Heroin Craving and Drug Use in Opioid-Maintained Volunteers: Effects of Methadone Dose Variations Mark K. Greenwald Wayne State University School of Medicine Recent data indicate that opioid agonist and antagonist challenges decrease and increase (respectively) heroin craving in physically dependent individuals. This study investigated effects of methadone dose variations on craving and new drug use in 18 outpatients who were given money contingencies. In Phase 1, volunteers were told in different test sessions that methadone dose would increase, decrease, or stay the same; drug-abstinence contingencies were suspended for 24 hr. Craving significantly increased and new heroin use marginally increased (relative to maintenance dose) only when a dose reduction was paired with a dose decrease instruction. In Phase 2 (detoxification), craving and heroin use significantly in- creased as methadone dose decreased. Thus, loss of -receptor agonist effect increased craving and risk of relapse. Drug craving is a verbal behavioral measure of drug-use intent among drug-abusing individuals that is acquired and maintained by environmental, pharmacological, and indi- vidual difference factors. The empirical relationship be- tween craving and drug use is not understood well and consequences of craving, for example, in predicting relapse to drug use, are not clear (Pickens & Johanson, 1992; Tiffany, 1992). Efforts have been made to improve craving assessment through the use of multidimensional scales that measure independent components (e.g., positive vs. nega- tive reinforcement and intensity) of craving. This study used the Heroin Craving Questionnaire (HCQ; Schuster, Green- wald, Johanson, & Heishman, 1995) to examine changes in craving among methadone-maintained individuals. Para- metric studies are needed to identify situations in which heroin craving (dependence symptom) is related or unre- lated to drug use (dependence sign). Pharmacological factors have been shown to modulate heroin craving. -opioid agonists decrease craving (Green- wald, Johanson, & Schuster, 1999; Greenwald & Roehrs, 2001) and naloxone challenge increases craving in opioid- maintained volunteers (Eissenberg et al., 1996; Schuster et al., 1995). Thus, in opioid-dependent individuals, pharma- cological agents produce differential (agonist vs. antago- nist-induced) craving changes along a continuum. Another pharmacological method to probe craving is to alter main- tenance dose. Stitzer, Bigelow, and Liebson (1984) studied the detectability and subjective effects (not including crav- ing) of single-day dose variations in 19 male methadone- maintained volunteers. Stitzer et al. (1984) varied size of the dose change (from 0% to 200% of maintenance), whether information (not blinded) versus no information (blinded) was given about the dose change, and whether taste cues were available. Larger dose changes were more readily detected, level of information had little effect, and with taste cues absent, volunteers only reliably detected dose de- creases. The investigators concluded that although a similar pattern of symptoms was observed under blinded and non- blinded dose changes, suggestibility might play an impor- tant role in clinical situations. Indeed, cognitive factors may also influence heroin crav- ing. Presenting heroin cues increases craving in untreated heroin users (Sherman, Zinser, Sideroff, & Baker, 1989), methadone-maintained volunteers (Childress, McLellan, & O’Brien, 1986; Sell, Cowen, & Robson, 1995), and those who are undergoing (Sideroff & Jarvik, 1980; Weinstein, Wilson, Bailey, Myles, & Nutt, 1997) or have completed methadone detoxification (Franken, de Hann, van der Meer, Haffmans, & Hendriks, 1999; Powell et al., 1990; Powell, Bradley, & Gray, 1992). In methadone-maintained volun- teers, a dose change instruction is a symbolic cue that could alter perceived adequacy of the daily methadone dose; this could indirectly prompt changes in heroin craving and drug use. The purpose of this two-phase study was to determine whether methadone dose variations precipitate changes in heroin craving and new drug use in recently abstinent vol- unteers. The first aim (Phase 1) was to extend the work of Stitzer et al. (1984) and Curran, Bolton, Wanigaratne, and Smyth (1999) by manipulating actual bioavailability of methadone (through dose changes) and expected availabil- ity of methadone (through instructions). It was predicted that a 1-day methadone dose decrease would increase heroin craving and that a 1-day dose increase would decrease This research was supported by National Institute on Drug Abuse Grant R29 DA11079 and Joe Young Funds from the State of Michigan. I thank Ken Bates, Debra Kish, Loraine DiCerbo, Ja’Near Mathis, Dawanda Cooper, and Ingrid Branch for research assistance; Karen Downey and John Hopper for diagnostic screen- ing; and Charles Schuster for commenting on earlier drafts of this article. Correspondence concerning this article should be addressed to Mark K. Greenwald, Substance Abuse Research Division, Depart- ment of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2761 East Jefferson Avenue, De- troit, Michigan 48207. E-mail: mgreen@med.wayne.edu Experimental and Clinical Psychopharmacology Copyright 2002 by the American Psychological Association, Inc. 2002, Vol. 10, No. 1, 39 – 46 1064-1297/02/$5.00 DOI: 10.1037//1064-1297.10.1.39 39