TMS for Cocaine Use Disorder
Recruiting in Palo Alto (17 mi)
Overseen byHeather Webber, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: The University of Texas Health Science Center, Houston
Must not be taking: Antidepressants, Antipsychotics, Stimulants, others
Disqualifiers: Substance use disorder, Heart disease, Stroke, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to assess effects of intermittent theta burst stimulation (iTBS) to left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to sham on electrophysiological indices of reward sensitivity and motivated attention in adults with cocaine use disorder.
Do I need to stop taking my current medications for the trial?
The trial requires participants to stop taking certain medications that increase the risk of seizures, such as clozapine, chlorpromazine, bupropion, and others, during the study. If you are on any of these medications, you will need to stop taking them to participate.
What data supports the effectiveness of this treatment for cocaine use disorder?
Research shows that intermittent theta burst stimulation (iTBS), a type of transcranial magnetic stimulation (TMS), can reduce cocaine use and cravings in people with cocaine use disorder. Studies have found that iTBS is as effective as traditional TMS methods but is quicker and more tolerable, making it a promising treatment option.
12345Is TMS safe for treating cocaine use disorder?
TMS, including iTBS, is generally considered safe and well-tolerated, with some participants experiencing mild side effects like headaches. In studies with cocaine users, most participants tolerated the treatment well, although one person experienced a temporary neurological event and cocaine-induced psychosis after stopping treatment.
12346How does the TMS treatment for cocaine use disorder differ from other treatments?
The TMS treatment for cocaine use disorder is unique because it uses intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation that is shorter and more tolerable than traditional methods. It targets specific brain areas involved in craving and cognitive control, potentially reducing cocaine use and cravings with fewer side effects and shorter session times compared to conventional high-frequency TMS.
13467Eligibility Criteria
This trial is for adults with cocaine use disorder who are not seeking treatment, have moderate to severe symptoms, and a recent positive urine test for cocaine. They must understand the consent form and provide contact details. Excluded are those with other substance disorders (except marijuana or nicotine), certain medical conditions, suicidal or homicidal risks, metal implants incompatible with TMS, unsafe medication doses, specific drug use within a week of enrollment or during the study.Inclusion Criteria
Be able to understand the consent form and provide written informed consent
I have tested positive for cocaine use.
Meet DSM-5 criteria for current cocaine use disorder of at least moderate severity (≥ 4 symptoms)
+2 more
Exclusion Criteria
I have moderate-to-severe heart disease.
I do not have any health conditions that could affect my study participation or safety.
Taking stimulants other than cocaine
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intermittent theta burst stimulation (iTBS) to left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to sham
Immediate sessions
Multiple sessions (in-person)
Follow-up
Participants are monitored for changes in electrophysiological indices of reward sensitivity and motivated attention
4 weeks
Participant Groups
The study tests intermittent theta burst stimulation (iTBS) on two brain regions: left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC), compared to sham treatment. It aims to see how iTBS affects reward sensitivity and attention in individuals with cocaine use disorder.
6Treatment groups
Experimental Treatment
Group I: shami iTBS then dmPFC then dl PFCExperimental Treatment3 Interventions
Group II: sham iTBS then dlPFC then dmPFCExperimental Treatment3 Interventions
Group III: dmPFC then sham iTBS then dlPFCExperimental Treatment3 Interventions
Group IV: dmPFC then dlPFC then sham iTBSExperimental Treatment3 Interventions
Group V: dlPFC then sham iTBS then dmPFCExperimental Treatment3 Interventions
Group VI: dlPFC then dmPFC then Sham iTBSExperimental Treatment3 Interventions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas Health Science Center at HoustonHouston, TX
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Who Is Running the Clinical Trial?
