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Official websites use. Share sensitive information only on official, secure websites. Reviewed by: Timothy J. Specialty section: This article was submitted to Motivation and Reward, a section of the journal Frontiers in Behavioral Neuroscience. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Retrieval-extinction memory reactivation procedures have been used to prevent the return of learned fear and drug seeking in preclinical models. These procedures first reactivate the original memory with a brief cue exposure i. The original memory is thought to be updated with the new information conveyed by extinction learning, resulting in a persistent therapeutic effect beyond that observed with extinction training alone i. Here, we attempted to replicate the therapeutic effects on cocaine seeking reported by Xue et al. Rats self-administered either cocaine or nicotine with contingent cues for weeks, and were then divided into two groups. The retrieval group underwent a min retrieval session wherein drug cues were available, but drug was not. Ten minutes later, they were allowed to continue cue extinction training for an additional 60 min. The no retrieval group underwent a contiguous min cue extinction session. These procedures continued for weeks, followed by a test for spontaneous recovery of drug seeking. No group differences were observed on any measure of cocaine seeking, although both groups exhibited extinction and spontaneous recovery. By contrast, for nicotine seeking, the retrieval group exhibited resistance to extinction, an effect that persisted on the spontaneous recovery test. These findings underscore the importance of drug type in the outcome of retrieval-extinction procedures and moreover indicate that retrieval-extinction procedures can be detrimental to nicotine seeking. Keywords: retrieval-extinction, reconsolidation, spontaneous recovery, nicotine, cocaine, self-administration. Cue exposure therapy has been used clinically in the treatment of both pathological fear and substance use disorders Kaplan et al. Unfortunately, extinction therapy has not been very effective on its own, especially for addiction treatment Niaura et al. An alternative approach is to attempt to weaken or erase the original memory associated with conditioned drug cues through a process of reconsolidation blockade Taylor et al. Reconsolidation is the process whereby memories enter into a labile state upon retrieval, typically by presentation of reminder cues Schwabe et al. Once the memory enters this labile state, it is subject to disruption by pharmacological agents such as protein synthesis inhibitors Nader et al. If the memory is disrupted during this sensitive period, it can be permanently weakened, even erased, along with the pathological behavioral response that is the goal of treatment Soeter and Kindt, Unfortunately, protein synthesis inhibitors like anisomycin and related pharmacological tools for reconsolidation blockade cannot be administered systemically in humans due to toxicity, although some success has been demonstrated with the beta adrenergic receptor antagonist propranolol in both fear as well as cocaine and nicotine addiction disorders Soeter and Kindt, ; Otis and Mueller, ; Saladin et al. Circumventing the need for such pharmacological approaches, Monfils et al. Monfils et al. Since this original report, many others have observed similar therapeutic effects of such retrieval-extinction memory reactivation procedures on fear, including translational work in humans Quirk et al. Corroborating and conflicting reports have been reported for aversive and appetitive behaviors, in both preclinical and clinical settings Flavell et al. In a seminal article by Xue et al. Addiction, unlike fear, develops gradually over a prolonged period of drug exposure. Similarly, extinction learning typically requires repetitive training to extinguish the drug-seeking response. Thus, Xue et al. In cocaine-seeking animals, these procedures successfully facilitated the rate of extinction and reduced cocaine-primed reinstatement, renewal, and spontaneous recovery after a day abstinence period. They also demonstrated that the therapeutic effect on drug-primed reinstatement extended to heroin-seeking animals, and were able to further extend their findings to human heroin users, using a similar min interval between retrieval and extinction of visual heroin cues in a clinical setting Xue et al. Given the striking efficacy of these retrieval-extinction procedures across drug classes and from preclinical to clinical paradigms, we designed experiments with two goals: 1 to replicate these findings in cocaine-seeking animals; and 2 to extend these findings to nicotine-seeking animals. Nicotine conditioned cues are unique in that they are necessary and sufficient to sustain nicotine-seeking, even in the absence of nicotine Caggiula et al. Nonetheless, cue-maintained responding of nicotine-seeking can be extinguished and reduces