“Silent Epidemic” of Overdoses from Co-Use of Stimulants and Opiates: The Potential Role of Functional Psychiatry

The Problem

Substance use is common in adults with mental health diagnoses and co-occurance is estimated to be around 50% excluding alcohol. In adolescents the rate is higher and estimated to be between 60-75%. Given this significant overlap, general psychiatrists deal with substance issues in their practices even when their specialty focus is not addiction medicine. In this article we will highlight the specific issue of overdoses from the concomitant use of stimulants and opiates and explore what functional psychiatry might have to offer. This issue has been relatively ignored by the public and health agencies as most of the attention and resources have been focused on opiate use and deaths. Although there was a decrease noted in overdose with co-use of opiates and stimulants from 2023- 2024, it remains a clinically significant issue and attention.¹

To put this into context, the opioid crisis has experienced three waves. The first was related to the increase of prescription opiates in the 1990’s for pain management. The second wave was related to the increase in deaths from heroin and fentanyl and the third wave is the co-involvement of opiates and stimulants. It is not only the intentional co-use, but stimulants may contain synthetic opiates like fentanyl unbeknownst to the user.

Deaths involving the use of opiates and stimulants—primarily cocaine and amphetamines—have been increasing in both the U.S. and Canada. In the US, the annual percent change(APC) has increased from 10 % for 1999-2006 to 32% for 2013-2021. In Canada, the ACP for co-use deaths was 21% from 2013-2022.²

SUDORS (a CDC surveillance system in the US with data  from 24 states and DC during January-June 2019) revealed that 32.6% of drug overdose deaths involved both opioids and stimulants.³  More recent SUDORS data from January 2021-June 2024 showed that 43.1% of overdose deaths co-involved stimulants and opioids. Overall, 59.0% of overdose deaths involved stimulants, 43.1% co-involved stimulants and opioids, and 15.9% involved stimulants and no opioids.⁴

Current Evidence Based Treatment Strategies for Opioid Use

The most effective interventions combine widespread naloxone distribution, medications for opioid use disorder (MOUD), and community-based harm reduction programs explicitly designed to address racial/ethnic inequalities. Recent evidence demonstrates that these strategies can significantly reduce polysubstance overdose deaths, particularly those involving fentanyl-stimulant combinations that disproportionately affect Black and Native American populations.

Overdose education and naloxone distribution (OEND) represents the cornerstone intervention, with proven effectiveness across all polysubstance combinations. The Communities That HEAL randomized trial demonstrated a 37% reduction in opioid-psychostimulant overdose deaths in intervention communities that implemented comprehensive OEND alongside communication campaigns emphasizing naloxone’s utility for all drug overdoses, not just opioid-only events.⁵

Drug checking services, including fentanyl test strips and Fourier-transform infrared spectroscopy (FTIR), can reduce overdose risk by detecting unexpected opioid contamination in stimulants. Evidence suggests people reduce consumption when fentanyl is detected, and comprehensive drug checking services are associated with lower overdose rates.

The American Academy of Addiction Psychiatry recommends that clinicians prescribe or distribute naloxone to all patients using stimulants from nonmedical sources, given the ubiquitous fentanyl contamination of the drug supply. Despite strong evidence, it remains federally illegal, limiting implementation.^6,7,8

Medications (primarily buprenorphine and methadone) reduce opioid-involved polysubstance deaths by decreasing opioid use frequency and occupying μ-receptors, thereby lowering overdose risk whether opioids are used alone or with stimulants. However, only 11% of people with opioid use disorder receive medications for opiate use disorder, and retention rates remain suboptimal.⁹ Among overdose survivors—a particularly high-risk group for subsequent fatal overdose—only about half engage in treatment despite elevated risk.¹⁰

Functional Psychiatry and Opiate and Stimulant Use Disorders

In functional psychiatry, we look to uncover biomedical conditions including nutrient deficiencies that may be causing or exacerbating the presenting mental health issue. Nutrition is particularly significant in people with opiate and stimulant use disorders and micronutrient deficiencies are common due to appetite suppression, poor dietary intake, altered absorption and hormonal disruptions that alter satiety and food intake.¹¹ Although the American Academy of Addiction Psychiatry recommends that clinicians inquire about diet, nutrition, and food security in patients using stimulants, as they face high risk for malnutrition, cachexia, and specific vitamin deficiencies, nutrient deficiencies go unrecognized and nutritional treatments are underutilized.¹²

Given the documented high prevalence of micronutrient deficiencies in this population including Vitamin D, B12 , and folate at a minimum and the safety profile of supplementation, assessment and correction of deficiencies represents a reasonable clinical approach despite the absence of RCT evidence specifically demonstrating efficacy for reducing substance use or improving treatment outcomes in polysubstance use disorders.

