CBD如何運作

HOW CBD WORKS

Learn how CBD works with your body's endocannabinoid system.

Cannabidiol (CBD), a non-intoxicating component of the cannabis plant, has generated significant interest among scientists and physicians in recent years—but how CBD exerts its therapeutic impact on a molecular level is still being sorted out. Cannabidiol is a pleiotropic drug in that it produces many effects through multiple molecular pathways. The scientific literature has identified more than 65 molecular targets of CBD.

CBD是這種無毒的大麻植物化合物，近些年來引起了科學家和醫師的興趣——但是CBD如何在分子水平上運作仍在被探索。CBD是一種多功效的藥物，它通過多種分子途徑產生多種作用。科學文獻已經驗證了超過65種CBD分子靶。

Although CBD has little binding affinity for either of the two cannabinoid receptors (CB1 and CB2), cannabidiol modulates several non-cannabinoid receptors and ion channels. CBD also acts through various receptor-independent pathways—for example, by delaying the 「reuptake」 of endogenous neurotransmitters (such as anandamide and adenosine) and by enhancing or inhibiting the binding action of certain G-protein coupled receptors.

雖然CBD對CB1和CB2這兩個受體只有一點點的親和力，但是CBD可以控制多個非大麻素受體和離子通道。CBD還通過各種獨立於受體的途徑發揮作用。例如，通過延遲內源性神經遞質（如腺苷醯胺和腺苷）的「再攝取」，以及增強或抑制某些G蛋白偶聯受體的結合作用。

Here are some of the ways that CBD confers its manifold therapeutic effects.

這是CBD賦予其多種治療方式的多種途徑。

SEROTONIN RECEPTORS

血清素受體

Jose Alexandre Crippa and his colleagues at the University of San Paulo in Brazil and King’s College in London have conducted pioneering research into CBD and the neural correlates of anxiety. At high concentrations, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor, thereby conferring an anti-anxiety effect. This G-coupled protein receptor is implicated in a range of biological and neurological processes, including (but not limited to) anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting.

Jose Alexandre Crippa 和他的大學校友San Paulo 在倫敦的一所學校（Brazil and King’s College）對——CBD和焦慮症的神經相關性——進行了研究。在高濃度下，CBD直接激活5-HT1A血清素受體，從而產生了抗抑鬱的作用。這種G耦合的蛋白質受體與系列生理學和神經學的過程有關，包括（但不僅限於）：焦慮，成癮，食慾，睡眠，疼痛感，噁心和想吐。

5-HT1A is a member of the family of 5-HT receptors, which are activated by the neurotransmitter serotonin. Found in both the central and peripheral nervous systems, 5-HT receptors trigger various intracellular cascades of chemical messages to produce either an excitatory or inhibitory response, depending on the chemical context of the message.

5-HT1A 是5-HT受體的家庭成員中的一員，是被神經遞質血清激活。在神經系統的中樞或周圍都可以被找到5-HT受體，它可以激活細胞中級聯的化學信息去產生興奮或抑鬱的回應，取決於信息的化學環境。

CBDA [Cannabidiolic acid], the raw, unheated version of CBD that is present in the cannabis plant, also has a strong affinity for the 5-HT1A receptor (even more so than CBD). Preclinical studies indicate that CBDA is a potent anti-emetic, stronger than either CBD or THC, which also have anti-nausea properties.

CBDA——在原始的，為加熱的CBD——出現在大麻植物中，對受體5-HT1A也具有非常強的親和性（甚至超過了CBD）。臨床前實驗表明CBDA是強有效止吐藥，比CBD和THC都強，它還有抗噁心的特性。

VANILLOID RECEPTORS

香草受體

CBD directly interacts with various ion channels to confer a therapeutic effect. CBD, for example, binds to TRPV1 receptors, which also function as ion channels. TRPV1 is known to mediate pain perception, inflammation and body temperature.