withdrawal-related incubation of craving in preclinical abstinence models Markou et al. Thus, retrieval-extinction procedures could be especially beneficial for reducing relapse associated with exposure to nicotine cues. Preliminary success has been reported using retrieval-extinction procedures to reduce nicotine seeking in a preclinical model in rats Auber et al. Food and water was available ad libitum in the home cage. All experimental procedures were performed during the dark phase of the cycle. Animals were initially kept in pairs but were housed individually following surgery in Makrolon type III cages. Intravenous catheter surgeries were performed to allow drug self-administration. Catheters were assembled from a cannula connector pedestal Plastics One Inc. Following arrival, rats were habituated to the animal facility for 1 week. The surgical procedure was executed as reported previously De Vries et al. Catheter tubing was tunneled from the scalp to an incision above the clavicle, where the catheter was inserted in the jugular vein and fixed in place using sterile sutures. A combination of 0. Both cocaine and nicotine solutions were sterilized through a 0. Animals were then placed in their home cage for 34 days of abstinence, followed by a spontaneous recovery test session 60 min. Rats were allowed to self-administer either cocaine or nicotine inside plexiglass operant chambers housed within sound-attenuating cubicles. These operant chambers contained a fan for ventilation, two nose-poke holes, a red house light, a tone generator, a liquid swivel arm with polyethylene tubing protected by a metal spring and an infusion pump. Responding in the active nose-poke hole resulted in a drug infusion and presentation of a s cue consisting of yellow light inside the nose-poke hole and a 3. For 15 s following a nose-poke in the active hole, responding in either the active or inactive nose-poke hole was without consequence i. Responding in the inactive nose-poke hole had no effect, but was recorded. Animals were first trained to self-administer nicotine or cocaine on a FR1 schedule for 10 daily sessions, followed by three sessions on an FR2 and three sessions on an FR4, for a total of 16 nicotine or cocaine self-administration sessions each 60 min. To reduce cocaine overdose, the maximum number of rewards was set to 60 during the first six cocaine self-administration sessions. Catheter patency was maintained through a daily regimen of flushing catheters with a 0. At the end of the self-administration phase, catheter patency was tested by infusing 0. Two rats were excluded from the cocaine experiment due to failed catheter patency, and one animal was excluded due to cocaine overdose. Twenty-four hours following the final self-administration session, cocaine or nicotine rats were assigned to extinction vs. During these sessions, the house light was turned on; cocaine or nicotine was unavailable, but response-contingent drug-conditioned cues were presented on an FR4 schedule of reinforcement. On each training day, the retrieval-extinction group was first placed in the operant chamber for a retrieval session of 10 min Ret , then returned to their respective home cages for 10 min Home. Afterward, rats were returned to the operant chamber for an additional 60 min of extinction training Ext , which concluded the total daily training duration of 70 min. The extinction group was simply placed in the operant chamber for a contiguous 70 min training session without retrieval No Ret. The first and second training days always occurred consecutively i. Following 16 training sessions, animals remained in their home cage for 34 days of abstinence. Following 34 days of home-cage abstinence, animals were returned to the operant chamber for a test of spontaneous recovery. This test was performed under extinction conditions response-contingent drug cues presented on an FR4 schedule, drug unavailable and lasted 60 min. Behavioral data were analyzed using two-way repeated measures ANOVAs with experimental group as a between-subject factor and both session and nose poke as a within-subject factor. Other than drug type, self-administration protocols for nicotine- vs. An increasing FR protocol was used to enhance rates of drug seeking and to verify successful acquisition of drug self-administration. Main effects of session were observed for both nicotine Figure 1A and cocaine Figure 1B ; nicotine: F 4. Whereas active nose pokes increased over sessions, inactive pokes decreased, indicating successful acquisition of drug seeking for both reinforcers. No group differences were detected, indicating that animals were appropriately balanced upon assignment to retrieval vs. Self-administration of nicotine vs. Nicotine A and cocaine B self-administration was conducted in daily sessions over weeks on an increasing FR schedule. Total active circles and inactive triangles lever presses on each daily session are depicted. After acquisition of drug self-administration, animals were assigned to experimental