Ranganathan Mohini, Braley Gabriel, Pittman Brian, Cooper Thomas, Perry Edward, Krystal John, D'Souza Deepak Cyril
Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA.
Psychopharmacology (Berl). 2009 May;203(4):737-44. doi: 10.1007/s00213-008-1422-2. Epub 2008 Dec 16.
Cannabis is one of the most widely used illicit substances, and there is growing interest in the therapeutic applications of cannabinoids. While known to modulate neuroendocrine function, the precise acute and chronic dose-related effects of cannabinoids in humans are not well-known. Furthermore, the existing literature on the neuroendocrine effects of cannabinoids is limited by small sample sizes (n = 6-22), heterogeneous samples with regard to cannabis exposure (lumping users and nonusers), lack of controlling for chronic cannabis exposure, differing methodologies, and limited dose-response data. Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce dose-related increases in plasma cortisol levels and decreases in plasma prolactin levels. Furthermore, relative to controls, frequent users of cannabis were hypothesized to show altered baseline levels of these hormones and blunted Delta-9-THC-induced changes of these hormones.
Pooled data from a series of laboratory studies with multiple doses of intravenous Delta-9-THC in healthy control subjects (n = 36) and frequent users of cannabis (n = 40) was examined to characterize the acute, chronic, and acute on chronic effects of cannabinoids on plasma cortisol and prolactin levels. Hormone levels were measured before (baseline) and 70 min after administration of each dose of Delta-9-THC. Data were analyzed using linear mixed models with +70 min hormonal levels as the dependant variable and baseline hormonal level as the covariate.
At socially relevant doses, Delta-9-THC raised plasma cortisol levels in a dose-dependent manner but frequent users showed blunted increases relative to healthy controls. Frequent users also had lower baseline plasma prolactin levels relative to healthy controls.
These group differences may be related to the development of tolerance to the neuroendocrine effects of cannabinoids. Alternatively, these results may reflect inherent differences in neuroendocrine function in frequent users of cannabis and not a consequence of cannabis use.
大麻是使用最为广泛的非法物质之一，人们对大麻素的治疗应用兴趣日增。虽然已知大麻素可调节神经内分泌功能，但其在人体中的精确急性和慢性剂量相关效应尚不明确。此外，现有关于大麻素神经内分泌效应的文献存在样本量小（n = 6 - 22）、大麻暴露样本异质性（将使用者和非使用者混在一起）、缺乏对慢性大麻暴露的控制、方法不同以及剂量反应数据有限等局限性。据推测，Δ-9-四氢大麻酚（Δ-9-THC）会使血浆皮质醇水平呈剂量相关升高，血浆催乳素水平降低。此外，相对于对照组，经常使用大麻者被推测会表现出这些激素的基线水平改变以及Δ-9-THC诱导的这些激素变化减弱。
对一系列实验室研究的汇总数据进行了分析，这些研究涉及在健康对照者（n = 36）和经常使用大麻者（n = 40）中多次静脉注射Δ-9-THC，以确定大麻素对血浆皮质醇和催乳素水平的急性、慢性以及急性加慢性效应。在每次注射Δ-9-THC之前（基线）和之后70分钟测量激素水平。使用线性混合模型进行数据分析，将 +70分钟时的激素水平作为因变量，基线激素水平作为协变量。
在社交相关剂量下，Δ-9-THC以剂量依赖方式升高血浆皮质醇水平，但与健康对照相比，经常使用者的升高幅度减弱。与健康对照相比，经常使用者的血浆催乳素基线水平也较低。
这些组间差异可能与对大麻素神经内分泌效应的耐受性发展有关。或者，这些结果可能反映了经常使用大麻者神经内分泌功能的固有差异，而非大麻使用的结果。
