Irimia Cristina, Polis Ilham Y, Stouffer David, Parsons Loren H
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2001, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
Psychopharmacology (Berl). 2015 Aug;232(16):3033-43. doi: 10.1007/s00213-015-3942-x. Epub 2015 Apr 30.
In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure.
To evaluate the effects of long-term exposure to Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, on indices of impulse control and attentional capacity using the rat 5-Choice Serial Reaction Time Task (5-CSRTT).
Ten 14-day cycles of Δ9-THC dosing and 5-CSRTT testing were employed, each comprised of 5-day Δ9-THC dosing (0.3 or 3 mg/kg b.i.d.) and 5-CSRTT testing during the 9 days of drug abstinence. Subsequent 5-CSRTT testing continued during 5 weeks of protracted abstinence.
Dose-dependent increases in motor impulsivity (premature responses) and behavioral disinhibition (perseverative responses) emerged following 5 cycles of Δ9-THC exposure that persisted for the remaining dosing and testing cycles. Δ9-THC-related disruptions in motor impulsivity and behavioral inhibition were most pronounced during cognitively challenging 5-CSRTT sessions incorporating varying novel inter-trial intervals (ITIs), and these disruptions persisted for at least 5 weeks of Δ9-THC abstinence. Δ9-THC-related impairments in attentional capacity (response accuracy) were also evident during variable ITI challenge tests, though these attentional disruptions abated within 3 weeks of Δ9-THC abstinence.
These observations demonstrate that long-term intermittent exposure to clinically meaningful Δ9-THC doses induces persistent impairments in impulse control and attentional function. If present in humans, these disruptions may impact academic and professional performance.
在人类中，长期使用大麻与冲动控制和注意力能力受损有关，尽管很难区分预先存在的认知缺陷与长期接触大麻可能产生的后果。
使用大鼠5选连续反应时任务（5-CSRTT）评估长期接触大麻中主要的精神活性成分Δ9-四氢大麻酚（Δ9-THC）对冲动控制和注意力能力指标的影响。
采用10个为期14天的Δ9-THC给药和5-CSRTT测试周期，每个周期包括5天的Δ9-THC给药（0.3或3mg/kg，每日两次）以及在停药9天期间进行的5-CSRTT测试。在延长的停药5周期间继续进行后续的5-CSRTT测试。
在5个周期的Δ9-THC暴露后，出现了剂量依赖性的运动冲动性（过早反应）增加和行为去抑制（持续性反应），并在剩余的给药和测试周期中持续存在。在包含不同新颖试次间隔（ITI）的具有认知挑战性的5-CSRTT实验环节中，与Δ9-THC相关的运动冲动性和行为抑制破坏最为明显，并且这些破坏在Δ9-THC停药至少5周内持续存在。在可变ITI挑战测试期间，与Δ9-THC相关的注意力能力（反应准确性）损害也很明显，尽管这些注意力破坏在Δ9-THC停药3周内减轻。
这些观察结果表明，长期间歇性接触具有临床意义的Δ9-THC剂量会导致冲动控制和注意力功能的持续损害。如果在人类中存在，这些破坏可能会影响学业和职业表现。
