Massachusetts General Hospital (MGH) Department of Psychiatry, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Neuropsychopharmacology. 2024 Aug;49(9):1481-1490. doi: 10.1038/s41386-024-01876-5. Epub 2024 May 7.
Neural states of impairment from intoxicating substances, including cannabis, are poorly understood. Cannabinoid 1 receptors, the main target of Δ9-tetrahydrocannabinol (THC), the primary intoxicating cannabinoid in cannabis, are densely localized within prefrontal cortex; therefore, prefrontal brain regions are key locations to examine brain changes that characterize acute intoxication. We conducted a double-blind, randomized, cross-over study in adults, aged 18-55 years, who use cannabis regularly, to determine the effects of acute intoxication on prefrontal cortex resting-state measures, assessed with portable functional near-infrared spectroscopy. Participants received oral THC (10-80 mg, individually dosed to overcome tolerance and achieve acute intoxication) and identical placebo, randomized for order; 185 adults were randomized and 128 completed both study days and had usable data. THC was associated with expected increases in subjective intoxication ratings (ES = 35.30, p < 0.001) and heart rate (ES = 11.15, p = 0.001). THC was associated with decreased correlations and anticorrelations in static resting-state functional connectivity within the prefrontal cortex relative to placebo, with weakest correlations and anticorrelations among those who reported greater severity of intoxication (RSFC between medial PFC-ventromedial PFC and DEQ scores, r = 0.32, p < 0.001; RSFC between bilateral mPFC and DEQ scores, r = -0.28, p = 0.001). Relative to placebo, THC was associated with increased variability (or reduced stability) in dynamic resting-state functional connectivity of the prefrontal cortex at p = 0.001, consistent across a range of window sizes. Finally, using frequency power spectrum analyses, we observed that relative to placebo, THC was associated with widespread reduced spectral power within the prefrontal cortex across the 0.073-0.1 Hz frequency range at p < 0.039. These neural features suggest a disruptive influence of THC on the neural dynamics of the prefrontal cortex and may underlie cognitive impairing effects of THC that are detectable with portable imaging. This study is registered in Clinicaltrials.gov (NCT03655717).
神经状态受损的物质，包括大麻，理解很差。大麻素 1 受体，主要目标的 Δ9-四氢大麻酚 (四氢大麻酚)，主要的大麻素在大麻中的致醉，密集位于前额皮质; 因此，前额叶脑区是检查急性中毒特征的脑变化的关键部位。我们进行了一项双盲、随机、交叉研究，纳入年龄在 18-55 岁之间的经常使用大麻的成年人，以确定急性中毒对前额叶皮层静息状态测量的影响，使用便携式近红外光谱进行评估。参与者接受口服四氢大麻酚 (10-80mg，个体化剂量以克服耐受性并达到急性中毒) 和相同的安慰剂，随机顺序; 185 名成年人被随机分配，128 名成年人完成了两天的研究并获得了可用数据。四氢大麻酚与预期的主观中毒评分增加有关 (ES=35.30，p<0.001) 和心率 (ES=11.15，p=0.001)。与安慰剂相比，四氢大麻酚与前额叶皮层内静息状态功能连接的相关性和反相关性降低，与报告中毒程度较高者相关性和反相关性最弱 (内侧前额叶皮层-腹内侧前额叶皮层和 DEQ 评分之间的 RSFC，r=0.32，p<0.001; 双侧 mPFC 和 DEQ 评分之间的 RSFC，r=-0.28，p=0.001)。与安慰剂相比，THC 与前额叶皮层静息状态功能连接的变异性 (或稳定性降低) 增加有关，在 p=0.001 时具有一致性，跨越一系列窗口大小。最后，使用频率功率谱分析，我们观察到与安慰剂相比，THC 与前额叶皮层广泛的频谱功率降低有关，在 0.073-0.1Hz 频率范围内，p<0.039。这些神经特征表明四氢大麻酚对前额叶皮层神经动力学的破坏影响，并且可能是可检测到的便携式成像中四氢大麻酚认知损害作用的基础。这项研究在 Clinicaltrials.gov 注册 (NCT03655717)。
