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Transcranial direct current stimulation tDCS has been shown to modulate subjective craving ratings in drug dependents by modification of cortical excitability in dorsolateral prefrontal cortex DLPFC. Given the mechanism of craving in methamphetamine meth users, we aimed to test whether tDCS of DLPFC could also alter self-reported craving in abstinent meth users while being exposed to meth cues. In this double-blinded, crossover, sham-controlled study, thirty two right-handed abstinent male meth users were recruited. Our findings showed a state dependent effect of tDCS: while active prefrontal tDCS acutely reduced craving at rest in the abstinent meth users, it increased craving during meth-related cue exposure. These findings reflect the important role of the prefrontal cortex in both cue saliency evaluation and urge to meth consumption. According to the world drug report, after cannabis, amphetamine-type stimulants ATS are the world's most widely used drugs. ATS has become an international public health problem with an estimation of Methamphetamine meth is an extremely potent psycho-stimulant and highly addictive drug, accompanied by cheap price, ease of synthesis and long lasting effects Henry et al. Relapse to drug use is a common phenomenon in the treatment of addiction that can occur after prolonged abstinence, and is often precipitated by the exposure to drug-associated cues that provoke drug craving Pickens et al. Drug craving is one of the most important factors in addiction that can lead to drug-seeking behaviour during abstinence. It represents a complex condition that includes emotional and cognitive aspects along with behavioural and physiological states. Emerging evidence suggests that craving induced by meth cues can be reliably measured in meth-dependent individuals and cue-induced craving is a strong predictor of subsequent meth use Culbertson et al. Accordingly, cue-elicited meth craving should be viewed as a clinically important phenomenon and one of the primary behavioural symptoms of meth dependence. According to several neuroimaging studies, the prefrontal cortex, especially the dorsolateral prefrontal cortex DLPFC , plays an important role in drug craving Brody et al. Additionally, modulation of DLPFC activity using repetitive transcranial magnetic stimulation rTMS , which is a non-invasive brain stimulation technique, has shown significant effects on nicotine Eichhammer et al. Hence, we aimed to test the effects of prefrontal cortex modulation using a technique that has been shown to induce significant behavioural effects and can interact with current neural processes to enhance neuroplasticity — transcranial direct current stimulation tDCS. TDCS is a method of non-invasive brain stimulation which has recently demonstrated promising neuro-rehabilitative effects in different types of neuropsychiatric disorders Demirtas-Tatlidede et al. TDCS delivers a weak and continuous current to the cortex through an electrode connection with the subject's scalp, and either inhibits or enhances neuronal firing in an area related to the location of the electrode. The interesting advantage of tDCS is its interactive effect with the ongoing neural process; thus it is an attractive technique to be used in combination with behavioural stimulation. A main drawback of these studies is the possible confounding effect of bilateral protocols, in the sense that excitatory effects of the anodal electrode are not distinguishable from inhibitory effects of the cathodal electrode. We therefore assessed the effects of unilateral stimulation of the right DLPFC on the immediate and cue-induced craving in abstinent meth-dependent subjects. We used a cue reactivity paradigm, which has been demonstrated to be a validated method for craving induction and thus, given the mechanism of tDCS, appropriate to be combined with tDCS of the prefrontal cortex. We chose the right DLPFC as we hypothesized that increasing ongoing activity of this area, would have an inhibitory effect on craving behaviour. Subjects were recruited from meth-dependent patients who were admitted to Vardij Abstinence-Based Residential Centre which is specialized for ATS dependence. This centre is located at Vardij, a rural area near Tehran, and is a part of the therapeutic network belonging to Rebirth Society Organization RSO , a non-profit charity. The setting was ideal for this study as the population was relatively homogeneous and given the large numbers of meth users in this facility, it also provided an adequate external validity. Thirty two right-handed male subjects were initially enrolled, although only 30 completed the whole procedure of the study. All the subjects had used meth at least 6 d a week in the last month before entering the treatment and the most common route of administration was smoking among all subjects. Subjects were excluded if their self-reported mean craving was below 20 out of We also excluded individuals with any current or past major clinical neurologic disorders, central nervous system-effective medication intake, history of