Department of Psychiatry, University of California Los Angeles, Los Angeles, California.
Pharmaco-Neuroimaging and Cognitive-Emotional Processing, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Apr;5(4):461-467. doi: 10.1016/j.bpsc.2019.12.007. Epub 2019 Dec 20.
The practice of "microdosing," or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.
The present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed.
LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.
These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug's purported antidepressant effect.
“微量用药”，即反复使用极低剂量的麦角酸二乙酰胺（LSD）来改善情绪或认知，这种做法受到了广泛关注，但缺乏经验研究。需要进行对照研究来探索这种药物治疗的潜在治疗效果和神经生物学基础。
本研究旨在研究单次低剂量 LSD（13μg）与安慰剂对健康年轻成年人静息态功能连接和脑血流的影响。20 名年龄在 18 至 35 岁之间的男性和女性参加了 2 次功能磁共振成像扫描，他们在双盲条件下接受安慰剂或 LSD。在每次扫描中，参与者完成药物效果和情绪问卷，并记录生理测量结果。在预期的药物峰值作用期间，他们接受了静息态血氧水平依赖和动脉自旋标记扫描。分析了脑血流以及杏仁核和丘脑的连接。
LSD 增加了杏仁核种子的功能连接，与右侧角回、右侧额中回和小脑有关，降低了杏仁核与左侧和右侧中央后回以及颞上回的连接。这种低剂量的 LSD 对情绪有微弱和可变的影响，但它对积极情绪的影响与杏仁核-额中回连接强度的增加呈正相关。
这些初步发现表明，极低剂量的 LSD（产生可忽略不计的主观变化）改变了边缘回路中的脑连接。进一步的研究，特别是重复给药的研究，将揭示这些神经变化是否与该药物据称的抗抑郁作用有关。
