Effectiveness Studies - Overview

The Last 50 years of Cranial Electrotherapy Research (click here to read)

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Harvard Medical School Researchers

Treating Depression, Anxiety and Insomnia in Substance Abuse Patients

Drug Alcohol Depend. 1991 Jan;27(1):1-6.

The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients.

Krupitsky EM, Burakov AM, Karandashova GF, Katsnelson JaS, Lebedev VP, Grinenko AJa, Borodkin JuS.

Source

Leningrad Regional Dispensary of Narcology, U.S.S.R.

Abstract

In a double blind placebo-controlled investigation it was shown that transcranial electric treatment (TET), comprising the combination of a constant current with a pulse current of square impulses of 70-80 Hz is an effective method to correct affective disturbances (anxiety, depression) in alcoholic patients. The medical effects of TET are accompanied by changes in the metabolism of GABA and monoamines, but not of beta-endorphin, and also by a decrease in the latency of alpha-rhythm appearance after closing of the eyes.

Alcohol Clin Exp Res. 1986 Mar-Apr;10(2):158-60.

Cranial electrotherapy stimulation as a treatment for anxiety in chemically dependent persons.

Schmitt R, Capo T, Boyd E.

Abstract

Cranial electrotherapy stimulation (CES) is reported to be an effective treatment for anxiety, a major presenting symptom among chemically dependent patients. In this study, 40 inpatient alcohol and/or polydrug users were given CES or sham CES in a double blind design. An additional 20 patients served as normal hospital routine controls. Dependent measures of anxiety were the Profile of Mood States, the Institute for Personality and Ability Testing Anxiety Scale, and the State/Trait Anxiety Index. CES-treated patients showed significantly greater improvement on all anxiety measures than did either control group. There were no differences in response between older and younger patients, or between the primarily drug or alcohol abusers. No placebo effect was found on any of our measures. It is concluded tht CES is a clinically significant addition to the treatment regimen for this patient population.

 Biological Psychiatry

Volume 29, Issue 5, 1 March 1991, Pages 451-456

Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients a double-blind study 

P. Philip^*, J. Demotes-Mainard^{, **}, M. Bourgeois^* and J.D. Vincent^**

^* UICA, Centre Hospitalier Spécialisé Charles Perrens, 121 rue de la Béchade 33000 Bordeaux, France

^** Laboratoire de Sommeil, Hopital St André, 1, rue Jean Burguet, 33000 Bordeaux, France

Received 30 April 1990;  revised 12 October 1990.  Available online 14 March 2003.

Abstract

In order to test the effectiveness of cerebral electrostimulation (electrosleep) as an alternative to drug therapy for the treatment of anxiety and insomnia, we conducted a double-blind study in a sample of 21 depressed inpatients submitted to a 5-day period of drug washout on admission to the psychiatric department. During this withdrawal period, anxiety and insomnia were exacerbated in the placebo group, whereas anxiety decreased and sleep duration improved in the active treatment group, with a divergent evolution during the 5-day washout period. The depressive criteria did not respond differentially to treatment, however. Thus, the effects of this drug washout period are markedly attenuated by cerebral electrostimulation, which is of possible interest in the management of psychotropic drug withdrawal.

Br J Psychiatry. 1979 Jan;134:111-3.

Treatment of methadone withdrawal with cerebral electrotherapy (electrosleep).

Gomez E, Mikhail AR.

Abstract

The use of cerebral electrotherapy (CET) in methadone detoxification was studied in 28 patients. Fourteen patients received active CET; the other 14 acted as controls and received either stimulated CET or only methadone detoxification therapy. One patient dropped out of the study. The Taylor Manifest Anxiety Scale and the Hamilton Anxiety Scale were administered before and after the study period. Nine of the patients receiving active CET were drug-free by the end of 8 to 10 days, and all experienced a marked reduction of their symptoms; the control group did not show significant changes. CET was clearly beneficial in the treatment of patients undergoing methadone withdrawal.

Alcohol Clin Exp Res. 1995 Aug;19(4):1004-10.

Effects of cerebral electrical stimulation on alcoholism: a pilot study.

Padjen AL, Dongier M, Malec T.

Source

Douglas Hospital Research Centre, Alcohol Research Program, Verdun, Que, Canada.

