Imaging the Effects of Intermittent Thetaburst Stimulation on Cannabis Self-Administration in Heavy Cannabis Users
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Frequency of cannabis use
研究概览
简要总结
The growing legalization of cannabis across the U.S. is associated with increases in cannabis use, and accordingly, an increase in the number of individuals with cannabis use problems, including cannabis use disorder (CUD). While there are several medications being investigated as treatment options for CUD, none have been FDA-approved, and there is limited efficacy of traditional behavioral therapy approaches for this population. Consequently, there is a pressing need for the development of new treatments, including approaches that specifically target the brain areas associated with problematic cannabis use behaviors. Elevated attention to drug cues is one of the primary causes of relapse in heavy cannabis users. Preliminary data suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, may be a novel brain-based tool to decrease heightened attention to drug cues in people with CUD. Building on prior data, the primary goal of this study is to evaluate the feasibility and effectiveness of TMS as a tool to decrease attention to drug cues and reduce cannabis use.
In this study, fifty (50) treatment-seeking, near-daily cannabis users will be recruited to receive either active or sham (placebo) repetitive TMS (rTMS). Participants will complete a total of 25 treatment sessions, delivered as five sessions per day across five days, with sessions flexibly scheduled over a two-week period. Measures of cannabis use and brain activity will be collected before and after treatment using real-time self-report assessments and functional magnetic resonance imaging (fMRI), respectively. Specifically, cannabis use will be assessed in participants' everyday environments using brief text-message surveys during a two-week baseline period, the two-week treatment period, and a four-week follow-up period.
The study aims to determine whether active rTMS reduces brain activity in response to cannabis cues, decreases automatic attention to cannabis cues, and leads to meaningful reductions in cannabis use compared to sham treatment.
详细描述
The expanding legalization of cannabis across the U.S. is associated with increases in cannabis use and, accordingly, an increase in the number of individuals with cannabis use disorder (CUD). One key predictor of relapse is elevated attentional bias to drug cues, coupled with attenuated cognitive control in the presence of those cues. Attentional bias to drug cues is associated with increased activity in the Salience Network (SN), including the anterior cingulate cortex and bilateral anterior insula, as well as reduced activity in the dorsolateral prefrontal cortex (DLPFC) and broader cognitive control circuitry during exposure to cannabis cues.
Our prior data demonstrate that neural responses to drug cues can be reduced by attenuating ventromedial prefrontal cortex (VMPFC) and reward circuitry using inhibitory repetitive transcranial magnetic stimulation (rTMS) (Strategy 1). An alternative approach, however, may be to enhance activity in the DLPFC and cognitive control circuitry, which may also reduce neural reactivity to drug cues by inversely regulating SN cue hyper-reactivity (Strategy 2, the focus of this K01). Through the research and training plan outlined in this K01 proposal, I seek to evaluate the ability of left DLPFC-targeted rTMS to attenuate SN drug cue reactivity and attentional bias, and to reduce cannabis use. This will be accomplished by applying accelerated intermittent theta burst stimulation (aiTBS), a novel patterned excitatory form of rTMS, to the L DLPFC in heavy cannabis users.
GOAL. The primary objectives of this K01 research project are to:
- determine whether L DLPFC aiTBS decreases cannabis use using real-time data collected in the natural environment;
- determine whether aiTBS-induced changes in cannabis use are associated with changes in Salience Network drug cue reactivity; and
- assess whether L DLPFC aiTBS is feasible, tolerable, and safe relative to sham stimulation.
DESIGN. Fifty (50) treatment-seeking, heavy (near-daily) cannabis users will be randomized to receive either active or sham aiTBS targeting the L DLPFC. Participants will complete a total of 25 treatment sessions, delivered as five sessions per day (50-min inter-session interval) across five treatment days, with visits flexibly scheduled over a two-week period. Cannabis use data will be collected throughout the study, and functional magnetic resonance imaging (fMRI) data will be collected before and after aiTBS treatment, as well as following a 4-week follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males/non-pregnant females, 18-65 years old
- •Current cannabis user
- •Able to perform all study procedures
排除标准
- •Regular use of other illicit drugs
- •If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
研究组 & 干预措施
Active
干预措施: iTBS (Device)
Sham
干预措施: iTBS (Device)
结局指标
主要结局
Frequency of cannabis use
时间窗: Two-week Pre-treatment/Baseline phase (Days 1-14), Two-week Treatment phase (Days 15-28), Four-week Post-treatment phase (Days 29-56)
On each study day, participants will receive EMA text surveys on their cellphones. For each participant, cannabis use frequency will be measured as the number of days per week they report cannabis use. During the two-week pre-treatment period, we will calculate the baseline frequency as the average number of use days per week across those two weeks. Cannabis use frequency will then be assessed during each of the two treatment weeks (Week 0-1) and during the four-week follow-up period (Weeks 2-5), and the follow-up period will subsequently be compared relative to baseline. This is corroborated by TLFB.
Quantity of cannabis use
时间窗: Two-week Pre-treatment/Baseline phase (Days 1-14), Two-week Treatment phase (Days 15-28), Four-week Post-treatment phase (Days 29-56)
On each study day, participants will receive EMA text surveys on their cellphones. For each participant, cannabis use quantity will be measured as the average number of grams used per use-day during each week in which they report cannabis use. During the two-week pre-treatment/baseline period (Days 1-14), we will calculate the baseline quantity as the average daily grams used per use-day across those two weeks. Cannabis use quantity will then be assessed during the treatment phase (Days 15-28) and during the 4-week follow-up period (Days 29-56), and the follow-up period will subsequently be compared relative to baseline. This will be corroborated by TLFB.
次要结局
- Salience Network drug cue reactivity(Pre-treatment/Baseline (Day 14), Immediate Post-treatment (Day 28), 4-Week Post-treatment Follow-up (Day 56))
- Feasibility (attendance)(Two-week Treatment phase (Days 15-28))
- Tolerability (withdrawals)(Two-week Treatment phase (Days 15-28))
- Safety (AEs)(Two-week Treatment phase (Days 15-28))
研究者
Tonisha Kearney-Ramos, PhD
Research Scientist III/Assistant Professor of Clinical Neurobiology (in Psychiatry)
New York State Psychiatric Institute