Curran H V, Monaghan L
Psychopharmacology Research Unit, Sub-department of Clinical Health Psychology, University College London, London, UK.
Addiction. 2001 May;96(5):749-60. doi: 10.1046/j.1360-0443.2001.96574910.x.
Ketamine, a non-competitive NMDA receptor antagonist, produces acute impairments of working, episodic and semantic memory along with psychotogenic and dissociative effects when a single dose is given to healthy volunteers. In recreational users, Curran & Morgan (2000) showed that ketamine produced the same acute effects but that 3 days after ingestion, ketamine users showed persisting memory impairment and elevated psychotogenic symptoms compared with controls. To explore whether such persisting effects reflect chronic effects of ketamine use, the present study compared frequent with infrequent users of ketamine on the night of drug use and again 3 days later.
Eighteen frequent and 19 infrequent ketamine users were assessed on each test day on a range of cognitive tasks tapping memory and attentional function and on subjective scales (schizotypal symptomatology, dissociation, mood).
Groups were broadly matched for polydrug use apart from ketamine which frequent users took significantly more often and in larger quantities than infrequent users. Acute effects on day 0 replicated previous findings. On day 3 frequent users showed significant impairments on tasks tapping episodic and semantic memory but there was no evidence of persisting dissociative or schizotypal symptoms.
These findings indicate that frequent use of ketamine produces long-lasting impairments in episodic memory and aspects of retrieval from semantic memory. Such effects accord with animal evidence of the effects of NMDA receptor blockade on memory. Those using, or contemplating using ketamine should be informed of these persisting, detrimental effects of the drug upon human memory.
氯胺酮是一种非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂,给健康志愿者单次给药时,会导致工作记忆、情景记忆和语义记忆出现急性损害,同时产生致幻和分离效应。在娱乐性使用者中,柯伦和摩根(2000年)发现氯胺酮会产生相同的急性效应,但在摄入后3天,与对照组相比,氯胺酮使用者仍存在记忆损害且致幻症状加剧。为了探究这种持续效应是否反映了氯胺酮使用的慢性影响,本研究比较了频繁使用和不频繁使用氯胺酮者在用药当晚以及3天后的情况。
在每个测试日,对18名频繁使用氯胺酮者和19名不频繁使用氯胺酮者进行了一系列认知任务评估,这些任务涉及记忆和注意力功能,同时还进行了主观量表(分裂型症状、分离、情绪)评估。
除氯胺酮外,两组在多药使用方面大致匹配,频繁使用者服用氯胺酮的频率和剂量明显高于不频繁使用者。第0天的急性效应重复了先前的研究结果。在第3天,频繁使用者在涉及情景记忆和语义记忆提取的任务上表现出显著损害,但没有证据表明存在持续的分离或分裂型症状。
这些研究结果表明,频繁使用氯胺酮会对情景记忆和语义记忆提取方面产生持久损害。这种效应与NMDA受体阻断对记忆影响的动物证据一致。应该告知那些正在使用或考虑使用氯胺酮的人该药物对人类记忆的这些持续有害影响。