Our case highlights an atypical method of opioid use, drinking PST, leading to OUD. Recent studies suggest that PST use is increasing in the United States (U.S.). An analysis of cases of U.S. poppy consumption reported to the National Poison Data Systems and the Food and Drug Administration from 1968 to 2018 reported 64 cases of intentional PST consumption [6]. There was a trend towards increased intentional use of poppy seed products from 2000 to 2018. There are reports of PST use in other countries as well. Among patients surveyed in a New Zealand opioid addiction clinic in 2007, 46% of patients reported past consumption of PST [7], and among those surveyed in a United Kingdom addiction treatment center in 1990, 93% of patients reported consumption of PST [8].

The high concentration of morphine in PST leads to risk for overdose and OUD. PST use is directly associated with at least five U.S. fatalities in the twenty-first century [6], and there are six case reports of OUD developing from routine use of PST (Table 2). All cases of OUD were evaluated and treated in addiction treatment centers, and there are no published cases of home initiation of buprenorphine, nor of evaluation and treatment in primary care.

Our patient’s prolonged withdrawal symptoms suggest that PST withdrawal may be challenging to manage. Two other case reports of PST withdrawal observed in addiction treatment units described prolonged and severe symptoms [11, 12]. In addition to the known symptomatology of morphine and codeine withdrawal, discontinuing PST involves clearance of other opioid (thebaine) and non-opioid (papaverine, noscapine) substances whose physiologic effects are poorly understood [1, 3].

The patient’s improved tolerability to BUP monotherapy is similar to a case [12] in which a patient with PST-related OUD better tolerated BUP than the BUP-NLX combination. In that case, the patient’s urine was consistently positive for morphine after initiation of BUP-NLX, and subsequently negative while taking BUP, suggesting that precipitated withdrawal while on BUP-NLX may have led to the patient’s perception of improved tolerability to monotherapy. There is no evidence in pharmacokinetic studies that BUP-NLX has higher risk of precipitated withdrawal due to naloxone SL absorption compared to BUP [13, 14]. We had no suspicion of ongoing PST or opioid use while our patient took BUP-NLX given negative urine drug screening. It is possible that our patient had acutely worsened anxiety from withdrawal of either oxycodone or PST, and there was a temporal association with improvement of anxiety 6 weeks into treatment when the switch to BUP monotherapy occurred. In another case report [10], a patient had increased anxiety when he discontinued PST and started methadone. Providers prescribed venlafaxine prescription for control of symptoms. Monitoring for the effects of opioid abstinence on mental health, even while patients take MOUD, is important to help patients to engage in treatment.

The misinterpretation of the patient’s prior UDS results, specifically that a positive result for opiates was thought by clinicians to be due to the patient’s oxycodone use, was a missed opportunity to identify the patient’s PST use at an earlier point in his care. Prior research suggests that many providers who order UDS have limited understanding of opioid metabolism and the cross-reactivity of immunoassays, and misinterpretation of urine drug tests is common [15]. Expansion of UDS interpretation support programs [16] may help to improve provider interpretation of complicated UDS results for opioids.

There are many parallels between PST and kratom, an herbal supplement derived from tree leaves containing alkaloids that are opioid receptor agonists. Like PST, kratom is commercially available from online and in-store vendors, and is not regulated by the FDA. Consumption of kratom through brewed teas, powders, or pills produces analgesic effects, and there are increasing cases of OUD developing from routine use, as well as cases of individuals using kratom as treatment for OUD from other opioids. With an estimated 0.7% annual use in the U.S. adult population [17], kratom is likely more widely consumed than PST in the U.S., but treatment guidelines for OUD resulting from either substance do not exist. Due to uncertainties in the relative strength of opioids consumed from these substances, it may be difficult for the treating clinician to determine a sufficient dosage for initiation of BUP, which may explain the varied BUP initiation doses reported in Table 2. There may be uncertainty around maintenance doses as well, as prior case reports indicate varied BUP maintenance dosing. In a recent analysis of patients with OUD from kratom [18], those with higher self-reported kratom use at baseline tended to require a higher maintenance dose of BUP to manage OUD. Our patient initially needed a high dosage of BUP to manage withdrawal symptoms, but was later able to tolerate 6 mg daily during sustained remission. Symptom-directed titration of BUP, along with short interval follow-up, were the keys to successful dosing in our case. Given the variability in initiation and maintenance dosages, it is important that withdrawal symptoms are monitored closely with results used to inform adjustments to BUP dosing.

This case encapsulates the important progress being made for the treatment of patients with OUD in the primary care setting. Historically, patients with OUD could only access MOUD through federally regulated Opioid Treatment Programs. With the substantial increase in OUD largely a result of increased U.S. opioid prescribing in the past several decades [19], these facilities have been unable to keep pace with the high demand for MOUD [20]. Congress passed the Drug Addiction Treatment Act of 2000 (DATA 2000), which allowed qualified providers to prescribe BUP and naltrexone across various healthcare settings, including primary care [21]. These medications effectively treat OUD by reducing or eliminating illicit substance use and lowering risk of fatal and non-fatal overdose, and are safe medications [22] for prescribing by a general practitioner. A shift that further facilitated prescribing in primary care was the introduction of home initiation of BUP [23]. Therefore, a variety of care models now exist to encourage PCPs to diagnose and to treat OUD [24].

The SUPPORT center at the VA Puget Sound Medical Center, funded by the Veterans Health Administration’s National Center for Patient Safety [25], is a unique model of care which offers PCPs a range of options for prescribing MOUD: (1) open-access consultation with a social worker specializing in OUD and an experienced BUP provider, who give recommendations to help the PCP to diagnose OUD and to initiate BUP independently; (2) initial diagnosis and treatment with BUP by the SUPPORT team, with transition of prescription to the PCP when the BUP dosage has stabilized; and (3) initiation and indefinite prescribing of BUP by the SUPPORT team if the PCP feels uncomfortable with managing BUP.

Although recently waivered by the Drug Enforcement Agency to prescribe BUP, the PCP in this case had never prescribed MOUD, and yet felt empowered to initiate BUP-NLX using the consultation model described above. The long-term relationship that existed between the PCP and the patient, the availability of help from the SUPPORT team, and the option to take BUP through PCC without the burden and stigma of an addiction treatment program were important components to success. Our model of care allows PCPs with limited experience with MOUD to manage OUD in primary care.