The Psychomotor Laboratory under the directorship of Jim Zacny, Ph.D. examines the effects of psychoactive drugs that are primarily analgesic in nature. Primarily I have examined opioids, but have also recently examined musculoskeletal relaxants and anticonvulsants. The primary focus is on subjective and psychomotor-impairing effects of these drugs. Study results have relevance in that they inform on potential abuse liability-related effects of such drugs and if the drugs produce behavioral toxicity (i.e., do they impair a person’s reaction time or ability to think logically).
I completed my first opioid study in 1992, and for the next ten years or so the focus was on opioids delivered via the intravenous route. These studies complemented studies done primarily at the NIDA Addiction Research Center and the Behavioral Pharmacology Research Unit at the Johns Hopkins University School of Medicine. In those studies opioid abusers not seeking treatment were studied for responses to opioids that to varying degrees had efficacy at the mu opioid receptor (MOR) and either agonist or antagonist properties at the kappa opioid receptor (KOR). In my lab these same opioids using similar testing instruments were tested in healthy volunteers with a very limited history of opioid use (i.e., these subjects were also called “non-drug-abusing” volunteers). Differences between subject populations were noted, as well as some similarities. My studies filled in a missing gap – one could not generalize from the opioid-abusing population and assume the effects they experienced would be the same effects that people without a history of abuse (e.g., many patients being administered these drugs for their analgesic properties) would experience. And indeed the studies I conducted in non-drug-abusing volunteers have borne out this out.
Beginning around 2000, I turned my attention to opioids being delivered via the oral route, i.e., prescription opioids. Shortly thereafter health, law enforcement, and regulatory agencies were reporting increases in abuse of prescription opioids, including Vicodin and OxyContin. Very few studies in either healthy non-drug abusing volunteer or in opioid abusing populations were published in the scientific literature, and thus my studies proved to be quite timely. In 2001 I was asked to chair a task force on prescription opioid abuse, commissioned by the oldest drug abuse organization in the country, the College on Problems of Drug Dependence. We published our position statement in 2003, and it has been cited over 200 times in the peer-reviewed literature. Besides characterizing effects of oft-prescribed opioids, I also asked questions as to whether their subjective effects could be modulated by such factors as drug use history (light vs. moderate use of alcohol), personality (sensation seeking), and other drugs ingested simultaneously (e.g., alcohol). These studies have all recently been published and one study I was particularly excited about in terms of its results was examining oxycodone in combination with alcohol. We know from epidemiological studies that prescription opioids and alcohol are sometimes used at the same time for recreational purposes. One interesting question to ask is whether the combination produces a different profile of effects from either drug alone. My lab found that a low dose of alcohol (1.5 drinks) in combination with oxycodone produced increased liking relative to a placebo condition, whereas either drug tested alone did not increase liking. I intend to follow up this study, not only examining opioids but also other abused prescription drugs (stimulants, sedatives, musculoskeletal relaxants). I was also recently awarded a grant from NIDA to examine whether and to what degree some subjective or side effects of morphine might be medicated by peripheral mechanisms. This study question can be addressed via the use of a recently FDA-approved opioid antagonist, methylnaltrexone. Unlike other opiate antagonists that when administered block CNS effects induced by opioids, methylnaltrexone cannot penetrate the CNS, and so any opioid effects observed would have to be due to peripheral mechanisms. It is possible that such opioid-induced side effects as nausea and pruritis might be reduced by the blocker. Over the next two years, I will be conducting a study to investigate this possibility.
I have been fortunate to work in an anesthesiology department. The drugs that I have studied are not without side effects, some of which could be quite serious (respiratory depression), and some drugs I have studied can only be administered in an anesthesiology department (inhaled general anesthetics at sub anesthetic doses). We have anesthetists provide medical coverage during our studies, because safety is of paramount concern to me. Many of my colleagues at other institutions cannot do the studies I have done because they do not have the unique safety systems afforded to me by the Department of Anesthesia and Critical Care at the University of Chicago.
Zacny JP: What do we know (and not know) about prescription opioid misuse in the context of pain management? Pain Manage 1:395-398, 2011
Zacny JP, Paice JA, Coalson DW: Subjective and psychomotor effects of carisoprodol in combination with oxycodone in healthy volunteers. Drug Alcohol Depend, in press, 2011. Doi:10.1016/j.drugalcdep.2011.07.006.