The University of Texas Health Science Center, HoustonLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
References
Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. [2020]Transcranial Magnetic Stimulation (TMS) is earning a role in the therapeutic arsenal of cocaine use disorder (CUD). A widespread and still growing number of studies have reported beneficial use of repeated TMS (rTMS) in reduction of craving, intake and cue-induced craving in cocaine addicts. In spite of these encouraging findings, many issues are still unresolved such as brain area to be stimulated, laterality of the effects, coil geometry and stimulation protocols/parameters. Intermittent theta burst stimulation (iTBS) is a more tolerable protocol administered at lower intensities and shorter intervals than conventional rTMS protocols. Yet, its effects on cocaine craving and length of abstinence in comparison with standard high frequency (10-15 Hz) protocols have never been evaluated so far. In the present paper, we describe the effect of the bilateral iTBS of the prefrontal cortex (PFC) in a population (n = 25) of treatment-seeking cocaine addicts, in an outpatient setting, and compare them with 15 Hz stimulation of the same brain area (n = 22). The results indicate that iTBS produces effects on cocaine consumption and cocaine craving virtually superimposable to the 15 Hz rTMS group. Both treatments had low numbers of dropouts and similar side-effects, safety and tolerability profiles. While larger studies are warranted to confirm these observations, iTBS appears to be a valid approach to be considered in treatment-seeking cocaine addicts, especially in light of its brief duration (3 min) vs. 15 Hz stimulation (15 min). The use of iTBS would allow increasing the number of patients treated per day with current rTMS devices, thus reducing patient discomfort and hopefully reducing drop-out rates without compromising clinical effectiveness.
Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study. [2023]Transcranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal-lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects.
Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. [2020]There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.
Intermittent Theta Burst Stimulation vs. High-Frequency Repetitive Transcranial Magnetic Stimulation in the Treatment of Methamphetamine Patients. [2022]In this brief report, we compare the effectiveness and safety of intermittent theta burst stimulation (iTBS) and conventional 10 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with methamphetamine use disorder (MAUD). Our study suggests that iTBS would also reduce drug craving in patients with MAUD just as the 10 Hz; thus, there may be no difference in treatment effects between these two methods.
Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis. [2022]CUD, like other addictions, is a chronic disease characterized by a high rate of relapse and drop-out (DO) from medical and behavioral treatment programs, which is positively correlated with relapse. Repetitive transcranial Magnetic Stimulation (rTMS) protocols have shown therapeutic potential in addiction in the short term, but only a few studies have explored their long-term efficacy, so far. This study explores the long-term outcome of bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex (PFC) in cocaine use disorder (CUD) and the possible influence of maintenance treatment in improving abstinence and decreasing DO rates. Eighty-nine treatment-seeking CUD patients were exposed to 20 sessions of iTBS. At the end of the treatment 61 (81%) abstinent patients underwent a 12 months follow-up. Among these, 27 patients chose to follow a maintenance treatment (M), whereas 34 patients chose not to adhere to a maintenance treatment (NM). Overall, among patients reaching the 12 months follow-up endpoint, 69.7% were still abstinent and 30.3% relapsed. In NM-patients the DO rate was significantly higher than in M-ones (58.82 vs. 29.63%). The present observations show the long-term therapeutic effect of bilateral PFC iTBS to decrease cocaine consumption. Moreover, they underline the importance to perform a maintenance protocol to consolidate abstinence and decrease DO rates over time.
Intermittent theta burst transcranial magnetic stimulation for methamphetamine addiction: A randomized clinical trial. [2021]Methamphetamine is the most commonly used illicit drug in China. We previously demonstrated that 10 Hz rTMS over the DLPFC reduces craving in methamphetamine users. Here, we applied intermittent theta burst stimulation (iTBS), a new form of rTMS, in a large sample at four clinical centers. 126 participants (age 31.64 ± 6.33; 106 men) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either iTBS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cue-induced craving and cognitive function were assessed before and after rTMS intervention. Relapse was followed up by urine test after discharge from the rehabilitation center. iTBS significantly reduced craving and improved cognition and sleep quality. This study suggests that rTMS may be a useful and safe treatment option for methamphetamine use disorder, warranting future large scale trials.
What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals. [2022]Vulnerability to drug related cues is one of the leading causes for continued use and relapse among substance dependent individuals. Using drugs in the face of cues may be associated with dysfunction in at least two frontal-striatal neural circuits: (1) elevated activity in medial and ventral areas that govern limbic arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or (2) depressed activity in dorsal and lateral areas that govern cognitive control (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. To date however, nearly all repetitive TMS studies in addiction have focused on amplifying activity in frontal-striatal circuits that govern cognitive control. This manuscript reviews recent work using TMS as a tool to decrease craving for multiple substances and provides a theoretical model for how clinical researchers might approach target and frequency selection for TMS of addiction. To buttress this model, preliminary data from a single-blind, sham-controlled, crossover study of 11 cocaine-dependent individuals is also presented. These results suggest that attenuating MPFC activity through theta burst stimulation decreases activity in the striatum and anterior insula. It is also more likely to attenuate craving than sham TMS. Hence, while many TMS studies are focused on applying LTP-like stimulation to the DLPFC, the MPFC might be a new, efficacious, and treatable target for craving in cocaine dependent individuals.