Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study
Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study
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DOI：
10.1162/jocn_a_00156
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发表时间：
2012-03-01
影响因子：
3.2
通讯作者：
Ramsey, Nick F.
中科院分区：
文献类型：
--
作者：
Bossong, Matthijs G.;Jager, Gerry;Ramsey, Nick F.
记忆功能缺陷是各种精神和神经疾病的一个丧失能力的方面。最近的动物研究提供了内源性大麻素（eCB）系统参与记忆功能的有力证据。对人类进行的神经心理学研究显示，没有那么令人信服的证据，但表明大麻素物质的使用影响的是编码，而不是信息的回忆。在这项研究中，我们研究了在编码和回忆过程中，eCB系统的扰动对记忆功能的影响。我们采用安慰剂对照交叉设计进行药理学MRI研究，研究吸入德尔塔9-四氢大麻酚（THC）对13名健康志愿者联想记忆相关脑功能的影响。在联想记忆过程中，表现和大脑活动是通过一个图像记忆任务来评估的，这个任务由独立的编码和回忆条件组成。四氢大麻酚的使用导致右侧脑岛、右侧额下回和左侧枕中回的编码活动减少，而在回忆过程中，整个网络的活动增加，这在双侧楔叶和楔前叶中最为突出。四氢大麻酚对任务表现没有影响，但在安慰剂期间，回忆活动显著地解释了表现的差异，在四氢大麻酚后，这种影响消失了。这些发现表明eCB参与了图像信息的编码。楔前叶活动增加可能反映了记忆功能受损，但四氢大麻酚对任务表现的影响缺失表明存在代偿机制。这些结果进一步强调了eCB系统是治疗记忆障碍的潜在新靶点，也是开发减少人类记忆缺陷的新疗法的有希望的靶点。
Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Delta 9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.