Use of Stimulants and Performance Enhancers During and After Trauma Exposure in a Combat Veteran: A Possible Risk Factor for Posttraumatic Stress Symptoms
Publication: American Journal of Psychiatry
The patient is a 31-year-old male student and army veteran who served two tours in Iraq as a medic. A year after returning from his last deployment, and 6 months after he separated from the military, he enrolled in classes at a community college with the goal of obtaining a professional degree (Figure 1). Two months later, he presented to a campus psychiatric student health clinic with the chief complaint of feeling “on edge all the time.… I keep thinking about what I saw in Iraq.”
History of Present Illness
During his deployments, the patient witnessed multiple injuries and casualties of comrades, civilians, and enemy combatants. More than a year later, within weeks of beginning his studies at the community college, he began to experience recurrent disturbing thoughts of combat experiences and frequent panic attacks (heart pounding, difficulty breathing, sweating), particularly during dissections in anatomy lab. These severe reactions often caused him to leave lab prematurely and miss assignments. He also became increasingly irritable, with frequent angry outbursts toward students and professors. He reported severe insomnia (difficulty falling and staying asleep, frequent snoring) and significant weight gain (30 pounds) since separating from the military.
He reported that at the start of the semester he had initiated a vigorous fitness regimen and had purchased a bodybuilding supplement online to lose weight. He followed the package instructions and used it orally twice daily before workouts. He could not remember the brand name of the supplement, but he said it was the same product he and many members of his military unit used during deployments in Iraq. He reported that use of bodybuilding supplements was extremely common in the military: “All of my friends used [supplements] to work out,” he recalled. He denied any other medication or substance use, with the exception of binge alcohol use approximately once a month with military friends. He reported feeling distanced and “cut off” from the emotional experiences of people other than his military friends.
The patient’s family history was notable for alcohol use disorder and posttraumatic stress disorder (PTSD) in an uncle who served in the military. The patient’s PTSD Checklist (1) score when he entered treatment was 65 (the cutoff range for PTSD is 45–50), with prominent hyperarousal, reexperiencing, and avoidance symptoms.
Course of Treatment
At the initial visit, the patient was diagnosed as having PTSD. He received a prescription for sertraline, a selective serotonin reuptake inhibitor (SSRI), to be taken at 25 mg/day for 7 days, then at 50 mg/day. He was referred for cognitive-behavioral therapy for PTSD and an evaluation for sleep apnea. He was encouraged to abstain from alcohol and educated about healthy drinking limits. He agreed to reduce his alcohol use and declined substance abuse treatment. He was also instructed to provide, on his next visit, a list of all supplements he was taking.
The patient returned for follow-up 1 month later. He reported adherence with the SSRI and therapy and no binge alcohol use. He noted some improvement of his PTSD scores (PTSD Checklist score, 55), with a reduction in avoidance symptoms. However, he continued to endorse prominent hyperarousal, panic, and reexperiencing symptoms that were interfering with his academic studies. He had been diagnosed with sleep apnea and had started using continuous positive airway pressure therapy, but he continued to report difficulty with sleep initiation and maintenance. He had lost 6 pounds on his fitness regimen, and he reported continued use of the bodybuilding supplement, which he identified as “Jack3d,” manufactured by USP Laboratories with the following ingredients: 1,3-dimethylamylamine (DMAA), arginine alpha-ketoglutarate, creatine monohydrate, beta alanine, schizandrol A, and caffeine. He reported using two 5.55 g scoops of the product with 8 ounces of water before workouts twice daily and denied compulsive use or overuse. His treatment team educated him about the risks of continued unprescribed supplement use and strongly advised him to stop using it, which he agreed to do. No other changes were made to his treatment plan.
Several weeks later, the patient returned for his second follow-up appointment. He had remained adherent with the treatment plan and had discontinued the supplement as recommended by his providers. At this visit, there was a notable drop in his self-reported PTSD symptoms (PTSD Checklist score, 36) and he no longer met full criteria for PTSD. In particular, hyperarousal, reexperiencing, and insomnia symptoms had noticeably improved since the previous visit. The patient was better able to tolerate anatomy lab without experiencing panic or extreme irritability. He had regained 5 pounds since discontinuation of the supplement, and he was referred to a nutritionist. He has continued to engage in weekly individual therapy and medication management every 1–2 months, and his PTSD symptoms have remained in remission since his discontinuation of the supplement.