groups. The retrieval group underwent the first 10 min of extinction, then returned to the home cage for 10 min, and then completed the last 60 min of extinction. The no retrieval group underwent a contiguous 70 min extinction session. Main effects of session were observed for both nicotine Figure 2A and cocaine Figure 2B during the first 10 min of retrieval or no retrieval nicotine: F 5. No group differences were detected. Drug seeking during the first 10 min of retrieval or no retrieval. Nicotine A and cocaine B seeking during retrieval vs. Total active circles and inactive triangles lever presses during the first 10 min of each daily retrieval-extinction session are depicted. Analyses conducted over the last 60 min of extinction similarly revealed main effects of session for both nicotine Figure 3A and cocaine Figure 3B ; nicotine: F 4. To determine whether groups showed equivalent extinction over days, one-way repeated measures ANOVAs were conducted on active nose pokes. Drug seeking during the last 60 min of extinction. Nicotine A and cocaine B seeking during extinction. Total active circles and inactive triangles lever presses during the last 60 min of each daily extinction session are depicted. Both nicotine and cocaine-seeking animals exhibited extinction over days, but only nicotine-seeking animals showed a main effect of group. To assess the effects of the retrieval-extinction procedure on spontaneous recovery of drug seeking, the last 60 min of extinction training on the last extinction session was compared to responding after 34 days of abstinence during the spontaneous recovery test also 60 min. No group differences were observed for cocaine. Thus, the retrieval-extinction procedure promoted nicotine seeking during both extinction and spontaneous recovery, but did not alter cocaine seeking. Spontaneous recovery of drug seeking after abstinence. Nicotine A and cocaine B seeking at the end of extinction Ext training vs. Total active circles and inactive triangles lever presses during the last 60 min of Ext is depicted, next to responding on the 60 min Test. Both cocaine- and nicotine-seeking animals exhibited spontaneous recovery. This study revealed a heretofore unreported and paradoxical detrimental effect of retrieval-extinction memory reactivation procedures on extinction of nicotine seeking, concomitant with enhanced spontaneous recovery of nicotine seeking. To our knowledge, this is the first report of detrimental effects using a standard retrieval-extinction procedure on any conditioned behavior. Others have reported null effects of the retrieval-extinction procedure Chan et al. Ma et al. Millan et al. The latter study underscores the possibility that similar behavioral manipulations can be both therapeutic and detrimental, depending on the outcome measure. In addition, spontaneous recovery is a commonly used outcome measure for the efficacy of retrieval-extinction procedures Monfils et al. In this study, we compared behavioral effects of retrieval-extinction procedures using two different reinforcers, nicotine and cocaine. Despite their different pharmacological mechanisms of action, both drugs result in an accumulation of dopamine in the nucleus accumbens during drug exposure, which is thought to underlie their rewarding and reinforcing effects Balfour et al. Dopamine is also important for encoding drug-conditioned cue associations, and over time with repeated drug use, these cues acquire incentive salience and the ability to promote, or sustain, drug seeking even under extinction conditions i. Drug-conditioned cues are essential for memory reactivation during retrieval, and the ability of memory reactivation to trigger reconsolidation is thought to be a critical determinant of retrieval-extinction therapeutic efficacy Auber et al. That is, the reconsolidation process must be initiated during retrieval in order for memory-updating to occur during the subsequent extinction phase Monfils et al. The duration of retrieval session 10 min in the present study was comparable to other studies that have demonstrated therapeutic success with retrieval-extinction procedures Flavell et al. Nonetheless, it is possible that we failed to trigger reconsolidation with our protocol. Given that the ability to induce reconsolidation is inversely related to the strength of the memory trace Eisenberg et al. Because retrieval-extinction produced an effect, albeit a detrimental one, in nicotine rats, another explanation is that reconsolidation was effectively triggered, and extinction training paradoxically strengthened the retrieved cue memory. In line with the latter interpretation, retrieval impaired extinction of nicotine seeking. This extinction impairment must be attributed to the retrieval-extinction procedure since extinction success was observed in the contiguous extinction group. Thus, retrieval-extinction induces extinction failure in nicotine rats under these conditions. Why might this occur? There are some notable distinctions in nicotine-conditioned