Objective: In preclinical studies, lobeline inhibited hyperactivity induced by nicotine and amphetamine, and improved performance and learning in studies utilizing radial-arm maze and spatial-discrimination water maze. This laboratory proof-of-concept study investigated lobeline as a treatment for ADHD symptoms in adults (31.11 ± 7.08 years). Method: Using cognitive tasks and self-report measures, the effects of lobeline (0, 7.5, 15, or 30 mg, s.l.) and methylphenidate (0, 15, or 30 mg, p.o.) were assessed in nine volunteers with ADHD. Results: Evidence suggested that lobeline could modestly improve working memory in adults with ADHD, but no significant improvement in attention was observed. Lobeline administration was associated with mild adverse side effects (nausea). Conclusion: Further investigation of lobeline on working memory may be warranted.

References

American Psychiatric Association . ( 1994 ). Diagnostic and statistical manual of mental disorders ( 4th ed. ). Washington, DC : Author .

Google Scholar

Arnsten, A. F. T., Dudley, A. G. ( 2005 ). Methylphenidate improves prefrontal cortical cognitive function through α2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in attention deficit hyperactivity disorder . Behavioral and Brain Functions, 1(2). Retrieved from http://www.behavioralandbrainfunctions.com/content/ 1/1/2

Google Scholar

Arnsten, A. F. T., Li, B.-M. ( 2005 ). Neurobiology of executive functions: Catecholamine influences on prefrontal cortical function . Biological Psychiatry, 57, 1377 - 1384 .

Google Scholar Crossref | Medline | ISI

Aron, A. R., Dowson, J. H., Sahakian, B. J., Robbins, T. W. ( 2003 ). Methylphenidate improves response inhibition in adults with attention deficit/hyperactivity disorder . Biological Psychiatry, 54, 1465 - 1468 .

Google Scholar Crossref | Medline | ISI

Barkley, R. A. ( 2006 ). Associated cognitive, developmental and health problems . In Barkley, R. A. (Ed.), Attention-deficit hyperactivity disorder: A handbook for diagnosis and treatment ( 3rd ed. , pp. 122 - 183 ). New York, NY : Guilford Press .

Google Scholar

Charach, A., Figueroa, M., Chen, S., Ickowicz, A., Schachar, R. ( 2006 ). Stimulant treatment over 5 years: Effects on growth . Journal of the American Academy of Child and Adolescent Psychiatry, 45, 415 - 421 .

Google Scholar Crossref | Medline | ISI

Decker, M. W., Majchrzak, M. J., Arnerić, S. P. ( 1993 ). Effects of lobeline, a nicotinic receptor agonist, on learning and memory . Pharmacology Biochemistry and Behavior, 45(3), 571 - 576 .

Google Scholar Crossref | Medline

Diak, I-L., Senior, J. ( 2009 ). Postmarket reviews . FDA Drug and Safety Newsletter, 2 .

Google Scholar

Dwoskin, L. P., Crooks, P. A. ( 2002 ). A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse . Biochemical Pharmacology, 63, 89 - 98 .

Google Scholar Crossref | Medline

Eiland, L. S., Guest, A. L. ( 2004 ). Atomoxetine treatment of attention-deficit/hyperactivity disorder . The Annals of Pharmacotherapy, 38, 86 - 90 .

Google Scholar SAGE Journals | ISI

Ejrup, B. ( 1960 ). Proposals for treatment of smokers with severe clinical symptoms brought about by their smoking habit . British Columbia Medical Journal, 2, 441 - 454 .

Google Scholar

Farook, J. M., Lewis, B., Gaddis, J. G., Littleton, J. M., Barron, S. ( 2009 ). Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice . Physiology & Behavior, 97(3-4), 503 - 506 .

Google Scholar Crossref | Medline

Hammerness, P. G., Perrin, J. M., Shelley-Abrahamson, R., Wilens, T. E. ( 2011 ). Cardiovascular risk of stimulant treatment in pediatric attention-deficit/hyperactivity disorder: Update and clinical recommendations . Journal of the American Academy of Child and Adolescent Psychiatry, 50(10), 978 - 990 .

Google Scholar Crossref | Medline

Harrod, S. B., Dwoskin, L. P., Crooks, P. A., Klebaur, J. E., Bardo, M. T. ( 2001 ). Lobeline attenuates d-methamphetamine self-administration in rats . Journal of Pharmacology and Experimental Therapeutics, 298, 172 - 179 .

Google Scholar Medline

Heishman, S. J., Henningfield, J. E. ( 1991 ). Discriminative stimulus effects of d-amphetamine, methylphenidate, and diazepam in humans . Psychopharmacology (Berl), 103, 436 - 442 .

Google Scholar Crossref | Medline | ISI

Jain, R., Segal, S., Kollins, S. H., Khayrallah, M. ( 2011 ). Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity disorder . Journal of the American of Child and Adolescent Psychiatry, 50, 171 - 179 .

Google Scholar Crossref | Medline | ISI

Kalyuzhny, V. V. ( 1968 ). The treatment of nicotinism with the aid of lobeline and its influence on vegetative and vascular reactions . Journal of Neurology and Psychiatry, 68, 1864 - 1870 .

Google Scholar

Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C. K., Demler, M., . . . Zaslavsky, A. M. ( 2006 ). The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication . American Journal of Psychiatry, 163, 716 - 723 .

