GUIDE
Substance Use Guidelines: Fentanyl Introduction
September 2023
• Fentanyl is a highly potent opioid in the same drug class as heroin, morphine, oxycodone, and other prescription opioid pain medications
• Fentanyl is a synthetic drug, meaning it is manufactured using all lab-derived ingredients. Fentanyl is 100 times more potent than morphine and 50 times more potent than heroin.
• Fentanyl entered the US drug supply starting around 2014 and has replaced heroin in most drug markets While many people now seek fentanyl as their drug of choice, this shift in use was experienced by many involuntarily as fentanyl took over the market and heroin was no longer available.
• Fentanyl is frequently found as a contaminant in other substances, including heroin, cocaine (powder and crack/freebase), methamphetamine, MDMA, and pressed pills. It is also possible to obtain pure powder fentanyl in some places in the U.S.
• Because of its potency and quick onset, fentanyl has a much higher risk of causing overdose compared to other opioids. Since 2013, consumption of synthetic opioids, including fentanyl, has led to a drastic increase in overdose mortality in the United States. During the COVID-19 pandemic, this trend was particularly stark for people experiencing homelessness.
• Increasing overdose awareness in the community, helping to support therapeutic and social connections, increasing access to Medications for Opioid Use Disorder (MOUD) like buprenorphine and methadone, and improving access to the opioid overdose reversal medication naloxone (name brand Narcan) can all help prevent fatal overdoses.
• Fentanyl, like other synthetic opioids, works by binding with opioid receptors in the brain. Opioids are analgesics, meaning that they relieve pain; they also frequently produce a sense of euphoria, or general well-being, for the consumer. The effect of fentanyl is achieved when the substance binds with mu-opioid receptors in the brain.
• Illicit fentanyl may be swallowed, smoked (vaporized), sniffed (insufflated), or injected (intravenous, intramuscular, and subcutaneous). Prescribed fentanyl is delivered as a lozenge, patch, or injectable.
• Common effects of synthetic and non-synthetic opioids include euphoria, drowsiness, nausea, confusion, constipation, sedation, slowed breathing, and loss of consciousness. Slowed breathing can lead to hypoxia, or reduced oxygen delivery to the brain; if untreated, hypoxia may result in coma, permanent disability, or death. When a person dies from a fentanyl overdose, they die from a lack of sufficient oxygen delivered to their brain because breathing has slowed too much or stopped.
• In many parts of the United States, drug overdose is the leading cause of mortality for people experiencing homelessness. Social isolation is a contributing factor to mortality related to drug overdose, and in many locations the rate of overdose death for unhoused people increased during the COVID-19 pandemic i
Key Terms and Definitions
• Trauma-Informed Care (TIC): A patient-centered approach to care that recognizes the impacts of trauma and actively works to prevent re-traumatization and promote recovery. The principles of TIC are grounded in establishing a trusting relationship and a safe physical and psychological space in which to address needs.
• Harm Reduction: A philosophical approach to care that establishes individual agency and selfdetermination as central to all efforts toward well -being. Harm reduction approaches call for the non-judgmental, non-coercive provision of services and resources to people who use substances to assist them in reducing harms related to their substance use or other health behaviors. Harm reduction-based care is collaborative, provides education on available interventions, and centers the goals of the individual in care planning.
Clinical Considerations
Physical and Behavioral Health Impacts
• Fentanyl causes euphoria, drowsiness, constipation, sexual dysfunction, reduced respiratory drive and, at high doses, respiratory and cardiac arrest leading to death.
• Clinical considerations and health risks of fentanyl partially vary by the route of administration. Injection use has the most significant risk profile because it has the potential to deliver a large amount of the drug rapidly and directly into the bloodstream, and because of the infection risks related to injection
• Utilizing shared injection equipment like syringes has the potential to expose the consumer to blood-borne pathogens including human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV).
• Other potential risks from injection include skin and soft tissue infections, also known as abscesses, and bacterial infections (from a variety of organisms). Untreated infections have the potential to lead to osteomyelitis, spinal abscess, endocarditis, and inflammation of cardiac tissue and valves, a potentially fatal condition.
