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Official websites use. Share sensitive information only on official, secure websites. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. 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. Here, 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. Of the drug users interviewed, subjects Interviews yielded a total of substitution events reported by users of cannabis, and substitution events reported by users of heroin. For responders who preferred cannabis, substitution for synthetic cannabinoid receptor agonists 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. 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. The concept of drug substitution is most commonly associated with opioid maintenance treatment OMT whereby a person who is dependent on opioids e. OMT is a widely accepted harm-reduction strategy that is medically viable, relatively safe, and effective Dreifuss et al. Conversely, non-medically sanctioned substitution—the focus of this study—can be conceptualized as a pattern of drug switching performed outside of the formal treatment setting and initiated by the druguser. User-initiated substitution of heroin and cocaine was documented as early as the first half of the 20th century Warburton, , and has since become a common feature of drug use with regular appearance of newer synthetic drugs that displace or replace older established drugs Henderson, A number of rationales behind substitution behavior have been described. When applied to drug markets, a substitution effect could explain observed variations in drug consumption patterns resulting from fluctuations in the street price of drugs e. Legal status, price, purity, and availability were some of the considerations for substitutions among a sample of ecstasy and cocaine users who substituted their preferred drug for stimulant NPS Brunt et al. Analyses of substitution patterns such as the substitution of alcohol, opioids, and prescription drugs for cannabis have shown that users prefer substitutes they perceive as having fewer side effects when self-treating a medical condition:Substitution of narcotic analgesics for cannabis has also been extensively documented among cannabis dispensary patients suffering from chronic pain. Lau et al. Users may also substitute their usual route of administration, e. Drug substitution with illicit or non-prescribed substances may have severe implications for the health of drug users. Acute drug related toxicities can arise when drug users substitute a familiar drug for one of higher potency. Drugs such as cannabis that are not considered highly toxic are sometimes substituted for more harmful substances such as synthetic cannabinoids Stevens et al. Substitution may also pose a health threat in that it serves as a behavioral link between drug initiation and polydrug use patterns. This further complicates the addiction syndrome. Polydrug use itself has been associated with mental ill-health Baggio et al. Together with the numerous putative demographic, substance-specific, and psychopathological risk factors for polydrug use, substitution could be considered to be a possible predictor of progression to polydrug use. Therefore, empirical characterization of a substitution phenomenon has considerable potential in research and can be used to develop informed mitigation and education strategies targeting prevention. Heroin remains the main drug-type for which people receive treatment in both Europe and Asia United Nations Office of Drugs and Crime, In Israel, heroin, cannabis and cocaine are the most commonly reported drugs among treatment seeking Substance Use Disorder SUD individuals Shapira, Cannabis use was also found to be prevalent as a primary substance among dual diagnosis patients being treated in Israel Rosca et al. In the last decade, opioids such as the fentanyl analogues have emerged in drug markets as potent and highly toxic replacements for older established opioids such as heroin and oxycodone Misailidi et al. Given the high prevalence of cannabis and heroin use—and current availability of various potential substitutes for heroin and cannabis—it is important to examine which drugs are frequently used to substitute for them. Accordingly, the main purpose of this study was to determine the most frequent substitutes of heroin and cannabis among those high-risk drugusers reporting a preference for either one of these aforementioned substances. We further aimed to identify demographic, treatment, and drug-use characteristics of substituters. Finally, we described correlates for various substitution patterns among substituters of heroin or cannabis. Segmentation by sex was done to provide a representation of the distribution of females among treatment-enrolled individuals, as reported by the Ministry of Health Rosca et al. Eligible and volunteer participants were provided with written informed consent forms. The consent form was read aloud to those who preferred so. The Individuals interviewed were not at comparable stages of treatment: In-patient and dual-diagnosis enrolled individuals were at the initial stages of their treatment, receiving pharmacological and psycho-social treatment. OMT patients interviewed received ambulatory maintenance and psycho-social treatment at dedicated centers, and were at a more advanced treatment stage, having previously attended in-patient or dual-diagnosis treatment. The interviews were conducted using a structured item questionnaire containing four sections. The first section was about the basic demographic characteristics of the interviewee including age, age at onset-of-use, sex, and population group. Responders could also report a drug not mentioned in the item list. The third section consisted of questions on drug preference, substitution, and motivations for substituting a drug-of-preference. We also recorded the circumstances of substitution place of substitution and substitute substance , and included questions on the lifetime frequency of substitution, the relationship between the drug-of-preference, the substance most used, and the substance most craved by the user. Additionally, we asked the responder about two separate substitution occasions that the user remembers: the substances used as substitutes and the motivations for substituting with these substances. The population groups were analyzed considered the fact that Arab and Jewish drugusers have different drug-use trajectories and drug-preferences that can manifest themselves in diverging substitution patterns. Previous studies have found differences in severity of addiction, personality structure Jaraisy, and rationality between Arab and Jewish drugusers in Israel Jaraisy, The last section contained further demographic and treatment-related questions on marital status, education, whether they were newly admitted patients, or readmitted patients. Interviews were conducted individually by research assistants trained by the main researcher and employed by the research university. All questions were read aloud to participants. No dedicated questionnaires on substitution were located from previous studies, so an unstandardized questionnaire was used with preliminary testing on 30 participants. This paper presents the secondary outcomes of a larger study that primarily examines the motivations of users to substitute their substance-of-preference. All participants of the current study were also asked questions on motivations for substitution in the same session. Hence, the results of this study are not expected to change with the conclusion of the main study. We described the most common substitution pattern reported for heroin or cannabis and used it as the reference category for analysis. Later, four lesser common substitutions were reported as the comparator variables. Lastly, multinomial logistic regression was performed to allow for comparisons of various potential predictors for the most commonly reported substitution patterns for heroin and for cannabis. The median age of the overall sample was 45 years range: 18—76 , and the age at onset-of-use was 16 range: 8— Lifetime substitution was reported by Among those reporting lifetime substitution, When a broad classification of drug groups was applied narcotics i. The overall sample characteristics are summarized in Table 1. No significant differences were identified for age, sex, education, marital status, and past-year use of cannabis and dissociatives between substituters and non substituters. The interviews of all participants who reported substitution yielded a total of substitution events reported by users who reported a preference for cannabis and substitution events from participants who reported a preference for heroin. The characteristics of heroin substituters are shown in Table 3. Note: Numbers were rounded to the next highest integer. Further regression analysis revealed that treatment-center type where the patient was enrolled at the time of the interview, age at onset-of-use, and education were significantly associated with some of the five analyzed substitution patterns for heroin Table 4 : The odds were 2. The odds were also 2. Benzodiazepines, e. Synthetic cathinones, e. Non-opioid analgesics, e. LSD, lysergic acid diethylamide. Other hallucinogenic drugs, e. Gabapentinoids, e. See Fig. Similarly, the odds were 3. Finally, the odds of substituting heroin for prescription opioids compared to street methadone decreased by a factor of 1. Thus, an older age at onset—of—use use increased the likelihood of substituting for street methadone. Among cannabis-preferring patients, substitution for SCRA synthetic cannabinoid receptor agonists was the most frequently reported pattern The characteristics of cannabis substituters are presented in Table 5. Prescription opioids, e. Table 6 shows that among cannabis substituters, age, treatment center type, readmission, education, and population group were significantly associated with substitution pattern. It was 5. This was 3. The odds were 3. Conversely, the odds of substituting cannabis for cocaine, compared to SCRA, were 7. Finally, the odds were 6. In this sample, more than three-quarters of treatment-enrolled drug dependent individuals reported having substituted their preferred drug making substitution the rule rather than the exception. In our analysis of substituters, past-year NPS use was significantly associated with substitution. Hence, it was expected that NPS would play a prominent role as substitutions for cannabis and heroin. However, besides the use of SCRA, there was no evidence that other NPS served as frequent and important substitutes for heroin and cannabis. The notion of pharmacological similarity as the basis of substitution potential is supported by numerous pre-clinical drug discrimination studies Solinas et al. Hence, in our sample, the substitutes did not necessarily share similar subjective or physiological effects with the drug they replaced. Nevertheless, findings show that the most commonly reported substitutions were for drugs within the same drug-class group and with similar effects e. Substitution for prescription opioids was the second most frequent substitution reported among heroin substituters. In this study, the patients did not report substitution with injectable or oral fentanyl. The use of potent fentanyl analogues by heroin users has been associated with many deaths and hospitalizations in North America Ciccarone, ; Pardo et al. Nonetheless, fentanyl patches have become increasingly available to heroin-users in the illicit drug market and have been implicated in at least three deaths in Israel Herman, Hence, the mounting evidence of substitution for prescription opioids among Israeli heroin-users is of concern. Substitution for cocaine was the third most prevalent pattern reported among heroin substituters. Similar substitutions were reported in earlier studies in which heroin unavailability was associated with increased consumption of cocaine Degenhardt et al. Thus, this study provides further evidence of the displacement of heroin by cocaine among some heroin users despite both drugs having dissimilar effects. Jewish cannabis substituters had higher odds for SCRA substitution. Additionally, a higher age at onset of drug-use was associated with lower odds for cocaine substitution versus SCRA substitution. In Israel, the mean age of onset of use for NPS among the general adult population Thus, the appeal of SCRA at a younger age could imply