Abstract

Cerebral electrical stimulation (CES), born from research on electroanesthesia in the seventies, consists of the application of a pulsating current of small intensity (usually less than 1 mA, and below the threshold of perception) through the skull, e.g., in daily 30-min sessions. Claims of biological effectiveness (neurochemical, hormonal and EEG changes, naloxone-reversible analgesia in rats, etc.) and of clinical effectiveness (anxiety, depression, cognitive functions in alcoholics) have often relied on poorly controlled data. A recent controlled study in the treatment of opiate withdrawal has been positive. The present double-blind controlled study compares active CES with sham stimulation in 64 alcohol-dependent males. Over 4 weeks, both treatment groups improved significantly in most aspects. In the active treatment group additional significant improvement was observed in week-end alcohol consumption, and in two psychological measures: depression and stress symptoms index, but not in general drinking behavior.

J Altern Complement Med. 1996 Winter;2(4):485-91.

Electrostimulation: addiction treatment for the coming millennium.

Patterson MA, Patterson L, Patterson SI.

Source

Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.

Abstract

At a period of fundamental review of the health care system, it is timely to re-assess one of medicine's most intractable problems--the treatment of addictions. The apparently insoluble dilemmas posed by the acute and chronic withdrawal syndromes underlie universally high drop-out and relapse rates. In a decade of HIV and AIDS infection, poly-substance addiction, potent street drugs, and ossified treatment strategies, it is urgent that policy formulators investigate seriously a flexible system of non-pharmacological transcranial electrostimulation treatment, based on its record of rapid, safe, and cost-effective detoxification in several countries, as one innovative contribution to the challenges presented by addiction in the 1990s. This is a brief report of the introduction of NeuroElectric Therapy (NET) into Germany, describing the responses of the first 22 cases. The daily progress of a heroin addict and a methadone addict are detailed: both were treated as outpatients for 8 hours daily, for 7 and 10 days respectively.

J Clin Psychiatry. 1984 Feb;45(2):60-1, 62-3.

Cranial electrotherapy stimulation treatment of cognitive brain dysfunction in chemical dependence.

Schmitt R, Capo T, Frazier H, Boren D.

Abstract

Several studies have shown that cranial electrotherapy stimulation (CES) is useful in treating brain dysfunction associated with alcoholism. A double-blind study replicated the latest of these findings in 60 inpatients and extended them by treating individuals with alcoholism and other chemical dependencies. Treatment effects were assessed on three subscales of the WAIS that are clinical indicators of organic brain syndrome. No placebo effect was found. CES appears to be a valuable adjunct to rehabilitation programs for addicted persons and can effect changes in areas not addressed by other treatment modalities.

Electrosleep (electrical transcranial stimulation) in the treatment of anxiety, depression and sleep disturbance in chronic alcoholics.

McKenzie, Richard E.; Costello, Raymond M.; Buck, Don C.

Journal of Altered States of Consciousness, Vol 2(2), 1975-1976, 185-196.

Abstract

Employed a double-blind design with treatment variables of current and suggestion, and outcome criteria of anxiety, depression, and sleep disturbance to test for effects of electrosleep (electrical transcranial stimulation) in 20 male hospitalized alcoholics (mean age, 51 yrs). Ss were randomly assigned to 1 of 4 groups; 2 groups received current and 2 did not; 1 current and 1 noncurrent group received sensation, the other 2 did not. Current was standardized at 1 mA; peak-to-peak amplitude was manipulated to control for physical sensation. Five outcome criteria were employed: 3 depression indices, 1 index of anxiety, and 1 index of quality of sleep. Results suggest that electrosleep could have both a direct effect attributable to intracranial current flow and an indirect effect attributable to the psychological influence of suggestion. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)

Dokl Biol Sci. 2001 Nov-Dec;381:516-8.

Opiate abstinent syndrome is rapidly blocked by electrostimulation.

Kharchenko EP, Shesternin SL, Klimenko MN.

Source

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Territorial Medical Association on Psychiatry no. 2, Pavlov State Medical University, St. Petersburg, Russia.

Biol Psychiatry. 1990 Oct 15;28(8):650-6.

Transcutaneous electrical stimulation with Limoge current potentiates morphine analgesia and attenuates opiate abstinence syndrome.

