Carter Lawrence P, Richards Brian D, Mintzer Miriam Z, Griffiths Roland R
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Neuropsychopharmacology. 2006 Nov;31(11):2537-51. doi: 10.1038/sj.npp.1301146. Epub 2006 Jul 26.
Although preclinical studies suggest that GHB has low likelihood for abuse, case reports indicate that GHB is abused. This study evaluated the relative abuse liability of GHB in 14 volunteers with histories of drug abuse. Psychomotor, subjective, and cognitive effects of a broad range of GHB doses (2-18 g/70 kg), up to a dose that produced severe behavioral impairment in each participant, were compared to placebo and two abused sedative/hypnotic drugs, triazolam (0.5 and 1 mg/70 kg) and pentobarbital (200 and 400 mg/70 kg), under double-blind, double-dummy conditions at a residential research facility. In general, GHB produced effects similar to triazolam and pentobarbital, although GHB was not identified as a benzodiazepine or barbiturate by participants that correctly identified triazolam and pentobarbital as such. On most measures of likelihood of abuse (eg ratings of liking, reinforcing effects), effects of pentobarbital were significantly greater than those of triazolam, with GHB being intermediate. GHB produced significantly greater negative subjective effects, including nausea, than the other drugs. Memory impairment after GHB was less than that after triazolam and pentobarbital. Within participants, the dose-effect function for sedation was steeper for GHB than for triazolam and pentobarbital. Also, at higher doses, GHB was associated with greater sedation and more variability across participants in sedation. Taken together, these data suggest that the profile of effects of GHB only partially overlaps with that of triazolam and pentobarbital. Although the likelihood for GHB to be abused is intermediate to triazolam and pentobarbital, the possibility of accidental overdose (ie greater sedation than intended) with GHB appears to be greater.
尽管临床前研究表明γ-羟基丁酸(GHB)滥用的可能性较低,但病例报告显示GHB存在被滥用的情况。本研究评估了14名有药物滥用史的志愿者中GHB的相对滥用倾向。在一家住院研究机构的双盲、双模拟条件下,将一系列GHB剂量(2 - 18 g/70 kg,直至达到使每位参与者出现严重行为损害的剂量)的精神运动、主观和认知效应,与安慰剂以及两种被滥用的镇静/催眠药物三唑仑(0.5和1 mg/70 kg)和戊巴比妥(200和400 mg/70 kg)进行了比较。总体而言,GHB产生的效应与三唑仑和戊巴比妥相似,不过能正确识别三唑仑和戊巴比妥为苯二氮䓬类或巴比妥类药物的参与者并未将GHB识别为这类药物。在大多数滥用可能性指标(如喜好评分、强化效应)方面,戊巴比妥的效应显著大于三唑仑GHB处于中间水平。GHB产生的负面主观效应(包括恶心)比其他药物更显著。GHB后的记忆损害小于三唑仑和戊巴比妥后的记忆损害。在参与者内部,GHB的镇静剂量效应函数比三唑仑和戊巴比妥更陡峭。此外,在较高剂量时,GHB与更强的镇静作用相关,且参与者之间的镇静作用变异性更大。综合来看,这些数据表明GHB的效应特征仅部分与三唑仑和戊巴比妥的效应特征重叠。尽管GHB被滥用的可能性介于三唑仑和戊巴比妥之间,但GHB意外过量(即镇静作用比预期更强)的可能性似乎更大。