大麻衍生制剂可能有助于第二型糖尿病


  【24drs.com】初步研究显示,大麻成分的非精神作用类似物,可能是可用于治疗第二型糖尿病的新制剂。
  
  英国Nottingham大学的Khalid A Jadoon等人将研究结果在线发表于8月29日的糖尿病照护期刊,这篇随机双盲安慰剂控制第2a阶段试验,探讨两种大麻生物碱(phytocannabinoids)用于第二型糖尿病患者的效果。
  
  作者们指出,内源性大麻素系统(ECS)的长期过度活化,之前已确定与肥胖和第二型糖尿病有关,而使用大麻与降低空腹胰岛素和更大的胰岛素敏感性有关。
  
  另外,在过去,合成大麻素rimonabant与大麻素受体的调节,可显著降低体重、腰围与三酸甘油脂,且增加HDL胆固醇,前述药物于欧洲获核准用于减重,但是在2008年因为精神方面的副作用而退出市场。
  
  现在,注意力转向另外两种可能更安全的大麻素受体调节剂:cannabidiol(CBD)与Δ9-tetrahydrocannabivarin(THCV),前者从大麻植物中提取,后者是Δ9-tetrahydrocannabinol (THC)的天然类似物,但具有不同的药理作用。在动物模式中,CBD显示有抗发炎和抗氧化性质,而THCV会导致摄食过量和体重减轻。
  
  Jadoon医师等人解释,不同于相关的且更知名的大麻成分THC,CBD与THCV并不会活化脑中的CB1受体,因此不具有THC的精神作用。
  
  在这两个成分用于第二型糖尿病与血脂异常患者的第一篇临床研究中,THCV改善了血糖控制,而CBD对于代谢没有任何可被侦测之影响,虽然它在一些脂肪因子和胃肠激素确实产生可望的变化。两组的副作用相似,没有新的安全顾虑出现。
  
  作者们写道,这些研究结果认为,对于第二型糖尿病患者,THCV可能代表一种新的血糖控制治疗剂。
  
  总共有62名不是使用胰岛素治疗的第二型糖尿病患被随机分组到以下五组之一:CBD (100 mg、每天两次),THCV (5 mg 、每天两次),1:1的CBD与THCV (5 mg/5 mg、每天两次),20:1的CBD与THCV (100 mg/5 mg、每天两次)或安慰剂,共进行13周。
  
  虽然THCV对于初级终点—HDL胆固醇相较于开始时的变化—或对LDL胆固醇值没有影响,它比开始时显著增加了脂蛋白元A (apoA)的浓度(P < .05),相对的,单用CBD与并用THCV对于任何的脂质参数没有影响。
  
  相较于安慰剂组, THCV组的空腹血糖值也比开始时降低,从约133 mg/dL降至121 mg/dL (P < .05),beta-细胞功能也有显著地同时增加(P < .01),不过,同样的,单用CBD与并用THCV对于血糖参数并无影响。
  
  相较于安慰剂组,THCV组的脂联素浓度也比开始时显著增加(差异P < .01 )。
  
  CBD有一些显著影响,包括脂肪细胞因子抵抗素降低(P<.05),这与肥胖和胰岛素阻抗性有关,以及肠激素葡萄糖依赖性促胰岛素胜肽浓度增加,这具有beta细胞保留性质(P < .05),不过,CBD对于瘦体素或脂联素值没有影响。
  
  两种制剂似乎都没有影响心血管参数、血管功能的血浆标记、发炎的血浆标记(C-反应蛋白质、肿瘤坏死因子-alpha以及介白素-6)、人体测量参数(体重、腰围、腰臀围比、皮褶厚度)、内脏脂肪或食慾。
  
  各组与安慰剂组最常报告的不良反应,大多是轻微到中度。食慾降低在大麻素组是常见的,治疗组的比率介于9%-33%,安慰剂组没有;THCV组有两例腹泻,安慰剂组没有;没有死亡或治疗相关的严重不良反应报告。
  
  作者们结论指出,THCV改善血糖控制,因此,需在此治疗领域进行后续研究。
  
  资料来源: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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