Fenethylline

Abstract: This is the peer-reviewed version of the following article: ‘Captagon: Use and Trade in the Middle East’, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/hup.2548/abstract . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Abstract: Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon.

Abstract: Captagon, known by its genetic name Fenethylline, is an addictive drug that complicates the War on Drugs. Captagon has a strong CNS stimulating effect than its primary metabolite, Amphetamine. However, multi-targets issues associated with the drug and metabolites as well as its underlying mechanisms have not been fully defined. In the present work, we applied our established drug-abuse chemogenomics-knowledgebase systems pharmacology approach to conduct targets/off-targets mapping (SP-Targets) investigation of Captagon and its metabolites for hallucination addiction, and also analyzed the cell signaling pathways for both Amphetamine and Theophylline with data mining of available literature. Of note, Amphetamine, an agonist for trace amine-associated receptor 1 (TAAR1) with enhancing dopamine signaling (increase of irritability, aggression, etc.), is the main cause of Captagon addiction; Theophylline, an antagonist that blocks adenosine receptors (e.g. A2aR) in the brain responsible for restlessness and painlessness, may attenuate the behavioral sensitization caused by Amphetamine. We uncovered that Theophylline's metabolism and elimination could be retarded due to competition and/or blockage of the CYP2D6 enzyme by Amphetamine; We also found that the synergies between these two metabolites cause Captagon's psychoactive effects to act faster and far more potently than those of Amphetamine alone. We carried out further molecular docking modeling and molecular dynamics simulation to explore the molecular interactions between Amphetamine and Theophylline and their important GPCRs targets, including TAAR1 and adenosine receptors. All of the systems pharmacology analyses and results will shed light insight into a better understanding of Captagon addiction and future drug abuse prevention.

Abstract: Indiscriminate killing, chemical warfare, the rise of extremists, and the worst humanitarian crisis since World War II make it easy to overlook important details of the Syrian conflict. The destabilization of Syria has created an environment uniquely suited for cultivating illicit economies, particularly the production and transportation of illegal drugs such as Captagon. Little known outside of the Middle East until 2014, Captagon production in Syria adds a new dimension to a conflict that already has numerous competing forces. Hezbollah, a known supporter of the Assad regime and ally of Iran, is most likely the major producer of Captagon within Syria. Meanwhile, the most prolific consumers of Captagon are in the Gulf nations of Saudi Arabia, Qatar, and the United Arab Emirates. While the Gulf states' governments are supporting the Syrian opposition against the Assad regime, their populations are financially supporting the Hezbollah and Assad. This article defines Captagon, uncovers its journey to Syria, and unpacks the evidence indicating Hezbollah's involvement in the Captagon trade. Nations of the Gulf need to bolster their partnerships with Western allies to put an end to illegal drug financing through acknowledgement, education, and increased enforcement. ********** Areas of conflict are a boon to the illicit economy, from human trafficking to drug smuggling. Globalization has brought about a fundamental change in the international system, including the erosion of territorial borders and the continued internationalization of non-state actors. Along with this, intrastate warfare dramatically undermines state capacity to regulate criminal activity, empowering transnational organized crime. The ongoing crisis in Syria is no different. Amid a death toll of more than 250,000, a widespread humanitarian crisis, and the increasing power of extremist ideologies, illicit trade networks play a significant role in fueling the conflict--a fact receiving greater attention from the international media. While the focus has been on the smuggling of oil, antiquities, and people, the narcotics trade is often left out of the equation. This trade centers around one of the most favored drugs in the Middle East, albeit one relatively unknown outside the region: Captagon, an illegal amphetamine stimulant sometimes referred to in Arabic as Abu Hilalain. It is in high demand in the Gulf countries of Saudi Arabia, the UAE, and Qatar, where its in expensive yet powerful high overshadows its highly addictive quality, for which it has been banned in most of the world. Historically, hubs of Captagon production have been centered in Eastern Europe, Turkey, and Lebanon. As of now, Captagon is produced almost exclusively in Syria. 2013 was a significant year in the Captagon trade, as patterns of confiscations led many to conclude that Syria was the new Captagon capital of the world. Because of this, many have associated the drug's boom with the conflict. Indeed, there has been a substantial decrease in Captagon confiscations in former centers of production, such as Lebanon's Bekaa Valley. International counterdrug agencies have noticed these trends, identifying Syria as the major production point for this substance. The beneficiaries of this shift in production remain unknown. Although a recent documentary by Radwan Mortada connected secular Syrian rebels to Captagon's spread, his research uncovers only a small part of this large and growing illicit trade. (1) Evidence strongly indicates that Hezbollah and their associated Syrian military connections are responsible for the increase in Syria's Captagon production and distribution. This evidence includes: (1) primary sourced information, (2) the timing of Captagon seizures, (3) the geographic history of the drug's production, and (4) the various actors in Syria's conflict. WHAT IS CAPTAGON? Captagon was the popular brand name for an amphetamine-type stimulant (ATS) called fenethylline. …