epilepsy, brain surgery, tumor, intracranial metal implantation, clinically significant head trauma, or any major clinical psychiatric disorders in axis I, except substance-related disorders. The experimental protocol was designed and carried out according to the Declaration of Helsinki principle. Since exposing patients to meth cues may increase the possibility of relapse, similarly to studies using cue-reactivity paradigms, we carefully addressed this important ethical concern by using images instead of real substance and paraphernalia and subjects received IEC-approved psychological interventions to manage potential drug craving after being exposed to drug cues. As the subjects were already admitted to a caring facility they were closely monitored through the following week for any sign of relapse. All subjects signed a written informed consent form. This study was a randomized, double-blinded, sham-controlled, crossover study. Participants and the evaluating investigators except the technician that applied tDCS were blinded to the intervention type. The procedure consisted of three separate sessions, a recruitment session followed by two intervention sessions. At the beginning of the recruitment session, all aspects of the experiment were explained completely to each individual, and then, in the case of full consent for participation, each individual was asked to sign the consent form. Basic demographic information, drug abuse and treatment history, and high risk behaviours of each subject were recorded during a structured interview by an expert drug counsellor. The next two intervention sessions consisted of an active and a sham stimulation session, the sequence of which was randomly chosen. All subjects were asked to abstain for cigarettes 1 h prior to intervention sessions to control for potential nicotine effect. At the beginning of the sessions, the subject was seated on a comfortable chair and was asked to complete the Persian version of Positive and Negative Affect Scale PANAS in order to control for his affective status before each session. Eventually, we assessed any possible side effects using a tDCS side-effect checklist at the end of the intervention sessions Fig. Intervention procedure. In both interventional sessions, the exact same procedure was followed, except for the type of the stimulation and task version. The sequence of stimulation and task type was randomized with permuted-block method. The same investigators carried out stimulation sessions, at the same time of the day and the same room. Duration of each trial was 24 s in which a visual cue an image accompanied by a computerized Visual Analog Scale cVAS were shown in a fixed and predefined order on the screen of a 14 in laptop and the subject was asked to rate his cue-induced craving on a scale of 0 to The total duration of the task was exactly 10 min, which contained twenty drug-related and five neutral cues Fig. Every subject completed five blocks of current task containing different stimuli from each cue group with the same sequence of the cues in each block. The task was completed in 10 min during which the craving elicited by each stimulus was rated 0— by the subject using a cVAS located under each image. This task was carried out in two equivalent versions with two different sets of images, CICT1 and CICT2 to avoid memory interference and training effects. Two versions were performed randomly for each subject during two intervention sessions, meaning that if CICT1 had been used in the first session, then CICT2 would be used in the second one and vice versa. The two series of images were counterbalanced for two equivalent versions based on their mean craving induction power, which was assessed in a previous study by Ekhtiari et al. Electrodes were standard carbonic, covered with a normal saline soaked sponge cases. Subjects were randomized to receive sham or anodal tDCS. During anodal tDCS, a 2 mA current was applied for 20 min. For the sham stimulation, the same montage was used, but the stimulator was turned off after gradually ramping up to 2 mA and down to 0 mA which took 1 min. The electrodes were on the scalp for the remaining 19 min and subjects were not informed that the device was turned off. Wash-out period between two sessions of intervention was at least 72 h to avoid any potential carry-over effects. Statistical analysis was performed by R v. Multiple comparison error was corrected by the Bonferroni method. Pearson's correlation coefficient was computed to test for bivariate correlation among potential confounder variables such as age, duration of abstinence, duration of addiction and marital status and explanatory variables. A total of 32 subjects initially entered the study, but two of them withdrew from the study. As this was a cross-over study, statistical analysis was performed on 30 subjects. Demographic and drug-related variables are summarized in Table 1. Baseline variables of age, duration of meth abstinence, duration of meth dependence, and marital status had no significant correlation with tDCS effect on craving. Also the results showed a marginal interaction effect