Division on Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Psychopharmacology (Berl). 2010 Aug;211(2):141-8. doi: 10.1007/s00213-010-1875-y. Epub 2010 May 19.
Studies in laboratory animals strongly suggest reciprocal modulation of the opioidergic and endocannabinoid systems, a relationship that has not been demonstrated in humans. This study sought to clarify this interaction by assessing how a range of naltrexone doses altered the subjective, cognitive, and cardiovascular effects of marijuana.
Daily marijuana smokers (n = 29) participated in this within-subject, randomized, double-blind, placebo-controlled study. Naltrexone (0, 12, 25, 50, or 100 mg) was administered before active or inactive marijuana (3.27 or 0% THC) was smoked.
Active marijuana increased subjective ratings of marijuana 'Strength,' 'High,' and positive subjective ratings of marijuana quality and drug effect including 'Liking,' 'Good,' and 'Take Again' compared to inactive marijuana. Naltrexone alone decreased ratings of 'Liking,' 'Take Again,' and 'Stimulated' compared with placebo, but increased ratings of drug 'Strength,' 'High,' 'Good,' 'Liking,' 'Stimulated,' and 'Take Again' when administered under active marijuana conditions. Active marijuana did not affect performance on cognitive tasks relative to inactive marijuana, whereas naltrexone decreased performance when administered alone or in combination with active marijuana. Active marijuana increased heart rate compared to inactive marijuana under placebo naltrexone conditions. Although naltrexone alone decreased heart rate, it further increased marijuana's cardiovascular effect.
In heavy marijuana smokers opioid-receptor blockade enhanced the subjective and cardiovascular effects of marijuana, suggesting that endogenous opioids dampen cannabinoid effects in this population. These findings demonstrate that a broad range of clinically used doses of naltrexone potentially increases the abuse liability and cardiovascular risks of cannabinoids.
动物实验研究强烈提示阿片系统与内源性大麻素系统之间存在相互调节作用，而这种关系尚未在人体中得到证实。本研究旨在通过评估不同剂量纳曲酮对大麻的主观、认知和心血管效应的影响，阐明这种相互作用。
本研究纳入了 29 名每日吸食大麻的受试者，采用自身前后对照、随机、双盲、安慰剂对照设计。在吸食活性（含 3.27% THC）或非活性大麻（含 0% THC）之前，受试者分别接受纳曲酮（0、12、25、50 或 100mg）或安慰剂处理。
与非活性大麻相比，活性大麻显著增加了大麻“效力”、“兴奋感”、积极的大麻质量和药物效应的主观评分，包括“喜欢”、“好”和“再用”。与安慰剂相比，纳曲酮单用时降低了“喜欢”、“再用”和“刺激”的评分，但在活性大麻条件下，增加了药物“效力”、“兴奋感”、“好”、“喜欢”、“刺激”和“再用”的评分。与非活性大麻相比，活性大麻对认知任务的影响无显著差异，而纳曲酮单用时或与活性大麻合用时降低了认知任务的表现。与安慰剂纳曲酮条件下的非活性大麻相比，活性大麻显著增加了心率。尽管纳曲酮单用时降低了心率，但它进一步增加了大麻的心血管效应。
在重度大麻吸食者中，阿片受体阻断剂增强了大麻的主观和心血管效应，提示内源性阿片类物质在该人群中抑制大麻素的作用。这些发现表明，广泛应用于临床的纳曲酮剂量可能会增加大麻素的滥用倾向和心血管风险。
