Highly Addictive Drug ‘Fenethylline’

Highly Addictive Drug ‘Fenethylline’

Presented by: Hagar Ahmad Supervised by: Prof. Dr. Medhat Attia Dr. Zeinab Shatta Course: Advanced Adult Mental Health Code: 0909(3)802 Date: 1-Apr-20

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Highly Addictive Drug ‘Fenethylline’

Introduction The increasing number of new psychoactive substances or the re-appearance of older ones, when the newer ones are not available, on the drug market is a major public health concern today. These designer drugs are being used to substitute or mimic the effects of traditional controlled drugs, when in shortage (1).

Novel psychoactive substances potentially pose similar health risks to classic illicit substances. Chemically, many novel psychoactive substances can be classified as phenethylamines, amphetamines, synthetic cathinones, piperazines, pipradrols/ piperidines, aminoindanes benzofurans, and tryptamines. Pharmacologically, these substances interact with various monoaminergic targets (2).

Definition: Fenethylline also known as amphetaminoethyltheophylline and amfetyline is a codrug of amphetamine and theophylline, which behaves as a prodrug to both of the aforementioned drugs. It is marketed for use as a psychostimulant under the brand names Captagon, Biocapton, and Fitton (3).

Historical Background: Fenethylline was first synthesized by Chemiewerk Homburg, a subsidiary of specialty chemicals company German Degussa AG in 1961 as a part of an investigational programme on side effects of theophylline derivatives. It was used for many years in the treatment of attention-deficit–hyperactivity disorder, and in a lower extent, in narcolepsy, epileptic absences and depression (4).

Fenethylline became illegal in most countries in 1986 after being listed by the World Health Organization for international scheduling under the Convention on Psychotropic Substances. It was considered too addictive and too dangerous given the potential for severe behavioural side effects, including increased aggressiveness and delusional symptoms (4).

Magnitude of the Problem: Although illegal, Captagon is now a major substance of misuse in Saudi Arabia, where it is used by a high majority (40%) of the overall substance users in the

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Highly Addictive Drug ‘Fenethylline’ country, mainly by young men aged 12–22. Additionally, because of its psychostimulant and cognitive‐enhancing properties, Captagon is also used by fighters of the Islamic State in Iraq and the Levant (ISIL) and other militant groups in Syria. The illicit trade is rapidly increasing, and more recently in 2016, 8.8 million pills, mainly containing Captagon, were found in Egypt (5).

Counterfeit captagon tablets, which contained mixtures of drugs with pharmacological effects similar to those of fenethylline, have been reported in the Saudi Arabian drug market, while they have also appeared in Europe and Turkey. The analysis of those counterfeit captagon tablets has demonstrated the presence of amphetamine and/or amphetamine- type derivatives, caffeine, theophylline, quinine, ephedrine, acetaminophen, diphenhydramine, lactose and other substances, while fenethylline was absent (6).

Overall, the Captagon trade in the Middle East, Arabian Gulf region, and the north of Africa is currently a prolific illegal trade with a high profit margin as it can be clandestinely synthesized, using simple and inexpensive chemistry techniques and raw materials and its illicit market contributes in funding global terroristic organizations, including ISIL (5).

Route of Administration: The routes of administration are various, including ingestion, subcutaneous, intravenous and intraperitoneal (3).

Mechanism of Action: Literature showed that there is no extended scientific research on fenethylline regarding its pharmacology and toxicology (3).

As mentioned above, fenethylline could be a pro-drug for amphetamine and/or theophylline. The 13.7% and 24.5% of an oral dose is apparently cleaved metabolically in human beings into theophylline (weak stimulant chemically and pharmacologically related to caffeine) and amphetamine (active stimulant), respectively. So, the final pharmacological effect is the result of the combined action of these two stimulant agents. Fenethylline seems to display also its own stimulatory effect to the same extent and at a similar time course as its precursors, amphetamine and theophylline (6).

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Highly Addictive Drug ‘Fenethylline’

Figure (1) Metabolic Scheme of Captagon (Fenethylline)

Pharmacological Effects: Fenethylline stimulates the central nervous system, increasing alertness, concentration ability and physical performance, while providing a feeling of well- being and appetite suppression, due to its amphetaminic structure and its chemical resemblance to natural neurotransmitters, like dopamine and adrenaline (6).

It causes dilation of bronchial vessels, and elevation of heart rate, body temperature, respiration and blood pressure. However, it does not increase blood pressure to the same extent as amphetamine due to the fact that theophylline is a vasodilator and amphetamine is vasoconstrictor. Fenethylline also demonstrated diuretic and positive nootropic effects similar to those observed after theophylline administration (7).

