Menninger Department of Psychiatry and Behavioral Sciences, Michael E. DeBakey VA Medical Center & Baylor College of Medicine, Houston, Texas.
Department of Pharmacology, Michael E. DeBakey VA Medical Center & Baylor College of Medicine, Houston, Texas.
Am J Addict. 2019 Nov;28(6):455-464. doi: 10.1111/ajad.12959. Epub 2019 Sep 4.
No medication has Food and Drug Administration approval for cannabis use disorder (CUD), and most medication development focuses on the withdrawal syndrome. We evaluated the effects of short-term treatment using the α-2A-adrenergic receptor agonist, guanfacine, on withdrawal symptoms in volunteers with CUD and a history of early onset of cannabis use.
Non-treatment-seeking healthy volunteers (n = 7) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for CUD participated in a two-phase, within-subjects study. Volunteers received placebo or guanfacine (3 mg/day) for the first 8-day inpatient study and the alternative medication for the second 8-day inpatient study. On day 1 of both treatment periods, participants received 30 mg of synthetic Δ -tetrahydrocannabinol for standardization of abstinence onset. On days 2 to 7, participants received study medication. Cannabis withdrawal symptoms, sleep, craving, and physiology were assessed on all inpatient days.
Compared with placebo, guanfacine did not show significant effects on withdrawal, craving, or sleep, although there were trends for guanfacine to increase positive mood symptoms and decrease craving-associated compulsivity.
Compared with former studies, we could not prove significant improvement in sleep or decrease of negative symptoms, but we found trends for increased positive mood symptoms. Our data did not show significant effects of guanfacine on withdrawal symptoms or craving. Due to early and longer cannabis use, our subjects indicate a great severity of illness increasing the likelihood of treatment resistance.
On the basis of trends demonstrated here and other lines of evidence, further investigation is warranted regarding the utility of guanfacine as a potential treatment for CUD. (Am J Addict 2019;00:1-10).
目前没有任何药物获得美国食品和药物管理局（FDA）批准用于治疗大麻使用障碍（CUD），而且大多数药物研发都集中在戒断综合征上。我们评估了短期使用α-2A 肾上腺素能受体激动剂胍法辛治疗 CUD 患者和早期大麻使用者戒断症状的效果。
非治疗寻求的健康志愿者（n=7）符合《精神疾病诊断与统计手册》第 4 版（DSM-IV）中 CUD 的诊断标准，参与了一项两阶段、自身对照的研究。志愿者接受安慰剂或胍法辛（3mg/天）治疗 8 天的住院研究，然后进行第二项 8 天住院研究，接受替代药物治疗。在两个治疗期的第 1 天，参与者接受 30mg 合成的 Δ-四氢大麻酚以标准化戒断的开始。在第 2 天至第 7 天，参与者接受研究药物。在所有住院日评估大麻戒断症状、睡眠、渴望和生理状况。
与安慰剂相比，胍法辛对戒断、渴望或睡眠没有显著影响，尽管有增加正性情绪症状和减少与渴望相关的强迫性的趋势。
与以前的研究相比，我们无法证明睡眠或负面症状的显著改善，但我们发现正性情绪症状有增加的趋势。我们的数据没有显示胍法辛对戒断症状或渴望有显著影响。由于早期和更长时间的大麻使用，我们的受试者表明疾病严重程度较大，增加了治疗抵抗的可能性。
基于这里显示的趋势和其他证据，进一步研究胍法辛作为 CUD 潜在治疗方法的效用是合理的。（美国成瘾杂志 2019；00：1-10）。