of time and tDCS condition. Percent change in craving for real and sham tDCS are shown in Fig. A comparison between mean self-reported CICT score of each participant in sham vs. For further investigation paired t -test was used to compare variation of induced craving among four groups of stimuli which were presented in both sham and active conditions. Results showed that the drug cues and associated cues induced highest and lowest craving, respectively. Detailed results are presented in Table 2. It appears that some stimuli induced more craving than others; therefore pictures with a median rating of over 30 were grouped as more provocative. As illustrated in Fig. Induced craving ratings for real and sham tDCS with more provocative stimuli. All participants tolerated tDCS without any major complications. According to Fisher's exact test, other side effects including headache, vertigo, drowsiness, dizziness and nausea, were not significantly different between two conditions. The most common side effects were drowsiness, itching and tingling. All side effects were temporary and mostly from mild to moderate in intensity. The purpose of this study was to investigate the effects of anodal stimulation of right DLPFC on the immediate and online cue-induced meth craving. The results showed a clear state dependent effect of tDCS: while active tDCS in comparison with sham stimulation led to a larger decrease of self-reported craving at rest, active stimulation of the right DLPFC compared to sham stimulation induced larger craving ratings during cue exposure. The first important finding to discuss is the decrease of craving at rest after 10 min of anodal stimulation on the right DLPFC of abstinent subjects. This change was observed before exposure to meth-related cues. This result is therefore consistent with previous findings from studies using tDCS to modulate other types of craving. Fregni et al. Furthermore Boggio et al. Finally, this effect was also found for marijuana craving. Boggio et al. Although effects on craving are similar across these studies, mechanisms may not be necessarily the same, as these studies used some variations in the assessments and parameters of stimulation. In spite of no direct measurement of neurophysiological parameters such as cortical excitability, these tDCS studies had targeted the DLPFC area as a common location for stimulation. Furthermore, drug-dependent individuals exhibit lower resting and metabolic activity in the prefrontal cortex Botelho et al. The DLPFC integrates cognitive and motivationally relevant information about decision making, reward, motivation, and internal state and uses this information to regulate drug seeking and drug avoiding behaviours Goldstein and Volkow, ; Bechara, ; McBride et al. According to these findings, and considering mechanisms of anodal tDCS in facilitating spontaneous neuronal activity and reinforcing local plasticity, we conjecture that anodal stimulation enhances DLPFC activity, which may inhibit drug seeking behaviour. The second important finding of our study was the small increase in craving ratings during cue exposure under anodal stimulation compared to sham. To date, few studies have investigated effects of online tDCS on induced craving. In fact, our results are inconsistent with the previous study conducted by Goldman et al. The increased cue-induced craving observed in our study could be due to an increase in the effective processing of drug cue saliency through enhancement of sustained attention under anodal stimulation of DLPFC. Nelson et al. Here, one provocative speculation is that enhancing the processing of a drug-related cue without the reward associated with the drug may in fact decrease the conditioning effect of the drug and result in a late decrease in relapse. Such a hypothesis needs to be tested in future studies. Although we have shown that 10 min of anodal tDCS stimulation on the right DLPFC can acutely reduce the immediate meth craving, the results of this study do not imply necessarily that this type of stimulation can lead to clinical applications for meth abstinence. It should be noted that this reduced craving might be transient. Although it is possible that repeated stimulation could enhance and prolong the effect of tDCS on clinical applications, as shown previously Boggio et al. As there is no clinically approved pharmacologic intervention to reduce meth craving and abstinence, further clinical trials with daily repeated tDCS sessions should be explored. Furthermore, our study was focused on abstinent and treatment-seeking patients, who have different patterns of brain activity from active drug users who do not seek treatment. Therefore single session tDCS studies could target non-treatment seekers, gender effects and other cognitive processing involved in continued drug use, including lack of insight, attentional bias towards drug cues and impaired motor control or even craving self-reports with other possible electrode montages over PFC. Our findings showed that active prefrontal tDCS reduces craving at rest in the abstinent meth users while it may increase craving