FIGURE 1. Timeline of Events in a Returned Veteran Who Developed PTSD Symptoms After Restarting a Stimulant-Containing Supplement He Had Used During Deploymenta
a PCL=PTSD Checklist.
Stimulant-Based Supplements: Difficult to Regulate, Easy Access
This case describes the onset and exacerbation of hyperarousal, panic, insomnia, and reexperiencing symptoms of PTSD with concomitant DMAA ingestion in a combat veteran. DMAA is a sympathomimetic amine stimulant (2) and is used as an ingredient in popular workout supplements marketed to promote weight loss and improve strength and performance. The patient was adherent with his SSRI regimen and outpatient therapy during the observed period, so it is possible that his symptom reduction resulted entirely from engagement in treatment. However, the temporal relationship between symptom onset and initiation of the supplement and remission of symptoms with discontinuation suggests an association, although causality cannot be established.
In response to numerous reports of adverse events associated with DMAA, including cardiac arrest, liver failure, hemorrhagic stroke, and death (2), the U.S. Food and Drug Administration banned products containing DMAA from the market in April 2013 (3). The Department of Defense prohibited DMAA use in military personnel and removed DMAA-containing products from military commissary shelves. While these actions have likely curtailed use of DMAA-containing products, DMAA and many other stimulant-containing nutritional supplements remain widely available to consumers and have been difficult to regulate (2). Examples of stimulant bodybuilding products available online include 1,3-dimethylbutylamine (DMBA) supplements such as “Frenzy” (Driven Sports) and “Contraband” (Iron Forged Nutrition) (4) and beta-methylphenylethylamine (BMPEA) products such as “Black Widow” (Hi-Tech Pharmaceuticals) and “Jet Fuel Superburn” (GAT) (5).
Performance-Enhancing Supplement and Stimulant Use in Active Duty Military Personnel and Veterans
Use of performance-enhancing supplements is widespread among younger generations of military personnel. Cross-sectional data from the Millennium Cohort Study, a survey of 106,698 active duty service members conducted from 2007 to 2008 during the wars in Afghanistan and Iraq, revealed that 46.7% of respondents reported use of bodybuilding, energy, and/or weight-loss supplements (6), and 22.0% reported use of multiple supplements. Among male respondents, the odds of using bodybuilding supplements were higher among those who were deployed (odds ratio=1.25; 95% CI=1.19, 1.31), those engaged in strength training (odds ratio=3.48; 95% CI=3.30, 3.67), and those born after 1980 (odds ratio=4.86; 95% CI=4.29, 5.50). A survey study of 329 active duty Marines deployed to Afghanistan found that 42% of female and 72% of male respondents reported supplement use while in the combat zone (7). In that study, 75% of supplement users reported use of stimulant-containing products.
Although less is known about supplement use in veterans, former service members may be likely to restart or continue supplement use after separation from the military. A retrospective longitudinal cohort analysis of Veterans Health Administration (VHA) records (N=496,722) revealed that 75% of treatment-seeking veterans of the Iraq and Afghanistan wars in VHA care are overweight or obese, and those with PTSD and depression were in the highest risk categories for obesity (8). Nutritional supplement manufacturers heavily market their products for weight loss, and former military personnel who used supplements during deployment may seek out these products after military service to lose weight.
In addition to supplements, prescription psychostimulants are also used in military settings to enhance performance and alertness, most commonly to combat fatigue in air force pilots (9). A Department of Defense survey of 28,546 military personnel reported an estimated past-year prevalence of prescription stimulant misuse of 2.3% (10). An anonymous survey of 498 active duty service members found that psychostimulant misuse in the past 5 years occurred at a rate of 5% and was associated with mental health conditions, deployment-related injuries, and new physical injuries (11).
Stimulant Use: A Risk Factor for PTSD?
In spite of the widespread use of stimulant-based supplements, little is known about the behavioral effects of chronic use of these products or whether they induce or exacerbate psychiatric symptoms. Stimulants in performance-enhancing supplements include amphetamines, caffeine, ephedrine, pseudoephedrine, and phenylephrine (12). Common behavioral effects of stimulants include increased alertness and wakefulness, anxiety, irritability, restlessness, mood swings, and psychosis (13).
