methadone is the first widely used drug to overcome the opioid withdrawal effects ( 1 , 2 ) . it acts by occupying the receptor affected by exogenous opioids leading to subsequent receptor activation . this activation leads to closing of voltage - sensitive calcium channel ( vscc ) and stimulation of potassium efflux causing hyperpolarization and inhibition of adenylyl cyclase activity ( 3 , 4 ) . successful approaches to pharmacotherapy in opioid addiction continue to rely largely on substitution of short - acting agonists such as heroin and oral administration of long acting high - efficacy agonists ( methadone ) or partial agonists ( buprenorphine ) ( 5 , 6 ) . notably , all opioids that produce analgesia also can cause tolerance , addiction and withdrawal , and all of the available opioids are misused ( 7 ) . it was shown that patients on long - term methadone maintenance treatment had longer qtc interval values than expected . withdrawal symptoms among methadone maintenance therapy ( mmt ) patients had been reported to become worse and last longer than those of heroin or morphine due to extremely longer methadone half life ( 8) . low patient s retention rates in the mmt programme was also reported , making them prone to re - injecting behaviour ( 9 - 11 ) . we believe that calcium channel blocking effect may play a crucial role in opioid dependent and withdrawal syndromes as shown by l - type voltage - dependent calcium antagonist role such as verapamil and felodipine in controlling the withdrawal syndromes effectively ( 12 - 15 ) . both central and peripheral mechanisms play an important role in attenuating opioid withdrawal syndrome via calcium channel blocking agents ( 16 ) . the effects produced by calcium channel blockers are proven to be independent from opioid receptor sites as there is no agents that can replace naloxone from its binding sites ( 17 ) . one study has reported that blockade of l - type voltage - dependent calcium channels by calcium channel blockers is responsible for the attenuation of morphine withdrawal ( 18 ) . other than that , t - type voltage dependent calcium channels have also been shown to play a critical role in the development of morphine dependence and withdrawal ( 19 ) . previous study reported medicinal plants , nigella sativa , a scientific name for islamic prophetic medicine , habbatus sauda to have l - type calcium channel blocking effect ( 20 ) . moreover , further study had also introduced its seeds as a novel treatment for opioid dependence and proven effective in long term treatment of opioid dependence ( 21 ) . this plant has green to blue flowers with small black seeds and grows natively in temperate and cold climate areas . the seed of n. sativa possesses a source of the main active ingredients such as thymoquinone , monotropens - like p - cymene and -pinene , nigellidine , nigellimine , and saponin ( 22 - 26 ) . considering its low toxicity ( 27 - 29 ) , we hypothesized that the main active compound of n. sativa , thymoquinone ( tq ) , has a role in treating opioid withdrawal syndrome . tq also exhibits calcium channel blocker properties via gut spasmolytic , tracheal , and airway relaxant , vasodilator and relaxant activities on the cardiac muscles ( 30 ) . thus , further study is needed in order to explore the biochemical effects and mechanism of action of n. sativa at cellular level . as a conclusion , we would like to suggest probably with the supplementation of n. sativa to methadone , it will indirectly be a starting point to answer the question of opioid dependency and withdrawal for better retention of patients in mmt .