Table 4.

Effects of Glial Modulators on the Abuse Potential of Nicotine and Cannabis

Preclinical Studies
Glial Modulator	Mechanism of Action	Dose	Behavioral Outcome	Result	Citation
Nicotine
Ceftriaxone	Cephalosporin Antibiotic & Upregulator of Glutamate Transporter-1 (GLT-1) and Cystine/Glutamate Antiporter (xCT)	200 mg/kg	Rewarding Effects	--	Alajaji et al., 2013
			Withdrawal	↓
			Reinstatement of Drug Seeking	↓
		200 mg/kg	Reinforcing Effects	↓	Sari et al., 2016
		200 mg/kg	Rewarding Effects	↓	Philogene-Khalid et al., 2017
N-Acetylcysteine	Upregulator of GLT-1 & Glial Cystine-glutamate Exchange Activator	15, 30 & 120 mg/kg,	Rewarding Effects	↓	Bowers et al., 2016
		15, 30 & 120 mg/kg	Withdrawal	↓
		100 mg/kg	Reinstatement of Drug Seeking	↓	Gipson et al., 2013
		60 mg/kg	Reinstatement of Drug Seeking	↓	Ramirez-Niño & D’Souza 2013
		60 mg/kg	Reinforcing Effects	↓
		100 mg/kg	Reinstatement of Drug Seeking	↓	Goenaga et al., 2019
		100 mg/kg	Withdrawal	↓
		100 mg/kg	Reinstatement of Drug Seeking	↓	Moro et al., 2019
		100 mg/kg	Reinstatement of Drug Seeking	↓	Namba et al., 2019
		100 mg/kg	Reinstatement of Drug Seeking	↓	Powel et al., 2019
Cannabis
Minocycline	Tetracycline Antibiotic & Microglial Inhibitor	40 mg/kg	Cognitive Deficits	↓	Cutando et al., 2013
Ibudilast	Phosphodiesterase (PDE) & Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor	3.5 mg/kg	Cognitive Deficits	↓	Zamberletti et al., 2015
Clinical Studies
Glial Modulator	Mechanism of Action	Dose	Behavioral Outcome	Result	Citation
Nicotine
Minocycline	Tetracycline Antibiotic & Microglial Inhibitor	200 mg	Craving	↓	Sofuoglu et al., 2009
Pioglitazone	Peroxisome Proliferator-Activated Receptor-Gamma Activator & Cytokine Inhibitor	45 mg	Craving	↓	Jones et al., 2017
N-Acetylcysteine	Upregulator of GLT-1 & Glial Cystine-glutamate Exchange Activator	2400 mg	Reinforing Effects, Craving, Abstinence, Withdrawal	--	Knackstedt 2009
		3600 mg	Craving	↓	Schmaal et al., 2011
		1200 – 3000 mg	Abstinence	↑	Grant et al., 2014
		2400 mg	Abstinence	↑	McClure et al., 2015
		2400 mg	Craving	↓	Froeliger et al., 2015
Cannabis
N-Acetylcysteine	Upregulator of GLT-1 & Glial Cystine-glutamate Exchange Activator	1200 mg	Craving	↓	Gray et al., 2010
		1200 mg	Abstinence	↑	Gray et al., 2012
		1200 mg	Abstinence	--	Gray et al., 2017