Background: Substitution can be defined as the consciously motivated choice to use one drug, either licit or illicit, instead of another, due to perceptions of cost, availability, safety, legality, substance characteristics, and substance attributions. Substitution represents a potential risk to drug users, mainly when substitutes are of higher potency and toxicity. This study offers a basic conceptualization of illicit substitution behavior and describes substitution patterns among users of two highly prevalent drugs of abuse—heroin and cannabis. Methods: Here, 592 high-risk drug users undergoing pharmacological and psycho-social treatment were interviewed. Patients were asked questions about current drug use, lifetime substitution, and substitution patterns. Descriptive statistics, chi-square tests of independence, and multinomial logistic regressions were used to identify and test correlates of substitution patterns for heroin and cannabis. Results: Of the 592 drug users interviewed, 448 subjects (75.7%) reported having substituted their preferred drug for another illicit substance. Interviews yielded a total of 275 substitution events reported by users of cannabis, and 351 substitution events reported by users of heroin. The most frequently reported substitution substances for responders who preferred heroin were illicit non-prescribed “street” methadone (35.9%), followed by oral and transdermal prescription opioids (17.7%). For responders who preferred cannabis, substitution for synthetic cannabinoid receptor agonists (33.5%) followed by alcohol (16.0%) were the most commonly reported. Age at onset–of–use (p < 0.005), population group (p = 0.008), and attending treatment for the first time (p = 0.026) were significantly associated with reported lifetime substitution. Past-year use of stimulants, heroin, hallucinogens, methylenedioxymethamphetamine (MDMA), and novel psychoactive substances were—at the 95% confidence level—also significantly associated with reported lifetime substitution. In multivariate analysis, the odds for methadone substitution among heroin users were significantly affected by age at onset-of-use, type of treatment center, and education. Odds for substitution for synthetic cannabinoid receptor agonists among cannabis users were significantly affected by age, population group, type of treatment center, and education. Conclusion: Self-substitution behavior should be considered by clinicians and policymakers as a common practice among most drugusers. Substitution for street methadone provides evidence for the ongoing diversion of this substance from Opioid Maintenance Treatment Centers, while the prominence of substitution of synthetic cannabinoids among dual-diagnosis patients should be regarded as an ongoing risk to patients that needs to be addressed by clinicians. Analysis of additional substitution patterns should provide further valuable insights into the behavior of drugusers.

Detection of Phosphodiesterase Type 5 (PDE-5) inhibitors and their analogues in “100% natural” or “herbal” supplements have been described in numerous reports. However, few reports have been published in relation to actual harm caused by counterfeit erectile dysfunction herbal supplements. We describe a case of a 65-year old male admitted to a tertiary hospital with acute liver toxicity, possibly induced by adulterated “Chinese herbal” supplement “Tiger King” for sexual enhancement. Chemical analysis of the tablets discovered the presence of therapeutic doses of sildenafil with no other herbal components. Other medications were excluded as potential causes of the hepatic impairment. According to the Naranjo adverse drug reaction scale and the Roussel Uclaf Causality Assessment Method (RUCAM) the probability of association of Hepatotoxicity with Sildenafil was “possible” and “probable” respectively (Naranjo score of 4, RUCAM score of 7). Within three days of admission, the patient’s clinical status and liver function improved without any specific treatment. His liver function tests normalized 30 days post discharge. Further pharmacovigilance actions should be taken by regulatory authorities and pharmaceutical companies in order to determine the relation between sildenafil and hepatotoxicity. This case emphasizes the importance of raising public awareness on the potential dangers of “Tiger king” in particular, and other counterfeit medications or herbal supplements of unknown origin.

