Nurul Farah Aina Md Fauzi, Nor Hidayah Abu Bakar?, Nasir Mohamad, Khairi Che Mat, Syed Hadzrullathfi Syed Omar, Mohd Shahril Othman, Rohayah Husain, Muhamad Zaid Ismail

1Faculty of Medicine, University of Sultan Zainal Abidin, Medical Campus, 20400 Kuala Terengganu, Terengganu Darul Iman, Malaysia

2Faculty of Contemporary Islamic Studies, University of Sultan Zainal Abidin, Gong Badak Campus, 21300 Kuala Terengganu, Terengganu Darul Iman, Malaysia

3Institute for Community Development & Quality of Life (iCODE), University of Sultan Zainal Abidin, Gong Badak Campus, 21300 Kuala Terengganu, Terengganu Darul Iman, Malaysia

4Institute for Product Research and Civilization (INSPIRE), University of Sultan Zainal Abidin, Gong Badak Campus, 21300 Kuala Terengganu,Terengganu Darul Iman, Malaysia

5Centre for Research in Addiction, University of Sultan Zainal Abidin, Gong Badak Campus, 21300 Kuala Terengganu, Terengganu Darul Iman,Malaysia

Dear Editor,

The prevalence of drug abuse has diverted from traditional drugs such as opioid and cannabis to modern, synthetic and psychoactive drugs such as amphetamine groups, the amphetamine (AT) and methamphetamine[1]. Amphetamine is used medically to treat several disorders such as attention deficit hyperactivity disorder, narcolepsy, depression and minor obesity[2]. However, AT has also gained its popularity as a recreational drug due to its psychostimulant effects. Parallel to that, illegal AT is increasingly manufactured by adding and mixing different drugs, binding agents and new psychoactive substances[3].

Amphetamine-like stimulants (predominantly AT and methamphetamine) are new trend among the youths and became the second most common forms of illicit substance abuse[4]. According to World Drug Report(2016), the global seizures of AT fluctuated annually between 20 and 46 tons since 2009. The number of amphetamines users was also showing an increasing trend from 33.9 million in 2015 to 35.7 million in 2016[5].

Amphetamine drug induces neurotoxicity through several mechanisms, with its predominant action on dopamine system causing dysfunction[6]. Overdose and uncontrollable consumption of AT will lead to addiction and unwanted psychological effects such as psychosis and anxiety[7,8]. Since early 1980, several studies were conducted to observe the effects of AT on behaviour,biochemical changes and neurotoxicity in order to explore potential treatments for AT abusers. But still,there is no substitute drugs or specific treatment for AT abusers as compared to the methadone substitute for opioid abusers which is used to reduce withdrawal symptoms and addiction[9-11].

In this current era, many natural compounds are explored for their therapeutic effects in healing various diseases instead of chemical drugs[12]. These include thymoquinone (TQ), the bioactive compound found inNigella sativaplant. It shows anti-oxidant, anti-inflammatory, anticancer as well as neuroprotective properties[13,14]. Previous studies highlighted TQ to have a great therapeutic potential in inhibiting the development of tramadol (an opioid drug) tolerance and dependence[15]. In another study, El-Shamyet al. (2013)reported that TQ has the potential to reduce monoamine neurotransmitter in the cortex and hippocampus of rats after treatment with nicotine[16]. A study also reported thatNigella sativapossesses the ability to modulate neurotransmitters release and reuptake such as dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine and gives a positive effect on reduction of drug tolerance[17].

To date, a recent study from El-Naggaret al.reported that methanol extraction fromNigella sativacan modify amino acid neurotransmitter level in rat brain region which can be used for the treatment of neurodegenerative disease[18]. Other study also mentioned that TQ has a potential to upregulate gene expression involved in morphine addiction pathways[19].

As a conclusion, we proposed that TQ might be a good candidate for the treatment of AT abuse through its interaction with dopamine neurotransmitter. Thus,further molecular studies are worth to be explored to prove its therapeutic effects in the treatment of AT abuse.

Conflict of interest statement

The authors declared that no conflict of interests based on this study.