Zacny JP, Paice JA, Coalson DW: Characterizing the subjective and psychomotor effects of carisoprodol in healthy volunteers. Pharmacol Biochem Behav 100:138-143, 2011
Zacny JP, Gutierrez, S: Subjective, psychomotor, and physiological effects of oxycodone alone and in combination with ethanol in healthy volunteers. Psychopharmacology epub ahead of print (PMID:21603891), 2011
Zacny JP, Gutierrez S, Kirulis K, McCracken SG: Psychopharmacological effects of oxycodone in volunteers with and without generalized anxiety disorder. Exp Clin Psychopharmacol 19:85-94, 2011
Niesters M, Dahan A, Kest B, Zacny J, Stijnen T, Aarts L, Sarton E: Do sex differences exist in opioid analgesia? A systematic review and meta-analysis of human experimental and clinical studies. Pain 151:61-68, 2010
Zacny JP, Jun JM: Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 112:251-254, 2010
Zacny JP, Drum M: Psychopharmacological effects of oxycodone in healthy volunteers: roles of alcohol-drinking status and sex. Drug Alcohol Depend 107:209-214, 2010
Zacny JP: A possible link between sensation-seeking status and positive subjective effects of oxycodone in healthy volunteers. Pharmacol Biochem Behav 95:113-120, 2010
Zacny JP, de Wit H: The prescription opioid, oxycodone, does not alter behavioral measures of impulsivity in healthy volunteers. Pharmacol Biochem Behav 94:108-113, 2009
Zacny JP, Gutierrez S: Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers. Drug Alcohol Depend 101:107-113, 2009
Zacny JP, Walker DJ, Derus LM: Choice of nitrous oxide and its subjective effects in light and moderate drinkers. Drug Alcohol Depend 98:163-168, 2008
Zacny JP, Lichtor SA: Nonmedical use of prescription opioids: Motive and ubiquity issues. J Pain 9:473-486, 2008
Zacny JP, Gutierrez S: Subjective, psychomotor, and physiological effects profile of hydrocodone/acetaminophen and oxycodone/acetaminophen combination products. Pain Med 9:433-443, 2008
Zacny JP, Lichtor SA: Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers. Psychopharmacology 196:105-117, 2008
Zacny JP: Chronic pain and driving: Proceed with caution. Pain 122:6-7, 2006
Beckman NJ, Zacny JP, Walker DJ: Within-subject comparison of the subjective and psychomotor effects of a gaseous anesthetic and two volatile anesthetics in healthy volunteers. Drug Alcohol Depend 81:89-95, 2006
Zacny JP: Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users. Drug Alcohol Depend 80:273-278, 2005
Zacny JP, Gutierrez S, Bolbolan SA: Profiling the subjective, psychomotor, and physiological effects of a hydrocodone/acetaminophen product in recreational drug users. Drug Alcohol Depend 78:243-252, 2005
Walker DJ, Beckman NJ, Zacny JP: Reinforcing and subjective effects of the volatile anesthetic, sevoflurane. Drug Alcohol Depend 76:191-201, 2004
Zacny JP, Beckman NJ: The effects of a cold water stimulus on butorphanol effects in males and females. Pharmacol Biochem Behav 78:653-659, 2004
Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP: Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 78:57-64, 2004
Zacny JP, Goldman RE: Characterizing the subjective, psychomotor, and physiological effects of oral propoxyphene in non-drug-abusers. Drug Alcohol Depend 73:133-140, 2004
Zacny JP, Gutierrez S: Characterizing the subjective, psychomotor, and physiological effects of oral oxycodone in non-drug-abusing volunteers. Psychopharmacology 170:242-254, 2003
Zacny J, Bigelow G, Compton P, Foley K, Iguchi M, Sannerud C: College on Problems of Drug Dependence Taskforce on Prescription Opioid Non-Medical Use and Abuse: Position Statement. Drug Alcohol Depend 69:215-232, 2003
Walker DJ, Zacny JP: Analysis of the reinforcing and subjective effects of different doses of nitrous oxide using a free-choice procedure. Drug Alcohol Depend 66:93-103, 2002
Zacny JP, Hurst RJ, Graham L, Janiszewski DJ: Pre-operative dental anxiety and mood changes during nitrous oxide inhalation. J Am Dent Assoc 133:82-88, 2002
Walker DJ, Zacny JP, Galva KE, Lichtor JL: Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action agonists in healthy volunteers. Psychopharmacology 155: 362-371, 2001
Walker DJ, Zacny JP: Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 64:85-96, 2001
Draganich LF, Zacny JP, Klafta J, Karrison T: The effects of antidepressants on obstructed and unobstructed gait in the healthy elderly. J Gerentol A Biol Sci Med Sci 56:M36-M41, 2001
Hill JL, Zacny JP: Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in normal volunteers. Psychopharmacology 152:31-39, 2000
Sadeghi P, Zacny JP: Anesthesia is a risk factor for drug and alcohol craving and relapse in ex-abusers: a hypothesis. Med Hypotheses 53:490-496, 1999