• There is little research on the impact of smoking, rather than injecting, as a method for using fentanyl, but in general this practice can exacerbate pre-existing lung disease, such as asthma or COPD. While smoking fentanyl can decrease overdose risk, people with pulmonary conditions are more at risk for fentanyl overdose due to reduced respiratory function at baseline. ii
• Because of its highly effective use as an analgesic and its ability to cause euphoria and sedation, fentanyl is often sought after for the reduction of negative physical and mental health symptoms. Many individuals seek out illicit fentanyl because they are not able to access prescribed medication or because of the stigma associated with accessing treatment.
• Fentanyl use, and stopping fentanyl use, can have a profound impact on a person’s mental health. Because fentanyl can be used as a form of self-medication, an individual may experience a resurgence of previous symptoms, including significant suffering from physical and psychological pain. Other supportive medications and therapies may need to be considered to address these symptoms.
Use of Fentanyl and Experiences of Homelessness
• Experiencing homelessness is difficult and painful from both a physical and psychological perspective. Many people who use fentanyl begin using opioids to address physical pain. Opioid use then often continues due to the euphoric effects of the drug and ability to mitigate some of the negative impacts of homelessness. As use continues, it may develop to be driven primarily by physiologic dependence and avoidance of withdrawal .
• Because it can be difficult to obtain prescription pain medications for chronic pain, and because buying pills in the community can be expensive, the low comparative cost of fentanyl also drives people who are experiencing homelessness and/or have very limited economic means to use fentanyl as their drug of choice, in spite of the known r isks of overdose.
• Some people without shelter use stimulants to stay safe and awake overnight and may use opioids like fentanyl to rest during the day. Concomitant use of stimulants and fentanyl (also known as speedballing) may be employed to blunt the more extreme effects of each substance.
• Using alone is the single biggest risk factor for a fatal opioid overdose. Due to lack of a safe place to use and the criminalization of homelessness, many people experiencing homelessness are forced to use fentanyl in situations that increase the likelihood of overdose, such as hidden from sight, in a restroom or tent, or in settings where peers and community may not be present.
• Fentanyl has a short half-life, meaning there is a fast onset of the drug’s effects that then wear off quickly. People who use fentanyl may find themselves needing to use every few hours to prevent withdrawal. This situation can make it difficult or impossible to adhere to shelter curfews and rules against on-site substance use, driving many people who use fentanyl to live in unsheltered locations or encampments. iii
• Across the country there are reports of a significant increase in deaths among people experiencing homelessness, largely fueled by fentanyl overdose. Black and African American, American Indian, and Native Alaskan people are experiencing a disproportionate increase in drug overdose deaths, especially those involving fentanyl. iv, v, vi
Harm Reduction Strategies
• Harm Reduction is a care modality that strives to reduce the negative impact of substance use and delivers services that are as free from stigma as possible. A primary goal for working with users of fentanyl is to reduce the burden of mortality due to fatal overdose. This model frequently uses peers who have lived expertise of substance use and/or homelessness and serve as trusted experts in the community.
• Naloxone is a potent and effective opioid antagonist that temporarily reverses the effect of opioids, including fentanyl. Coupled with strategies for safer use, naloxone has the potential to reduce mortality in communities impacted by fentanyl use.
• Increasing naloxone access in the broader community of people who interact with our unhoused neighbors helps prevent opioid mortality. Service providers, patients, and community members at large should be trained how to recognize overdose and appropriately respond with naloxone.
• Harm reduction strategies related to fentanyl use include syringe service programs (SSP), distribution of sterile injection and smoking equipment, fentanyl test strips (FTS), distribution of
naloxone kits and training, overdose prevention sites/safe consumption sites, and health education specific to substance use (including vein health and injection technique).