The long-term use of fenethylline leads to remarkable side effects. The most common of them are extreme depression, lethargy, sleep deprivation (insomnia), occasional palpitation, heart and blood vessel toxicity and malnutrition. Other side effects that have been experienced by regular users include blurred vision, vertigo, mouth dryness, breathing difficulties, irregular heartbeat, gastrointestinal

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Highly Addictive Drug ‘Fenethylline’ symptoms, muscle and/or joint pain, muscle cramping, anxiety, mood swings, confusion, feelings of anger or rage, irritability and impatience (7). The chronic use of fenethylline has been also correlated with hemorrhagic central retinal vein occlusion and acute myocardial infarction (8,9).

It has to be stated here that similar symptoms can be developed after the consumption of counterfeit captagon pills that usually contain amphetamines (where fenethylline is sometimes absent) and ephedrine, theophylline, caffeine, acetaminophen and/or other substances (3).

Possible Preventive Strategies (10): Prevention is understood as any activity designed to avoid captagon use and reduce its health and social consequences. It includes: 1) Primary prevention which involves interventions take place before the onset of symptoms and is classified into universal, selective and indicated, according to the level of risk of using captagon. a) Universal preventive interventions target the general public or the whole population groups regardless to their risk of captagon use.

These broad interventions can incorporate actions aimed to reduce supply (based on the principle that the decreased availability of captagon reduces the opportunities for use and dependence) and actions aimed to reduce demand (including health promotion and disease prevention) within an integrated strategy.

Reducing the supply of captagon may encompass efforts aimed at prosecution of big scale traffickers and captagon dealers, and reduction of captagon availability on the streets.

Demand reduction can be accomplished through special programs aimed to promote protective factors in the individual and the environment; such as school-based skill building programs and family-based parenting programs.

b) Selective preventive interventions are those aimed at subgroups of the population whose risk of developing captagon use disorder is significantly higher than average (these persons may be at imminent risk or have a lifetime risk).

Risk factors can be found in different domains: at the individual level (e.g., some mental disorders or a sensation- seeking personality, history of child abuse); in the family (e.g., living with a depressed or substance dependent parent,

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Highly Addictive Drug ‘Fenethylline’ poverty); at school (e.g., poor academic performance); among peers (e.g., friends that use captagon), in the community (e.g., easy availability and social acceptance of captagon, inequity, lack of health and social services, neighborhood disorganization).

Therefore, at the selective prevention level, societies can reduce the burden of captagon use by treating early onset mental disorders, integrating social minorities, providing services to less advantaged groups and facilitating community networks.

c) Indicated preventive interventions are defined as those targeting high-risk individuals who are identified as having minimal but detectable signs or symptoms foreshadowing the disorder, but who do not meet diagnostic levels at the present.

2) Secondary prevention which involves early detection of captagon use e.g. through urine screening for amphetamines, in addition to early intervention with individuals that have experimented with captagon but are not severely dependent and may therefore be “reeducated” about the harms of captagon use, in order to abolish false claims about captagon’s ability to increase concentration and to emphasize the psychiatric and medical conditions that

may be associated with chronic captagon use.

3) Tertiary prevention which involves treatment of intoxication and dependence, relapse prevention, and social reintegration. Treatment includes pharmacological and non-pharmacological (i.e. psychosocial) interventions. The 12 steps model, cognitive behavior therapy, and mindfulness-based relapse prevention are some of the psychosocial programs used in treating captagon use disorder.

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Highly Addictive Drug ‘Fenethylline’

References: 1. United Nations Office on Drugs and Crime (UNODC). World Drug Report. Vienna, Austria: UNODC; 2013. 2. Liechti M. Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling. Swiss Med Wkly. 2015; 145:w14043. 3. Katselou M, Papoutsis I, Nikolaou P, Qammaz S, Spiliopoulou C., Athanaselis S. Fenethylline (Captagon) Abuse—local problems from an old become universal. Basic Clin Pharmacol Toxicol. 2016; 119(2), 133-40. 4. Kristen G, Schaefer A, von Schlichtegroll A. Fenethylline: therapeutic use, misuse, and/or abuse. Drug Alcohol Depend.1986; 17:259-71. 5. AL‐Imam A, Santacroce R, Roman‐ Urrestarazu A, et al. Captagon: Use and trade in the Middle East. Hum Psychopharmacol Clin Exp. 2017; 32 (3):e2548. 6. Alabdalla M. Chemical characterization of counterfeit Captagon tablets seized in Jordan. Forensic Sci. Int.2005; 152(2): 185-188. 7. Brayfield A. Martindale: The Complete Drug Reference. 38th ed. London, UK: Pharmaceutical Press; 2014. 8. Al-Ghadyan A, Rushood AA, Alhumeiden AA. Fenethylline as a possible etiology for retinal vein occlusion. Ann Ophthalmol (Skokie). 2009; 41: 199– 202. 9. Ulucay A, Kargi CA, Aksoy MF. Acute myocardial infarction associated with captagon use. Anadolu Kardiol Derg. 2012; 12:181–6. 10. Medina-Mora ME. Prevention of substance abuse: a brief overview. World Psychiatry. 2005; 4(1):25–30.

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