Janiri Luigi, Martinotti Giovanni, Tonioni Federico, Ghelardini Carla, Nicolai Raffaella, Galeotti Nicoletta, Mosconi Luigi, Calvani Menotti, Bartolini Alessandro, Iannoni Emerenziana
Department of Psychiatry, Catholic University Medical School, Rome, Italy.
Clin Neuropharmacol. 2009 Jan-Feb;32(1):35-40. doi: 10.1097/WNF.0B013E31815DD465.
This study was designed to determine the short-term effect of acetyl-l-carnitine (ALC) on symptoms of withdrawal in opiate-dependent subjects and animals and, in particular, on pain, given the efficacy of ALC in other typologies of pain. The study consists of 2 branches: a clinical study and a preclinical one, both with a randomized placebo-controlled design.
Thirty subjects meeting clinical criteria for methadone dependence were consecutively recruited and treated with ALC 2 g/d or placebo for a 3-week detoxification period. Withdrawal symptoms and pain were evaluated through the Short Opiate Withdrawal Syndrome scale, and the Huskisson's analogue scale for pain. In the preclinical study, mice previously received a pretreatment (saline solution or morphine), and subsequently, each group was randomly divided in 4 subgroups that received a treatment of saline, methadone, ALC, or amitriptyline, respectively. Hot plate test and Writhing test were used to evaluate pain intensity.
Average Short Opiate Withdrawal Syndrome total scores during the first 5 days of treatment resulted significantly higher in controls than in the ALC group (P < 0.05). Pain scores in the Huskisson's analogue scale were considerably lower in the group of patients taking ALC than in the control group after 1 week of ALC treatment until the end of the study. Results of the preclinical study show that the administration of methadone for 7 days in morphine-tolerant mice did not produce any modification of the pain threshold. By contrast, the 7-day coadministration of methadone and ALC in morphine-tolerant mice induced an analgesic effect evaluated 3 hours after the last injection.
Acetyl-L-carnitine acted as an effective antihyperalgesic agent for relieving opiate-withdrawal hyperalgesia in animals and displayed clinical efficacy on other withdrawal symptoms such as muscular tension, muscular cramps, and insomnia. Considering its tolerability, the excellent side effect profile, the absence of significant interactions, and the lack of abuse potential, ALC can be considered as a useful pharmacological adjunct in the treatment of opiate withdrawal.
鉴于乙酰左旋肉碱（ALC）在其他类型疼痛中的疗效，本研究旨在确定其对阿片类药物依赖的受试者和动物戒断症状的短期影响，尤其是对疼痛的影响。该研究包括两个分支：一项临床研究和一项临床前研究，均采用随机安慰剂对照设计。
连续招募30名符合美沙酮依赖临床标准的受试者，在为期3周的戒毒期内给予2 g/d的ALC或安慰剂治疗。通过短阿片戒断综合征量表以及Huskisson疼痛模拟量表评估戒断症状和疼痛。在临床前研究中，小鼠先接受预处理（生理盐水或吗啡），随后每组随机分为4个亚组，分别接受生理盐水、美沙酮、ALC或阿米替林治疗。采用热板试验和扭体试验评估疼痛强度。
治疗前5天，对照组的平均短阿片戒断综合征总分显著高于ALC组（P < 0.05）。在接受ALC治疗1周后直至研究结束，服用ALC的患者组在Huskisson疼痛模拟量表上的疼痛评分明显低于对照组。临床前研究结果表明，在吗啡耐受的小鼠中给予7天美沙酮并未改变疼痛阈值。相比之下，在吗啡耐受的小鼠中，美沙酮与ALC联合给药7天，在最后一次注射后3小时评估产生了镇痛效果。
乙酰左旋肉碱可作为一种有效的抗痛觉过敏药物，缓解动物的阿片戒断痛觉过敏，并对肌肉紧张、肌肉痉挛和失眠等其他戒断症状显示出临床疗效。考虑到其耐受性、良好的副作用谱、无显著相互作用以及无滥用潜力，ALC可被视为治疗阿片戒断的一种有用的药理学辅助药物。