cues that are worth considering. Whereas nicotine alone is a relatively weak reinforcer, it is very effective at enhancing the incentive salience, and reinforcing properties, of cues paired with nicotine Chaudhri et al. In rats that acquire nicotine self-administration paired with conditioned cues similar to the ones used in the present study, cessation of the nicotine conditioned-cue availability leads to faster extinction than cessation of nicotine availability Caggiula et al. Furthermore, acquisition of nicotine self-administration is impaired if such nicotine conditioned cues are never available Caggiula et al. The aforementioned findings have led some to propose that nicotine-seeking behavior is primarily maintained not by nicotine itself but by its ability to enhance the reinforcing properties of both pharmacological and non-pharmacological i. This hypothesis is supported by observations that rats will respond more for cues in the presence of nicotine, even when the cues and nicotine are self-administered on separate levers Palmatier et al. Cocaine, by contrast, is a much more powerful primary reinforcer Risner and Goldberg, , and rats will readily acquire cocaine self-administration in the absence of cocaine-associated cues Fuchs et al. The relative importance of the drug-conditioned cues vs. We observed enhanced spontaneous recovery and impaired extinction after retrieval-extinction procedures in nicotine, but not cocaine rats. It is important to note, however, that the increase in spontaneous recovery may be attributed, at least in part, to the extinction failure induced by retrieval-extinction in nicotine rats. Because we were unable to fully extinguish nicotine seeking after retrieval-extinction, the two experimental groups Ret vs. No Ret were tested for spontaneous recovery despite their pre-existing difference in extinction baseline. Additional experiments are necessary to determine whether the Ret group would eventually extinguish nicotine seeking to levels achieved in the No Ret group and if spontaneous recovery would remain elevated in the Ret group under such circumstances. Furthermore, additional studies should extend these findings to other measures of nicotine seeking, such as renewal, reinstatement e. The lack of effect of retrieval-extinction procedures on cocaine seeking differs from that reported by Xue et al. Retrieval-extinction enhanced the rate of extinction of cocaine seeking, although the magnitude of this effect differed across three independent experiments. In each experiment, however, retrieval-extinction procedures attenuated the reinstatement, renewal, or spontaneous recovery of cocaine seeking. This was in contrast to the complete blockade of cocaine conditioned place preference, which relies on purely Pavlovian drug-cue associations. Indeed, there is some evidence that operant, response-outcome memories may be less prone to undergo reconsolidation Hernandez and Kelley, However, even well-trained instrumental behaviors have been shown to undergo reconsolidation Exton-McGuinness et al. It is also worth noting that the unconditioned stimulus, nicotine or cocaine itself, can be an effective trigger for reconsolidation Xue et al. Other potential differences that could account for the apparent discrepancy between this study and Xue et al. Clearly, more work is needed to fully understand the boundary conditions limiting the efficacy of retrieval-extinction procedures. Though the retrieval-extinction procedures used in the present study induced unexpected increases in nicotine seeking, some positive outcomes have been reported using other retrieval-extinction procedures in rats Auber et al. In contrast with the present study, which used response-contingent nicotine cues during retrieval in the same context where nicotine was taken, both of the aforementioned studies used non-contingent i. Interestingly, Xue et al. Germeroth et al. However, retrieval-extinction did not alter physiological responses to nicotine cues, relapse, or days abstinent Germeroth et al. Thus, certain components of the nicotine memory may be more receptive to retrieval-extinction therapy than others, and the method in which retrieval is triggered may be an important variable. While it may be possible to weaken some aspects of the nicotine memory, our data suggest it is also possible to strengthen nicotine seeking with retrieval-extinction under certain conditions. These findings add to a growing literature indicating highly variable effects of retrieval-extinction procedures across both preclinical and clinical models Auber et al. Future work should continue with a careful examination of the boundary conditions determining the outcome of these memory reactivation procedures, which were originally identified as therapeutic Monfils et al. We hypothesize that the detrimental effects of retrieval-extinction procedures on nicotine seeking may be due to the fact that nicotine-associated cues are so essential to the reinforcing properties of nicotine, perhaps even more than nicotine itself Caggiula et al. Given the high rates of smoking and vaping nicotine amongst people who abuse psychostimulants and other substances Tzilos et al. RS, JP, and TV designed the experiments, interpreted the data, contributed intellectually to the project, edited and finalized the manuscript. RS and JP drafted the manuscript. RS acquired and analyzed the data. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 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. Front Behav Neurosci. Find articles by Roeland F Struik. Find articles by Taco J De Vries. Find articles by Jamie Peters. Received Jul 16; Accepted Sep 27; Collection date Open in a new tab. 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.