CBD直接作用於多種離子通道來提供治療的作用。例如CBD和 TRPV1 受體結合，後者也可以充當離子同道。TRPV1可以傳導疼痛，炎症和體溫。

vanilloid cannabinoid receptor

香草大麻素受體

TRPV is the technical abbreviation for 「transient receptor potential cation channel subfamily V.」 TRPV1 is one of several dozen TRP (pronounced 「trip」) receptor variants or subfamilies that mediate the effects of a wide range of medicinal herbs.

TRPV是transient receptor potential cation channel subfamily V的縮寫，TRPV1是幾十個TRP受體變體或亞科，可介導多種草藥的作用。

Scientists also refer to TRPV1 as a 「vanilloid receptor,」 named after the flavorful vanilla bean. Vanilla contains eugenol, an essential oil that has antiseptic and analgesic properties; it also helps to unclog blood vessels. Historically, the vanilla bean has been used as a folk cure for headaches.

科學家通常將TRPV1稱為香草受體，以香草豆命名。香草中含有丁香酚，這是一種具有防腐和止痛性能的香精油。它還有助於疏通血管。從歷史上看，香子蘭豆一直用作頭痛的民間療法。

CBD binds to TRPV1, which can influence pain perception. 

CBD 和TRPV1結合，可以影響疼痛感。

Capsaicin—the pungent compound in hot chili peppers—activates the TRPV1 receptor. Anandamide, the endogenous cannabinoid, is also a TRPV1 agonist.

辣椒素——辣椒中的刺激性化合物，可激活TRPV1受體。內源性大麻素Anandamide也是TRPV1激動劑。

GPR55—ORPHAN RECEPTORS

Whereas cannabidiol directly activates the 5-HT1A serotonin receptor and several TRPV ion channels, some studies indicate that CBD functions as an antagonist that blocks, or deactivates, another G protein-coupled receptor known as GPR55.

CBD直接激活 5-HT1A受體和多種TRPV離子通道，而另一些一些研究表面GPR55受體，CBD可以作為拮抗劑來阻止另一種G蛋白耦合受體。

GPR55 has been dubbed an 「orphan receptor」 because scientists are still not sure if it belongs to a larger family of receptors. GPR55 is widely expressed in the brain, especially in the cerebellum. It is involved in modulating blood pressure and bone density, among other physiological processes.

GPR55被稱為「孤兒受體」因為可以家們還不能確定它是否屬於某一類受體。GPR55在腦部較為廣泛，尤其是在小腦中。和其他生理過程一起調節血壓，骨質密度等。

GPR55 promotes osteoclast cell function, which facilitates bone reabsorption. Overactive GPR55 receptor signaling is associated with osteoporosis.

GPR55增強破骨細胞的功能，促進骨的在吸收。過度活躍的GPR55受體信號與骨質疏鬆有關。

GPR55

GPR55, when activated, also promotes cancer cell proliferation, according to a 2010 study by researchers at the Chinese Academy of Sciences in Shanghai. This receptor is expressed in various types of cancer.

當GPR55被激活，也會促進癌細胞的增殖，根據在上海中國科學研究院的研究員2010年的研究《The putative cannabinoid receptor GPR55 promotes cancer cellproliferation》。這個受體被表現在多種癌症中。

CBD is a GPR55 antagonist, as University of Aberdeen scientist Ruth Ross disclosed at the 2010 conference of the International Cannabinoid Research Society in Lund, Sweden. By blocking GPR55 signaling, CBD may act to decrease both bone reabsorption and cancer cell proliferation.

CBD是GPR55拮抗劑，正如阿伯丁大學的科學家Ruth Ross在2010年在瑞典隆德舉行的國際大麻素研究協會會議上所披露的那樣。 通過阻斷GPR55信號傳導， CBD可能會減少骨吸收和癌細胞的增殖。

PPARS - NUCLEAR RECEPTORS

PPARS——細胞核受體

PPARs receptor CBD

CBD also exerts an anti-cancer effect by activating PPARs [peroxisome proliferator activated receptors] that are situated on the surface of the cell’s nucleus. Activation of the receptor known as PPAR-gamma has an anti-proliferative effect as well as an ability to induce tumor regression in human lung cancer cell lines. PPAR-gamma activation degrades amyloid-beta plaque, a key molecule linked to the development of Alzheimer’s disease. This is one of the reasons why cannabidiol, a PPAR-gamma agonist, may be a useful remedy for Alzheimer’s patients.

