Stimulant deaths around the world are on the rise. In the UK, the number of deaths involving cocaine is 11 times higher than in 2011. In the US, deaths involving stimulants have more than quadrupled since 2014, largely driven by a sharp increase of deaths involving stimulants and opioids. Exploding production of stimulants in Asia is driving use in the region and beyond. Diversity in the stimulant market is also increasing. Along with reports of increased use of traditional stimulants such as cocaine and methamphetamines, new psychoactive substances like synthetic cathinones are contaminating pre-existing stimulant markets, while new drug cocktails like tusi are creating new ones.
Researchers and clinicians are exploring whether a new medical and harm reduction strategy of stimulant replacement therapy could reduce the harms of cocaine and methamphetamine dependence.
What is Stimulant Replacement Therapy?
Stimulant Replacement Therapy (SRT) is an intervention that prescribes safer, legal stimulants to people dependent on drugs such as cocaine, methamphetamine or other amphetamine-type stimulants. The idea is to replace unpredictable illegal supplies with controlled, pharmaceutical-grade medication — most often methylphenidate or dextroamphetamine — to reduce harm, stabilise use, and improve health outcomes.
Unlike Opioid Substitution Therapy (OST), where medications like methadone and buprenorphine act as partial agonists to ease withdrawal, there are no equivalent long-acting “partial” stimulants. Instead, SRT relies on using existing medicines that act on similar neural pathways as illegal stimulants, but in more predictable ways, usually with more diminished psychoactive effects.
Similar to OST, SRT participants usually receive a daily prescription dose alongside psychological and social support. The goal is not abstinence but reducing risks: fewer binges, lower exposure to adulterated substances, and improved engagement with housing, employment, and healthcare.
Stimulant harm reduction is more important than ever
Globally, stimulant use and related harms are rising. The UN Office on Drugs and Crime (UNODC) reports record-high trafficking and use of amphetamine-type stimulants, with production expanding across every region. In the UK, deaths involving cocaine have tripled in a decade, reaching 1,254 in 2024. In the US, overdose deaths involving psychostimulants exceeded 34,000 in 2022 — nearly six times higher than in 2015.
These trends are often tied to polydrug use. Many fatalities labelled as “opioid-related” also involve stimulants. Combining drugs like fentanyl and cocaine dramatically raises overdose risk because stimulants mask opioid sedation, encouraging higher doses of both. Researchers point to several overlapping drivers. A post-pandemic rebound in global drug markets has made synthetic stimulants cheaper and more available. Rising homelessness in many cities has led to increased “functional” stimulant use: people use methamphetamine or crack cocaine to stay awake in unsafe environments, or to counter opioid sedation when using multiple substances. For some, stimulants can be a form of temporary relief from exhaustion and fear, a way to “keep going” rather than to get high.
Stimulants also play a role in chemsex practices, in which drugs like methamphetamine or mephedrone are used to enhance or prolong sexual activity, especially between men who have sex with men. Research links chemsex practices to elevated risks of dependence, injecting, and greater sexual-health harms — making it a key context for stimulant-specific harm reduction responses.
The cautious promise and acceptance of stimulant replacement therapy
Over the past decade, clinical trials have shown positive results in how prescribed stimulants can help people reduce or quit illegal stimulant use. An early randomised trial found that sustained-release methylphenidate reduced cocaine use and improved treatment retention. Similar results were reported for methamphetamine dependence in Iran. Later meta-analyses have found that prescribed psychostimulants can modestly improve abstinence and retention, especially at individually titrated doses, for those living with stimulant use disorder and amphetamine-type stimulant use disorder.
As with all harm reduction interventions, it is important to ensure those receiving these treatments have a say. Studies into people’s views on SRT are still few and far between. A small, qualitative study found that all participants reported perceived positive benefits of their methamphetamine use, giving them energy to stay alert on the streets, get things done and socialise. While most were enthusiastic about prescribed alternatives, they expressed skepticism about how medication alone could address the root causes of their methamphetamine use. This highlights the need improve social and psychological support, alongside introducing pharmacological treatments for stimulant use disorder.
A 2023 commentary argued that prescribed stimulants should be considered “part of the continuum of care” for stimulant use disorder, similar to how methadone and buprenorphine transformed opioid treatment. The same paper noted that regulatory limits and stigma, more than clinical uncertainty, are the main barriers to wider use. The British Columbia Centre on Substance Use (BCCSU) has taken the lead, issuing national guidelines in 2022 recommending methylphenidate and dextroamphetamine as first-line options under supervision. Pilot services report improved engagement and reduced illegal use among participants.
In Europe, where a pilot crack cocaine safe supply programme may soon take off in Amsterdam, there’s appetite for exploring these safer alternatives to the illegal market.
“The single most important thing I can think of is that stimulant replacement therapy should take into account the context, needs and wishes of the most marginalised groups,” Ancella Voets from Mainline, a Dutch harm reduction organisation, told TalkingDrugs.
“Fortunately the City agreed on this and our outreach workers will conduct interviews with those marginalised people using crack to find out how best to tailor a new programme to their needs.”
Moral opposition hinders harm reduction
Despite promising evidence, SRT remains rare outside small pilots. Regulatory constraints are one obstacle. In the UK, dexamphetamine, methylphenidate and lisdexamphetamine are licensed for attention deficit disorders (and some formulations for narcolepsy) — but they are not authorised for treating stimulant-use disorder, so any use for dependence would be off-label and require clinicians to follow GMC guidance on controlled-drug governance. Growing clinical evidence on SRT’s efficacy should open the way for off-label prescribing. However, as recently as 2024, the Welsh Government has denied there is any evidence supporting SRT.
There are cultural and political barriers too. Governments have been slow to extend harm reduction principles from opioids to stimulants. Stimulant use is often framed as chaotic and associated with moral panics, and policymakers hesitate to sanction medical prescribing in that context. Clinicians and regulators also cite stigma and fear of diversion as deterrents, even when evidence supports safe prescribing under supervision. Services are often under-funded and fragmented, leaving little capacity for the follow-up support that SRT requires. In Canada, where SRT is integrated into a broader harm reduction system, clinicians report that prescribed stimulants help patients “stabilise, re-engage with care, and reduce chaotic use”.
Safe supply for stimulant replacement therapy
Important, but even less popular harm reduction strategies for stimulant harm reduction, such as safe supply, face even greater opposition. Safe supply of illegal stimulants puts into practice consumer-led recommendations of providing people with access to stimulants that have been tested for adulterants. Generally, this is done outside of medical contexts and relies on consumers and harm-reduction practitioners to develop their own practices.
For example, the Drug User Liberation Front’s (DULF) Compassion Club operates outside of a medical framework and offered members non-prescribed heroin, cocaine and methamphetamine of tested composition and purity for purchase and supervised consumption. No one has overdosed from the drugs procured and tested by the Compassion Club. DULF’s radical approach has been met with intense resistance and criminalisation from the Canadian state.
While SRT is distinct from safe supply, both are common sense from a public-health perspective. As Transform and many others argue, “regulation and medical prescribing should be guided by evidence, not stigma.” Politicians and regulators need to abandon the “tough on drugs” ideology, and acknowledge the growing evidence that SRT and safe supply could both reduce harm.
