{"doi":"10.1111/add.16374","title":"Commentary on Foot <i>et al</i>.: Clinical considerations in addressing comorbid stimulant use in opioid use disorder","abstract":"The opioid overdose crisis has been worsened by the increasing prevalence of comorbid stimulant use together with opioid use disorder. Individuals who also use stimulants are at higher risk of relapse and treatment dropout. Further research is desperately needed to guide clinicians in the treatment of this high-risk population. The United States opioid overdose crisis continues to claim tens of thousands of lives a year [1]. This crisis has been worsened by the introduction of high-potency synthetic opioids into the illicit drug supply, but is further complicated by the increasing prevalence of comorbid stimulant use together with opioid use disorder [2, 3]. In some cases, illicit drug suppliers are adding synthetic opioids to products sold as crystal methamphetamine or other stimulants, and in others, stimulants (usually methamphetamine) are being mixed with opioids to increase the potency of the ‘high’ or to counteract the sedating effects of high-dose opioids [4-6]. Although the increase in overdose deaths is probably fentanyl-associated, there might be a synergistic increase in the toxicity and lethality in individuals combining illicit stimulants with fentanyl [2, 7]. Three effective medications are approved by the US Food and Drug Administration (FDA) for the treatment of opioid use disorder: an opioid agonist (methadone), a partial agonist (buprenorphine) and an antagonist (XR-naltrexone) [8]. Despite these treatments, only a fraction of patients engage in treatment and, among those who initiate the medication, many continue to use illicit opioids and discontinue medication for OUD within the first few months of treatment [9]. The increase in comorbid stimulant use among individuals with opioid use disorder (OUD) only exacerbates these issues, as Foot and colleagues demonstrated in their secondary analysis of a series of large community-based opioid use disorder treatment trials [10]. Our experience in more recent OUD treatment trials echo these findings and has highlighted a clinical challenge for medication-based opioid treatment programs, which primarily have a medical focus. These programs may not be adequately prepared to treat patients presenting with concurrent opioid and stimulant addiction, especially those with major behavioral pathology (e.g. psychosis). Conversely, general addiction treatment programs, which are mainly behaviorally focused, might not be positioned to offer pharmacotherapy for opioid or stimulant use disorder. Unfortunately, decades of pharmacological research trials have yielded no FDA-approved treatments for stimulant use disorders [11], but there are several medications and psychosocial approaches that have proven effective in clinical trials that providers may integrate into treatment of individuals with comorbid opioid and stimulant use disorder. While there might not be an intervention reliably producing abstinence, treatments may be able to facilitate reduction of use. A recent large multi-site trial testing the combination of long-acting injectable naltrexone (XR-naltrexone) and bupropion for methamphetamine use disorder showed that the combination product was more effective than placebo [12]. Although this trial did not specifically recruit individuals with comorbid methamphetamine use disorder and OUD, XR-naltrexone is approved for the treatment of opioid use disorder, and the addition of bupropion for methamphetamine use disorder treatment in individuals maintained on XR-naltrexone for OUD is a straightforward clinical intervention [12]. In individuals maintained on buprenorphine, the addition of bupropion may also be a reasonable intervention, as its partial agonism at the opioid receptor may have some similar benefit to naltrexone on methamphetamine, although no trials have been performed using this combination. Other medication-based options include the noradrenergic and specific serotonergic antidepressant mirtazapine, which has shown some promise for methamphetamine use disord","journal":"Addiction","year":2023,"id":412946,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":977685,"name":"Miranda Greiner","orcid":"0000-0003-3768-527X","position":1,"is_corresponding":false},{"id":1076952,"name":"Adam Bisaga","orcid":"0000-0003-4243-6462","position":2,"is_corresponding":false},{"id":896906,"name":"Matisyahu Shulman","orcid":"0000-0002-2941-8895","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-19T01:21:53.745400Z","pmid":"37853655","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}