Cannabinoid effects on HIV/AIDS

描述（由申请人提供）：随着高效抗逆转录病毒疗法的出现，人类免疫缺陷病毒（HIV）感染已成为一种慢性疾病，经常与长期使用处方、实验和非法药物（包括大麻素）共存。四氢大麻酚（delta9-THC）是大麻中最有效的精神活性成分，除了公认的神经行为破坏外，还具有多种系统效应，包括免疫功能的显着改变。了解德尔塔9-四氢大麻酚对HIV感染患者免疫和神经行为功能的影响尤为重要，因为它已被批准作为获得性免疫缺陷综合征（AIDS）患者食欲刺激的辅助治疗。然而，其长期使用的代谢影响以及艾滋病毒感染者的免疫和神经行为后果尚未得到仔细检查。我们在非人类灵长类动物SIV感染模型中验证的工作假设是，慢性德尔塔9-四氢大麻酚治疗将：a)增加热量摄入，防止脂肪量减少，但不改善瘦体重的保留；b)对免疫功能产生不利影响，增加血浆和脑脊液病毒载量；c)揭示艾滋病相关的神经行为缺陷。这些研究的具体目的是确定长期服用δ 9-四氢大麻酚对a)热量摄入、体重和组成以及骨骼肌蛋白质合成和分解的平衡（瘦体重的主要决定因素）的影响；b) siv感染恒河猴血浆和脑脊液病毒载量、免疫表型和免疫能力标志物；c) siv感染恒河猴神经行为功能障碍的发生及炎症和轴突损伤的神经病理指标。总的来说，拟议的研究将检查慢性δ 9-四氢大麻酚管理对三个关键方面的影响；在一个控制的实验环境中，在SIV感染的整个过程中，直到艾滋病晚期，身体成分、免疫功能和认知表现。这些研究的结果将为长期滥用大麻的影响提供客观的科学证据，并将为艾滋病毒感染/艾滋病患者使用大麻素的潜在健康后果提供重要信息。

DESCRIPTION (provided by applicant): With the advent of highly active antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a chronic disease frequently co-existing with chronic use of prescribed, experimental and illicit drugs, including that of cannabinoids. Tetrahydrocannabinol (delta9-THC) the most potent psychoactive constituent of marijuana, exerts multiple systemic effects in addition to the well recognized neurobehavioral disruption, including marked alterations in immune function. Understanding the impact of delta9-THC, on immune and neurobehavioral function in HIV infection is particularly important, as its use has been approved as adjuvant therapy for appetite stimulation in acquired immunodeficiency syndrome (AIDS) patients. However, the metabolic impact of its chronic use as well as the immune and neurobehavioral consequences in the HIV-infected individual have not been carefully examined. Our working hypothesis to be tested in this non-human primate model of SIV infection is that chronic delta9-THC treatment will: a) increase caloric intake and prevent loss of fat mass without improving retention of lean body mass, b) adversely affect immune function, increasing plasma and cerebrospinal fluid viral load and c) unmask the AIDS-related neurobehavioral deficits. The specific aims of the studies are to determine the impact of chronic delta9-THC administration on a) caloric intake, body weight and composition and the balance of skeletal muscle protein synthesis and breakdown, the main determinants of lean body mass; b) plasma and cerebrospinal fluid viral load, immune phenotype and markers of immune competence and c) the occurrence of neurobehavioral dysfunction and neuropathological indices of inflammation and axonal damage in SIV-infected rhesus macaques. Overall, the proposed studies will examine the impact of chronic delta9-THC administration on three key aspects; body composition, immune function and cognitive performance throughout the course of SIV infection until the terminal AIDS stage in a controlled experimental setting. Findings from these studies will provide objective scientific evidence on the effects of chronic marijuana abuse and will provide critical information about the potential health consequences of cannabinoid use in individuals with HIV infection/AIDS.