Auriacombe M, Tignol J, Le Moal M, Stinus L.

Source

Inserm U. 259, Université de Bordeaux II, France.

Abstract

Transcutaneous electrostimulation is a somewhat controversial technique used in the management of the opiate withdrawal syndrome. We report an animal study of a particular transcutaneous electrostimulation called transcutaneous cranial electrostimulation, based on a technique used for many years on heroin addicts for the rapid severance of their addiction, which has been validated in a clinical setting by a double-blind trial. This technique involves the application of an intermittent high-frequency current (Limoge's current). Our experimental data show that this transcutaneous cranial electrostimulation increases morphine analgesia by threefold on the tail flick latency measure and produces a 48% attenuation of the abstinence syndrome observed after abrupt cessation of morphine administration. These results were obtained using a double-blind paradigm.

Neuroelectric Therapy (NET) in Addiction Detoxification.

Meg Patterson, M.D., F.R.C.S.E., Noel V. Flood, R.M.N. & Lorne Patterson, R.M.N.

Abstract

NeuroElectric Therapy (NET) is a benign and rapid, non-pharmacological detoxification treatment for the chemical dependent, either in-patient or out-patient, using very small amounts of electric current transcranially, with electrodes applied above the mastoid process. The pocket-size stimulator is used continuously for 7 to 10 days (3-4 days for nicotine), without supplementary drugs. Within this treatment period it eliminates the acute symptoms and also ameliorates the Chronic Withdrawal Syndrome, which otherwise could last 18 months or longer, to a very substantial degree. By the end of treatment, 95% of 102 consecutive patients claimed they were free of craving, 75% that they were free of anxiety. NET has a reported drop-out rate of 1.6% over a period of seven years. The basis of this therapeutic success has been the marriage of precision clinical techniques to highly specific combinations of electrical current parameters, both developed over 20 years of reported clinical and research work. It is suggested that the mechanism of action may be the rapid restoration to normal of abnormal neurotransmitter levels by specific electrical signals. Clinical treatments and double-blind studies are briefly described and reviewed, with new data on sleep effects.

Biol Psychiatry. 1975 Dec;10(6):675-80.

Electrosleep in the management of alcoholism.

Smith RB, O'Neill L.

Bianco, Faust.

The effectiveness of cranial electrotherapy stimulation (CES) for the relief of anxiety and depression among polysubstance abusers in chemical dependency treatment.

Ph.D. dissertation, The University of Tulsa, 1994.

Device: LB 2000, 100 Hz, 2mS, <1.5 mA, electrodes behind the ears at the mastoid process