Self-substitution is the conscious switch from one drug to another for reasons such as price, availability, desired effect, or perceived benefit of the substitute drug. Purpose/Objectives: This study aimed to describe drug use patterns and motivations associated with substitution. We examined correlates of lifetime substitution among individuals with substance use disorder. Methods: A cross-sectional study of 771 treatment-enrolled individuals. We used self-report for determining the lifetime prevalence, correlates, and motivations for substitution. Results: Of the 771 respondents, 570 (73.9%) reported ever substituting their preferred substance. The main incentives for substitution were availability (23.7%) and curiosity (20.2%). Among heroin or cannabis preferers, improved effects or less adverse effects of the substitute drug, self-medication, and managing withdrawal symptoms were significant substitution incentives. Increased odds for substitution were observed for past 12 months use of cannabis (OR = 1.51, CI = 1.06-4.52), prescription opioids (OR = 2.86, CI = 1.81-4.52), novel psychoactive substances (OR = 2.68, CI = 1.64-4.36), and repeated admission (OR = 1.50, CI = 1.05-2.14). Older age at onset-of-use was negatively associated with substitution (OR = 0.95, CI = 0.93-0.98). Conclusions: Self-substitution of one substance for another is a highly prevalent behavior among treatment-enrolled patients with substance use disorder. Clinicians caring for substance use disorder patients should be aware of substitution patterns involving the use of highly potent substances, which constitutes a risk to patients. Results underscore the benefit of substitution patterns analyses, as they reveal important information on the characteristics of persons who use drugs and their motivations.

Background: In the last twenty years, there was a documented increase in prescription opioid procurement in Israel. However, there is still little evidence of the association between opioid procurement rates, health service utilisation in secondary care, and enrollment rates to substance use disorder treatment programmes. In this study, we show trends in the reports of opioid-related hospitalisations, emergency department visits, enrollment to community-based outpatient treatment for Prescription Opioid Use Disorder and opioid-related mortality rates. Additionally, we examine potential correlations between these health service utilisation rates and prescription opioid procurement rates at the population level, with a focus on transdermal fentanyl. Methods: A longitudinal study at the population level. We used seven-year data on indicators of opioid-related morbidity, prescription opioid procurement data for 2015–2021, and six-year opioid-related mortality data for 2015–2020. We measure the correlation between procurement rates of prescription opioids in Oral Morphine Equivalent per capita, and aggregated rates obtained from hospital administrative data for hospitalisations, emergency department visits, and patient enrolment in specialised prescription opioid use disorder outpatient treatment in the community setting. Results: Between 2015 and 2021, procurement rates in primary care per capita for all prescription opioids increased by 85%, while rates of transdermal fentanyl procurement increased by 162%. We found a significant positive correlation at the population level, between annual opioid procurement rates, and rates per population of opioid-related visits to emergency departments (r = 0.96, p value < 0.01, [CI 0.74–0.99]), as well as a positive correlation with the rates per population of patient enrolment in specialised prescription opioid use disorder outpatient treatment (r = 0.93, p value = 0.02, [CI 0.58–0.99]). Opioid-related mortality peaked in 2019 at 0.31 deaths per 100,000 but decreased to 0.20 deaths per 100,000 in 2020. Conclusion: Data shows that all-opioid and transdermal fentanyl procurement has increased yearly between 2015 and 2021. This increase is positively correlated with a growing demand for community-based Prescription Opioid Use Disorder outpatient treatment. Efforts to reduce opioid-related morbidity may require effective approaches toward appropriate prescribing, monitoring, and further increasing access to prescription opioid outpatient treatment.

Sibutramine, an oral anorexiant, is often found as an adulterant in various counterfeit herbal slimming products and dietary supplements. The use of sibutramine has been associated with various cardiovascular and psychiatric symptoms. Here, we report a rare case of psychomotor disturbances, in a patient with no previously diagnosed movement disorders. A 26-year-old woman developed abnormal behavior, visual hallucinations, hyperkinesia, facial flushing, and dizziness after taking a counterfeit dietary supplement which contained undeclared sibutramine and phenolphtalein. Laboratory work-up revealed microcytic anemia; leucopenia; and elevated erythrocyte sedimentation rate, C-reactive protein levels, and antistreptolysin O titer, but rheumatic fever was ruled out. After a neurologic examination, involuntary movements were classified as chorea. The psychiatric examination result was unremarkable. The patient responded well to haloperidol therapy. Body temperature, erythrocyte sedimentation rate, and C-reactive protein levels eventually normalized. The patient was discharged. This is the first report we are aware of about a transient, chorea-like psychomotor movement disorder associated with sibutramine. Although the causal relationship between sibutramine and the patient's symptoms cannot be proven definitely, the temporal dimension does suggest sibutramine initiation and termination led to onset and resolution of symptoms, respectively. Furthermore, because of the widespread availability of adulterated food supplements containing sibutramine, physicians should be more aware of their implications for patients.