The CalmBox

50 years of clinical studies

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Cranial Electric stimulator
Why the CES Ultra is Special

Below you can see a compilation of scientific studies on CES. The CES Ultra stands apart from all other devices, especially in the context of Meta-analyses. A Meta-analysis contrasts and combines the results from many different studies rather than relying on a single study to draw particular conclusions.

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Meta-analyses yielding positive results from the use of have been conducted at the University of Tulsa and at the Harvard University School of Public Health. The major meta-analysis of the Harvard School of Public Health, which found that CES has a statistically significant effect on alleviating anxiety, focused entirely on units using the configuration in the CES Ultra.

Eighty-five percent of the independent research on the efficacy of CES is based on the configuration of the CES Ultra medical device. Other units on the market may have the same frequency, but they do not measure up to the amplitude, wavelength, duty cycle and frequency found only in the CES Ultra.

That means that while other companies may cite research studies, those studies are often company-based and company-funded and hence are not truly independent and fully objective. Only the CES Ultra has the configuration that was used in independent, university-based studies.

Cranial Electric stimulator
Research on Anxiety

Anxiety is defined as "mental uneasiness" or "distress arising from fear of what may happen." It has several different manifestations. Individuals suffering from panic disorder experience recurrent, unexpected panic attacks. Those with generalized anxiety disorder (GAD) chronically worry too much about a variety of things, and experience symptoms such as restlessness, agitation, or feeling keyed up, muscle tension, fatigue, irritability, and trouble with concentration and sleep. Persons suffering from social anxiety disorder experience extreme fear and avoidance of social and/or performance situations.

Anxiety disorders, as a group, are the most common mental illness in America. More than 19 million American adults are affected by these debilitating illnesses each year. Children and adolescents can also develop anxiety disorders. Anxiety is currently perhaps the most fashionable idiom in the parlance of American psychiatry and medicine. It is used almost synonymously with stress which in turn has been associated with everything from increased risk of heart attack and cancer to the common cold. The general consensus within the medical community is that anxiety can in many instances, be a causative factor in physical illness as well as exacerbate it.

Seven separate studies of 220 hospitalized psychiatric inpatients. All were controlled scientific studies employing measures of anxiety with known reliability and validity. There are four replications using the state anxiety scale (STAI-S) and three using the tension/anxiety factor on the Profile of Mood States (POMS-T/A). Most of the studies were for fifteen days-Monday through Friday over a period of three weeks. The TMAS (Taylor Manifest Anxiety Scale) study was for ten days only and the IPAT (Institute for Personality and Ability Testing) for six. Studies using the STAI-S used five or six thirty minute sessions whereas one of the POM-T/A studies used CES for thirty minutes a day over ten days and two others at a rate of one forty minute session per day for fifteen days

The findings of all tests conducted were consistent: Most patients responded positively to CES treatment within the first week or ten days; the more entrenched forms of anxiety, within ten days to three weeks. Resultant post CES test scores shows improvement ranging from approximately 30 percent to almost 65 percent. The variation was due to different anxiety scales measuring different facets of anxiety, only some of which are shared in common. In one study, investigators deliberately used patients with low suggestibility levels and compared them with those with high suggestibility levels. No differences were found, thus ruling out a placebo effect.The net result of these studies shows CES to be a predictably effective treatment for anxiety and related disorders as measured by these scales. There has never been a controlled study of anxiety in which CES patients did not improve more significantly than did the controls.

Graphical Interpretation
The red bar represents the patients' scores on the anxiety measure before CES treatment (PRE); the blue bar, their score after CES therapy (POST).

More Science

List of Studies and Clinical Research


The role of ventromedial and dorsolateral prefrontal cortex in attention
and interpretation biases in individuals with general anxiety disorder
(GAD): A tDCS study Journal of Psychiatric Research, Volume 144, 2021,
pp. 269-277

Oliveira, J.F.; Zanão, T.A.; Valiengo, L.; Lotufo, P.A.; Benseñor, I.M.;
Fregni, F.; Brunoni, A.R. Acute working memory improvement after tDCS
in antidepressant-free patients with major depressive disorder.
Neurosci. Lett. 2013, 537, 60–64.

