1 Introduction

A strong evidence-base has now been established for the clinical effectiveness of supervised injectable opioid treatment (SIOT) as a second-line treatment for people experiencing opioid dependence for whom standard opioid agonist treatment (OAT), such as methadone or buprenorphine, has not been effective [1-3]. As research in the field has turned its attention to the challenges of implementation [4-6], crucial questions surrounding SIOT initiation remain under-explored [7]. Initiation is, Mayer et al. [7] argue, a ‘critical point in treatment engagement that is not well-understood in relation to these treatment options’. This paper seeks to address this gap in the literature.

Drawing on qualitative data collected from participants of the Australian ‘Feasibility of Opioid Injectable Treatment’ study (FOpIT), we examine: (i) why participants joined the trial—their initial hopes, expectations and goals? And (ii) what were their early experiences of the treatment medication, injectable hydromorphone? Adding a further layer of complexity and interest to our analysis is the time-limited nature of the treatment and the newness and novelty of both SIOT and hydromorphone within the Australian context. How, in the absence of prior experience, did FOpIT participants come to know this new treatment and medication?

The general OAT literature emphasises the importance of initiation in shaping onward treatment trajectories [7], describing it as ‘a critical site of narrative formation’ [8] affecting subsequent retention and outcomes [9, 10]. Past research has shown that what both distinguishes SIOT from standard OAT and defines its appeal to consumers, is the free, legal and safe access to a short-acting, injectable opioid—typically diacetylmorphine (pharmaceutical heroin) but also hydromorphone [11, 12]. It is the appeal of a more rewarding experience of treatment with these medication that underpins the success of SIOT. Such appeal is likely to matter, not only in terms of attracting people into treatment but retaining them. Treatment satisfaction, consistently high among SIOT recipients [13-15], has been identified as an indicator of both treatment retention and response [13].

A range of other motivations underpinning people's engagement with SIOT have also been noted, including improving one's health and social circumstances; avoiding trouble with the police; restoring familial relations; alleviating financial stress; achieving ‘stability’; and returning to ‘normal’ life [7, 15-17]. It is important to recognise that SIOT affords people a continuum of legitimate treatment aspirations, from reducing harm to achieving abstinence, or over time, a combination of both [16, 18]. Given its standing as a ‘second line’ treatment, people enrolling on a SIOT program have invariably attempted other treatment options, including standard OAT. People initiating SIOT tend to report high levels of motivation and readiness for change [7, 14, 16] underpinned by a conviction that (for a range of reasons) oral OAT has not worked for them [7, 19, 20]. For some, the experience of previous ‘unsuccessful’ efforts on OAT becomes the motivation to try something new, especially in settings where SIOT remains a novelty [16]. Here, in part at least, SIOT becomes attractive simply by virtue of what it is not [16].

While the extant SIOT literature affords us some valuable insights regarding treatment motivations and initiation, there is a dearth of literature in relation to the second thread of our analysis: participants' initial experiences of injectable hydromorphone. The majority of SIOT RCTs compared the use of injectable diacetylmorphine with oral methadone alone, although two Canadian studies (NAOMI and SALOME) included injectable hydromorphone as a potential treatment alternative [19, 21]. While both studies found that the latter yielded comparable results to diacetylmorphine when compared with oral methadone alone, they also noted that participants were unable to ascertain, beyond what could be expected by chance, which of the two injectable medications they had been allocated [22]. Although the literature includes some firsthand accounts of the two medications, the participants remained blinded as to which one they were describing [22].

The Canadian findings consolidated the case for hydromorphone as an alternative SIOT medication [23] in jurisdictions like Australia, where regulatory and political challenges exist regarding the use of diacetylmorphine [6, 24]. Until the advent of FOpIT, Australia has been stuck in somewhat of a political and policy impasse regarding short-acting injectable treatment [24]. While a ‘heroin trial’ was proposed for the Australian Capital Territory in the late 1990s, the proposal faced vehement opposition by elements of the tabloid press and was ultimately vetoed by a conservative Federal Government ideologically suspicious of the initiative [20, 23, 25, 26]. In Australia, hydromorphone remains largely unknown among people who inject drugs. For FOpIT participants, this meant that not only was the treatment modality new and novel, but so too was the treatment medication. Given that much of the appeal and the effectiveness of SIOT hinges on the provision of a ‘rewarding’ medication, participants' experience of injectable hydromorphone will form an important part of evaluating the trial's overall acceptability.