Prior to clinical trials the literature of CES for chemical dependency was subjected to meta-analysis. Initially 180 studies on CES from 1964 through 1987 were reviewed. 8 studies provided the necessary information to calculate means and standard deviations for meta-analysis. The largest effect sizes pertained to the primary withdrawal symptoms of drug use, drug craving, and anxiety specifically among methodone users. In addition the results showed effect sizes beyond that of a placebo effect in several studies relating to anxiety as a secondary withdrawal symptom. However, some studies that considered anxiety as a secondary withdrawal symptom were below the placebo effect level. The analysis displayed an average effect size of 0.940 SD units when comparing CES plus a standard treatment to a CES sham plus a standard treatment, and an effect size of 1.68 when comparing CES plus a standard treatment to standard treatments alone. The average effect sizes for the within groups studies were 0.534 SD units for CES treatments (P<.10), 0.391 SD units for CES sham treatment plus the standard treatment (P<..05) and, 0.171 SD units for the standard treatment alone. The range of the effect sizes for the within group studies were between 0.25 and 0.83 units. The authors concluded that the statistical significance of the within group analysis is quite impressive. To put this into perspective, the average effect size of all psychotherapies are between 0.70 and 0.80 SD units when compared to no treatment (roughly 75% of the pts who receive psychotherapy improve in their condition relative to controls who receive no therapy). The average effect size for non-specific factors or placebo effects among psychotherapies as compared to wait-list controls is about 0.40 SD units. After achieving IRB approval and informed consent, 65 polysubstance abusers with no history of psychosis were recruited from the Oklahoma Department of Human Services and split into 3 groups for this double-blind study using blinding boxes. Pts were at a lock-in unit at the Chemical Dependency Unit. 36 subjects (18 CES, 16 controls, and 5 sham CES) left AMA. 20 males and 9 females from 20 to 49 years old (mean of 31.3) completed the full course of 45 minutes daily for 6 - 14 days. 9 pts in group 1 (31%) were non-CES controls receiving standard treatment, 9 pts (31%) in group 2 received simulated CES plus standard treatment, 11 pts (38%) received active CES plus standard treatment. The revised Beck Anxiety and Depression Inventories, and the Symptom Check List of the Himmelsbach Scale were administered, along with an attention placebo control interview, and observer-rated measures employed by 2 researchers: the Structured Interview Guide for the Hamilton Anxiety and Depression Scales. In order to achieve a power of .8 (beta = .2), alpha was calculated at .05, effect size at .60, and N at 30 (10 per group). Scheffe tests were performed to determine the significance between the means of each of the 3 groups. There was no significant difference between variables at pretest. Analysis of variance (ANOVA) revealed significant post test group differences. Hamilton Anxiety means for CES pretest was 24.44 9.22 to a post test of 7.09 3.21, for sham CES pretest was 22.56 9.95 and post test was 15.67 7.92, and for controls pretest was 20.56 6.21 and posttest was 16.89 9.06. Scheffe post hoc tests for Hamilton was significant between the CES and controls (P<.05) and between the CES and sham (P<.05), but not the sham and control (P>.05) as measured by the observer ratings. Beck Anxiety post test means were not significant, means for CES pretest was 22.91 10.99 to a post test of 5.27 5.23, for sham CES pretest was 28.78 15.21 and post test was 9.33 7.97, and for controls pretest was 21.44 9.89 and posttest was 9.78 12.17. Although the self reports showed no statistical differences between groups, there was a trend towards significance. The study did not control for medications. The author concluded that the active CES, when combined with the normal treatment regimen given at the treatment facilities was more effective in reducing anxiety and depression than the normal treatment regimen alone and the sham CES plus normal treatment regimen. Thus, the anticipated results regarding CES was supported, while the anticipated results regarding placebo effect was not supported. No side effects were reported.

A retrospective chart review of cranial electrotherapy stimulation for clients newly admitted to residential drug treatment

David A. Deitch, Ph.D., Jennifer Butler, B.S., Charles A. Fisher, Sidney Hargrave, M.A., Norman John

Abstract

This pilot program was designed to determine if using CES affected retention rates among new drug rehab patients arriving at Phoenix House, the nations largest non-profit drug rehab center.  The study included 392 subjects consisting of heroin and cocaine addicts; 293 patients did not receive CES (control) and 99 patients received an average of 5 CES treatments total per patient.  A 50% increase in retention after 90 days was seen among patients who received CES versus patients who did not receive CES.  Patients who received CES also reported significant decreases in anxiety and insomnia.

Phoenix House pilot program (2009) with the Fisher Wallace Cranial Stimulator

Phoenix House pilot program patient reports (large file)

Other Published Research

List of Peer Reviewed Research

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Non-invasive electrical stimulation of the brain (ESB) modifies the resting-state network connectivity of the primary motor cortex: A proof of concept fMRI study

Brain Research, June 2011

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Cranial electrotherapy stimulation for the treatment of depression.

J Psychosoc Nurs Ment Health Serv. 2010 Nov;48(11):37-42. doi: 10.3928/02793695-20100701-01. Epub 2010 Jul 22.

Gunther M, Phillips KD.

Abstract

More prevalent in women than men, clinical depression affects approximately 15 million American adults in a given year. Psychopharmaceutical therapy accompanied by psychotherapy and wellness interventions (e.g., nutrition, exercise, counseling) is effective in 80% of diagnosed cases. A lesser known adjunctive therapy is that of cranial electrotherapy stimulation (CES). The major hypothesis for the use of CES in depression is that it may reset the brain to pre-stress homeostasis levels. It is conjectured that the pulsed electrical currents emitted by cranial electrical stimulators affect changes in the limbic system, the reticular activating system, and/or the hypothalamus that result in neurotransmitter secretion and downstream hormone production. While evidence is good for applied research, basic research about the mechanisms of action for CES remains in its infancy. A review of the literature provides an overview of current research findings and implications for clinical mental health practice.