Cranial electrotherapy stimulation (CES): a safe and effective low cost
means of anxiety control in a dental practice. Winick R.L. Gen Dent.
1999; 47: 50-55

The effect of cranial electrotherapy stimulation on preoperative anxiety
and hemodynamic responses. Kim H.J. Korean J Anesthesiol. 2008; 55:

Cranial electrotherapy stimulation for the treatment of anxiety,
depression, insomnia and other conditions. Insert: Giordano, James.
Illustrating how CES works. Kirsch D.L.Nat Med. 2006; 23: 118-120

Effects of cranial electrotherapy stimulation with novel in-ear
electrodes on anxiety and resting-state brain activity: A randomized
double-blind placebo-controlled trial, 2021, Journal of Affective

A meta-analysis of cranial electrotherapy stimulation in the treatment
of depression, 2021, Journal of Psychiatric Research

Differential effects of cranial electrotherapy stimulation on changes in
anxiety and depression symptoms over time in patients with
generalized anxiety disorder, 2020, Journal of Affective DisordersCranial electrotherapy stimulation in the treatment of posttraumatic
stress disorder: A feasibility, safety, and preliminary efficacy study,
2022, Personalized Medicine in Psychiatry

A pilot study of cranial electrotherapy stimulation for generalized
anxiety disorder, A. Bystritsky et al., J. Clin. Psychiatry (2008)

A clinical trial of cranial electrotherapy stimulation for anxiety and
comorbid depression, T.H.Barclay Raymond D.Barclay ; Journal of
Affective Disorders, Volume 164, 1 August 2014, Pages 171-177

Cranial electrotherapy stimulation for treatment of anxiety, depression,
and insomnia D.L. Kirsch et al. Psychiatr.Clin.N.Am (2013)


Efficacy of cranial electric stimulation for the treatment of insomnia: A
randomized pilot study, R. Gregory Lande; Complementary Therapies in
Medicine, Vol 21, Issue 1, Feb 2013.

Transcranial Electrical Stimulation targeting limbic cortex increases the
duration of human deep sleep Sleep Medicine, Volume 81, 2021, pp.

Neurostimulation techniques to enhance sleep and improve cognition
in aging, Neurobiology of Disease, Volume 141, 2020, Article 104865
Transcranial Electrical Stimulation targeting limbic cortex increases the
duration of human deep sleep, Sleep Medicine, Volume 81, 2021, pp.

Epidemiology of alcohol and medication as aids to sleep in early
adulthood E.O. Johnson et al. Sleep (1998)

Ten-year trends in the pharmacological treatment of insomnia, J.K.
Walsh et al. Sleep (1999)
The medicalization of sleeplessness: a public health concern M.E.
Moloney et al. American Journal of Public Health (2011)

Impact of transdermal trigeminal electrical neuromodulation on
subjective and objective sleep parameters in patients with insomnia: a
pilot study 2022, Sleep and Breathing

Cranial electrostimulation improves slow wave sleep in collegiate
population: A polysomnographic study 2022, Sleep Science
Imaging of current flow in the human head during transcranial
electrical therapy, Brain Stimulation, Volume 10, Issue 4, 2017, pp. 764-

Effects of cranial electrical stimulation on sleep disturbances,
depressive symptoms, and caregiving appraisal in spousal caregivers of
persons with Alzheimer's disease K.M. Rose et al. Applied Nursing
Research (2009)

Quantitative analysis of the electroencephalogram during cranial
electrotherapy stimulation, M.J. Schroeder et al.Clinical
Neurophysiology (2001)

Effects of cranial electrical stimulation on sleep disturbances,
depressive symptoms, and caregiving appraisal in spousal caregivers of
persons with Alzheimer's disease, K.M. Rose et al. Applied Nursing
Research (2009)

A systematic review of insomnia and complementary medicine, J. Sarris
et al. Sleep Medicine Reviews (2011)

Chronic insomnia, C.M. Morin et al. Lancet (2012)

Sleep disturbances and suicidal ideation in sleep medical center
patients ,B. Krakow et al. Journal of Affective Disorders (2011)

Insomnia severity is an indicator of suicidal ideation during a
depression clinical trial, W.V. McCall et al. Sleep Medicine (2010)

Maintenance treatment of insomnia: what can we learn from the
depression literature? R.D. Jindal et al. American Journal of Psychiatry

CES in the treatment of insomnia: a review and meta-analysis. Kirsch
D.L. Pract Pain Manag. 2007; 7: 30-43

Cumulative response from cranial electrotherapy stimulation (CES) for
chronic pain. Holubec J.T. Pract Pain Manag. 2009; 9: 80-83


IBrain Performance Research
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current stimulation (tDCS) produces localized and specific alterations in
neurochemistry: a 1H magnetic resonance spectroscopy study.
Neurosci Lett. 2011;500(1):67–71.

Wagner T, Zahn M, Grodzinsky A, Pascual-Leone A. Three-dimensional
head model simulation of transcranial magnetic stimulation. IEEE Trans
Biomed Eng. 2004;51:1586–98.

Miranda PC, Lomarev M, Hallett M. Modeling the current distribution
during transcranial direct current stimulation. Clin Neurophysiol.

Stagg, C.J. The Physiological Basis of Brain Stimulation. In The
Stimulated Brain; Cohen Kadosh, R., Ed.; Elsevier: Amsterdam, The
Netherlands, 2014.

