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Bangladesh Journal of Medical Science Vol. 14 No. 02 April’15

Letter to editor

Opiate Dependence and withdrawal: Role of oxidative stress in opiate regulations 
Hashim SNB 1,  Bakar NHA2, Mohamad N3

Corresponds to: Dr	Nasir	Mohamad,	Professor	and	Deputy	Dean,	(Innovation	and	Research)
Faculty	 of	 Medicine	 and	 Health	 Sciences,University	 Sultan	 Zainal	 Abidin, 20400, Kuala Terengganu, 
Terengganu, Malaysia.Email: drnasirmohamadkb@yahoo.com

1. Siti	Norhajah	bt	Hashim	PhD	student,	Faculty	of	Medicine	and	Health	Sciences.
2. Nor	Hidayah	Abu	Bakar,	Lecturer.
3. Nasir	Mohamad,	Professor	and	Deputy	Dean,	(Innovation	and	Research),
FPSK,	University	Sultan	Zainal	Abidin	(UniSZA),	20400,	Kuala	Terengganu,	Terengganu,	Malaysia.

Opiate	 dependence	 is	 defined	 as	 the	 need	 to	 take	
opiate	 at	 regular	 interval	 to	 avoid	 withdrawal	
syndrome. It occurs because of changes in the 
brain system especially at the base of the brain in 
the locus ceruleus. Absence of exogenous opioids 
will	 stimulate	 locus	 ceruleus	 brain	 cells	 to	 release	
excessive	amounts	of	noradrenaline	triggering	jitter,	
anxiety, muscle cramps and diarrhea, increased heart 
rate,	increased	blood	pressure,	widening	of	pupils	and	
widening	of	air	passages	in	the	lungs	and	narrowing	
of blood vessels in non-essential organs. On the other 
hand,	when	opiate	molecule	binds	to	mµ	receptors	
on brain cells in midbrain dopaminergic regions , 
they suppress the release of noradrenaline resulting 
in	drowsiness,	slow	respiratory	rate	and	low	blood	
pressure 1.
One of the proposed mechanisms that regulate the 
opiate	 dependency	 and	 withdrawal	 is	 oxidative	
stress.	 There	 are	 two	 mechanisms	 involved	 in	 the	
development	of	oxidative	stress;	 formation	of	 free	
radicals and reduce activity of antioxidant2. The 
neurotransmitter and gasotransmitters involved 
are predominantly glutamate and nitric oxide. This 
proposed	 mechanism	 was	 further	 supported	 by	

pretreatment	with	free	radicals	scavengers	attenuated	
the	 expression	 of	 morphine	 induced	 withdrawal	
syndrome3.
In	our	study,	we	are	trying	to	explore	the	ability	of	
honey as a supplementary therapy to methadone 
to reduce opiate addiction. This is because honey 
contains	 phenolic	 compound	 which	 have	 higher	
antioxidant properties. Antioxidants reduce free 
radicals	 in	 oxidative	 stress	 pathway.	 Hence,	 it	
blocks	of	oxidative	stress	in	opiate	dependence	and	
tolerance4. Phenolic compound has an ability to 
increase radical scavenging activity by cutting off 
the formation of free radicals. When the free radicals 
concentration in the cell is reduced, the oxidative 
stress	was	noted	to	be	reduced5. 
This study is further supported by the fact that 
the property of honey is healing for human6. It 
corresponded	with	the	result	of	studies	that	phenolic	
compound in honey that actively involved in reducing 
oxidative	stress	which	occurs	due	to	the	presence	free	
radicals presence in the cells. Better understanding 
on the effect of honey on oxidative stress produced 
by	honey	to	opiate	dependency	and	withdrawal	need	
to be further explored.

DOI: http://dx.doi.org/10.3329/bjms.v14i2.22784 
Bangladesh Journal of Medical Science Vol.14(2) 2015 p.215

References:
1. Abdel-Zaher	 AO,	 Abdel-Rahman	 MS,	 ELwasei	 FM.

Blockade	 of	 nitric	 oxide	 overproduction	 and	 oxidative	
stress by Nigella sativa oil attenuates morphine-induced 
tolerance and dependence in mice. Neurochem Res. 2010; 
35(10):1557-1565.

2. Jitka	 S,	 Zdenka	 D,	 Jiri	 N.	 Morphine	 as	 a	 Potential
Oxidative Stress-Causing Agent. Mini -Reviews in
Organic Chemistry.2013; 10:367-372.

3. Kishore	RK,	Ahmad	SH,	Syazana	N,	Sirajudeen	KNS.
Tualang honey has higher phenolic content and greater
radical	 scavenging	 activity	 compared	 with	 other	 honey

sources. Nutrition Research. 2011; 31 (4);	322-325.

4. Kosten TR and George TP. The neurobiology if opioid
dependence: Implications for treatment. Sci Pract
Perspect. 2002; 1: 12-20.

5. Mori	T,	Ito	S,	Matsubayashi	K,	Sawaguchi	T.	Comparison
of nitric oxide synthase inhibitors, phospholipase A2
inhibitor and free radical scavengers as attenuators of
opioid	 withdrawal	 syndrome.	 Behav Pharmacol.	 2007;
18:725–729.

6. Tahereh EO and Moslem N.Traditional and Modern Uses
of	Natural	Honey	in	Human	Diseases:	A	Review.	Iranian
Journal of Basic Medical Sciences.	2013;	16	(6);	731-742.