Evidence for Micronutrient Treatment in Substance Abuse Disorders

There are no published randomized controlled trials or systematic reviews specifically evaluating treatment effects of micronutrient supplementation in patients with polysubstance use disorders. The available evidence comes primarily from observational studies in opioid use disorder populations, preclinical models, and one case study. No data for opiate plus stimulant use exists.

Vitamin D deficiency is relevant to opioid addiction. Although Vitamin D deficiency is widespread in normal populations, patients with opioid use disorder show increased prevalence of vitamin D deficiency, with levels inversely correlated with self-reported opioid use. Since Vitamin D is the rate-limiting step for the transcription of the enzyme responsible for serotonin synthesis, we can surmise Vitamin D  may help via modulation of mood and anxiety states. Preclinical research using mouse models demonstrated another possible  pathway since vitamin D deficiency was found to amplify exogenous opioid responses, while restoration normalized these responses and thus may reduce opioid-seeking behavior.¹³

Omega-3 polyunsaturated fatty acids show promise in preclinical models but lack human trial data. In a rodent self-administration model of chronic opioid exposure, omega-3 supplementation reduced oxycodone-seeking behaviors during periods without drug availability, decreased anxiety during withdrawal, altered gut microbiome composition favorably, and reduced microglial activation in the striatum.¹⁴

A narrative review identified omega-3 fatty acids and specific amino acids as potentially decreasing relapse risk and improving mental health during treatment, but explicitly noted that high-quality human studies are needed.¹⁵

Broad-spectrum multivitamin-mineral supplementation has a limited data base in substance use disorders. An RCT study of alcohol-dependent patients during rehabilitation showed improvement in several markers of nutritional status but it was not tied to clinical outcome.¹⁶ A case study using a reversal design, demonstrated that micronutrient supplementation simultaneously controlled psychiatric symptoms (ADHD, depression, anxiety) and reduced cannabis and nicotine use, with substance use returning when micronutrients were withdrawn. The proposed mechanisms included improved mood regulation, reduced anxiety, and direct effects on brain reward circuitry by providing neurotransmitter precursors and cofactors.¹⁷

Theoretically, micronutrients could influence addiction through several pathways.

1. Repair of oxidative stress and mitochondrial dysfunction central to substance-induced neurotoxicity . Vitamins C, E and E, selenium and zinc may help mitigate this damage.¹⁸
2. Coenzyme Q10, though technically not a vitamin, shows promise in preclinical models by reducing oxidative damage, preserving neurotransmitter systems, and improving behavioral outcomes in cocaine, alcohol, and opioid addiction.¹⁹
3. Replenishment of vitamin and mineral co-factors required for neurotransmitter synthesis for regulation of mood, anxiety, ADHD and other psychiatric comorbidities.
4. Modulation of DNA methylation patterns. Folate and vitamin B12-dependent pathways control S-adenosylmethionine (SAM) levels, which regulate DNA methylation—a key epigenetic mechanism altered by drugs of abuse. Alcohol, dopamine, and morphine can disrupt glutathione-based redox status, subsequently affecting SAM levels and DNA methylation patterns involved in addiction.^{20, 21}

Conclusion

Overdose deaths from the co-use of opioids and stimulants represent a significant and often under-recognized clinical problem, as public health efforts have largely focused on the opioid crisis alone. Co-use may be intentional or unintentional, the latter frequently resulting from fentanyl contamination of the stimulant supply.

Chronic substance use is associated with compromised nutritional status, making attention to diet and the repletion of vitamins, minerals, and other nutrients clinically relevant, despite the limited evidence base. Functional medicine practitioners can contribute this important therapeutic layer in the treatment of individuals with substance use disorders. In non-using patients, particularly adolescents—among whom psychiatric disorders co-occur with substance use in 60–75% of cases—addressing nutritional status may also serve a preventive role.