A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants’ drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21–31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs’ effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants’ responses to the three drugs were unrelated. Unexpectedly, “wanting more” alcohol was inversely correlated with “wanting more” THC. Additionally, in women, but not in men, “disliking” alcohol was negatively correlated with “disliking” THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a “drug of choice” model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs.Trial RegistrationClinicalTrials.gov NCT02485158

多药使用现象较为普遍，其发生可能源于部分个体在用药早期可从多种不同药物中获得正向体验。本研究针对健康社交饮酒者，探究其单次口服右旋苯丙胺（d-amphetamine）、酒精及δ-9-四氢大麻酚（delta-9-tetrahydrocannabinol, THC）后的主观反应个体差异。上述三种药物均可在至少部分个体中引发愉悦感，我们假设受试者对这三种药物的主观反应呈正相关。此外，本研究还探究了受试者的药物反应与药物使用相关人格特质之间的关联。

本项探索性初步研究共纳入24名健康轻度药物使用者（12名男性、12名女性），年龄介于21至31岁之间。研究采用完全被试内随机平衡对照设计，共设置6次时长5.5小时的实验环节，受试者分别接受右旋苯丙胺（20mg）、酒精（0.8g/kg体重）或THC（7.5mg）干预，每次干预均匹配安慰剂对照环节。受试者针对整体指标（如是否感知到药物作用）以及药物特异性指标对药物效应进行评分。

总体而言，受试者对三种药物的反应并无关联。出乎意料的是，“渴望更多酒精”与“渴望更多THC”呈负相关。此外，仅在女性受试者中，“厌恶酒精”与“厌恶THC”呈负相关，男性受试者中未观察到此关联。酒精与右旋苯丙胺的正向反应存在关联，但仅见于感受到酒精兴奋作用的个体。最后，高特质克制力（即低冲动性）与对酒精的喜爱度自评更低相关。未发现任何人格特质可预测受试者对多种药物的反应。

总体而言，本研究结果不支持“特定个体在多种药物类别中均可获得更强正向体验”这一假说，反而为“药物选择偏好模型”提供了部分证据：该模型认为个体会对主观效应相似的特定药物类别产生正向反应，而厌恶其他类型的药物。临床试验注册：ClinicalTrials.gov 编号NCT02485158