ClinicalTrials.gg
RecruitingNCT07924852NEMOUpdated Nov 9, 2026

Neuromodulation of Motivation and Reward Oscillations

An interventional study of Transcranial Alternating Current Stimulation Sham and Transcranial Alternating Current Delta Stimulation. in Cannabis Use Disorder, Major Depression and Anhedonia, sponsored by Florida State University. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-09.

Sponsored by Florida State University · Not applicable, Interventional, and Basic science

Updated Nov 9, 2026Newly registeredGo to Updates ↓
Phase
Not applicable
Study type
Interventional
Enrollment
54
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

Cannabis use disorder (CUD) and major depressive disorder (MDD) are among the most prevalent psychiatric conditions in the United States, affecting an estimated 20.6 million and 21 million adults respectively. Both disorders are characterized by anhedonia, diminished motivation, and blunted neural reward sensitivity. This shared dysregulated reward-processing may reflect a common prefrontal oscillatory dysfunction, centralized in mesolimbic dopaminergic reward pathways. This proposed project aims to investigate if transcranial alternating current (tACS) can modulate motivational behaviours and neural reward responsivity in participants with MDD and/or CUD during an effortful reward task. The investigators hypothesize that delta transcranial alternating current stimulation will produce a greater neural reward responsivity (RewP), and motivational behaviour during an effortful reward task.

Read the detailed description

Disrupted reward processing is a transdiagnostic feature that plays a central role in the development, and maintenance of anhedonia in Cannabis Use Disorder (CUD) and Major Depressive Disorder (MDD). Reward positivity (RewP) is an event-related potential (ERP) component derived from electroencephalogram (EEG) data, associated with motivation, reward responsivity and valuation. This neural signature originates in the medial and dorsolateral prefrontal cortexes. In MDD, reduced RewP has been associated with decreased willingness to expend effort for reward. Research of CUD and RewP is scarce, but dampened RewP has been demonstrated across different substances use disorders (SUDs) in response to monetary reward tasks. Taken together, these findings signal an emerging research frontier to establish RewP as a clinical biomarker and create a compelling mandate for causal investigation. Low-frequency neural oscillations are the key mechanisms facilitating long-distance prefrontal connectivity and interregional communication. Delta oscillations (2.5Hz) in medial and left lateral prefrontal cortexes are closely linked to RewP and reward prediction error signaling, while theta oscillations (6Hz) index cognitive control and prefrontal regulatory engagement during reward processing. Disruptions in both bands have been well documented in MDD, to a more limited extent, in cannabis-using populations. The proposed experiment will causally test whether sham, delta, and theta frequency tACS can alter motivation and reward responsivity (behaviourally [Effort behaviour] and neurally [RewP, delta power]), in participants with disorder of reward dysfunction, CUD, MDD, and healthy controls. Findings from the proposed study will aid in mechanistic understanding of prefrontal circuits underlying reward impairment in CUD and MDD, and ultimately enable for the development of novel brain stimulation techniques to target disorder-maintaining anhedonia. The investigators hypothesise that delta tACS will modulate reward responsivity in participants with disorders of reward. Such that, during the EEfRT Task delta stimulation will enhance reward responsive goal directed behaviour (Behavioral H1) and delta phase connectivity between left lateral and medial frontal electrodes (Neural H1) at effort decision period. As well as greater reward positivity (RewP; Neural 2), and win vs. loss delta power and phase coherence at feedback (Neural H3).

02

Conditions studied

  • Cannabis Use Disorder
  • Major Depression
  • Anhedonia
  • Transcranial Alternating Current Stimulation

Keywords

  • Cannabis Use Disorder
  • Depression
  • Neurostimulation
  • Reward Responsivity
03

In context

Depressive Disorder, Major

3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.

This study's planned enrollment of 54 is below the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.

Browse Depressive Disorder, Major studies →

Lead sponsor

Florida State University is the lead sponsor of 249 studies on the registry; 47 are open to participants now.

Of its 16 completed or terminated interventional studies of FDA-regulated products, 9 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Aged between 18 - 55 years old.
  • Able to provide
  • Have normal to corrected vision
  • Willing to comply with all study procedures and be available for the duration of the study
  • Speak and understand English.
  • Negative THC saliva test and alcohol breathalyzer at all lab visits.
  • Negative UTOX for any substance other than THC.

