados, outros organismos ainda são capazes de processar os endocanabinoides por meio de outras técnicas.
History of medicinal cannabis
The use of cannabis originated in central Asia or western China. Cannabis has been used for its alleged healing properties for millennia. The first documented case of its use dates back to 2800 BC, when it was listed in the Emperor Shen Nung's (regarded as the father of Chinese medicine) pharmacopoeia.
Today there is much discussion and debate over cannabis and its use in healthcare. But what is often left out of the dialogue is the more than 6000 years of documented experience people have had with this
plant. Historically, cannabis’ medical applications appear to have been realized by most cultures,
however, it appears that much of our modern day cultural perspective on cannabis is based neither on
historical evidence nor recent discovery. As with many scientific disciplines, much can be learned from
our collective history.
4000 BC: Pan-p’o village
Cannabis was regarded among “five grains” in China, and was farmed as a major food crop.
2737 BC: Pen Ts’ao Ching
Earliest record of cannabis as a medicinal drug. At this time, Emperor Shen-Nung recognized its treatment properties for over 100 ailments such as gout, rheumatism, and malaria.
2000-1400 BC: Scythians
Nomadic Indo-European peoples used cannabis in steam baths, and also burned cannabis seeds in burial rituals.
2000-1000 BC: Atharva Vedas
Cannabis was described as a “source of happiness”, “joy-giver”, and “bringer of freedom” in these Hindu religious texts. At this time, cannabis was smoked at daily devotional services and religious rituals.
2000-1000 BC: Ayurvedic Medicine
Open religious use of cannabis allowed for exploration of medical benefits. During this period, it was used to treat a variety of ailments such as epilepsy, rabies, anxiety, and bronchitis.
1550 BC: Ebers Papyrus
Egyptian medical papyrus of medical knowledge notes that medical cannabis can treat inflammation.
1213 BC: Ramesses II
Cannabis pollen has been recovered from the mummy of Ramesses II, the Egyptian pharaoh who was mummified after his death in 1213 BC.
900 BC: Assyrians
Employed the psychotropic effects of cannabis for recreational and medical purposes.
450-200 BC: Greco-Roman use
Physician Dioscorides prescribed cannabis for toothaches and earaches. Greek doctor Claudius Galen noted it was widely consumed throughout the empire. Women of the Roman elite also used cannabis to alleviate labor pains.
207 AD: Hua T’o
First recorded physician to describe cannabis as an analgesic. He used a mixture of cannabis and wine to anesthetize patients before surgery.
1000 AD: Treats Epilepsy
Arabic scholars al-Mayusi and al-Badri regard cannabis as an effective treatment for epilepsy.
1025 AD: Avicenna
The medieval Persian medical writer publishes “Avicenna’s Canon of Medicine”, stating that cannabis is an effective treatment for gout, edema, infectious wounds, and severe headaches. His work was widely studied from the 13th to 19th centuries, having a lasting impact on Western medicine.
1300 AD: Arab traders
Arab traders bring cannabis from India to Eastern Africa, where it spreads inland. It is used to treat malaria, asthma, fever, and dysentery.
1500 AD: Spanish Conquest
The Spanish brought cannabis to the Americas, where it was used for more practical purposes like rope or clothes. However, years later, it would be used as a psychoactive and medicinal drug.
1798: Napoleon
Napoleon brought cannabis back to France from Egypt, and it was investigated for its pain relieving and sedative qualities. At this time, cannabis would be used to treat tumors, cough, and jaundice.
1839: William O’Shaughnessy
Irish doctor William O’Shaughnessy introduced the therapeutic uses of cannabis to Western medicine. He concluded it had no negative medicinal effects, and the plant’s use in a pharmaceutical context would rapidly rise thereafter.
1900: Medical Cannabis
Medical cannabis was used to treat nausea, rheumatism, and labor pain. At this point in time, it is available over-the-counter in medications such as “Piso’s cure” and “One day cough cure”.
1914: Harrison Act
Drug use was declared a crime in the U.S., under the Harrison Narcotics Tax Act in 1914.
1937: Marihuana Tax Act
The Marihuana Tax Act banned the use and sales of cannabis in the United States.
1964: Discovery of THC
The molecular structure of THC, an active component of cannabis, was discovered and synthesized by Israeli chemist Dr. Raphael Mechoulam.
1970: Classified as Schedule 1 Drug
Cannabis became categorized as a Schedule 1 Drug in the U.S., which limited further research into the plant. It was listed as having “no accepted medical use”.
1988: CBD Receptors Discovered
The CBD1 and CBD2 cannabinoid receptors were discovered. Today, we know they are some of the most abundant neuroreceptors in the brain.
2000-2018: Medical cannabis legalization
Governments, such as those of Canada and various states, begin to legalize cannabis for medical purposes from licensed producers. Recreational legalization quickly starts to follow./
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