As most chronic heroin users in our study were under methadone treatment, what effects of methadone would have on the functional connectivity is an interesting question. Known as a drug that prolongs opioid dependence, methadone has similar effects as addictive drugs to some extent (Connock et al., 2007). For example, studies have found that methadone can prime heroin cue response and craving (Curran et al., 1999) and enhance brain response to drug cues (Langleben et al., 2008), which are similar to those in untreated heroin dependence (Daglish et al., 2003). Thus, we speculate that the alteration of functional connectivity related to methadone might be in same direction as that related to heroin addiction. However, as the effect of methadone was not sufficiently controlled in current study, its effect on functional connectivity needs to be clarified in further studies. Nonetheless, as chronic heroin users under methadone treatment are thought to be still at states of addiction (Connock et al., 2007), our findings of alteration in brain functional connectivity in HU may be mainly related to their opioid addiction.