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How can I buy cocaine online in Zootermeer

These datasets underpin the analysis presented in the agency's work. Most data may be viewed interactively on screen and downloaded in Excel format. All countries. Topics A-Z. The content in this section is aimed at anyone involved in planning, implementing or making decisions about health and social responses. Best practice. We have developed a systemic approach that brings together the human networks, processes and scientific tools necessary for collecting, analysing and reporting on the many aspects of the European drugs phenomenon. Explore our wide range of publications, videos and infographics on the drugs problem and how Europe is responding to it. All publications. More events. More news. We are your source of drug-related expertise in Europe. We prepare and share independent, scientifically validated knowledge, alerts and recommendations. About the EUDA. Key findings and threat assessment. Global context. Trafficking and supply. Criminal networks. Prices, purities and offences. Retail markets. Actions to address current threats and increase preparedness. Heroin is obtained from morphine, an alkaloid that occurs naturally in opium. The process by which morphine and heroin are produced from opium harvested from poppies comprises six main steps see Figure Overview of heroin production :. Morphine, and therefore heroin, may also be produced by a synthetic route without the use of opium. Although these approaches have garnered much academic interest over the years, they are unlikely to be used for illicit heroin production, given the comparatively low yields and the large number of steps required Zerell, This was the sixth consecutive year in which production in the country exceeded 6 tonnes UNODC, , a. These figures represent opium cultivation in Afghanistan in the first cultivation season following the Taliban takeover in August 1 and the announced ban shortly before the opium harvest began on poppy cultivation and other drugs in April see Section Key developments in the opiate trade in Afghanistan. The source data for this graphic is available in the source table on this page. The European heroin market is closely bound to the fate of the Afghan opium market as it is almost exclusively supplied with heroin from Afghanistan, via Turkish, Iranian and Pakistani organised crime networks see Section Criminal networks operating in the heroin market. With widespread socioeconomic insecurity, it has become apparent that the production of opiates, a major illicit economic activity in Afghanistan, could be subject to significant change. In April , the Taliban announced a ban on opium poppy cultivation, raising the question of the implications this will have for Europe. Data for shows that the prices of opium have continued to rise to an average of USD per kilogram, nearly five times greater than the average price two years prior to the Taliban takeover UNODC, c. The reduction in the area under opium cultivation includes an estimated reduction of cultivation in Helmand, the main poppy cultivating province in Afghanistan, from more than hectares in to less than 1 hectares in Mansfield, The significant drop in , if sustained beyond , would have major implications for the European drug market, highlighting the importance of intensifying monitoring of opium cultivation in Afghanistan see Box Challenges and opportunities in estimating opium poppy cultivation in Afghanistan. The long-term impact of the ban on opium cultivation is difficult to predict for a number of reasons. Importantly, the Taliban is deeply fragmented, likened to a loose conglomerate of members chasing frequently conflicting agendas and positions for power Sharifi, As such, it is unclear whether and how they will continue to enforce the ban, particularly in the context of frozen international aid programmes and the economic hardship faced by farmers in the country, which may make sustaining the ban politically difficult domestically. How the European heroin market will be affected by the new political situation in Afghanistan is uncertain. The existence of stocks held by individuals along the opiate production chain in Afghanistan and the trafficking chain to Europe, and