CBD通過激活細胞核表面的PPARS受體來實現抗癌的作用。PPAR受體激活具有抗繁殖的功能，也能促使人體肺癌細胞系腫瘤的退化。PPAR -γ活化可降解澱粉樣蛋白-β斑塊，這是與阿爾茨海默氏病發展有關的關鍵分子。這就是為什麼大麻素PPAR- γ激動劑可能對阿爾茨海默氏症患者有用的原因之一。

PPAR receptors also regulate genes that are involved in energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic functions. Diabetics, accordingly, may benefit from a CBD-rich treatment regimen.

PPAR受體還調節與能量穩態，脂質攝取，胰島素敏感性和其他代謝功能有關的基因。因此，糖尿病患者可受益於富含CBD的治療方案。

CBD AS A REUPTAKE INHIBITOR

CBD作為再攝取抑制劑

How does CBD, an exogenous plant compound, get inside a human cell to bind to a nuclear receptor? First it has to pass through the cell membrane by hitching a ride with a fatty acid binding protein (FABP), which chaperones various lipid molecules into the cell’s interior. These intracellular transport molecules also escort tetrahydrocannabinol (THC) and the brain’s own marijuana-like molecules, the endocannabinoids anandamide and 2AG, across the membrane to several targets within the cell. CBD and THC both modulate receptors on the surface of the nucleus, which regulate gene expression and mitochondrial activity.

外源植物化合物CBD是怎樣進入人體細胞與細胞核受體結合的呢？首先他需要通過與脂肪酸結合蛋白搭接而穿過細胞膜，該分子將各種脂質分子的伴侶分子帶入細胞內部。這些細胞內轉運分子還護送四氫大麻酚（THC）和大腦自己的大麻樣分子，內源性大麻素anandamide和2AG穿過細胞膜到達細胞內的多個靶標。CBD和THC均調節細胞核表面的受體，從而調節基因表達和線粒體活性。

Cannabidiol, it turns out, has a strong affinity for three kinds of FABPs, and CBD competes with our endocannabinoids, which are fatty acids, for the same transport molecules. Once it is inside the cell, anandamide is broken down by FAAH [fatty acid amide hydrolase], a metabolic enzyme, as part of its natural molecular life cycle. But CBD interferes with this process by reducing anandamide’s access to FABP transport molecules and delaying endocannabinoid passage into the cell’s interior.

事實證明，大麻二酚對三種FABP具有很強的親和力，而CBD與我們的內源性大麻素（脂肪酸）競爭相同的轉運分子。一旦進入細胞內，作為其天然分子生命周期一部分的代謝酶FAAH（脂肪酸醯胺水解酶）會分解成花生四烯醯胺。但是，CBD通過減少anandamide接觸FABP轉運分子並延遲內源性大麻素進入細胞內部來幹擾這一過程。

According to a team of Stony Brook University scientists, CBD functions as an anandamide reuptake and breakdown inhibitor, thereby raising endocannabinoid levels in the brain’s synapses. Enhancing endocannabinod tone via reuptake inhibition may be a key mechanism whereby CBD confers neuroprotective effects against seizures, as well as many other health benefits.Cannabidiol, it turns out, has a strong affinity for three kinds of FABPs, and CBD competes with our endocannabinoids, which are fatty acids, for the same transport molecules. Once it is inside the cell, anandamide is broken down by FAAH [fatty acid amide hydrolase], a metabolic enzyme, as part of its natural molecular life cycle. But CBD interferes with this process by reducing anandamide’s access to FABP transport molecules and delaying endocannabinoid passage into the cell’s interior.

