TY - JOUR
T1 - Effects of modafinil on dopamine and dopamine transporters in the male human brain clinical implications
AU - Volkow, Nora D.
AU - Fowler, Joanna S.
AU - Logan, Jean
AU - Alexoff, David
AU - Zhu, Wei
AU - Telang, Frank
AU - Wang, Gene Jack
AU - Jayne, Millard
AU - Hooker, Jacob M.
AU - Wong, Christopher
AU - Hubbard, Barbara
AU - Carter, Pauline
AU - Warner, Donald
AU - King, Payton
AU - Shea, Colleen
AU - Xu, Youwen
AU - Muench, Lisa
AU - Apelskog-Torres, Karen
PY - 2009/3/18
Y1 - 2009/3/18
N2 - Context Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. Objective To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. Design, Setting, and Participants Positron emission tomography with [11C]ra- clopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [ 11C]co-caine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007-2008) at Brookhaven National Laboratory. Main Outcome Measures Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. Results Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%];95% confidence interval [CI], 1.5% to 10.8%; P =.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P =.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P =.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P< .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P< .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P =.001), reflecting occupancy of dopamine transporters. Conclusions In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.
AB - Context Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. Objective To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. Design, Setting, and Participants Positron emission tomography with [11C]ra- clopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [ 11C]co-caine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007-2008) at Brookhaven National Laboratory. Main Outcome Measures Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. Results Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%];95% confidence interval [CI], 1.5% to 10.8%; P =.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P =.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P =.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P< .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P< .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P =.001), reflecting occupancy of dopamine transporters. Conclusions In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.
UR - http://www.scopus.com/inward/record.url?scp=62649136134&partnerID=8YFLogxK
U2 - 10.1001/jama.2009.351
DO - 10.1001/jama.2009.351
M3 - Article
C2 - 19293415
AN - SCOPUS:62649136134
SN - 0098-7484
VL - 301
SP - 1148
EP - 1154
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 11
ER -