Kessler, S.K.; Minhas, P.; Woods, A.J.; Rosen, A.; Gorman, C.; Bikson, M.
Dosage considerations for transcranial direct current stimulation in
children: A computational modeling study. PLoS ONE 2013, 8, e76112.
Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current
stimulation. Neuroscientist. 2011;17(1):37–53.

Kanai R, Paulus W, Walsh V. Transcranial alternating current stimulation
(tACS) modulates cortical excitability as assessed by TMS-induced
phosphene thresholds. Clin Neurophysiol. 2010;121:1551–4.Russell, M.; Goodman, T.; Wang,

Q.; Groshong, B.; Lyeth, B.G. Gender
differences in current received during transcranial electrical
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Rudro, T.; Workman, C.D.; Fietsam, A.C.; Kamholz, J. Response variability
in transcranial direct current simulation: Why sex matters. Front.
Psychiatry 2020, 11, 585.

Krishnan, C.; Santos, L.; Peterson, M.D.; Ehinger, M. Safety of
noninvasive brain stimulation in children and adolescents. Brain Stimul.
2015, 8, 76–87.

Pena-Gomez, C.; Vidal-Piñeiro, D.; Clemente, I.C.; Pascual-Leone, A.;
Bartrés-Faz, D. Down-regulation of negative emotional processing by
transcranial direct current stimulation: Effects of personality
characteristics. PLoS ONE 2011, 6, e22812.

Krause, B.; Cohen Kadosh, R. Not all brains are created equal: The
relevance of individual differences in responsiveness to transcranial
electrical stimulation. Front. Syst. Neurosci. 2014, 8, 25.

Madhavan, S.; Stinear, J.W. Focal and bidirectional modulation of lower
limb motor cortex using anodal transcranial direct current stimulation.
Brain Stimul. 2010, 3, 42–50.

Bikson, M.; Rahman, A.; Datta, A.; Fregni, F.; Merabet, L. High-resolution
modeling assisted design of customized and individualized transcranial
direct current stimulation protocols. Neuromodulation Technol. Neural
Interface 2012, 15, 306–315.

Opitz, A.; Paulus, W.; Will, S.; Antunes, A.; Thielscher, A. Determinants of
the electric field during transcranial direct current stimulation.
Neuroimage 2015, 109, 140–150.Javadi, A.H.; Cheng, P.; Walsh, V. Short duration transcranial direct current stimulation (tDCS) modulates verbal memory. Brain Stimul.
2012, 5, 468–474.

Ruffini, G.; Fox, M.D.; Ripolles, O.; Miranda, P.C.; Pascual-Leone, A.
Optimization of multifocal transcranial current stimulation for weighted
cortical pattern targeting from realistic modeling of electric felds.
Neuroimage 2014, 89, 216–225.

Bikson, M.; Grossman, P.; Thomas, C.; Zannou, A.L.; Jiang, J.; Adnan, T.;
Mourdoukoutas, A.P.; Kronberg, G.; Truong, D.; Boggio, P.; et al. Safety
of Transcranial Direct Current Stimulation: Evidence Based Update
2016. Brain Stimul. 2016, 9, 641–661

QEEG analysis of cranial electrotherapy: a pilot study. Kennerly R. J
Neurother. 2004; 8: 112-113

Effects of cranial electrotherapy stimulation on resting state brain
activity. Feusner J.D., Brain Behav. 2012; 2: 211-220

Kennerly RC. Changes in quantitative EEG and low resolution
tomography following cranial electrotherapy stimulation. Ph.D.
Dissertation, the University of North Texas. 529 pp, 81 tables, 233
figures, 171 references, 2006.

Physiological and therapeutic effects of high frequency electrical pulses.
Integr Physiol Behav Sci. 1996; 31: 88-96

Cranial electrotherapy stimulation alleviates depression-like behavior of
post-stroke depression rats by upregulating GPX4-mediated BDNF
expression, 2023, Behavioural Brain Research

Cerebrospinal Fluid and Plasma Neurochemicals: Response to Cranial
Electrical Stimulation, C. Norman Shealy, M.D., Ph.D., et al; J Neurol
Orthop Med Surg (1998) 18:94-97

Cognative Function

Cohen Kadosh R. Using transcranial electrial stimulation to enhance
cognitive functions in the typical and atypical brain. Transl Neurosci.

Tseng, P.; Hsu, T.Y.; Chang, C.F.; Tzeng, O.J.; Hung, D.L.; Muggleton, N.G.;
Juan, C.H. Unleashing potential: Transcranial direct current stimulation
over the right posterior parietal cortex improves change detection in
low-performing individuals. J. Neurosci. 2012, 32, 10554–10561.