during cue exposure. This may reflect the role of the prefrontal cortex in both cue saliency evaluation and top-down craving modulation. These results offer preliminary promising data to support further studies investigating tDCS as a clinical application for craving control among meth-dependent subjects. The authors are grateful to the participants for committing the time to this study. Bechara A Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nat Neurosci 8 : — Google Scholar. Drug Alcohol Depend 92 : 55 — Neurosci Lett : 82 — Drug Alcohol Depend : — Neuropsychol Rehabil 21 : — Brain Stimul 5 : — Ann N Y Acad Sci : — Arch Gen Psychiatry 59 : — Biol Psychiatry 62 : — Am J Psychiatry : — Drug Alcohol Depend 86 : 91 — Pharmacol Biochem Behav 96 : — Neuropharmacol 64 : — J Clin Psychiatry 64 : — Ekhtiari H Alam-Mehrjerdi Z George S Mokri A Designing and evaluation of reliability and validity of visual cue-induced craving assessment task for methamphetamine smokers. Basic Clin Neurosci 1 : 33 — Pain : — J Clin Psychiatry 69 : 32 — Garavan H Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Arch Gen Psychiatry 58 : — Appetite 56 : — Goldstein R Volkow N Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Addict Behav 35 : — Neuroimage 57 : — Ann Phys Rehabil Med 55 : — Brain Stimul 1 : — Biol Psychiatry 73 : — Neuropsychopharmacol 31 : — Brain Stimul 4 : 38 — Neuropsychopharmacol 29 : — Int J Alzheimers Dis : 1 — 5. Neuroimage 85 Pt 3 : — Exp Neurol : 14 — Neuroimage 85 : — Neuropsychopharmacol 26 : 53 — Drug Alcohol Depend 93 : 93 — Trends Neurosci 34 : — Biol Psychiatry 65 : — Drug Alcohol Depend 96 : — New York. Google Preview. Schizophr Res : — Wickham H ggplot2: elegant graphics for data analysis , 1 st edn. New York : Springer. Nat Neurosci 7 : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign in through your institution. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Methods and materials. Statement of Interest. Journal Article. State dependent effect of transcranial direct current stimulation tDCS on methamphetamine craving. Alireza Shahbabaie , Alireza Shahbabaie. Oxford Academic. Mehrshad Golesorkhi. Behnam Zamanian. Mitra Ebrahimpoor. Fatemeh Keshvari. Vahid Nejati. Felipe Fregni. Hamed Ekhtiari. Address for correspondence: Dr H. Revision received:. Select Format Select format. Permissions Icon Permissions. Abstract Transcranial direct current stimulation tDCS has been shown to modulate subjective craving ratings in drug dependents by modification of cortical excitability in dorsolateral prefrontal cortex DLPFC. Addiction , cue-induced craving , methamphetamine , non-invasive brain stimulation , transcranial direct current stimulation. Open in new tab Download slide. Table 1 Open in new tab. Demographic and substance abuse characteristics. Descriptive statistics. Table 2 Open in new tab. T p -value. Drug Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Google Scholar Crossref. Search ADS. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Cumulative priming effects of cortical stimulation on smoking cue-induced craving. Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease. Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. Examining transcranial direct-current stimulation tDCS as a treatment for hallucinations in schizophrenia. One session of high frequency repetitive transcranial magnetic stimulation rTMS to the right prefrontal cortex transiently reduces cocaine craving. Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging. High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking. Designing and evaluation of reliability and validity of visual cue-induced craving assessment task for methamphetamine smokers. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Prefrontal cortex transcranial direct current stimulation tDCS temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Amplitude low-frequency oscillation abnormalities in the heroin users: a resting state fMRI study. Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: a review. The use of repetitive transcranial magnetic stimulation rTMS and transcranial direct current stimulation tDCS to relieve pain. Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study. Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study. Reducing procedural pain and discomfort associated with transcranial direct current stimulation. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Effect of transcranial brain stimulation for the treatment of Alzheimer disease: a review. Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation tDCS. Treatment of depression with transcranial direct current stimulation tDCS : a review. Behavioural and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects. Differences in cortical activity between methamphetamine-dependent and healthy individuals performing a facial affect matching task. Impaired prefrontal cortical function and disrupted adaptive cognitive control in methamphetamine abusers: a functional magnetic resonance imaging study. