Biobehavioral effects of topiramate on cannabis-related outcomes in adolescents

托吡酯对青少年大麻相关结局的生物行为影响

基本信息

批准号：
7687244
负责人：
ROBERT MIRANDA
金额：
$ 56.05万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-15 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7687244
关键词：
Accounting Acute Admission activity Adolescent Adult Affect Age Agonist Alcohols Anticonvulsants Attenuated Cannabinoids Cannabis Cannabis Abuse Cannabis Smoking Clinical Clinical Trials Cocaine Cues Data Dependence Disease Dopamine Drug usage Electronics Environment Frequencies Glutamate Receptor Glutamates Goals Gray unit of radiation dose Human Intervention Laboratories Light Measures Mediating Methods Monitor National Institute of Drug Abuse Neurons Nicotine Nicotine Withdrawal Oral Outcome Participant Pathway interactions Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Placebos Probability Psychophysiology Public Health Randomized Reflex action Reporting Rewards Severities Smoke Smoker Stimulus Students Substance abuse problem Teenagers Testing Tetrahydrocannabinol Time Treatment outcome United States Substance Abuse and Mental Health Services Administration Withdrawal Withdrawal Symptom Youth alcohol craving base biobehavior cocaine use cost craving cue reactivity diaries drug of abuse effective therapy excitatory neuron gamma-Aminobutyric Acid high school improved male meetings neurotransmission psychosocial public health relevance topiramate

项目摘要

DESCRIPTION (provided by applicant): Cannabis use disorders are a significant public health concern that disproportionately affect youth. Although promising psychosocial interventions are being developed, most youth do not benefit from these interventions alone. In light of the clinical demand for improved treatments for youth, NIDA recently identified the critical need for data on the tolerability and potential efficacy of medications in adolescents (RFA-DA-09- 001). The major objective of this application is to test whether topiramate (TPM), an anticonvulsant medication under intense study for treating several drugs of abuse, affects cannabis use and related phenotypes in youth. TPM facilitates gamma aminobutyric acid (GABA) neurotransmission and blocks AMPA/kainite glutamate receptors. Because mesocorticolimbic dopamine (DA) release, which contributes to the rewarding effects of acute drug use, is under tonic inhibitory control via GABAergic neurons and excitatory control via glutamatergic neurons, TPM's concurrent GABAergic agonism and glutamatergic antagonism is thought to reduce drug use, in part, by attenuating craving. Indeed, TPM reduces alcohol, nicotine, and cocaine use. Although the effects of TPM on cannabis abuse are untested, cannabis exerts its reinforcing effects by activating the same mesolimbic DA pathways as most abused drugs and therefore is also likely to be influenced by TPM. We propose to randomize nontreatment seeking youth (n = 132; ages 15-18) with cannabis abuse or dependence to TPM (200 mg/day) or placebo for 6 weeks. Youth will monitor their cannabis use, craving, acute subjective effects of smoked cannabis, and withdrawal symptoms for the 6-week period using handheld electronic diaries. In addition, participants will complete a laboratory assessment of reactivity to cannabis-related cues. This comprehensive yet efficient analysis will provide much needed data on the effects of TPM on cannabis use in adolescents while adding important new information about the biobehavioral mechanisms of TPM action on cannabis use. PUBLIC HEALTH RELEVANCE: This study will help to determine whether the medication, topiramate, reduces cannabis use among adolescents with cannabis abuse or dependence. It also will help answer the question, "How does topiramate reduce cannabis use?" Understanding how topiramate may reduce cannabis use among adolescents would allow for a more targeted pharmacotherapeutic approach to treatment and help to identify additional medications that may hold promise for improving cannabis treatment outcomes for youth.

描述（由申请人提供）：大麻使用障碍是一个重大的公共卫生问题，对青少年的影响尤为严重。尽管正在开发有前景的社会心理干预措施，但大多数年轻人并不能仅从这些干预措施中受益。鉴于改善青少年治疗的临床需求，NIDA 最近发现迫切需要有关青少年药物耐受性和潜在疗效的数据 (RFA-DA-09-001)。本申请的主要目的是测试托吡酯 (TPM)（一种正在深入研究的用于治疗多种滥用药物的抗惊厥药物）是否影响青少年的大麻使用和相关表型。 TPM 促进 γ 氨基丁酸 (GABA) 神经传递并阻断 AMPA/红藻氨酸谷氨酸受体。由于中皮质边缘多巴胺 (DA) 的释放有助于急性药物使用的奖赏效应，它受到 GABA 能神经元的强直抑制控制和谷氨酸能神经元的兴奋控制，因此 TPM 并发的 GABA 能激动和谷氨酸能拮抗作用被认为可以部分减少药物使用，通过减弱渴望。事实上，TPM 可以减少酒精、尼古丁和可卡因的使用。尽管 TPM 对大麻滥用的影响尚未经过测试，但大麻通过激活与大多数滥用药物相同的中脑边缘 DA 途径来发挥其增强作用，因此也可能受到 TPM 的影响。我们建议对滥用大麻或依赖 TPM（200 毫克/天）或安慰剂的未寻求治疗的青少年（n = 132；15-18 岁）进行随机分组，为期 6 周。青少年将使用手持电子日记在 6 周内监测他们的大麻使用、渴望、吸食大麻的急性主观影响以及戒断症状。此外，参与者将完成对大麻相关线索反应性的实验室评估。这项全面而有效的分析将提供有关 TPM 对青少年大麻使用影响的急需数据，同时添加有关 TPM 对大麻使用的生物行为机制的重要新信息。公共卫生相关性：这项研究将有助于确定药物托吡酯是否可以减少大麻滥用或依赖的青少年对大麻的使用。它还将有助于回答“托吡酯如何减少大麻使用？”的问题。了解托吡酯如何减少青少年的大麻使用，将有助于采取更有针对性的药物治疗方法，并有助于确定可能有望改善青少年大麻治疗结果的其他药物。