2 Methods

FOpIT began in April 2022 via a public, outpatient OAT program run by St Vincent's Hospital, Sydney; a detailed account of the trial setting and design can be found in Rodgers et al. [1]. The primary aims of the trial were to assess the feasibility and acceptability of a time-limited, integrated SIOT using injectable hydromorphone. Participants were offered intensive, highly-structured treatment comprising up to twice daily, supervised injectable hydromorphone in conjunction with standard OAT. A novel feature of the trial was the time-limited availability of hydromorphone treatment (up to 2 years) after which participants were offered maintenance on standard OAT [1]. Quantitative and qualitative interview data were collected at three timepoints during the trial. This paper analyses qualitative data collected during the first tranche of semi-structured, in-depth interviews held with participants shortly after commencing injectable treatment.

Following their induction onto injectable treatment, participants were introduced to a member of the University of New South Wales research team (J.R.) to schedule an initial research interview. This interview comprised a series of quantitative measures, including quality of life, mental health, and recent illicit drug use [1]. All participants were expected to participate in the collection of quantitative data. Twenty-one of the 22 enrolled participants took part, with one participant voluntarily discontinuing treatment.

During this initial research interview, participants were offered the opportunity to take part in an additional, qualitative interview, with a maximum of 15 set by the study team. Participants were assured that all interviews were strictly confidential and anonymous, and that the researcher conducting the interviews was not part of the trial's clinical operations. All interviews were conducted by the first author (J.R.) and took place in a private room within the centre. Interviews lasted 25–85 min. All participants provided written consent. Interviews were conducted within 3 weeks of participants' first dose of injectable hydromorphone, with an average of 9 days and a range of 1–21 days. It is important to recognise that individual variability in the induction process and the timing of interviews would likely have affected participants' experiences of hydromorphone and its ‘effects’. Full details regarding the trial's hydromorphone dosing protocol can be found in Rodgers et al. [1].

Interview questions included: participant histories of opioid use and treatment; motivations for joining FOpIT; hopes, expectations and possible goals for treatment; navigating daily service delivery; sense of agency in treatment decision-making; relationships with staff; and finally, initial experiences of injectable hydromorphone (including intravenous or intramuscular administration). Participants were reimbursed for their time and expertise with a $50AUD voucher. Interviews were digitally recorded, professionally transcribed, checked for accuracy and deidentified.

Our analysis followed the basic tenets of thematic analysis [27], combining data-driven (inductive) and analyst-driven (deductive) approaches. Inductive themes were identified by the first author (J.R.) during initial, close readings of the transcripts. These emergent themes, along with indicative quotes, were subsequently discussed with members of the study team, A.R. and C.T. Our combined knowledge of the extant SIOT and OAT literature, including gaps identified in the former, served as our analytical framework, guiding our discussion of inductive themes and the ultimate determination of our two research questions: treatment initiation and early hydromorphone experiences.

Aided by our knowledge of the opioid treatment literature, our analysis of the data was further informed by conceptual insights drawn from the sociological literature on alcohol and other drugs, such as Berridge's ‘futurizing history’ [28] and Hardon's ‘fluid drugs’ [29]. We also note the important contribution of the research interview itself and the opportunity it afforded participants to think-aloud and think-through, to clarify their thoughts, and to find, shape and account for themselves. Our final analysis, including primary themes and associated secondary themes or subheadings under which our findings are organised, reflect this combination of inductive and deductive analysis; or what Fereday and colleagues refer to as a ‘hybrid’ approach [30]. The writing process was led by J.R., including decision-making about content, analysis and structure, and reviewed by A.R. and C.T. At critical junctures, drafts of the manuscript were distributed among the broader co-authorship team. All feedback was reviewed by J.R., discussed with A.R., and integrated within the manuscript where appropriate.

Approval for this study was provided by St Vincent's Hospital Human Research Ethics Committee (2019/ETH00418). Pseudonyms have been used throughout the paper. Pseudonyms were chosen to loosely reflect the typically Anglo-European names of participants. Plural pronouns have been used exclusively to ensure the anonymity of the participant identifying as non-binary.

3 Results

A total of 15 participants were interviewed, ranging in age from 28 to 58 and including eight men, six women and one participant who identified as non-binary. Two of the men and the non-binary participant identified as gay and one as bisexual; two of the women identified as lesbian. All 15 participants reported receiving some form of social welfare support payment, with three also reporting part-time employment and one full-time. Two participants reported being homeless, while another faced imminent eviction. All participants reported prior periods on OAT, albeit varying considerably in duration from months to decades. Thirteen participants were receiving OAT at the time of enrolment on FOpIT, including 11 on methadone, one on sublingual buprenorphine-naloxone (‘Simon’) and one on long-acting injectable buprenorphine (‘Ben’). The two participants not on OAT, ‘Billie’ and ‘Jean’, were started on methadone as part of their induction on the study.