At the time of a traumatic event, a cascade of noradrenergic signaling occurs in the brain, promoting the consolidation of fear-based memories in the amygdala (Figure 2). CNS stimulants, such as DMAA, trigger the release of dopamine, serotonin, and norepinephrine (14). If an individual is using stimulants at the time of a traumatic event, this may contribute to excessive noradrenergic activity during trauma, enhancing the encoding of the traumatic memory and subsequently leading to exaggerated fear responses (e.g., heightened arousal). Noradrenergic overactivation of the amygdala from stimulant use and enhancement of trauma-related memory consolidation may thus predispose trauma-exposed individuals to subsequent PTSD symptoms and may exacerbate PTSD symptoms in those already diagnosed with PTSD (15, 16).
FIGURE 2. Putative Conceptual Model of Stimulant-Induced PTSD Symptomsa
a Question marks indicate potential, unconfirmed mechanisms.
It is unclear whether noradrenergic activation from stimulant use precipitates or worsens symptoms of PTSD. A recent analysis of medical and pharmacy records in active duty military personnel found a strong relationship between receipt of a prescription stimulant and later PTSD diagnosis at follow up several years later (hazard ratio=5.09, 95% CI=3.05, 8.50) (17). The study’s authors concluded that stimulant use may contribute to the pathogenesis of PTSD. Other preclinical data and a small (N=32) randomized controlled trial have found that psychostimulants may improve PTSD symptoms, possibly by enhancing learning, promoting a feeling of well-being, and targeting attention and concentration difficulties (14, 18, 19). Dopaminergic and serotonergic mechanisms may be implicated in the ameliorative effect of psychostimulants observed in these studies (14, 19). It is likely that the relationship between stimulants and PTSD symptoms varies depending on timing, quantity, and duration of stimulant use during or after traumatic exposures as well as individual genetic and environmental factors (17). Notably, the dose of stimulant is difficult to establish in unregulated supplement products, unlike in prescribed psychostimulants in therapeutic dosages. Many stimulant supplements have never been tested in humans, and their safety has not been established (4, 5). Some workout products, including “Jack3d,” which our patient used, contain caffeine and multiple other ingredients in addition to the amine stimulant. Prospective studies and larger randomized controlled trials are urgently needed to clarify the relationship between stimulant use and PTSD.
In the present case, the patient reported use of DMAA both during traumatic combat experiences in Iraq and about a year after his last deployment, when he restarted supplement use some 6 weeks before he presented for treatment. It is possible that stimulant use in the peritraumatic period made him vulnerable to developing PTSD symptoms, or that his PTSD symptoms worsened with the resumption of stimulant use after deployment. Off-label stimulant use from workout supplements may thus be a previously unknown risk factor for PTSD.
Conclusions
This case highlights the potential association between a stimulant-containing dietary supplement and PTSD symptom exacerbation in a recently returned college-age combat veteran. Noradrenergic overactivation in the amygdala and enhanced consolidation of traumatic memories may mediate the observed relationship between stimulant use and PTSD symptoms. While severe adverse effects of DMAA and other stimulant nutritional products have been described, the impact of DMAA on psychiatric symptoms, including PTSD, has not previously been reported. This case also highlights the importance of comprehensive assessment of dietary and herbal supplements in mental health settings. Given the popularity and continued availability of stimulant-containing nutritional supplements, health care providers should be aware of the potential behavioral effects of these products in addition to medical adverse effects. With increasing numbers of veterans seeking care in non-VA settings (20), mental health providers should be aware of the high prevalence of supplement use in this population. Screening for supplement use is especially important in high-risk groups, including young adults, athletes, high school and college students, military personnel, and veterans (6, 7, 12). Future studies will be critical in elucidating whether stimulant use during or after traumatic events contributes to the pathogenesis of PTSD.
Acknowledgments
Dr. Ellen Herbst has grants through the UCSF Hellman Fellows Fund, the Department of Defense, and a gift through Northern California Institute on Research and Education. Dr. Kalapatapu is currently funded by National Institute on Drug Abuse grant K23DA034883.