Copyright 2010, SLACK Incorporated.

PMID: 20669869 [PubMed - in process]

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A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder.

 J Clin Psychiatry. 2008 Mar;69(3):412-7.

Bystritsky A, Kerwin L, Feusner J.

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095-6968, USA. abystritsky@mednet.ucla.edu

Abstract

BACKGROUND: Cranial electrotherapy stimulation (CES) is a noninvasive procedure that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. Whether CES is an effective treatment for patients with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not previously been explored. The goal of this study was to evaluate the efficacy of CES in alleviating anxiety in patients with DSM-IV-diagnosed GAD.

METHOD: Twelve patients from 29 to 58 years of age with a DSM-IV diagnosis of GAD were enrolled from August 2005 to March 2006 through the University of California, Los Angeles (UCLA) Anxiety Disorders Program. Cranial electrotherapy stimulation treatment was administered for 6 weeks using the Alpha-Stim Stress Control System at 0.5-Hz frequency and 300-muA intensity. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of 1 or 2 ("much improved" or "very much improved," respectively).

RESULTS: Cranial electrotherapy stimulation was associated with a significant decrease in HAM-A scores (t = 3.083, p = .01). At endpoint, 6 patients (50% of the intent-to-treat sample and 67% of completers) had a 50% decrease in HAM-A score and a CGI-I score of 1 or 2. One additional patient significantly improved in anxiety scores but did not meet criteria for response. Adverse events were generally mild in severity, mostly consisting of headache and nausea.

CONCLUSION: This preliminary study suggests that CES may reduce symptoms of anxiety in GAD. We hope that these preliminary results will encourage further research to explore the use of CES in clinical settings.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00539357.

PMID: 18348596 [PubMed - indexed for MEDLINE]

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Chronic Pain Research

Pain reduction using transcranial electrostimulation: a double blind "active placebo" controlled trial.

J Rehabil Med. 2009 Mar;41(4):256-61.

Gabis L, Shklar B, Baruch YK, Raz R, Gabis E, Geva D.

Weinberg Child Development Center, Safra Children's Hospital at Sheba Medical Center, Affiliated to the Tel-Aviv University Sackler School of Medicine, Tel Hashomer, Israel. gabis@post.tau.ac.il

RESEARCH OBJECTIVE: To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain. DESIGN: A randomized, double-blind, placebo-controlled trial. SUBJECTS: A total of 119 patients with chronic pain. METHODS: Patients were treated with either transcranial electrical stimulation or an active placebo device. Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables: visual analogue scale (pain level), SLEEP (how often does pain disturb sleep), FREQ (frequency of pain) and MED (frequency of use of medications to relieve pain). RESULTS: Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment (p = 0.0017 between groups). Other parameters did not demonstrate significant differences. Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements. CONCLUSION: Transcranial electrical stimulation is an effective non-invasive method for pain relief. The active placebo device has a powerful effect on reported pain, which diminishes in the long-term. The involvement of possible neural mechanisms is discussed.

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The treatment of fibromyalgia with cranial electrotherapy stimulation.

J Clin Rheumatol. 2001 Apr;7(2):72-8; discussion 78.

Lichtbroun AS, Raicer MM, Smith RB.

Robert Wood Johnson Medical School, East Brunswick, NJ 07719, USA.

In cranial electrotherapy stimulation (CES), micro-current levels of electrical stimulation are passed across the head via electrodes clipped to the ear lobes. After successful clinical use of CES with fibromyalgia patients in our clinic, it was decided to test these results with a double-blind, placebo-controlled study in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES treatments, sham CES treatments, or were held as wait-in-line controls for any placebo effect in the sham-treated patients. Treated patients showed a 28% improvement in tender point scores, and a 27% improvement in self-rated scores of general pain level. The number of subjects rating their quality of sleep as poor dropped from 60% at the beginning of the study to 5%. In addition, there were significant gains in the self-rated feelings of well-being and quality of life, plus gains in six stress-related psychological test measures. No placebo effect was found among the sham-treated controls. A theoretical role of CES in affecting the brain's pain message mechanisms and/or neurohormonal control systems is discussed. It is concluded that CES is as effective as the drug therapies in several trials, with no negative side effects, and deserves further consideration as an additional agent for the treatment of fibromyalgia. 