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. United Nations Office on Drugs and Crime. Transcranial direct current stimulation influences probabilistic association learning in schizophrenia. Neurocognitive deficits are associated with unemployment in chronic methamphetamine users. Issue Section:. Download all slides. Views 4, More metrics information. Total Views 4, Email alerts Article activity alert. Advance article alerts. New issue alert. In progress issue alert. Receive exclusive offers and updates from Oxford Academic. Citing articles via Web of Science Working memory performance predicts, but does not reduce, cocaine- and cannabinoid-seeking in adult male rats. More from Oxford Academic. Science and Mathematics. Authoring Open access Purchasing Institutional account management Rights and permissions. Get help with access Accessibility Contact us Advertising Media enquiries.

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Official websites use. Share sensitive information only on official, secure websites. Injection drug use has been increasing over the past decade in Iran. This study aims to review the epidemiological and qualitative evidence on factors that facilitate or protect against transition to injection in Iran. Two trained researchers screened documents to identify relevant studies and independently extracted data using a pre-specified protocol. A thematic analysis was applied to the qualitative data and a random effect meta-analysis model was used to determine age of first injection. The weighted mean age of first injection was Overall, drug users had used drugs for 6 to 7 years before starting to inject. Heroin was the first drug of injection in the majority of cases. Factors influencing transition to injection included 1 individual pleasure-seeking behavior and development of drug dependency , 2 social network role of peer drug users in first injection use , and 3 environmental the economic efficiency associated with injection and the wide availability of injectable form of drugs in the market. Harm reduction policies in Iran have almost exclusively focused on drug injectors. However, given the extent of non-injection drug use, evidence from this study can provide insight on points of interventions for preventing transition to injection use. Keywords: Substance use, harm reduction, risk factors for injecting, protective factors for injecting, first injection episode, systematic review, Iran. A report from estimated that 2. Smoking opium for medicinal and recreational purposes is deeply rooted in the Iranian culture and is considered less stigmatized than heroin use and drug injection. However, in the last decade, Iran has witnessed major changes in the pattern of substance use. In three national studies of drug use conducted between and , the proportion of those who use heroin or Kerack a crystallized form of heroin increased considerably Narenjiha et al. Also since , there has been an emerging epidemic of methamphetamine-based substance use although compared to opioids the overall figures are relatively low. In a recent systematic review of HIV among substance users, the prevalence rate was 4. However, until now, there has been little if any attention paid to preventing drug users from transitioning to injection drug use. This systematic review is the first of its kind, summarizing the existing evidence on factors that may influence transitions to or away from injection among substance users in Iran. We conducted a systematic review to identify studies in Iran reporting on the age of initiation of drug injection and the factors influencing transition. The review involved: 1 searching for scientific documents; 2 screening documents to identify relevant studies; 3 extracting data from included studies, and 4 synthesizing data. We have described these stages below. The search strategy involved: 1 comprehensive searching of electronic databases for published peer-reviewed articles, as well as other scientific documents grey literature ; 2 hand-searching of the reference section of relevant scientific documents; and 3 contacting experts in the field of substance use in Iran. An initial search of Medline — involved an iterative process to refine the search strategy through the testing of several search terms, incorporating new terms as relevant citations were identified. Multiple combinations of keywords and phrases were used to specify geographic location, population of interest e. We did not limit searches by language. For Iranian databases, we used both Farsi and English key terms. We also contacted other researchers in academic and governmental organizations. We imported all citations to an Endnote library. Since the automatic export of citations for Iranian databases was not available, we reviewed retrieved citations in Microsoft Word and manually entered relevant titles into Endnote. We hand-searched the reference section of relevant review studies or national program reports to identify studies containing primary data. Two of the co-authors reviewed retrieved scientific documents, applying pre-specified criteria to identify relevant studies through a step-wise process. Studies conducted on physiological, hormonal, and pathological changes