Our findings are organised into two sections. The first section examines participants' reflections on their motivations, hopes and goals following their initiation on injectable treatment; the second focuses on participant accounts of injectable hydromorphone and its effects.

4 Discussion

A defining feature of SIOT and a key to its effectiveness lies in offering a more rewarding medication to attract and retain people in structured treatment whilst simultaneously creating an opportunity to effect other changes in lifestyle and well-being. Our findings appear to support this core principle, with the attraction of a short-acting, injectable opioid seemingly effective in motivating FOpIT participants to initiate treatment. In keeping with previous findings [7, 16, 33], the sense of frustration and futility participants associated with previous experiences of oral OAT, coupled with a desire and a readiness for change, appeared to have fuelled their sense of hope and expectation for a new and novel treatment.

It is important to acknowledge, however, that the appeal of something ‘new and novel’ alone does not explain the specific appeal of SIOT. Witness, for example, the recent popularity surrounding the introduction of long-acting injectable buprenorphine, characterised by some as ‘a game changer’ [34]. We contend that beyond the appeal of newness and novelty, it is the core elements of SIOT which underpinned participants' sense of shock and disbelief that such a ‘ground-breaking’ trial was taking place in Australia. For FOpIT participants, SIOT offered a treatment approach and a medication that not only acknowledged the sought-after effects of street heroin relative to existing OAT options, but for many, their deeply-held attachment to the practice of injecting. Perhaps participant Ezra put it best when he described the appeal of FOpIT as ‘injectable and closer to heroin’.

Among trial participants, motivations to initiate treatment ranged from a sense of desperation to try something new, to cogent arguments as to why SIOT was the treatment option most likely to ‘work’ for them. Some participants were also motivated by a sense of altruism and collective responsibility, describing their determination for FOpIT to succeed so others could also benefit from the same opportunity. We note this sense of shared purpose and responsibility for collective change is similarly evident in clinical trials, especially in cancer research (e.g., [35]). While some treatment narratives were orientated around a primary goal of ceasing or ‘abstaining’ from illicit heroin use, others were organised around a desire to regain ‘stability’ and ‘structure’ vis-à-vis their long-term heroin use. Irrespective of their intentions, the respite from the demands of the illicit market afforded participants a therapeutic hiatus, a chance to review and perhaps revise their initial intentions—an opportunity described elsewhere as ‘a chance to stop and breathe’ [15]. For some participants, their treatment goals incorporated a desire for change more broadly: in relation to housing, family relationships, intimate partnerships, money and a sense of (legal) legitimacy.

The relationship between treatment sought and treatment received is more complex and nuanced than simply the provision of a sought-after injectable opioid. As Ellefsen et al. [36] note, ‘[p]atient satisfaction with prescribed medical heroin cannot be detached from the setting in which [heroin assisted treatment] is provided and the way clinicians provide it’. Participant reports of their early experiences of hydromorphone varied, with heroin invariably functioning as an interpretative lens and comparative benchmark. The absence of heroin's ‘taste’, noted by a number of FOpIT participants, has similarly been reported by participants on previous SIOT trials that used pharmaceutical heroin [37]. Given hydromorphone is rarely found in Australia's illicit drug market, participants were unable to compare the effects of the study medication with any previous, non-clinical experiences.

We also need to recognise that with the co-prescription of methadone (or buprenorphine), participants may have struggled to disentangle the effects of the two drugs—something participants themselves observed anecdotally regarding the ‘blocking’ effects of methadone. Given methadone is considered an opioid agonist, the use of the term ‘blocking’ may seem erroneous here. However, it is well recognised among those with lived experience, and in the treatment literature, that methadone at sufficient doses can minimise, even negate, the effects of heroin and other opioids, such as hydromorphone. In a recent study examining the analgesic effectiveness of hydromorphone among hospitalised individuals on methadone treatment, the authors concluded that ‘methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone’ ([38] emphasis added). On the other hand, the co-prescription of buprenorphine and hydromorphone might reasonably seem more likely to present problems, given the potential for precipated withdrawal associated with the former. However, as noted earlier, neither Simon nor Ben, the only two participants on buprenorphine formulations, reported any adverse experiences, with both describing their early experiences of hydromorphone favourably. Finally, given the mandatory co-prescription of methadone, another distinguishing feature of the trial, it is possible that FOpIT was the first time some participants had received a regular dose of methadone—an experience previously reported by participants of a Canadian trial [15].