that the easier access and lower street price of these NPS is particularly attractive to younger drugusers. Moreover, the results demonstrate that being enrolled in OMT was significantly associated with substitution for street methadone. This premise could explain how some of the illicit methadone is made available to patients outside treatment. Some hypotheses could be proposed for this common pattern of heroin substitution for illicit methadone. The pattern could be partly explained by the need of patients to manage withdrawal symptoms. Methadone dose is indeed, an important predictor of success of, and continued compliance to OMT Strain, Furthermore, most guidelines require methadone doses to be tailored using clinical discretion because some patients require higher doses than those usually indicated for OMT Baxter et al. In Israel, OMT and in-patient centers are usually located in industrial areas in the periphery of cities with limited hours of operation. They are not easily accessible by public transport. The Ministry of Health in Israel has indeed affirmed that the present geographic distribution of OMT and in-patient units remains insufficient despite significant investment in new drug treatment centers Rosca et al. Moreover, within OMT centers, one-third of treated patients were found to be active users of street drugs Rosca et al. The figures may be higher considering under-reporting and the use of substances not detectable by current kits. The Israeli public drug-treatment system uses a mix of sanctions and incentives when patients fail to comply with center regulations requiring abstinence from street drug use. Sanctions range from simple warnings to the transfer of a patient to another facility Department for the Treatment of Substance Abuse, Hence, another reason for the frequent substitution of heroin for street methadone may be that its use does not incriminate users when it is detected by current urine screening methods employed by centers because it is routinely prescribed to users. Accordingly, heroin-dependent patients may be able to access higher drug doses of methadone in the streets without being incriminated during treatment. Further inquiry into the motivations for substitution for street methadone among drugusers could shed light on this phenomenon. SCRA was the most common substitution substance reported among cannabis substituters. SCRA are highly potent and toxic drugs and are associated with severe health consequences including psychosis Fattore, ; Tait et al. In this study, dual-diagnosis patients using cannabis had comparatively higher odds of substituting it for SCRA versus other substances. Another study demonstrated a high prevalence of concurrent SCRA and cannabis use among Israeli psychiatric patients Shalit et al. Concurrent use could be partially attributed to mutual substitution between these substances. In general, dual-diagnosis has been associated with increased exposure to drugs, disinhibition, and drug experimentation Kessler, This factor could favor the use of NPS and other novel substances. Cannabis use is also a form of symptom management among dual-diagnosis patients suffering from depression and anxiety Santucci, It is possible that substitution of cannabis for SCRA among dual-diagnosis patients provides similar relief. Alcohol was the second most frequent substitution substance reported among cannabis substituters. Individually, the substitution patterns included in these groups were reported with limited frequency. Some substances like SCRA and street methadone have distinctive appearances and presentations. Street methadone in Israel is usually diverted from OMTs and thus commonly appears in liquid form when mixed with concentrated strawberry or raspberry juice. Finally, this study employed a non-probabilistic quota sampling method. The choice of this sampling method was due to the difficulty of recruiting hard-to-access populations to report on the consumption of illicit substances—an act that is criminalized in most jurisdictions. A larger sample could aid in the analysis of the substitution patterns of these groups. This research demonstrates that substitution is not an unusual pattern of drug-use behavior. Substitution analysis is a promising and revealing avenue of research for understanding the behavior of drugusers and the effect of treatment policy on user behavior. Separate conclusions could be inferred from both analyses of cannabis and heroin substitution. Concerning heroin, current patterns demonstrating prominence of illicit substitution for street methadone—particularly among OMT patients—are evidence of ongoing diversion, and possible deficiencies in treatment. Second, the continuous availability of SCRA as a highly toxic alternative to cannabis must be recognized as a significant phenomenon affecting dual-diagnosis patients. More efforts should be invested in monitoring and mitigating the use of SCRA among these patients. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Paola Rosca and Ronny Berkovitz conceived and designed the experiments, authored or reviewed drafts of the paper, and approved the final draft. Igor Gorjaltsan conceived and designed the experiments, authored or reviewed drafts of the paper, helped in recruiting patients and in questionnaire building, and approved the final draft. Yehuda Neumark conceived and designed the experiments, analyzed the data, authored or reviewed drafts of the paper, and approved the final draft. The following information was supplied relating to ethical approvals i. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Find articles by Barak Shapira. Find articles by Paola Rosca. Find articles by Ronny Berkovitz. Find articles by Igor Gorjaltsan. Find articles by Yehuda Neumark. Received Jan 29; Accepted Jun 10; Collection date Open in a new tab. N Percent Treatment Center type Opioid maintenance treatment N Percent Treatment Center type Opioid maintenance treatment 55 The authors declare there are no competing interests. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Stimulants a. Hallucinogens b. Dissociatives c. NPS d. Marital status —not married c ref: married. Marital status —Not married c ref: married.

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