Walker DJ, Zacny JP: Subjective, psychomotor, and physiological effects of cumulative doses of opioid mu agonists in healthy volunteers. J Pharmacol Exp There 289:1454-1464, 1999
Black ML, Hill JL, Zacny JP: Behavioral and physiological effects of remifentanil and alfentanil in healthy volunteers. Anesthesiology 90:718-726, 1999
Zacny JP, Galinkin JL: Psychotropic drugs used in anesthesia practice: abuse liability and epidemiology of abuse. Anesthesiology 90:269-288, 1999
Zacny JP, Hill JL, Black ML, Sadeghi P: Comparing the subjective, psychomotor, and physiological effects of intravenous pentazocine and morphine in healthy volunteers. J of Pharmacol Exp There 286:1197-1207, 1998
Walker DJ, Zacny JP: Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers. Psychopharmacology 140:191-201, 1998
Zacny JP, Cho AM, Toledano AY, Galinkin J, Coalson DW, Klock PA, Klafta J M, Young CJ: Effects of information on the reinforcing, subjective, and psychomotor effects of nitrous oxide in healthy volunteers. Drug and Alcohol Depend 48:85-95, 1997
Zacny JP, Conley K, Galinkin J: Comparing the subjective, psychomotor, and physiological effects of buprenorphine and morphine in healthy volunteers. J Pharmacol Exp There 282:1187-1197, 1997
Young CJ, Coalson DW, Klock A, Klafta J, Goldsher G, Apfelbaum JL, Zacny JP: Analgesic and other effects of thiopental at steady-state concentrations in human volunteers. Acta Anaesthesiol Scand 41:903-910, 1997
Hasegawa AE, Zacny JP: Effects of three L-type calcium channel blockers on morphine effects in healthy volunteers. Anesth Analg 85:633-638, 1997
Conley KM, Toledano AY, Apfelbaum JL, Zacny JP: The modulating effects of a cold water stimulus on opioid effects in volunteers. Psychopharmacology 131: 313-320, 1997
Zacny JP, Conley K, Marks S: Comparing the subjective, psychomotor, and physiological effects of intravenous nalbuphine and morphine in healthy volunteers. J Pharmacol Exp There 280:1159-1169, 1997
Zacny JP: Should people taking opioids for medical reasons be allowed to work and drive? (Invited editorial). Addiction 91:1581-1584, 1996
Zacny JP, McKay MA, Toledano AY, Marks S, Young CJ, Klock PA, Apfelbaum JL: The effects of a cold-water immersion stressor on the reinforcing and subjective effects of fentanyl in healthy volunteers. Drug Alcohol Depend 42:133-142, 1996
Zacny JP, Cho AM, Coalson DW, Rupani G, Young CJ, Klafta JL, Klock PA, Apfelbaum JL: Differential acute tolerance development to effects of nitrous oxide in humans. Neurosci Lett, 209:73-76, 1996
Zacny JP, Lichtor JL, Klafta JM, Alessi R, Apfelbaum JL: The effects of transnasal butorphanol on mood and psychomotor functioning in healthy volunteers. Anesth Analg 82:931-935, 1996
Zacny JP: A review of the effects of opiates on psychomotor and cognitive functioning in humans. Exp Clin Psychopharmacol 3:432-466, 1995
Patil PG, Apfelbaum JL, Zacny JP: The effects of a cold-water stressor on psychomotor and cognitive functioning in humans. Physio Behav 58:1281-1286, 1995
Klafta JM, Zacny JP, Young CJ: Neurological and psychiatric adverse effects of anesthetics: Epidemiology and treatment. Drug Saf 13:281-295, 1995
Zacny JP, Yajnik S, Coalson D, Lichtor JL, Thapar P, Apfelbaum JL, Rupani G, Young C, Klafta J: Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report. Pharmacol Biochem Behav 51:815-819, 1995
Pirec V, Coalson DW, Lichtor JL, Klafta J, Young C, Rupani G, Apfelbaum JL, Zacny JP: Cold water immersion modulates the reinforcing effects of nitrous oxide in healthy volunteers. Exp Clin Psychopharmacol 3: 148-155, 1995
Thapar P, Zacny JP, Choi M, Apfelbaum JL: Objective and subjective impairment from often-used sedative combinations in ambulatory surgery, using alcohol as a benchmark. Anesth Analg 80:1092-1098, 1995
Zacny JP, Lichtor JL, Thapar P, Coalson DW, Flemming D, Thompson W: Comparing the subjective, psychomotor, and physiological effects of intravenous butorphanol and morphine in healthy volunteers. J Pharmacol Exp There 270:579-588, 1994
Zacny JP, Lichtor JL, Flemming D, Coalson DW, Thompson WK: A dose-response analysis of the subjective, psychomotor, and physiological effects of intravenous morphine in healthy volunteers. J Pharmacol Exp There 268:1-9, 1994
Zacny JP, Lichtor JL, Thompson W, Apfelbaum JL: Propofol at a sub anesthetic dose may have abuse potential in healthy volunteers. Anesth Analg 77:544-552, 1993
Zacny JP, Lichtor JL, Zaragoza JG, de Wit H: Subjective and behavioral responses to intravenous fentanyl in healthy volunteers. Psychopharmacology 107:319-326, 1992