related to drug use were excluded. Another co-author MA reviewed titles and abstracts of any papers which the initial screener was uncertain whether to include or not. A senior researcher ARM reviewed and adjudicated on studies where the reviewers had disagreed. No restriction was placed on study design, language, or publication year. Data were extracted on: 1 authors, year, type, and language of the publication; 2 study implementation year; 3 study design and setting; 4 study site i. In cases of ambiguity in the published data, we contacted authors for further clarification. If a document reported on more than one research project, each project was considered as an independent study and cited separately. For research projects reported in different forms i. Given that reported data on factors influencing the transition to injection use were sparse regarding geography, methods and context, we conducted formal quantitative meta-analysis only on the age of initiation of injection use. We calculated a summary mean and standard error for age of initiation, weighted by inverse of variance using a random-effect meta-analysis model in Stata version 13 and illustrated data in the form of forest plot. We applied principles of thematic analysis for qualitative data on the factors facilitating or protecting against injection drug use. We summarized these findings under thematic headings, aggregated them into categories, and presented them collectively in a table. Figure 1 presents the number of studies identified at each step of searching, screening, and data extraction. From a total of retrieved scientific documents after de-duplication , we identified and included 39 relevant scientific documents, reporting on a total of 31 original research studies; the co-authors were directly involved in 14 studies. Unpublished data from five studies were also used for data analysis. Table 1 presents characteristics of the 31 included studies. These were carried out between and , with more than half being conducted between and All studies, except for one longitudinal study Jafari, et al. Investigating the transition to injection drug use and correlated factors was not a main objective of most included studies so little data were available on this issue. The study utilized combination of methods. The method that provided information on transition to injection drug use is described in this table. From the 20 studies that reported on age at first injection AFI , we were able to retrieve the mean and standard error for 18 mean range: 24 to With respect to recruitment site, in two studies, there was no difference in mean AFI between PWID recruited from community, treatment centers, and prisons Narenjiha, et al. While one study reported no difference in mean AFI between those who had shared needles and syringes and those who had not Rafiey et al. Six studies reported on the length of time between the initiation of drug use and the transition to injection. Due to the heterogeneity of studies and reported outcomes, we did not calculate a summary mean for the length of time to transition. Four studies found that, on average, drug users were using drugs for six to seven years before their first injection Amin-Esmaeili, et al. Four studies reported on the proportion of PWID who had initiated drug use with injection Jafari, et al. From a total of PWID in three different cities, Seven studies provided information on the place or context of the first injection Haghdoost, Osouli, et al. Given the heterogeneity of terminologies used to describe place type, we did not calculate pooled frequencies. Other venues indicated as PFI included: public places e. Four studies reported data on the first drug of injection FDI. In the same year in the smaller city of Darab Jafari, et al. In , in Tehran, the majority of a small sample of PWID reported kerack as FDI, though a few participants had started with other drugs heroin, temgesic, and morphine Rahimi-Movaghar, et al. Sixteen studies reported on factors influencing the transition to drug injection Table 2. Social and individual factors were reported more frequently than familial factors. Two studies reported that in two-thirds of PWID participating in surveys, the first person to suggest using drug via injection was a friend Jafari, et al. The second most common social factor was the high price of drugs and economic efficiency 13 studies i. Another significant factor was the greater availability of injectable drugs e. In addition, given that injection drugs are odorless and smokeless, injections were considered a safer drug use route for indoor and populated places e. Social marginalization, manifested by unemployment, poverty, and homelessness, was also an important factor for the initiation of injection use 5 studies. Overall, six studies provided information about factors influencing the transition to injection in the context of prison, including the need for hiding drug use four studies , low availability and high price of drugs three studies , low availability of smoking paraphernalia inside prison one study , and presence of injecting prisoners one study. The