根據美國石溪大學的一個研究小組的研究，CBD起到了anandamide再攝取和分解抑制劑的作用，從而提高了大腦突觸中的內源性大麻素水平。通過抑制再攝取來增強內源性大麻素音調可能是關鍵的機制，從而使CBD賦予神經保護作用，防止癲癇發作以及許多其他健康益處。

CBD’s anti-inflammatory and anti-anxiety effects are in part attributable to its inhibition of adenosine reuptake. By delaying the reuptake of this neurotransmitter, CBD boosts adenosine levels in the brain, which regulates adenosine receptor activity. A1A and A2A adenosine receptors play significant roles in cardiovascular function, regulating myocardial oxygen consumption and coronary blood flow. These receptors have broad anti-inflammatory effects throughout the body.

CBD的抗炎和抗焦慮作用部分歸因於其對腺苷再攝取的抑制作用。通過延緩這種神經遞質的再攝取，CBD可提高大腦中的腺苷水平，從而調節腺苷受體的活性。A1A和A2A腺苷受體在心血管功能，調節心肌耗氧量和冠狀動脈血流中起重要作用。這些受體在全身具有廣泛的抗炎作用。

CBD AS AN ALLOSTERIC MODULATORCBD作為變構調節劑

CBD also functions as an allosteric receptor modulator, which means that it can either enhance or inhibit how a receptor transmits a signal by changing the shape of the receptor.

CBD還可以用作變構受體調節劑，這意味著它可以通過改變受體的形狀來增強或抑制受體如何傳輸信號。

Australian scientists report that CBD acts as a 「positive allosteric modulator」 of the GABA-A receptor. In other words, CBD interacts with the GABA-A receptor in a way that enhances the receptor’s binding affinity for its principal endogenous agonist, gamma-Aminobutyric acid  (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. The sedating effects of Valium and other Benzos are mediated by GABA receptor transmission. CBD reduces anxiety by changing the shape of the GABA-A receptor in a way that amplifies the natural calming effect of GABA.

澳大利亞科學家報告說，CBD是GABA -A受體的「正變構調節劑」。換句話說，CBD與GABA -A受體相互作用的方式增強了受體對其主要內源性激動劑γ-氨基丁酸（GABA）的結合親和力，γ-氨基丁酸是哺乳動物中樞神經系統的主要抑制神經遞質。纈氨酸和其他苯並的鎮靜作用是由GABA受體傳遞介導的。CBD通過改變GABA -A受體的形狀來增強GABA的自然鎮靜作用，從而減輕焦慮。

CBD non-psychoactive allosteric modulator

Canadian scientists have identified CBD as a 「negative allosteric modulator」 of the cannabinoid CB1 receptor, which is concentrated in the brain and central nervous system. While cannabidiol doesn’t bind to the CB1 receptor directly like THC does, CBD interacts allosterically with CB1 and changes the shape of the receptor in a way that weakens CB1’s ability to bind with THC.

加拿大科學家已將CBD確定為大麻素CB1受體的「負變構調節劑」，該受體集中在大腦和中樞神經系統中。儘管大麻二酚不像THC那樣直接與CB1受體結合，但CBD與CB1發生變構相互作用，並改變受體的形狀，從而削弱CB1與THC的結合能力。

As a negative allosteric modulator of the CB1 receptor, CBD lowers the ceiling on THC’s psychoactivity—which is why people don’t feel as 「high」 when using CBD-rich cannabis compared to when they consume THC-dominant medicine. A CBD-rich product with little THC can convey therapeutic benefits without having a euphoric or dysphoric effect.

作為CB1受體的負變構調節劑，CBD 降低了THC的心理活性上限，這就是為什麼人們在使用富含CBD的大麻時與食用THC佔主導地位的藥物相比不會感到「高」 。甲CBD富很少產物THC可以傳達治療益處而無需欣快或煩躁不安的效果。

Photo credits: CPD events, Lafaza, CGStudio

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