Methamphetamine (METH), is a potent stimulant drug that significantly alters the function of the central nervous
system (CNS). MTTHS’s abuse may be linked with a variety of psychiatric diseases and cognitive deficits, mostly
via affecting the reward system. Cannabidiol (CBD), a primary cannabinoid component of the Cannabis plant has
been shown to affect reward system, candidated it for the modulation of addictive behaviors. On the other hand,
deep brain stimulation (DBS) of the nucleus accumbens (as one of the most important brain regions implicated in
mediating rewards) is effective in the alleviation of drug-seeking behaviors. The present research aimed to
evaluate the effects of low frequency DBS, CBD, and combination of both on the reinstatement of METH-
induced conditioned place preference (CPP). CBD was injected into the later ventricle at the doses of 2.5, 5, and
10 μg/5 μL, and low frequency DBS (10 Hz, for 30 minutes) was administered to the nucleus accumbens, both
during the extinction phase. The results showed CBD (10 µg/5 µL) or DBS facilitated extinction. CBD at all
doses in combination with DBS induced a more significant decrease in mean extinction latency. However, both
CBD (10 µg/5 µL) and DBS did not alter the CPP score on the reinstatement day. Interestingly, combination of
DBS and CBD administration (at all doses) significantly decreased the CPP score on the reinstatement day.