most commonly reported factor at the individual level was pleasure-seeking behavior, particularly with substances that had a rapid effect 9 studies. This factor has not been reported for the initiation of injecting with temgesic mainly used as a self-medication for quitting other opioids, as mentioned in two studies and norjisak primarily used for weight gain and healthier look, as well as cessation of other opioid use, mentioned in one study. Development of drug dependence, seeking a less expensive method for controlling withdrawal, and reaching the same level of pleasure compared to when drug was ingested via non-injection route was also reported frequently in 7 studies and regarded as the most important factor in two studies Rahimi-Movaghar, et al. Curiosity was reported as a factor influencing the transition to injection use in 8 studies, though findings were not consistent on the importance of this factor Jafari, et al. Lack of knowledge and misconceptions about the consequences of injection e. With respect to familial factors, three studies found that having a family member e. Family intolerance of drug use was also reported as a factor resulting in the transition to injection use as it could be more easily hidden from family. With respect to gender, being the sexual partner of a male drug injector, being involved in sex work, and being homeless were reported as the main transition factors for female drug users Rahimi-Movaghar, et al. Only one qualitative study reported on protective factors Rahimi-Movaghar, et al. Being female, having knowledge about negative consequences of injection use, and having negative attitudes toward injections e. Other factors included: individual, e. Another study showed that using opioids is the main gateway to injection and those people who stay away from opiates are very likely to avoid injecting Vazirian, et al. To our knowledge this is the first comprehensive review of 31 Iranian studies on factors influencing the initiation of, or transition to, drug injection. The review showed that the mean age at first injection in Iran was around 26 years and the median in most studies was 25 years. In addition, no specific change was observed in the AFI in studies conducted between and The AFI reported from the 18 studies in Iran was higher than that reported in other countries. Some studies have reported a lower average age of initiation, such as 17 years in Moldova Rhodes et al. Many studies have shown that early-onset injection use is associated with homelessness Abelson, et al. Most studies in our review reported an average of 6 to 7 years of drug use before injecting. Although some time lag is common in many parts of the world Abelson, et al. For Iranian drug users who generally start injecting as adults, the long interim period is an opportune time for preventing the transition to injection use. Our review also showed that, up to 10 years ago, heroin was the FDI for almost all cases. Since , other drugs such as norjisak and temgesic, followed by kerack of heroin, have appeared as the first drugs of injection. No document in this review reported the initiation of drug injection by stimulants or cocaine. Heroin smoking and opium smoking were the predominant patterns of drug use before first injection. This finding suggests that among opioid users, growing tolerance and the high costs of large amounts of heroin - which has been reported frequently in the reviewed studies - may have played a major role in the initiation of injection drug use. Vazirian, et al showed that few non-opioid users had ever injected drugs. Accordingly, avoiding opiate use is a likely preventative strategy against injecting in Iran. In Iraq and Pakistan, prescription drugs such as antihistamines and opioid analgesics are the primary injected drugs Rahimi-Movaghar, et al. In the available studies from other parts of the world, cocaine was reported to be the drug of choice for initiating injection use, followed by amphetamines in Brazil Oliveira et al. Many have used these drugs by non-injection route before their first injection, thus indicating that high levels of dependence facilitate injection use Harocopos, et al. Generally, heroin is the drug with high liability for injection use. In areas with higher rates of heroin use among non-injecting drug users, such as Iran and other countries in Middle and South Asia, one might expect a higher rate of transition to injection use than in areas with higher use of stimulants Cheng, et al. However, this review also showed that an average of This finding is similar to findings from Australia Abelson, et al. The role of peer drug users was the most frequently reported influential factor in the studies included in this review. Other studies have identified social network factors as important determinants in the transition to injecting. In Northern India, the vast majority of first injections were witnessed by at least one friend and the injection was usually administered by someone who was well-known to the injected Kermode, et al. In a multi-city study in Australia, early-onset injection was associated with group