Acknowledgements

This project is supported by UniSZA/NRGS/2013 (RR057-1) grant from Malaysia Ministry of Higher Education.

[1] Adnan LHM, Bakar NHA, Mohamad N. Post millennium preference of substance abuse among teenagers: Fast and furious.J Appl Pharm Sci2014;4(6): 131-132.

[2] Moszczynska A, Callan SP. Molecular, behavioral and physiological consequences of methamphetamine neurotoxicity: Implications for treatment.J Pharm Exp Ther2017;362(3):474-488.

[3] Uddin MS, Sufian MA, Kabir MT, Hossain MF, Nasrullah M,Islam I, et al. Amphetamines: Potent recreational drug of abuse.J Addict Res Ther2017;8(4): 1-12.

[4] United Nations Office on Drugs and Crime.World drug report 2015. United Nations Publication, 2015. [Online]Available from: http://www.unodc.org/wdr2015/.

[5] United Nations Office on Drugs and Crime.World drug report2016. United Nations Publication, 2016. [Online]Available from: http://www.unodc.org/wdr2016/.

[6] Schrantee A, Vaclav? L, Heijtel DF, Caan MWA, Gsell W,Lucassen PJ, et al. Dopaminergic system dysfunction in recreational dexamphetamine users.Neuropsychopharmacol2015;40(5): 1172-1180.

[7] Ringen PA, Melle I, Birkenaes AB, Engh JA, Faerden A,Vaskinn A, et al. The level of illicit drug use is related to symptoms and premorbid functioning in severe mental illness.Acta Psychiat Scand2008;118: 297-304.

[8] Valente MJ, Bastos MDL, Fernandes E, Carvalho F, De Pinho PG, Carvalho M. Neurotoxicity of β-Keto amphetamines:Deathly mechanisms elicited by methylone and MDPV in human dopaminergic SH-SY5Y cells.ACS Chem Neurosci2017;8(4):850-859

[9] Ciccarone D. Stimulant abuse: Pharmacology, cocaine,methamphetamine, treatment, attempts at pharmacotherapy.Prim Care2011;38(1): 41-58.

[10] Norliza C, Norni A, Anandjit S, Mohd FM. A review of substance abuse research in Malaysia.Med Journal Malays2014;69: 55-58.

[11] Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: A systematic review and meta-analysis.JAMA Psychiatry2017;74(5): 511-519.

[12] Zulkipli NI, David RS, Rajan R, Adi A. Medicinal plants: A potential source of compounds for targeting cell division.Drug Target Insights2015;9: 9-19.

[13] Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential ofNigella sativa: A miracle herb.Asian Pac J Trop Biomed2013;3(5):337-352.

[14] Beheshti F, Khazaei M, Hosseini M. Neuropharmacological effects ofNigella sativa.Avicenna J Phytomed2016;6(1): 104-116.

[15] Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM. Protective effect ofNigella sativaoil against tramadol-induced tolerance and dependence in mice: Role of nitric oxide and oxidative stress.Neurotoxicology2011;32: 725-733.

[16] El-Shamy AK, Khadrawy AY, El-Feki AM, Refaat HI, Sawie GH.The Effect of both vitamin E and thymoquinone on monoamine neurotransmitter changes induced by nicotine treatment and withdrawal in the cortex and hippocampus of rat brain.J Appl Sci Res2013;9(6): 4030-4040.

[17] Jukic M, Politeo O, Maksimovic M, Milos M.In vitroacetylcholinesterase inhibitory properties of thymol,carvacrol and their derivatives thymoquinone and thymohydroquinone.Phytother Res2007;21: 259-261.

[18] El-Naggar T, Carretero ME, Arce C, Gómez-Serranillos MP.Methanol extract ofNigella sativaseed induces changes in the levels of neurotransmitter amino acids in male rat brain regions.Pharm Biol2017;55(1): 1415-1422.

[19] Adnan LHM, Mohamad N, Mat KC, Yeo CC, Bakar NHA, Ismail R. Thymoquinone regulates gene expression levels in morphine addiction pathways in opioid receptor expressing cells (U87 MG).Electron J Biol2017;13(2): 166-173.