that it takes at least 12 months before the opium harvest appears on the European retail market as heroin, makes it too early to predict the impact on drug availability in Europe. At the moment there are no signals of heroin shortages on the European market. If opiate production continues at the present low level, the market may take time to adapt and alternative supply sources may not be immediately accessible. It should be noted, however, that criminal networks are highly flexible. Experience with previous periods of reduced supply suggests that this can lead to changes in patterns of drug trafficking and use. For instance, there are historical examples of shortages in heroin supply to the European market where the use of fentanyl increased to fill the gap Caulkins et al. In this context, the potential consequences of sustained disruption of the supply of heroin to Europe would be increased rates of polysubstance use among heroin users or an increase in the European market for synthetic opioids, including fentanyl and its derivatives, new synthetic opioids and prescription opioid medicines. While it is possible to estimate the global production of heroin, a number of limitations and data gaps mean that it is difficult to provide accurate estimates. It is also difficult to determine the exact locations where the drug is produced. Opium production can be more accurately quantified and located because poppies are grown in specific geographic regions and can be identified through satellite imagery coupled with knowledge of average opium yield per hectare. The average opium yield can, in turn, be used to estimate potential heroin production. While the estimates show the potential amount of heroin that could have been manufactured from the opium produced each year, a number of factors and information gaps may have a significant impact on these estimates. Historically, Afghanistan is the country that has reported the largest numbers of dismantled heroin production facilities, indicating that large quantities of opium are processed into heroin in the country UNODC, a. It should be noted that Afghanistan ceased reporting on the dismantling of heroin production facilities in , when 41 facilities were seized. Following a period of declining morphine seizures starting in , Afghanistan seized 47 tonnes in , the largest quantity in the world, and seizures increased further to 63 tonnes in Large opium consumer markets exist in Iran and to some extent in Pakistan. However, the very large seizures of opium and morphine in these countries indicate that some of these products may be further processed into heroin there or further along the trafficking chain see Box Seizures of opium, morphine and heroin in Iran and Pakistan. Notably, in , Europol reported that both processing and production of heroin take place in Pakistan and Iran, in addition to Afghanistan Europol, a. However, the scale of production in these countries remains unknown, and neither country has reported dismantling heroin production facilities. Acetic anhydride is the main drug precursor used in the processing of morphine into heroin and is subject to international control in accordance with the UN Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. Acetic anhydride is, however, also used in a broad range of legitimate industries, and these have grown considerably since the precursor was placed under international control. This includes use for both industrial purposes and consumer goods such as plastics, dyes and medicines. Coupled with the fact that relatively small amounts of acetic anhydride are required for illicit heroin production, these issues make preventing its diversion for illicit heroin production a challenging task. Globally, almost 1. To put these global figures into context, according to UNODC estimates, the opium harvested in in Afghanistan would potentially require between and litres of acetic anhydride for conversion into between and tonnes of heroin. This represents roughly 0. Seizures of acetic anhydride reported to the International Narcotics Control Board INCB have been declining substantially since , a trend that continued in According to the INCB, possible reasons for this significant decrease might include a decline in the number of diversion attempts and in the subsequent trafficking of the substance, compared with the peak period of to ; the emergence of trafficking in acetyl chloride, a potential substitute for acetic anhydride that is not yet under international control see Box Acetyl chloride seizures ; and a shift to alternative trafficking routes INCB, a, Global seizures of acetic anhydride between and averaged litres per year or approximately tonnes whereas the amount seized globally in the years to averaged litres per year, or approximately tonnes. In , 58 litres or approximately 62 tonnes was seized worldwide. At European level, this was a slight increase from the previous year, when 5 litres was seized, but a significant drop from , when five European countries