presence at the first injection and cases in which the first injection was administered by someone else Abelson, et al. We also found pleasure and curiosity as the most common individual factor reported in the studies from Iran. A belief that injection administration increases the effect of the drug and curiosity to experience this effect increase the likelihood of injection Roy, Godin, et al. Injecting peers usually evoke curiosity by highlighting the potency of injected drugs. Prison was a common first place of injection in the latest study. Incarceration was described as a context which facilitated the transition to injecting because of low availability, poor quality, and high cost of drugs, as well as the normalization of injecting as the main form of drug use in prison. This finding is in line with results from studies conducted in other developing countries Cheng, et al. However, expansion of harm reduction interventions, including opioid substitution treatment inside prisons, can prevent such transition. Female gender has been reported as a protective factor against injection drug use. This might be because of cultural factors, like a very high stigma attached to female injection drug use, or because of a higher level of fear of injection and its consequences in the female population Rahimi-Movaghar, et al. In two studies, having a family member or a sexual partner who injects drugs was reported as the main factor influencing the initiation of injection use in women. Gender differences on this issue have been documented in other countries. Studies have repeatedly reported that women had been injected first by a male friend, sexual partner, or relative Bravo et al. Since Iran has adopted large-scale harm reduction policies i. Although MMT is the most essential preventive measure against drug use injection Bridge, , lessons learned from other settings e. For instance, addressing individual susceptibility, by educating non-injecting drug users to control their substance use Roy, Godin, et al. This finding suggests that family-based strategies for the prevention of injection drug use should be explored. Further high quality research i. Although 31 studies provided some evidence regarding the initiation of injection drug use, only a few studies had assessed the influential factors extensively and only one study provided longitudinal data. We were unable to identify any study addressing drug transitions among street youth in Iran, nor about the role of alcohol in initiation to injection. A thorough assessment of interactions between individual and social network factors on the transition to injecting drug use may provide further insight on intervention points. Also, greater assessment of protective factors against transition to injection, especially among those not enrolled in MMT programs, is essential. Most studies in the review reported an average of 6 to 7 years of drug use before starting to use injections. The long interim period is an opportune time for preventing mechanisms of the transition to injection use in Iran. An average of The funding source had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; and in the decision to submit the article for publication. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Afarin Rahimi-Movaghar, Email: rahimia tums. Masoumeh Amin-Esmaeili, Email: dr. Behrang Shadloo, Email: behrang. Mohsen Malekinejad, Email: MMalekinejad ucsf. As a library, NLM provides access to scientific literature. Int J Drug Policy. Published in final edited form as: Int J Drug Policy. Find articles by Afarin Rahimi-Movaghar. Find articles by Masoumeh Amin-Esmaeili. Find articles by Behrang Shadloo. Find articles by Mohsen Malekinejad. Issue date Sep. PMC Copyright notice. The publisher's version of this article is available at Int J Drug Policy. Open in a new tab. Characteristics of 31 studies on transition to injecting drug use conducted in Iran. Factors facilitating transition to injection reported in 16 studies, in Iran. Factors No. 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. Rahimi-Movaghar, et al. Haghdoost, Osouli, et al. Jamali, First drug of injection, factors of initiation. Samimi-Rad, et al. Shoghli et al. Zamani, Radfar, et al. Dolan et al. Afsar Kazerooni et al. Narenjiha, et al. Saberi- Zafarghandi, et al. Amin-Esmaeili, et al. Malekinejad, Zamani, Jafari, et al. Kheirandish et al. Razani, et al. Interviews: Median: Zamani, Farnia, et al. Mohammad, et al. Farhoudian, et al. Vazirian, et al. Rahimi-Movaghar et al. Rahimi-Movaghar, ; Rahimi-Movaghar, et al. Duration of DU before first injection, factors of initiation. Seeking pleasure and rapid induction of high via injection. Severity of addiction and development of tolerance. Preference for easier and quicker mode of drug administration. Lack of knowledge and misconceptions about harms of injection. Good socio-economic status and having private place for injection. Social and environmental factors. High cost of drugs and lower cost of injection. Social disadvantages e. Low availability of the drug, mainly in prison.

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