While interventions, such as DCTs, are progressively being promoted as strategies to support safer stimulant use, these often fail to account for the lived realities of those most vulnerable to drug-related risks (e.g., overdose). Recent studies have found acceptability of DCTs to be high among people who use drugs [22, 23], but also that these are of low priority within the context of an established dealer-client relationship [24]. Further, those among the most marginalized members of society (e.g., homeless and racialized individuals) have expressed a low likelihood of actually utilizing these services, as they are unable to easily replace drugs found to be adulterated due to extreme poverty [22], and adulteration is becoming an expectation of the street-level drug supply [23]. DCTs are also often implemented in supervised consumption sites (SCS), which themselves serve as overdose prevention interventions. Within North America’s limited number of SCSs, these have largely focused on injecting and only one regulated supervised inhalation site exists [25], rendering people who smoke stimulants vulnerable to overdose and other harms associated with unsupervised drug use.

Solutions that seek to minimize, or eliminate altogether, the risks of an adulterated drug supply through the provision of a safe supply (i.e., legal, non-adulterated, of known quality, and with user agency in consumption practices) of stimulants are urgently needed as part of a more comprehensive response to the overdose crisis. There has been recent debate regarding the need for a legal and safe supply for opioids, administered as a part of health and social care. Multiple studies have also piloted innovative injectable diacetylmorphine and hydromorphone [26, 27] as medications for addressing the harms of opioid use disorder and providing alternatives to illicit drugs. The promise of these approaches in addressing both overdose-related risks and experiences related to structural vulnerability (e.g., illicit income generation) points to the need to advance similar approaches to address the risk of overdose and other harms among people who use stimulants, particularly within the context an adulterated stimulant supply.

The United Nations Office on Drugs and Crime’s (UNODC) recent report on treatment of stimulant use disorders summarizes emerging evidence demonstrating the treatment potential of prescription psychostimulant substitution and provides recommendations for a pharmacological treatment model that is instructive for stimulant safe supply approaches [1]. The report discusses that, for example, the psychostimulant methylphenidate may be an appropriate treatment for methamphetamine use disorder [28] but not for cocaine use disorder [29]; whereas high doses of extended-release amphetamines have been found to be useful for addressing cocaine dependence [30]. Other psychostimulants that have been considered and reported on in recently published systematic reviews include modafinil, bupropion, dexamphetamine, and mazindol [31, 32]. Notably, there are currently no approved pharmacotherapies for treatment of stimulant use disorder and any practical uses of these medications would be considered “off-label.” Methylphenidate, extended-release amphetamines, and other candidate medications for use as a safe supply, which all can be taken orally every day, have potential because they have a similar pharmacological effect to their illicit counterparts [1]. In treatment-oriented trials these stimulant substitutes were administered in dosages and formulations (e.g., extended-release) that provided a consistent level of stimulation throughout the day, as opposed to a single large, rapidly acting dose that produces a “high.” Given that many stimulant users desire the “high,” any proposals for stimulant safe supply would need to acknowledge and emphasize user agency in diverse consumption practices.

Access to a consistent supply of stimulants of known quality can possibly lead to the same improved health outcomes observed among participants in injectable hydromorphone and diacetylmorphine interventions, such as reductions in abscesses [33], transmission of infectious disease (e.g., hepatitis C, HIV) [34], early mortality [35], and reduced engagement with law enforcement [36]. Additionally, stimulant safe supply approaches may provide opportunities to engage hard-to-reach populations in care in situations that are not informed by crisis (e.g., hospitalization, overdose). Ongoing engagement in safe supply programming could also allow for medical staff to monitor and care for participants whose use could be associated with risk for coronary disease, low body weight, anxiety, psychosis, and other health concerns [37]. Through therapeutic and nonjudgmental service provision, providers may also be able to facilitate access to other forms of treatment, although the harm reduction goals (e.g., overdose prevention) should be prioritized.

Drug user activist groups have recently argued the necessity of a safe stimulant supply in Canada, acknowledging that any form of medication-based approach is likely to fail if it does not mirror what people who use drugs seek (i.e., the “high”) in the illicit market [38]. Current candidate medications have thus far only been studied in the context of treatment of stimulant use disorder, with the eventual goal of reductions in, or abstinence from, stimulant use. To date, trials have not included doses that would enable participants to achieve the “high” associated with a medication’s illicit proxy or to freely use these medications (e.g., user agency in dose amount, frequency, method of consumption). Thus, to study current candidate medications in a safe supply context will require that medications be administered in potentially larger doses than have previously been investigated, and potentially more frequently than once per day. Efforts are urgently needed to investigate the feasibility of pharmacological stimulant-based interventions that address safe supply needs and the underlying risk that a fentanyl-contaminated supply poses to people who use stimulants or are polysubstance users, as well as the lack of non-abstinence-based treatment options.

Meaningfully involving people who use stimulants in intervention planning and implementation will be further important in acknowledging their lived realities. Models that include people with lived experience as partners in their own care exist and have demonstrated success in implementing programs and interventions that are more responsive and relevant which, importantly, have a high likelihood of uptake within their intended communities [39, 40]. This is also a necessary process to design a stimulant safe supply intervention that is low threshold, and thus, accessible to structurally vulnerable people who use stimulants. These populations, who are often considered to be “hard to reach” due to stigma and systematic marginalization, experience challenges in accessing traditional health care, let alone innovative harm reduction interventions. Research on low-threshold programs involving the use of injectable hydromorphone and diacetylmorphine has characterized the primary goal as harm reduction, rather than abstinence or reduced drug use, and emphasized that participation in such interventions must not be punitively impacted by ongoing illicit drug use [41]. Questions surrounding low-threshold delivery for prospective stimulant safe supply interventions should be guided by participatory planning so as not to reproduce operating procedures (e.g., attendance policies, urine drug testing) that create barriers to access and engagement.