reported a total of over 20 litres seized, in addition to 7 litres from stopped shipments in three countries see Figures Acetic anhydride: quantity seized and quantity in stopped shipments, EU, and Acetic anhydride: number of seizures and number of stopped shipments, EU, In the Netherlands, the 5 litres seized across two incidents in represented a sixfold increase from the litres seized in In one of these cases, 2 litres of acetic anhydride was seized in a warehouse together with litres of glacial acetic acid, 60 kilograms of sodium carbonate and a large quantity of heroin. The circumstances of this case pointed to the illicit manufacture of heroin in the country. Overall in , 10 sites believed to be associated with illicit heroin manufacture were identified and dismantled in the Netherlands. In recent years, illicit heroin laboratories have also been identified in other EU Member States see Section Opiate production in Europe: a relativtely rare occurence. Source: EU drug precursors database. Information available to Europol suggests that criminal networks active in the Netherlands orchestrate the acquisition and smuggling of acetic anhydride from the EU to heroin producing countries. Criminal networks take advantage of the lack of strict controls on consignments leaving the EU to smuggle acetic anhydride. In addition, limited resources and capabilities to thoroughly check cargo in transit and receiving countries may encourage criminals to smuggle the precursor along particular routes. Despite the continued cultivation of opium poppies in Afghanistan, seizures of acetic anhydride in the country have significantly declined since their peak in , when 37 litres was seized. However, these decreasing amounts do not reflect a diminished need for the precursor in the illicit manufacture of heroin. This is further corroborated by seizures of large amounts of acetic anhydride elsewhere, including in Europe and West Asia, believed to be destined for Afghanistan. Seizures of acetic anhydride have also continued to be made in countries neighbouring Afghanistan, such as Iran and Pakistan, and in the UAE. In , Iran reported seizing a shipment of 13 litres of acetic anhydride, misdeclared as paint, in the seaport of Bandar Abbas. In , Pakistan reported three seizures of acetic anhydride amounting to 5 litres. The largest of these took place in the port of Karachi and involved 2 litres, allegedly originating from China INCB, b. Production of heroin is uncommon in Europe, although the final step of the production process — the acetylation of morphine into heroin — has been reported in Germany, the Netherlands and France. Most of the facilities associated with illicit heroin production reported in the EU between and were sites for processing, i. At cutting and packaging facilities, heroin is adulterated to increase the volume of the drug and packaged for onward distribution. For example, Dutch criminal groups appear to specialise in the preparation of heroin cutting mixtures for these types of facilities typically using caffeine and paracetamol see Section Heroin adulteration and Box Dutch criminal networks specialise in heroin cutting mixtures. Importantly, a facility associated with heroin production may be involved in several of these activities simultaneously see Table Facilities associated with heroin production in Europe. At least 15 sites associated with illicit heroin production were dismantled in the EU between and Ten of those sites were dismantled in the Netherlands in , clustered around Alkmaar, The Hague and Rotterdam, with confirmed heroin production at three of the sites. Preliminary data related to two laboratories dismantled in The Hague region indicate that heroin production or processing continued in the Netherlands in Politie, While there is limited information about the heroin production facilities identified in the EU, including their production capacities and the source of the morphine used in the process, the evidence indicates that heroin production in the EU persists, albeit at a low level, and is made possible by the ease with which acetic anhydride can be diverted from legitimate suppliers in Europe. Heroin production or processing has also been noted in countries bordering the EU. In , Kosovo 2 reported dismantling two facilities set up for the processing and packaging of heroin. Seizures of morphine, possibly intended for processing into heroin, have also been noted in several EU countries. In , Spain reported the seizure of 3. In addition, seizures of opium have been noted in several EU countries. In , Bulgaria reported seizing 27 kilograms of opium, while Spain and Sweden reported seizing The opium available in Europe could be used for heroin production or by individual consumers where demand exists. In addition to the production of heroin from imported morphine or opium, since Czechia has reported dismantling three small-scale heroin production facilities that were using poppy straw or morphine extracted from medicines. The illicit production