• Safer use is a framework that helps users of fentanyl to limit the occurrence of overdose and other negative consequences of opioid consumption. Strategies for safer use include going slow (injecting slowly), using less/starting with a test dose (you can always use more), testing the product using a fentanyl test strip (FTS), changing the route of administration (smoking or snorting instead of injecting), staggering use so a group member is always alert, knowing the signs of an overdose, carrying naloxone and knowing how to use it, and utilizing the Never Use Alone Hotline. If someone makes the decision to use alone, discuss a safety plan with them and encourage utilization of other safer use strategies.
• Syringe Service Programs (sometimes called needle exchanges) provide low-barrier access to harm reduction supplies for safer use, including sterile syringes of different types and sizes, clean cookers, filters, tourniquets, sterile water, wound care supplies, fentanyl test strips (FTS), and naloxone. These programs also provide safer use education and serve the function of safely disposing of used injection equipment.
• As a result of fentanyl’s high potency, people can smoke fentanyl and have effects similar to injecting heroin. This is sometimes used by some people as a harm reduction strategy to decrease overdose and infection risks. Typically, a person smokes fentanyl using aluminum foil, inhaling vapors as the liquified substance rolls down the foil. Many former injection heroin users transitioned to smoking fentanyl when fentanyl first entered the drug market, resulting in reduced skin and soft tissue infections and other medical complications of injection drug use. vii Over time, people smoking fentanyl pills or powder may experience higher tolerance and start injecting powder fentanyl, which increases the risk of medical complications.
• It is important to recognize that people’s recovery goals can vary widely, from not wanting to stop using, to seeking drugs that contain less fentanyl, to wanting to decrease use or stop altogether. It is important to meet people where they are and co- create a plan to increase safety and decrease risk.
Treatment and Supportive Services
• Treatment for users of fentanyl may be provided through the development of therapeutic relationships, positive social support, medication, and addressing underlying drivers of use like physical pain and mental suffering.
• Medications to treat opioid use disorder address both the physical and psychological desire to consume opioids and prevent withdrawal symptoms. The framework for delivering these medications is referred to as Medications for Opioid Use Disorder (MOUD). Medications to treat opioid use disorder include methadone (oral), buprenorphine (sublingual and subcutaneous injection), and naltrexone (oral and intramuscular injection). Methadone and buprenorphine are discussed in depth in separate guides
• People who start treatment for fentanyl use with MOUD may need additional support with withdrawal management as it can be difficult to quickly get to a dose that adequately prevents withdrawal from fentanyl; this is a result of fentanyl’s potency. This issue is discussed more in the MOUD guidelines.
• Fentanyl is highly lipophilic, meaning that it dissolves in fat and with regular use may become sequestered in fat cells or other tissues, leading to prolonged clearance from the body. With isolated/limited use of 1-4 doses, fentanyl is cleared from the body after 2-4 days, however one study demonstrated that with regular use, the mean time for clearance of fentanyl from urine drugs screens was 7 days, with norfentanyl (a metabolite) remaining 13 days after last use viii Slow clearance, coupled with fentanyl’s potency, can make it difficult for individuals to start buprenorphine and control withdrawal symptoms, potentially due in part to remaining fentanyl in the body. ix There is no current consensus on optimal treatment with buprenorphine for people using fentanyl, but both microdosing and macrodosing buprenorphine have emerged as possible options. This issue is discussed more in the MOUD guidelines.
• People who start MOUD may also require additional support for withdrawal symptoms from other drugs that were mixed with the fentanyl , for example, xylazine. Fentanyl is increasingly cut with xylazine, an animal tranquilizer. Xylazine is discussed in depth in another guide. People who are using fentanyl contaminated with xylazine may need additional education and support with wound care and how to manage xylazine withdrawal symptoms, most notably anxiety and panic.
• It is important to recognize that a person may want treatment for their opioid use while wanting to continue the use of other drugs. These goals must be respected and incorporated into an effective treatment plan.
Models of Care Delivery
• Leveraging an interdisciplinary model is vital for supporting people who use drugs, including fentanyl. Developing a level of trust between the recipient and provider of services is also an integral component to providing substance use services. Trauma-informed care and harm reduction strategies are central to working with people who use fentanyl. The role of peers can be particularly effective at engaging individuals and building trust.
