Background and Hypothesis Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total n = 130), we hypothesized that a modest dose of THC would worsen cognitive function but not psychosis. Study Design Effects of single-dose oral THC (15 mg dronabinol) or smoked 3.5% THC cigarettes vs placebo in SCZ-CUD or CUD-only on positive and negative symptoms of schizophrenia (only for SCZ-CUD), cognition, and drug experiences assessed several hours after drug administration. SCZ-only and healthy control participants were also assessed. Study Results Drug liking was higher in THC groups vs placebo. Neither smoked THC nor oral dronabinol predicted positive or negative symptom subscale scores 2 and 5 h, respectively, after drug exposure in SCZ-CUD participants. The oral dronabinol SCZ-CUD group, but not smoked THC SCZ-CUD group, performed worse than placebo on verbal learning (B = −9.89; 95% CI: −16.06, −3.18; P = .004) and attention (B = −0.61; 95% CI: −1.00, −0.23; P = .002). Every 10-point increment in serum THC + THCC ng/ml was associated with increased negative symptoms (0.40 points; 95% CI: 0.15, 0.65; P = .001; subscale ranges 7–49) and trends were observed for worse positive symptoms and performance in verbal learning, delayed recall, and working memory. Conclusions In people with SCZ-CUD, a modest single dose of oral THC was associated with worse cognitive functioning without symptom exacerbation several hours after administration, and a THC dose-response effect was seen for negative symptoms.

中文翻译：

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单剂量大麻、屈大麻酚和安慰剂治疗精神分裂症和大麻使用障碍患者的随机实验室研究


背景和假设 高达 43% 的精神分裂症患者患有终生大麻使用障碍 (CUD)。四氢大麻酚 (THC) 已被证明会以剂量依赖性方式加剧精神病，但很少有研究评估其对精神分裂症和并发 CUD (SCZ-CUD) 的影响。在这项双模拟安慰剂对照试验（总计 n = 130）中，我们假设适量的 THC 会恶化认知功能，但不会恶化精神病。研究设计 SCZ-CUD 或仅 CUD 中单剂量口服 THC（15 毫克屈大麻酚）或吸 3.5% THC 香烟与安慰剂相比，对精神分裂症阳性和阴性症状（仅适用于 SCZ-CUD）、认知和药物体验的影响给药后数小时进行评估。还对仅使用 SCZ 的参与者和健康对照参与者进行了评估。研究结果 THC 组的药物偏好高于安慰剂组。 SCZ-CUD 参与者在药物暴露后 2 小时和 5 小时，吸食 THC 或口服屈大麻酚均不能预测阳性或阴性症状分量表评分。口服屈大麻酚 SCZ-CUD 组（但未吸食 THC SCZ-CUD 组）在语言学习（B = −9.89；95% CI：−16.06，−3.18；P = .004）和注意力（B = .004）方面表现比安慰剂差。 -0.61；95% CI：-1.00，-0.23；P = .002）。血清 THC + THCC ng/ml 每增加 10 分，阴性症状就会增加（0.40 分；95% CI：0.15，0.65；P = 0.001；子量表范围 7-49），并且观察到阳性症状恶化的趋势以及言语学习、延迟回忆和工作记忆方面的表现。结论 在 SCZ-CUD 患者中，少量单剂量口服 THC 与认知功能较差相关，且给药后数小时内症状不会恶化，并且对于阴性症状存在 THC 剂量反应效应。