Although we often talk about individual drugs and drug use disorders in isolation, the reality is that many people use drugs in combination and also die from them in combination. Although deaths from opioids continue to command the public’s attention, an alarming increase in deaths involving the stimulant drugs methamphetamine and cocaine are a stark illustration that we no longer face just an opioid crisis. We face a complex and ever-evolving addiction and overdose crisis characterized by shifting use and availability of different substances and use of multiple drugs (and drug classes) together.
Overdose deaths specifically from opioids began escalating two decades ago, after the introduction of potent new opioid pain relievers like OxyContin. But actually, drug overdose deaths have been increasing exponentially since at least 1980, with different substances (e.g., cocaine) driving this upward trend at different times. Overdose deaths involving methamphetamine started rising steeply in 2009, and provisional numbers from the CDC show they had increased 10-fold by 2019, to over 16,500. A similar number of people die every year from overdoses involving cocaine (16,196), which has increased nearly as precipitously over the same period.
Although stimulant use and use disorders fluctuate year to year, national surveys have suggested that use had not risen considerably over the period that overdoses from these drugs escalated, which means that the increases in mortality are likely due to people using these drugs in combination with opioids like heroin or fentanyl or using products that have been laced with fentanyl without their knowledge. Fentanyl is a powerful synthetic opioid (80 times more potent than morphine) that since 2013 has driven the steep rise in opioid overdoses.
During the last half of the 1980s, when cocaine surged in popularity, many overdoses occurred in people combining this drug with heroin. The recent rise in deaths from co-use of stimulants and opioids seems to reflect a similar phenomenon. According to a recent examination of barriers to syringe services programs published in the International Journal of Drug Policy, staff at some programs report that increasing numbers of individuals are injecting methamphetamine and opioids together. Some also report that individuals are switching from opioids to methamphetamine because they fear the unpredictability of opioid products that may contain fentanyl (even though methamphetamine may be laced with fentanyl too).
A 2018 study by researchers at Washington University in St. Louis and published in Drug and Alcohol Dependence found that methamphetamine use has increased significantly among people with an existing opioid use disorder (OUD). People with OUD in their study reported substituting methamphetamine for opioids when the latter are hard to obtain or are perceived as unsafe, or that they sought a synergistic high by combining them. People who purposefully combine heroin and cocaine or methamphetamine report that the stimulant helps to balance out the soporific effect of opioids, enabling them to function “normally.” However, the combination can enhance the drugs’ toxicity and lethality, by exacerbating their individual cardiovascular and pulmonary effects.
Much more research is needed on the co-use of stimulants and opioids as well as how their combination affects overdose risk. Unfortunately, death certificates do not always list the drugs involved, and when they do, they may not always be accurate about which drugs principally contributed to mortality, making it difficult to know exactly the role opioids and stimulants play in mortality when people deliberately or unknowingly take the two together.
Overdose is not the only danger. Persistent stimulant use can lead to cognitive problems as well as many other health issues (such as cardiac and pulmonary diseases). Injecting cocaine or methamphetamine using shared equipment can transmit infectious diseases like HIV or hepatitis B and C. Cocaine has been shown to suppress immune-cell function and promote replication of the HIV virus and its use may make individuals with HIV more susceptible to contracting hepatitis C. Similarly methamphetamine may worsen HIV progression and exacerbate cognitive problems from HIV.
The use of methamphetamine by men who have sex with men has been found to be an important factor in the transmission of HIV in that population. According to a new study in the Journal of Acquired Immune Deficiency Syndromes by researchers at the City University of New York and the University of Miami, more than a third of the gay and bisexual men in their sample who acquired HIV in a 12-month study period reported that they used methamphetamine both before and during that period. Among the variables examined, methamphetamine use was the single biggest risk factor for becoming HIV positive, pointing to use of this drug as an important target for intervention in this group. Another NIH-funded study by a team at the University of California San Francisco School of Nursing published in the Journal of Urban Health in 2014 found that delivering cognitive-behavioral therapy for SUD as a harm reduction measure reduced stimulant use and sexual risk-taking behavior in a sample of men who have sex with men.
For now, the best available treatments for stimulant use disorders are behavioral interventions. Contingency management, which uses motivational incentives and tangible rewards to help a person attain their treatment goals, is the most effective therapy, particularly when used in conjunction with a community reinforcement approach. Despite its effectiveness for treating both methamphetamine and cocaine use disorders, contingency management is not widely used, stemming in part from a policy limiting the monetary value of incentives allowable as part of treatment.
Currently, there are no approved medications for the treatment of stimulant use disorders, but hopefully that will change in the not-too-distant future. Multiple NIDA-funded research teams have been hard at work, in some cases for many years already, testing new medication targets as well as immunotherapies for methamphetamine addiction, such as vaccines.
Linda Dwoskin, a NIDA-funded researcher at the University of Kentucky College of Pharmacy, is developing compounds that will alter the function of molecules called vesicular monoamine transporters that affect how neurons recycle dopamine and that are targets for methamphetamine’s activity, in order to reduce craving and relapse in people addicted to the drug. (Her two-decade quest to develop a medication for methamphetamine addiction is chronicled in a multi-part series in NIDA Notes—the most recent installment is here.)
Apart from medications, another novel approach being tested to treat several substance use disorders is compounds that recruit the body’s own immune system against specific types of drugs, or the direct delivery of antibodies to neutralize a drug’s effects. A team at the University of Arkansas for Medical Sciences and the biotech company InterveXion Therapeutics is currently conducting Phase 2 trials of a monoclonal antibody capable of holding methamphetamine in the bloodstream and disabling its entry into the brain. (A recent NIDA Notes series also details this research program.)
Unfortunately, the COVID-19 pandemic and its associated stresses have made the need for new prevention and treatment approaches more urgent. Researchers at the Department of Health and Human Services and Millennium Health recently published in JAMA that since the beginning of the national emergency in March there has been a 23 percent increase in urine samples taken from various healthcare and clinical settings testing positive for methamphetamine nationwide, a 19 percent increase in samples testing positive for cocaine, and a 67 percent increase in samples testing positive for fentanyl. Another recent study of urine samples by researchers at Quest Diagnostics, published in Population Health Management, found significant increases in fentanyl in combination with methamphetamine and with cocaine during the pandemic.
Efforts to address stimulant use should be integrated with the initiatives already underway to address opioid addiction and opioid mortality. The complex reality of polysubstance use is already a research area that NIDA funds, but much more work is needed. The recognition that we face a drug addiction and overdose crisis, not just an opioid crisis, should guide research, prevention, and treatment efforts going forward.