Here, an argument posed by critical drug scholars warrants consideration [39]. Positing that no ‘pure’ pharmaceutical object precedes its socialisation, they contend that instead of explaining the effects of hydromorphone solely in terms of chemical determinism—as fixed, universal, and pre-determined—we should understand them as ‘something in the making’, under ‘negotiation’, and inextricably contextualised [40]. As Hardon [29] argues, ‘pharmaceutical action is not reducible to the chemical properties of pharmaceuticals but is articulated, elicited, and informed within a meshwork of experimental, regulator, and care settings’. For most participants the practice of injecting was an important actor in the ‘making up’ of their hydromorphone experience. In the absence of injecting street heroin, injectable treatment worked both literally and symbolically to satisfy participants that they had had ‘their shot’, even among some who injected intramuscally. FOpIT participants also described the contingent, situated nature of pharmaceutical effects when observing how different settings (such as clinic and home) or the presence or absence of certain practices (such as smoking or listening to music) reconfigured their experience of hydromorphone. Finally, we note the therapeutic and pragmatic potential of pleasure in treatment [41]. Relative to standard OAT, SIOT recognises the importance of not only affording a more rewarding medication or pharmacotherapy [12] but a route of administration that is deeply meaningful for some—one that need not necessarily be foregone as a condition of treatment [42].

Mayer et al. [7] draw our attention to the role of the ‘structural vulnerabilities’ that inevitably shape people's sense of agency and decision-making regarding SIOT, with the latter necessarily embedded within its own broader medical and political contexts. Within the lives of most participants, drug treatment with its attendant stigmatisation and marginalisation [43], has played a defining role. Virginia Berridge's [13] notion of ‘futurizing history’ draws our attention to the critical role of history in understanding and shaping the possible future(s) of addiction and its treatment, both for the individual (such as a FOpIT participant) and the collective (such as Australian drug treatment policy). Importantly, attending to the history of drug treatment alerts us to ‘the wolf of drug control dressed in the sheep's clothing of medicine’ [15], reminding us how ‘notions of “care” for undesirable Others [can] very quickly descend into techniques of control’ [44].

We recognise that the design and setting of the study may have unintentionally affected our findings. The significance of FOpIT being the first, long-awaited trial of short-acting, injectable opioid treatment in Australia, coupled with its newness in the local treatment context, may have contributed to the relatively high motivation reported among participants to achieve ‘positive’ treatment outcomes. It is also seems likely that the novelty of hydromorphone in the Australian context (as both an injectable treatment and diverted street drug) will have influenced participant experiences and accounts of the medication. These factors may limit the degree to which our findings are generalisable.

5 Conclusion

Both for those seeking and delivering treatment, the period of initiation is a crucial one, potentially setting the stage for and shaping subsequent treatment trajectories. In this sense, understanding the complexities of why and how people initiate SIOT has clear implications for clinical practice, including the potential realisation of improved therapeutic and clinical outcomes. How FOpIT participants accounted for their initial engagement in SIOT and for the effects of a new treatment medication revealed a diversity of motivations, hopes, goals, and effects. The extent to which these are carried through to treatment outcomes is the subject of ongoing research.

Author Contributions

Each author certifies that their contribution to this work meets the standards of the International Committee of Medical Journal Editors.

Conflicts of Interest

J.R., V.B., J.B., N.E., M.J., A.R., D.M.R., C.R., K.J.S., C.T.: none declared. N.L. has received funding for undertaking research studies with buprenorphine products from Camurus AB and Indivior and received honoraria from Camurus AB for a conference presentation. W.B. has received honoraria from Camurus, Indivior, Takeda and Mundipharma, none related to the treatment or study being described in this paper. J.S. has worked with pharmaceutical and technology companies to investigate new or improved medications for reducing opioid related harm: none is related to the treatment or study being described in this paper. A.J.D. is employed by a local health district which has received funds from Camurus AB and Indivior to conduct clinical research studies on long acting injectable buprenorphine, unrelated to the treatment or study described in this paper. Several of the authors (J.B., A.J.D., J.S., N.L., W.B., E.O.-J. and C.R.) have each been, at different times, clinicians directly providing SIOT, and been active in seeking clinical funding support for SIOT. M.J. is the Director of the Sydney, Medically Supervised Injecting Centre. Many authors (J.B., A.J.D., J.S., N.E., C.R., D.M.R., W.B., N.L. and E.O.-J.) have been providing opioid agonist treatments more broadly for a number of years.