• Medical outreach and street medicine models of care are particularly effective at engaging individuals who use drugs into care. Providing syringe access, naloxone distribution, wound care, and MOUD on the streets is essential , as many people may not feel comfortable or are not able to access more traditional models of care.
• Medical respite may be a vital resource for supporting someone who needs additional assistance with wound care or who would benefit from monitoring during MOUD induction or separating from the environment where they used fentanyl during that process.
• Syringe access and safer use kits are important harm reduction services to provide for people who use fentanyl. In addition to providing new syringes, SSPs provide the opportunity to engage in conversations around safer use practices, as well as open the door for conversations about wounds, MOUD, and other health care or social service needs Federally Qualified Health Centers can become SSPs. This allows the health centers to pair this harm reduction service with MOUD and allows staff to distribute these supplies directly. Another model for FQHCs is to partner with SSPs in their community to provide health care services alongside the harm reduction services of the SSP. Both models are effective ways to build trust and increase health services for the community of people who use drugs.
Additional Resources
• National Harm Reduction Coalition: Fentanyl Resources
• USICH: Strengthening Local Responses to Opioid Misuse Among Individuals Experiencing Homelessness
• HHS: Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health
• Drug Enforcement Administration: Acetyl Fentanyl
• National Institute of Health: The Impact of Homelessness on Mortality of Individuals Living in the United States: A Systematic Review of the Literature
• JAMA Open Network: Drug Overdose Mortality Among People Experiencing Homelessness, 2003 to 2018
• National Institute of Health: Mortality Among People Experiencing Homelessness in San Francisco During the COVID-19 Pandemic
• Homeless Deaths Count: 2020 Homeless Deaths
• NHCHC: The Opioid Epidemic & Homelessness: An Action Agenda for the HCH Community
• National Harm Reduction Coalition: Getting Off Right: A Safety Manual for Injection Drug Users
• Bevel Up
References
i Cawley, C., Kanzaria, H. K., Zevin, B., Doran, K. M., Kushel, M., & Raven, M. C. (2022). Mortality among people experiencing homelessness in San Francisco during the COVID-19 pandemic. JAMA network open, 5(3), e221870e221870.
ii Dolinak, D. (2017). Opioid toxicity. Academic Forensic Pathology, 7(1), 19–35. https://doi.org/10.23907/2017.003
iii Metraux, S., Cusack, M., Graham, M., Metzger, D., Culhane, D. (2019). An Evaluation of the City of Philadelphia’s Kensington Encampment Resolution Pilot. University of Pennsylvania. Retrieved from: https://www.phila.gov/media/20190312102914/Encampment-Resolution-Pilot-Report.pdf
iv Otterman, S. (2023, February 2). Inside the Medical Examiner’s Office, Where Opioids Fuel Surge in Deaths. New York Times. https://www.nytimes.com/2023/02/20/nyregion/sudden-deaths-overdoses-fentanyl-nyc.html
v Center for Disease Control and Prevention (2022, July 19). Overdose death rates increased significantly for Black, American Indian/Alaska Native people in 2020 https://www.cdc.gov/media/releases/2022/s0719-overdose-ratesvs.html
vi Han B., Einstein E. B., Jones C. M., Cotto J., Compton W. M., Volkow N. D. (2022) Racial and Ethnic Disparities in Drug Overdose Deaths in the US During the COVID-19 Pandemic. JAMA network open, 5(9)
vii Kral A. H., Lambdin B. H., Browne E. N., Wenger L. D., Bluthenthal R. N., Zibbell J. E., Davidson P. J. (2021) Transition from injecting opioids to smoking fentanyl in San Francisco, California. Drug alcohol depend, 1;227:109003
viii Huhn, A. S., Hobelmann, J. G., Oyler, G. A., & Strain, E. C. (2020). Protracted renal clearance of fentanyl in persons with opioid use disorder. Drug and alcohol dependence, 214, 108147.
ix Varshneya, N. B., Thakrar, A. P., Lambert, E., & Huhn, A. S. (2022). Opioid use disorder treatment in the fentanyl era. Journal of Addiction Medicine, 10-1097.