Berryhill, M.E.; Jones, K.T. tDCS selectively improves working memory in
older adults with more education. Neurosci. Lett. 2012, 521, 148–151.

Andrews, S.C.; Hoy, K.E.; Enticott, P.G.; Daskalakis, Z.J.; Fitzgerald, P.B.
Improving working memory: The effect of combining cognitive activity
and anodal transcranial direct current stimulation to the left
dorsolateral prefrontal cortex. Brain Stimul. 2011, 4, 84–89.

Monte-Silva, K.; Kuo, M.F.; Liebetanz, D.; Paulus, W.; Nitsche, M.A.
Shaping the optimal repetition interval for cathodal transcranial direct
current stimulation (tDCS). J. Neurophysiol. 2010, 103, 1735–1740.

Li, L.M.; Uehara, K.; Hanakawa, T. The contribution of interindividual
factors to variability of response in transcranial direct current
stimulation studies. Front. Cell. Neurosci. 2015, 9, 181.

Bikson, M.; Datta, A.; Rahman, A.; Scaturro, J. Electrode montages for
tDCS and weak transcranial electrical stimulation: Role of “return”
electrode’s position and size. Clin. Neurophysiol. 2010, 121, 1976–1978.

Moliadze, V.; Antal, A.; Paulus, W. Electrode-distance dependent after-
effects of transcranial direct and random noise stimulation with
extracephalic reference electrodes. Clin. Neurophysiol. 2010, 121,

Kwon, Y.H.; Kwon, J.W. Response inhibition induced in the stop-signal
task by transcranial direct current stimulation of the pre-supplementary
motor area and primary sensoriomotor cortex. J. Phys. Ther. Sci. 2013,
25, 1083–1086.

Stramaccia, D.F.; Penolazzi, B.; Altoè, G.; Galfano, G. TDCS over the right
inferior frontal gyrus disrupts control of interference in memory: A
retrieval-induced forgetting study. Neurobiol. Learn. Mem. 2017, 144,

Frings, C.; Brinkmann, T.; Friehs, M.A.; van Lipzig, T. Single session tDCS
over the left DLPFC disrupts interference processing. Brain Cogn. 2018,
120, 1–7.

Jeon, S.Y.; Han, S.J. Improvement of the working memory and naming by
transcranial direct current stimulation. Ann. Rehabil. Med. 2012, 36,

Loftus, A.M.; Yalcin, O.; Baughman, F.D.; Vanman, E.J.; Hagger, M.S. The
impact of transcranial direct current stimulation on inhibitory control in
young adults. Brain Behav. 2015, 5, e00332.

Friehs, M.A.; Frings, C. Offline beats online: Transcranial direct current
stimulation timing influences on working memory. Neuroreport 2019,
30, 795–799

Hurley, R.; Machado, L. Using tDCS priming to improve brain function:
Can metaplasticity provide the key to boosting outcomes? Neurosci.
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Alonzo, A.; Brassil, J.; Taylor, J.L.; Martin, D.; Loo, C.K. Daily transcranial
direct current stimulation (tDCS) leads to greater increases in cortical
excitability than second daily transcranial direct current stimulation.
Brain Stimul. 2012, 5, 208–213.

Lefaucheur, J.P.; Antal, A.; Ayache, S.S.; Benninger, D.H.; Brunelin, J.;
Cogiamanian, F. Evidence-based guidelines on the therapeutic use of
transcranial direct current stimulation (tDCS). Clin. Neurophysiol. 2017,
128, 56–92.

Sports and eSports Performance
Davis, N.J. Neurodoping: Brain stimulation as a performance-enhancing
measure. Sports Med. 2013, 43, 649–653.

Datta, A.; Bansal, V.; Diaz, J.; Patel, J.; Reato, D.; Bikson, M. Gyri-precise
head model of transcranial direct current stimulation: Improved spatial
focality using a ring electrode versus conventional rectangular pad.
Brain Stimul. 2009, 2, 201–207.

Park, J.H.; Hong, S.B.; Kim, D.W.; Suh, M.; Im, C.H. A novel array-type
transcranial direct current stimulation (tDCS) system for accurate
focusing on targeted brain areas. Magn. IEEE Trans. 2011, 47, 882–885.

Wiethoff, S.; Hamada, M.; Rothwell, J.C. Variability in response to
transcranial direct current stimulation of the motor cortex. Brain
Stimul. 2014, 7, 468–475.

Borducchi, D.M.; Gomes, J.S.; Akiba, H.; Cordeiro, Q.; Borducchi, J.H.;
Valentin, L.S.; Borducchi, G.M.; Dias, Á.M. Transcranial Direct Current
Stimulation Effects on Athletes’ Cognitive Performance: An Exploratory
Proof of Concept Trial. Front. Psychiatry 2016, 7, 183.