The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Department of Veterans Affairs.
References
1.
Blake DD, Weathers FW, Nagy LM, et al: The development of a Clinician-Administered PTSD Scale. J Trauma Stress 1995; 8:75–90
2.
Karnatovskaia LV, Leoni JC, Freeman ML: Cardiac arrest in a 21-year-old man after ingestion of 1,3-DMAA-containing workout supplement. Clin J Sport Med 2015; 25:e23–e25
3.
US Food and Drug Administration: DMAA in dietary supplements. July 16, 2013. http://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm346576.htm
4.
Cohen PA, Travis JC, Venhuis BJ: A synthetic stimulant never tested in humans, 1,3-dimethylbutylamine (DMBA), is identified in multiple dietary supplements. Drug Test Anal 2015; 7:83–87
5.
Cohen PA, Bloszies C, Yee C, et al: An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements. Drug Test Anal 2016; 8:328–333.
6.
Jacobson IG, Horton JL, Smith B, et al: Bodybuilding, energy, and weight-loss supplements are associated with deployment and physical activity in US military personnel. Ann Epidemiol 2012; 22:318–330
7.
Cassler NM, Sams R, Cripe PA, et al: Patterns and perceptions of supplement use by US Marines deployed to Afghanistan. Mil Med 2013; 178:659–664
8.
Maguen S, Madden E, Cohen B, et al: The relationship between body mass index and mental health among Iraq and Afghanistan veterans. J Gen Intern Med 2013; 28(suppl 2):S563–S570
9.
Gore RK, Webb TS, Hermes ED: Fatigue and stimulant use in military fighter aircrew during combat operations. Aviat Space Environ Med 2010; 81:719–727
10.
Jeffery DD, Babeu LA, Nelson LE, et al: Prescription drug misuse among US active duty military personnel: a secondary analysis of the 2008 DoD survey of health related behaviors. Mil Med 2013; 178:180–195
11.
Kennedy JN, Bebarta VS, Varney SM, et al: Prescription stimulant misuse in a military population. Mil Med 2015; 180(suppl):191–194
12.
Momaya A, Fawal M, Estes R: Performance-enhancing substances in sports: a review of the literature. Sports Med 2015; 45:517–531
13.
Kirkpatrick MG, Johanson CE, de Wit H: Personality and the acute subjective effects of d-amphetamine in humans. J Psychopharmacol 2013; 27:256–264
14.
Toledano D, Gisquet-Verrier P: Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: an effect abolished by a single amphetamine injection. Behav Brain Res 2014; 272:165–174
15.
Dębiec J, Bush DE, LeDoux JE: Noradrenergic enhancement of reconsolidation in the amygdala impairs extinction of conditioned fear in rats: a possible mechanism for the persistence of traumatic memories in PTSD. Depress Anxiety 2011; 28:186–193
16.
O’Donnell T, Hegadoren KM, Coupland NC: Noradrenergic mechanisms in the pathophysiology of post-traumatic stress disorder. Neuropsychobiology 2004; 50:273–283
17.
Crum-Cianflone NF, Frasco MA, Armenta RF, et al: Prescription stimulants and PTSD among US military service members. J Trauma Stress 2015; 28:585–589
18.
McAllister TW, Zafonte R, Jain S, et al: Randomized placebo-controlled trial of methylphenidate or galantamine for persistent emotional and cognitive symptoms associated with PTSD and/or traumatic brain injury. Neuropsychopharmacology 2016; 41:1191–1198.
19.
Aga-Mizrachi S, Cymerblit-Sabba A, Gurman O, et al: Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model. Transl Psychiatry 2014; 4:e447
20.
Department of Veterans Affairs: Expanded access to non-VA care through the Veterans Choice Program: interim final rule. Fed Regist 2015; 80:74991–74996
Information & Authors
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History
Received: 5 January 2016
Revision received: 19 April 2016
Accepted: 3 May 2016
Published online: 1 February 2017
Published in print: February 01, 2017
Keywords
Authors
Funding Information
National Institute on Drug Abuse10.13039/100000026: K23DA034883
Department of Medicine, University of California, San Francisco10.13039/100008070: Hellman Foundation
The authors report no financial relationships with commercial interests.Metrics & Citations
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