Exclusion criteria

Exclusion Criteria (General):

  • Mania history (Bipolar I, or current mania).
  • Psychosis history.
  • Current suicide intent (score >4 on C-SRSS, or intent >0 on SRA)
  • Current moderate-to-severe SUD or AUD (Except CUD and nicotine for NEMO-CUD).
  • Current pregnancy.
  • Seizure, neurological conditions, or brain surgery history.
  • Implanted medical devices (e.g., cochlear implants, cardiac pacemakers).
  • Change in psychotropic medication in the past 3 months (i.e., medication needs to be stable for 12 weeks).
  • Use of seizure threshold lowering medication (e.g., Stimulants, Benzos, SNRIs, Antipsychotics [Adderall, Vyvanse, Xanax, Wellbutrin, Cymbalta, Lithium] - SSRIs not exclusionary).

Specific CUD Inclusion:

  • Avg. 6+ cannabis use days per week over the past 3-months, and 24+ cannabis use days in the past 30 days.
  • Primary delta-9 or THC-A cannabis flower or vape concentrate user.
  • Current moderate-to-severe CUD (4+ criteria in the past year, at least one criterion other than craving must be met in the past three months).
  • Cannabis is the primary substance of use (Nicotine dependence is allowable)
  • Not currently receiving treatment for cannabis, planning to immediately quit or reduce use.
  • Lifetime history of MDE/PDD must have lifetime anhedonia symptom and/or heavy cannabis user (3+ sessions daily for at least past year including the past 3-months and past 30 days).

Specific MDD Inclusion:

  • Current MDE diagnosis.
  • No lifetime history of severe SUD.
  • No current moderate-to-severe SUD.
  • 100% of NEMO-MDD participants elevated anhedonia on TEPS-C (i.e., 32 or lower on TEPS-C subscale).

Specific Control Inclusion:

  • No current or historical psychiatric diagnosis.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
54 participants (estimated)

Study arms

  • Experimental
    Delta tACS

    All participants receive delta (2.5 Hz), theta (6 Hz), and sham tACS across three separate sessions, separated by a 7-10 day washout. Session order is randomised and counterbalanced using a balanced Latin square, within each diagnostic group (CUD, MDD, healthy control). Stimulation is interleaved between the 8 blocks of the EEfRT (e.g., block 1 with stimulation, block 2 without, etc.). EEG activity will be recorded throughout the non-stimulation 4 blocks and proceeding interleaved non-stimulation blocks.

    Device: Transcranial Alternating Current Delta Stimulation.

  • Active comparator
    Theta tACS

    All participants receive delta (2.5 Hz), theta (6 Hz), and sham tACS across three separate sessions, separated by a 7-10 day washout. Session order is randomised and counterbalanced using a balanced Latin square, within each diagnostic group (CUD, MDD, healthy control). Stimulation is interleaved between the 8 blocks of the EEfRT (e.g., block 1 with stimulation, block 2 without, etc.). EEG activity will be recorded throughout the non-stimulation 4 blocks and proceeding interleaved non-stimulation blocks.

    Device: Transcranial Alternating Current Theta Stimulation

  • Sham comparator
    Sham tACS

    All participants receive delta (2.5 Hz), theta (6 Hz), and sham tACS across three separate sessions, separated by a 7-10 day washout. Session order is randomised and counterbalanced using a balanced Latin square, within each diagnostic group (CUD, MDD, healthy control). Stimulation is interleaved between the 8 blocks of the EEfRT (e.g., block 1 with stimulation, block 2 without, etc.). EEG activity will be recorded throughout the non-stimulation 4 blocks and proceeding interleaved non-stimulation blocks.

    Device: Transcranial Alternating Current Stimulation Sham

Interventions

  • DeviceTranscranial Alternating Current Stimulation Sham

    The tACS stimulation is briefly turned on and off over the course of 15-30 seconds.

  • DeviceTranscranial Alternating Current Delta Stimulation.

    Approximately 20-minutes of delta stimulation (2.5Hz) applied to F3 (returns AF7, FC5, FC1) and AFz (returns Fp1, Fp2, F2). Transcranial Alternating Current Stimulation Device is NeuroConn DC-Stimulator MC.

  • DeviceTranscranial Alternating Current Theta Stimulation

    Approximately 20-minutes of theta stimulation (6Hz) applied to F3 (returns AF7, FC5, FC1) and AFz (returns Fp1, Fp2, F2). Transcranial Alternating Current Stimulation Device is NeuroConn DC-Stimulator MC.

06

What researchers measure

Primary outcomes

  1. Effort-updating behavior during decision period.

    The % of hard effort choices selected following a win versus following a loss.

    Time frame: Baseline (Day 0), Sham Session (Day 1-10, or Day 10-20, or Day 20-30), Theta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30), Delta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30). Specific range depends on particular counterbalanced order.