Google Scholar Crossref | Medline | ISI

Korczyn, A. D., Bruderman, I., Braun, K. ( 1969 ). Cardiovascular effects of lobeline . Archives Internationales de Pharmacodynamie et de Therapie, 182, 370 - 375 .

Google Scholar Medline

Lambert, N. M., Hartsough, C. S. ( 1998 ). Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants . Journal of Learning Disabilities, 31, 533 - 544 .

Google Scholar SAGE Journals | ISI

Levin, E. D. ( 1992 ). Nicotinic systems and cognitive function . Psychopharmacology (Berl), 108, 417 - 431 .

Google Scholar Crossref | Medline | ISI

Levin, E. D., Christopher, C. N. ( 2003 ). Lobeline-induced learning improvement of rats in the radial-arm maze . Pharmacology Biochemistry and Behavior, 76(1), 133 - 913 .

Google Scholar Crossref | Medline

Martin, W. R., Sloan, J. W., Sapira, J. D., Jasinski, D. R. ( 1971 ). Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazin, and methylphenidate in man . Clinical Pharmacology & Therapeutics, 12, 245 - 258 .

Google Scholar Crossref | Medline | ISI

McCabe, S. E., West, B. T., Cranford, J. A., Ross-Durow, P., Young, A., Teter, C. J., Boyd, C. J. ( 2011 ). Medical misuse of controlled medications among adolescents . Archives of Pediatrics & Adolescent Medicine, 165(8), 729 - 735 .

Google Scholar Crossref | Medline

Miller, D. K., Crooks, P. A., Dwoskin, L. P. ( 2000 ). Lobeline inhibits nicotine-evoked [(3)H]dopamine overflow from rat striatal slices and nicotine-evoked (86)Rb(+) efflux from thalamic synaptosomes . Neuropharmacology, 39, 2654 - 2662 .

Google Scholar Crossref | Medline

Miller, D. K., Crooks, P. A., Teng, L., Witkin, J. M., Munzar, P., Goldberg, S. R., . . . Dwoskin, L. P. ( 2001 ). Lobeline inhibits the neurochemical and behavioral effects of amphetamine . Journal of Pharmacology and Experimental Therapeutics, 296, 1023 - 1034 .

Google Scholar Medline

Miller, D. K., Harrod, S. B., Green, T. A., Wong, M. Y., Bardo, M. T., Dwoskin, L. P. ( 2003 ). Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats . Pharmacology Biochemistry and Behavior, 74, 279 - 286 .

Google Scholar Crossref | Medline

Miller, D. K., Lever, J. R., Rodvelt, K. R., Baskett, J. A., Will, M. J., Kracke, G. R. ( 2007 ). Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists . Drug and alcohol dependence, 89, 282 - 291 .

Google Scholar Crossref | Medline

Polston, J. E., Cunningham, C. S., Rodvelt, K. R., Miller, D. K. ( 2006 ). Lobeline augments and inhibits cocaine-induced hyperactivity in rats . Life Sciences, 79, 981 - 990 .

Google Scholar Crossref | Medline

Scahill, L., Chappell, P. B., Kim, Y. S., Schultz, R. T., Katsovich, L., Shepherd, E., . . . Leckman, J. F. ( 2001 ). A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder . American Journal of Psychiatry, 158, 1067 - 1074 .

Google Scholar Crossref | Medline | ISI

Schoenlin, C., Engel, R. R. ( 2005 ). Neuropsychological performance in adult attention-deficit hyperactivity disorder: Meta analysis of empirical data . Archives of Clinical Neuropsychology, 20, 727 - 744 .

Google Scholar Crossref | Medline

Sonuga-Barke, E. J. S. ( 2003 ). The dual pathway model of AD/HD: An elaboration of neuro-developmental characteristics . Neuroscience & Biobehavioral Reviews, 27, 593 - 604 .

Google Scholar Crossref | Medline | ISI

Spencer, T., Biederman, J., Wilens, T., Prince, J., Hatch, M., Jones, J., . . . Seidman, L. ( 1998 ). Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder . American Journal of Psychiatry, 155, 693 - 695 .

Google Scholar Crossref | Medline | ISI

Stead, L. F., Hughes, J. R. ( 2000 ). Lobeline for smoking cessation . Cochrane Database Syst Rev : CD000124 .

Google Scholar

Teng, L., Crooks, P. A., Sonsalla, P. K., Dwoskin, L. P. ( 1997 ). Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine: Differential inhibition of synaptosomal and vesicular [3H]dopamine uptake . Journal of Pharmacology and Experimental Therapeutics, 280, 1432 - 1444 .

Google Scholar Medline

Volkow, N. D., Wang, G., Fowler, J. S., Logan, J., Gerasimov, M., Maynard, L., Ding, Y., . . . Franceschi, D. ( 2001 ). Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain . Journal of Neuroscience, 21, 1 - 5 .

Google Scholar Crossref

Wilens, T. E., Bukstein, O., Brams, M., Cutler, A. J., Childress, A., Rugino, T., . . . Youcha, S. ( 2012 ). A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder . Journal of the American Academy of Child and Adolescent Psychiatry, 51, 74 - 85 .

Google Scholar Crossref | Medline | ISI