of all plant-based and synthetic drugs entails a range of environmental harms. With regard to heroin, most of the environmental impacts and harms relate to the cultivation of opium poppies that takes place outside the EU. Field preparation requires agricultural inputs, including pesticides and irrigation, leading to energy and land use, to water, soil and air pollution, and to emissions of biogenic volatile organic compounds UNODC, a. The dumping of waste materials from production threatens fragile ecosystems, and the extensive cultivation of these crops leads to a range of environmental harms, including soil erosion. Specifically, in Afghanistan, the use of pesticides and of solar- or fuel-powered irrigation methods has led to soil depletion and reduced groundwater levels Mansfield, In the EU, the identification of laboratories associated with heroin production, albeit in small numbers, indicates more direct damage pathways in terms of the dumping of toxic waste. From to , at least 15 sites associated with the production of heroin were identified and dismantled see Section Opiate production in Europe: a relatively rare occurrence. While the number of reported dumping sites related to heroin production is low compared to the number of dumping sites related to synthetic drug production, the use of precursors, water and electricity may cause direct harms to the environment in the EU. The market for synthetic opioids has been growing in Europe, and it appears that most illegally produced synthetic opioids distributed in the EU originate from non-EU countries. Depending on the destination country and the mode of distribution, the three main source countries for synthetic opioids available on the European drug market are believed to be China, India and, to a lesser extent, Russia. Some production of synthetic opioids, including new synthetic opioids, may occasionally occur in the EU, although currently this would appear to be marginal compared with the manufacturing of other illicit drugs. Laboratories carrying out the full production cycle of synthetic opioids are rarely found, and there does not appear to be any widespread or sustained illicit production of these substances. However, because these substances are very potent often orders of magnitude greater than morphine , even a small illicit laboratory could produce sufficient material to satisfy national or even EU demand. France and Estonia each reported dismantling a small-scale laboratory for the production of fentanyl in and , respectively UNODC, c. In May , the Latvian police seized a large quantity of fentanyl approximately 5 kilograms together with fentanyl precursors, which suggests that fentanyl production might have taken place in the country Valsts policija, Overall, with a few possible exceptions in the Baltic countries and in countries bordering the EU, there is no strong evidence of significant fentanyl production currently occurring elsewhere in the EU. Nonetheless, this situation may change rapidly should market conditions become favourable in the future see Box Factors that could increase the threat of synthetic opioid production in Europe. While no fentanyl production sites have been identified in the Netherlands, seizures of fentanyl have been reported there Openbaar Ministerie, , a. Furthermore, in , the National Police of the Netherlands reported the seizure of chemicals used in the production of fentanyl, along with the final product, indicating that fentanyl production may take place in the country see Box Signals of possible fentanyl production in the Netherlands. Cutting and packaging facilities for synthetic opioids are more commonly detected in the EU than laboratories producing these substances. However, reporting rarely differentiates between the two. In , Latvia reported detecting and dismantling one small-scale site for the manufacture or packaging of the benzimidazole isotonitazene UNODC, c. The illicit production of methadone is also known to take place in the northeast of Europe. For example, a small-scale illicit laboratory producing methadone using precursors diverted from the legal market was dismantled in Latvia in Ukraine reported dismantling three medium-scale methadone production laboratories in and two medium- and one small-scale laboratories in UNODC, c. This estimate considers only the main season, as the second harvest is marginal in comparison, based on the evidence available UNODC, b. Consult the list of references used in this module. Homepage Quick links Quick links. GO Results hosted on duckduckgo. Main navigation Data Open related submenu Data. Latest data Prevalence of drug use Drug-induced deaths Infectious diseases Problem drug use Treatment demand Seizures of drugs Price, purity and potency. Drug use and prison Drug law offences Health and social responses Drug checking Hospital emergencies data Syringe residues data Wastewater analysis Data catalogue. 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How can I buy cocaine online in Zootermeer