Pupillary dynamics as a marker of acute cannabis inhalation

Acute cannabis use has been found to affect pupil size and pupillary dynamics. Law enforcement may consider ocular changes in their examinations to determine drug impairment and the source, including from cannabis. A limited number of studies have used pupillometer technology to provide an objective measure of pupillary changes associated with cannabis use. The purpose of the study was to examine the sensitivity and specificity of pupil size and dynamics, measured with a pupillometer, associated with recent cannabis inhalation. Participants (<i>n</i> = 126) completed a pupillometer assessment, using the NeurOptics PLR-3000 at three times. Of the 126 participants, 95 completed assessments at baseline, and at 40 min and 100 min following 15 min of <i>ad libitum</i> inhalation of self-provided cannabis flower or concentrate products. Thirty-one participants completed the same assessments without using cannabis. Sensitivity, specificity and accuracy were calculated for pupil size and dynamics measures associated with recent cannabis use versus no use, for both post-use time points. Least absolute shrinkage and selection operator models were used to identify the combination of ocular metrics that were most predictive and parsimonious. Following cannabis use, the pupillary measure with the highest area under the curve was percent change in pupil size, which decreased after cannabis use, with an area under the curve of 0.73 at 40 min and 0.75 at 100 min following cannabis use. Considering variables together in a least absolute shrinkage and selection operator model did not meaningfully improve prediction over individual measures. Consistent with some prior studies, we did not find that cannabis use was associated with substantial and consistent change in the maximum pupil size (measured in darkness) relative to controls. However, diminished pupil dynamics, such as constriction in response to light and recovery dilation, were more predictive of recent cannabis use, consistent with limited prior studies. Pupillary dynamics, when measured with an objective test, may contribute to providing an indication of recent cannabis inhalation.

现有研究表明，急性大麻使用会影响瞳孔大小及瞳孔动态反应（pupillary dynamics）。执法人员在执法检查中可参考眼部变化，以判断是否存在药物致损情况及致损源，其中也包括大麻摄入相关情形。目前已有少量研究采用瞳孔测量仪（pupillometer）技术，对大麻使用相关的瞳孔变化进行客观量化评估。本研究旨在探讨通过瞳孔测量仪采集的、与近期大麻吸入相关的瞳孔大小及动态反应指标的灵敏度与特异度。

本研究共纳入126名受试者，采用NeurOptics PLR-3000型瞳孔测量仪完成3次瞳孔评估。其中95名受试者完成了基线评估，以及在自由吸入自制大麻花蕾或浓缩制品15分钟后的40分钟、100分钟两次评估；剩余31名受试者在未使用大麻的情况下完成了相同流程的评估。

研究分别计算了大麻使用后两个时间点下，与近期大麻使用/未使用相关的瞳孔大小及动态反应指标的灵敏度、特异度及准确率。本研究采用最小绝对收缩与选择算子（Least Absolute Shrinkage and Selection Operator, LASSO）模型，筛选出预测效能最优且最为简约的眼部指标组合。

大麻使用后，曲线下面积最高的瞳孔测量指标为瞳孔大小变化率：受试者在使用大麻后该指标出现下降，在用药后40分钟与100分钟的曲线下面积分别为0.73与0.75。将多项指标纳入LASSO模型联合分析，并未较单一指标显著提升预测效能。与部分既往研究结果一致，本研究未发现大麻使用与对照组相比，会引发瞳孔最大尺寸（黑暗环境下测量）出现显著且稳定的变化。但与少量既往研究结论相符，本研究发现瞳孔动态反应受损——如对光反射收缩及恢复性扩张能力下降——可更有效地预测近期大麻吸入行为。通过客观检测手段采集的瞳孔动态反应指标，或可为判断近期大麻吸入行为提供辅助依据。