(Click here to view the article)

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Cranial electrotherapy stimulation and fibromyalgia.

Expert Rev Med Devices. 2007 Jul;4(4):489-95.

Gilula MF. President and Director, Life Energies Research Institute, 2510 Inagua Avenue, Miami, FL 33133, USA. mgilula@mindspring.com

Cranial electrotherapy stimulation (CES) is a well-documented neuroelectrical modality that has been proven effective in some good studies of fibromyalgia (FM) patients. CES is no panacea but, for some FM patients, the modality can be valuable. This article discusses aspects of both CES and FM and how they relate to the individual with the condition. FM frequently has many comorbidities such as anxiety, depression, insomnia and a great variety of different rheumatologic and neurological symptoms that often resemble multiple sclerosis, dysautonomias, chronic fatigue syndrome and others. However, despite long-standing criteria from the American College of Rheumatology for FM, some physicians believe there is probably no single homogeneous condition that can be labeled as FM. Whether it is a disease, a syndrome or something else, sufferers feel like they are living one disaster after another. Active self-involvement in care usually enhances the therapeutic results of various treatments and also improves the patient's sense of being in control of the condition. D-ribose supplementation may prove to significantly enhance energy, sleep, mental clarity, pain control and well-being in FM patients. A form of evoked potential biofeedback, the EPFX, is a powerful stress reduction technique which assesses the chief stressors and risk factors for illness that can impede the FM patient's built-in healing abilities. Future healthcare will likely expand the diagnostic criteria of FM and/or illuminate a group of related conditions and the ways in which the conditions relate to each other. Future medicine for FM and related conditions may increasingly involve multimodality treatment that features CES as one significant part of the therapeutic regimen. Future medicine may also include CES as an invaluable, cost-effective add-on to many facets of clinical pharmacology and medical therapeutics.

(Click here to view the article)

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Transcutaneous Electrical Nerve Stimulation: The Treatment of Choice for Pain and Depression

The Journal of Alternative and Complementary Medicine.  2003  Volume 9, p. 619 - 623.

Shealy, Norman C, MD, PhD

Holos University Graduate Seminary, Fair Grove, MO

(Click here to view the article)

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Neurochemical Production - Overview

There are several peer-reviewed studies that demonstrate our technology’s success in treating depression, anxiety and insomnia and its ability to stimulate the production of serotonin and dopamine. Dr. Felipe Fregni (Harvard Medical School) et al. (2009) notes that several studies indicate that CES evokes changes in neurotransmitter and endorphin release. There has been evidence that CES evokes changes in urinary free catecholamines and 17-ketosteroids (Briones and Rosenthal 1973), increases the number of presynaptic vesicles (Kirsch and Smith 2004), and directly engages the serotonin-releasing raphe nuclei, norepinephrine-releasing locus ceruleus, and/or other structures of the brainstem (Kirsch 2002). Researchers have proposed that the mechanisms for CES function in the following manner: 1) by inducing synchronous changes in the brain’s activity, 2) by altering the release of synaptic vesicles, stimulating the neurotransmitter and endorphin release and/or 3) other secondary actions such as the introduction of cortical noise and peripheral craniospinal nerve stimulation.

See below for relevant research citations:

Briones DF, Rosenthal SH. 1973. Changes in urinary free catecholamines and 17-ketosteroids with cerebral electrotherapy (electrosleep ). Dis Nerv Syst 34:57-58

Bystritsky A, Kerwin L, Feusner J. 2008. A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder. J Clin Psychiatry 69(3):412-7

Fregni F, Zaghi S, Acar M, Hultgren B, Boggio PS,. 2009. Non invasive brain stimulation with low-intensity electrical currents: Putative mechanisms of action for direct and alternating current stimulation. Neuroscientist Online December 29, 2009.

Kirsch D. 2002. The science behind cranial electrotherapy stimulation. 2^nd ed. Edmonton: Medical Scope Publishing Corporation.

Kirsch D, Daniel L, Smith R. 2004. Cranial electrotherapy stimulation for anxiety depression, insomnia, cognitive dysfunction, and pain. In: Rosch PJ, Markov MS, editors. Bioelectromagnetic medicine. New York: Marcel Dekker, Inc. p727-40.