  2. Delta phase coherence between left lateral and medial frontal electrodes during decision period following a win versus following a loss.

    Electrical activity of the brain will be recorded via EEG during performance of the task and neurostimulation. Delta phase connectivity between left lateral and medial frontal electrodes during the decision period following a win versus following a loss.

    Time frame: Baseline (Day 0), Sham Session (Day 1-10, or Day 10-20, or Day 20-30), Theta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30), Delta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30). Specific range depends on particular counterbalanced order.

  3. Reward positivity amplitude

    Electrical activity of the brain will be recorded via EEG during performance of the task and neurostimulation. Reward positivity amplitude to wins vs. losses.

    Time frame: Baseline (Day 0), Sham Session (Day 1-10, or Day 10-20, or Day 20-30), Theta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30), Delta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30). Specific range depends on particular counterbalanced order.

Secondary outcomes

  1. Delta event-related spectral power

    Electrical activity of the brain will be recorded via EEG during performance of the task and neurostimulation. Delta power to wins vs. losses.

    Time frame: Baseline (Day 0), Sham Session (Day 1-10, or Day 10-20, or Day 20-30), Theta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30), Delta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30). Specific range depends on particular counterbalanced order.

  2. Delta intertrial phase coherence

    Electrical activity of the brain will be recorded via EEG during performance of the task and neurostimulation. Delta intertrial phase coherence to wins vs. losses.

    Time frame: Baseline (Day 0), Sham Session (Day 1-10, or Day 10-20, or Day 20-30), Theta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30), Delta Stim. Session (Day 1-10, or Day 10-20, or Day 20-30). Specific range depends on particular counterbalanced order.

07

Study locations

1 of 2 sites recruiting
  • The BRAINS Lab at Florida State University
    Tallahassee, Florida 32306-4301, United States
    Not yet recruiting
  • The Riddle Lab at Florida State University
    Tallahassee, Florida 32306-4301, United States
    Recruiting
08

References and documents

Publications

  • Byrd KJ, Johnston BW, Culp S, Kreutzer KA, Way BM, Phan KL, Gorka SM. Neural reward sensitivity and longitudinal patterns of alcohol and cannabis use in college-aged youth. Drug Alcohol Depend. 2026 Apr 1;281:113079. doi: 10.1016/j.drugalcdep.2026.113079. Epub 2026 Feb 10. PubMed 41713074 ↗
  • Proudfit GH. The reward positivity: from basic research on reward to a biomarker for depression. Psychophysiology. 2015 Apr;52(4):449-59. doi: 10.1111/psyp.12370. Epub 2014 Oct 17. PubMed 25327938 ↗
  • Murray CH, Glazer JE, Lee R, Nusslock R, de Wit H. Delta9-THC reduces reward-related brain activity in healthy adults. Psychopharmacology (Berl). 2022 Sep;239(9):2829-2840. doi: 10.1007/s00213-022-06164-y. Epub 2022 May 25. PubMed 35612654 ↗
  • Joyner KJ, Bowyer CB, Yancey JR, Venables NC, Foell J, Worthy DA, Hajcak G, Bartholow BD, Patrick CJ. Blunted Reward Sensitivity and Trait Disinhibition Interact to Predict Substance Use Problems. Clin Psychol Sci. 2019;7(5):1109-1124. doi: 10.1177/2167702619838480. Epub 2019 Sep 1. PubMed 31853427 ↗
  • Riddle J, Alexander ML, Schiller CE, Rubinow DR, Frohlich F. Reward-Based Decision-Making Engages Distinct Modes of Cross-Frequency Coupling. Cereb Cortex. 2022 May 14;32(10):2079-2094. doi: 10.1093/cercor/bhab336. PubMed 34622271 ↗

Individual participant data

Plan to share: No — The IPD will only be shared under reasonable request. The investigators might not share IPD in order to keep participant confidentiality paramount.

09

Updates

1 registry update since Sep 25, 2026
Registered
First appeared on the registry. No changes since
Nov 9, 2026
Show all 1 update
  1. Nov 9, 2026
    First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07924852
Responsible party
Rick James Macatee (Associate Professor, Florida State University) — Principal investigator
First posted
Nov 9, 2026
Start date
Nov 1, 2026 (estimated)
Primary completion
Apr 1, 2027 (estimated)
Completion
May 1, 2027 (estimated)
Last update
Nov 9, 2026

Study contacts

Zoe Howell Doctoral Student PI, M.Res.
Contact
brains@psy.fsu.edu
850-644-2445
Richard J Macatee, Ph.D.
principal investigator · Florida State University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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