大麻衍生製劑可能有助於第二型糖尿病


  【24drs.com】初步研究顯示,大麻成分的非精神作用類似物,可能是可用於治療第二型糖尿病的新製劑。
  
  英國Nottingham大學的Khalid A Jadoon等人將研究結果線上發表於8月29日的糖尿病照護期刊,這篇隨機雙盲安慰劑控制第2a階段試驗,探討兩種大麻生物鹼(phytocannabinoids)用於第二型糖尿病患者的效果。
  
  作者們指出,內源性大麻素系統(ECS)的長期過度活化,之前已確定與肥胖和第二型糖尿病有關,而使用大麻與降低空腹胰島素和更大的胰島素敏感性有關。
  
  另外,在過去,合成大麻素rimonabant與大麻素受體的調節,可顯著降低體重、腰圍與三酸甘油脂,且增加HDL膽固醇,前述藥物於歐洲獲核准用於減重,但是在2008年因為精神方面的副作用而退出市場。
  
  現在,注意力轉向另外兩種可能更安全的大麻素受體調節劑:cannabidiol(CBD)與Δ9-tetrahydrocannabivarin(THCV),前者從大麻植物中提取,後者是Δ9-tetrahydrocannabinol (THC)的天然類似物,但具有不同的藥理作用。在動物模式中,CBD顯示有抗發炎和抗氧化性質,而THCV會導致攝食過量和體重減輕。
  
  Jadoon醫師等人解釋,不同於相關的且更知名的大麻成分THC,CBD與THCV並不會活化腦中的CB1受體,因此不具有THC的精神作用。
  
  在這兩個成分用於第二型糖尿病與血脂異常患者的第一篇臨床研究中,THCV改善了血糖控制,而CBD對於代謝沒有任何可被偵測之影響,雖然它在一些脂肪因子和胃腸激素確實產生可望的變化。兩組的副作用相似,沒有新的安全顧慮出現。
  
  作者們寫道,這些研究結果認為,對於第二型糖尿病患者,THCV可能代表一種新的血糖控制治療劑。
  
  總共有62名不是使用胰島素治療的第二型糖尿病患被隨機分組到以下五組之一:CBD (100 mg、每天兩次),THCV (5 mg 、每天兩次),1:1的CBD與THCV (5 mg/5 mg、每天兩次),20:1的CBD與THCV (100 mg/5 mg、每天兩次)或安慰劑,共進行13週。
  
  雖然THCV對於初級終點—HDL膽固醇相較於開始時的變化—或對LDL膽固醇值沒有影響,它比開始時顯著增加了脂蛋白元A (apoA)的濃度(P < .05),相對的,單用CBD與併用THCV對於任何的脂質參數沒有影響。
  
  相較於安慰劑組, THCV組的空腹血糖值也比開始時降低,從約133 mg/dL降至121 mg/dL (P < .05),beta-細胞功能也有顯著地同時增加(P < .01),不過,同樣的,單用CBD與併用THCV對於血糖參數並無影響。
  
  相較於安慰劑組,THCV組的脂聯素濃度也比開始時顯著增加(差異P < .01 )。
  
  CBD有一些顯著影響,包括脂肪細胞因子抵抗素降低(P<.05),這與肥胖和胰島素阻抗性有關,以及腸激素葡萄糖依賴性促胰島素胜肽濃度增加,這具有beta細胞保留性質(P < .05),不過,CBD對於瘦體素或脂聯素值沒有影響。
  
  兩種製劑似乎都沒有影響心血管參數、血管功能的血漿標記、發炎的血漿標記(C-反應蛋白質、腫瘤壞死因子-alpha以及介白素-6)、人體測量參數(體重、腰圍、腰臀圍比、皮褶厚度)、內臟脂肪或食慾。
  
  各組與安慰劑組最常報告的不良反應,大多是輕微到中度。食慾降低在大麻素組是常見的,治療組的比率介於9%-33%,安慰劑組沒有;THCV組有兩例腹瀉,安慰劑組沒有;沒有死亡或治療相關的嚴重不良反應報告。
  
  作者們結論指出,THCV改善血糖控制,因此,需在此治療領域進行後續研究。
  
  資料來源:http://www.24drs.com/
  
  Native link:Cannabis-Derived Agent May Offer Type 2 Diabetes Benefit

Cannabis-Derived Agent May Offer Type 2 Diabetes Benefit

By Miriam E Tucker
Medscape Medical News

A nonpsychoactive analog of a cannabis component may represent a new agent for treating type 2 diabetes, early research suggests.

