Pfisterer Marlen, Teetzmann Anton, Vetter Sina, Baeßler Joscha, Schreckenberger Lena, Zaiser Judith, Stenger Manuel, Bach Patrick
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5/68159, Mannheim, Germany.
German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim, Germany.
Psychopharmacology (Berl). 2025 Aug 29. doi: 10.1007/s00213-025-06860-5.
Negative affect is a key factor in Alcohol Use Disorder (AUD) associated with craving and relapse risk that is insufficiently treated by approved medications. Cannabidiol (CBD) has shown promising effects on negative affect, indicating its potential for addressing the neurocircuitry underlying negative affect in AUD.
This study investigates CBD's effects on neural response to negative emotional stimuli and subjective alcohol craving in individuals with AUD.
We conducted the first neuroimaging study investigating CBD's effects on neural responses to negative emotional stimuli and craving in AUD. The study was designed as two armed, 1:1 randomized, double blind, parallel group neuroimaging trial, enrolled N = 28 individuals with AUD. It compared the effects of 800 mg oral CBD versus matched Placebo (PLC) on blood oxygenated level dependent (BOLD) response in the amygdala during a validated emotion processing task and explored associations with CBD plasma levels and subjective alcohol craving.
CBD versus PLC attenuated bilateral amygdala reactivity to angry and fearful faces (p <.05, small volume corrected), while CBD showed no effect on amygdala activation during the presentation of neutral shape stimuli. Amygdala response to negative emotional stimuli correlated positively with the extent of subjective alcohol craving (r =.52, p =.01; r =.52, p =.01) and negatively with CBD plasma levels (r = -.68, p = 0.002; r = -.65, p = 0.002).
In summary, CBD's effects on amygdala reactivity to negative emotional stimuli in individuals with AUD support CBD's potential for modulating emotion-processing circuits in AUD and CBD's treatment potential for craving and relapse driven by negative affective states.
消极情绪是酒精使用障碍（AUD）的关键因素，与渴望及复发风险相关，而目前获批的药物对其治疗并不充分。大麻二酚（CBD）已显示出对消极情绪有良好效果，表明其在解决AUD中消极情绪背后神经回路问题方面具有潜力。
本研究调查CBD对AUD患者负面情绪刺激的神经反应及主观酒精渴望的影响。
我们开展了第一项神经影像学研究，调查CBD对AUD患者负面情绪刺激的神经反应及渴望的影响。该研究设计为双臂、1:1随机、双盲、平行组神经影像学试验，纳入了N = 28名AUD患者。在一项经过验证的情绪处理任务中，比较了800毫克口服CBD与匹配安慰剂（PLC）对杏仁核血氧水平依赖（BOLD）反应的影响，并探讨了与CBD血浆水平及主观酒精渴望的关联。
与PLC相比，CBD减弱了双侧杏仁核对愤怒和恐惧面孔的反应性（p <.05，小体积校正），而在呈现中性形状刺激时，CBD对杏仁核激活无影响。杏仁核对负面情绪刺激的反应与主观酒精渴望程度呈正相关（r =.52，p =.01；r =.52，p =.01），与CBD血浆水平呈负相关（r = -.68，p = 0.002；r = -.65，p = 0.002）。
总之，CBD对AUD患者杏仁核对负面情绪刺激的反应性的影响，支持了CBD在调节AUD情绪处理回路方面的潜力，以及其对由消极情感状态驱动的渴望和复发的治疗潜力。