Findings from a randomized, double-blind, placebo-controlled phase 2a trial investigating two different phytocannabinoids in type 2 diabetes patients were published online August 29 in Diabetes Care by Khalid A Jadoon, of the University of Nottingham, Derby, United Kingdom, and colleagues.

Chronic overactivation of the endocannabinoid system (ECS) has previously been identified in obesity and type 2 diabetes, while marijuana use has been linked to lower fasting insulin and greater insulin sensitivity, the authors note.

Also in the past, modulation of the cannabinoid receptors with the synthetic cannabinoid rimonabant led to significant reductions in body weight, waist circumference, and triglycerides and increased HDL cholesterol. That drug was approved for weight loss in Europe but then removed from the market in 2008 due to adverse psychiatric events.

Now, attention has turned to two other potentially safer cannabinoid receptor modulators: cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV), the former derived from the cannabis plant and the latter a naturally occurring analog of Δ9-tetrahydrocannabinol (THC), but with different pharmacological effects. In animal models, CBD demonstrated anti-inflammatory and antioxidant properties, while THCV caused hypophagia and weight loss.

Unlike the related — and better-known — cannabis constituent THC, CBD and THCV don't activate CB1 receptors in the brain and therefore lack the psychotropic actions of THC, Dr Jadoon and colleagues explain.

In this first clinical study of both compounds in people with type 2 diabetes and dyslipidemia, THCV improved glycemic control, whereas CBD failed to show any detectable metabolic effects, although it did produce desirable changes in some adipokines and gut hormones. Adverse events were similar between groups and no new safety concerns arose.

"These findings suggest that THCV may represent a new therapeutic agent for glycemic control in subjects with type 2 diabetes," the authors write.

Major Effects Seen With THCV, Fewer for CBD

A total 62 subjects with non–insulin-treated type 2 diabetes were randomized to one of five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks.

Although THCV had no effect on the primary end point — change in HDL cholesterol from baseline — or on LDL-cholesterol levels, it did significantly increase apolipoprotein A (apoA) concentrations from baseline (P < .05). In contrast, CBD alone and in combination with THCV did not affect any of the lipid parameters.

Fasting plasma glucose was also lower with THCV from baseline compared with placebo, from about 133 mg/dL to 121 mg/dL (P < .05), along with a significant concurrent increase in beta-cell function (P < .01). But again, neither CBD alone nor in combination with THCV affected glycemic parameters.

Adiponectin concentrations were also significantly increased from baseline with THCV and significantly reduced with placebo (P < .01 for the difference).

There were some significant effects for CBD, including a reduction in the adipokine resistin (P <.05), which is associated with obesity and insulin resistance, and an increase in the concentration of the gut hormone glucose-dependent insulinotropic peptide, which appears to have beta-cell–preserving properties (P < .05). But CBD had no effect on leptin or adiponectin levels.

Neither agent appeared to influence cardiovascular parameters, plasma markers of vascular function, plasma markers of inflammation (C-reactive protein, tumor necrosis factor-alpha, and interleukin-6), or anthropomorphic parameters (body weight, waist circumference, waist-to-hip ratio, or skinfold thickness), visceral adiposity, or appetite.

Safety Profile Favorable

Adverse events were reported by majorities of all groups, including placebo, and were mostly mild to moderate. Reduced appetite was common with the cannabinoids, reported in 9% to 33% of the treatment groups vs none in placebo. Two people reported diarrhea with THCV vs none in the other groups. There were no deaths or treatment-related serious adverse events.

"THCV improved glycemic control and therefore warrants further investigation in this therapeutic area," the authors conclude.

Dr Jadoon has no relevant financial relationships. Disclosures for the coauthors are listed in the article.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

Diabetes Care. Published online August 29, 2016.

    
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