Although alcohol and nicotine administration studies have demonstrated that manipulating subjects' expectancies regarding drug content affects drug response, research with marijuana has not adequately studied drug expectancy effects. The present pilot study was the first to evaluate the credibility and effect of expectancy manipulation on subjective measures and smoking patterns using a marijuana administration balanced-placebo design (BPD). In a 2 × 2 instructional set (told delta-9-tetrahydrocannabinol [THC] vs. told no THC) by drug (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, the authors examined the effect of marijuana expectancy manipulation and the pharmacologic effect on affective and physiologic measures, cigarette ratings, and smoking behavior with 20 marijuana smokers (mean age = 20 years; 25% female). Large main effects of expectancy were found on ratings of cigarette potency, strength, taste, smell, and satisfaction, and observed smoking behavior. Pharmacologic effects were particularly evident for self-reported physical reactions to marijuana and cigarette potency and satisfaction ratings. This study demonstrated the feasibility of the BPD research with marijuana and yielded promising results for future studies examining the independent and combined effects of marijuana pharmacology and expectancies. Keywords marijuana; cannabis; placebo; expectancy; drug Expected effects of drugs are considered important determinants of behavioral and subjective responses to a drug independent of the pharmacological action of that drug (Vogel-Sprott & Fillmore, 1999). A drug-taking situation involves expectations that a particular drug was administered (i.e., stimulus expectancy) and expectancies about the effects or consequences associated with using the drug (i.e., outcome expectancies). The balanced-placebo design (BPD) is the optimal method for separating pharmacological effects from the cognitive expectations of receiving the drug and its effects (Marlatt & Rohsenow, 1980). This 2 × 2 Correspondence concerning this article should be addressed to Jane Metrik, Center for Alcohol and Addiction Studies, Brown University, Box G-S121-5, Providence, RI 02912. Jane_Metrik@brown.edu. NIH Public Access Author ManuscriptExp Clin Psychopharmacol. Author manuscript; available in PMC 2010 January 25. factorial design crosses the substance that is administered to the participant (drug or placebo) with instructions that are given to the participant about the drug content (drug or placebo). Thus, half of the participants are told they are receiving a drug, and half are told they are receiving no drug (i.e., instructional set manipulation). Half of the participants in each of those instructional conditions actually receive the drug and half do not. This improves on the standard placebo-controlled design by allowing a determination of expectancy effects independent of pharmacologic effects and vice versa (Rohsenow & Marlatt, 1981) and the "antiplacebo" effect of the pharmacological action of the...

Associations of alcohol dehydrogenase (ADH) gene polymorphisms (ADH1B*2 and ADH1C*1) with a lifetime alcohol use disorder (AUD) were examined in White college students. Alcohol-related endophenotypes likely to be influenced by elevations in acetaldehyde were also assessed. Individuals with an ADH1B*2 allele had lower rates of AUDs, consumed a lower maximum number of drinks in a 24-hr period, reported a greater level of response to alcohol, were more likely to have experienced alcohol-induced headaches following 1 or 2 drinks, and reported more severe hangovers than those lacking this allele. These findings are consistent with the hypothesis that enhanced sensitivity to alcohol and lower levels of alcohol use reflect the mechanism by which ADH1B*2 protects against developing an AUD.

This study examined aldehyde dehydrogense (ALDH2) gene status, alcohol dehydrogense (ADH2) gene status, conduct disorder, and alcohol dependence in Chinese, Korean, and White American college students. Chinese had a lower rate of alcohol dependence (5%) than Koreans (13%) and Whites (17%). Koreans had a higher rate of conduct disorder (15%) than Whites (9%) and Chinese (6%). The relationship of ethnicity to alcohol dependence was mediated by ALDH2 status and conduct disorder, although Chinese ethnicity remained significant. ADH2 status was not related to alcohol dependence with ALDH2 included, and no interactions were significant. Results suggest that different rates of risk (e.g., conduct disorder) and protective (e.g., ALDH2 status) factors partially account for ethnic differences in rates of alcohol dependence.

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This article summarizes a symposium that was organized by Dr. Kim Fromme and presented at the 2003 annual meeting of the Research Society on Alcoholism in Ft. Lauderdale, Florida. The four presentations illustrate the emerging technologies and methods that are now being used to investigate the genetic basis of differential sensitivity to alcohol and their behavioral manifestations. Combining human genotyping with laboratory measures of behavior and subjective reports, these presentations represent state-of-the-art approaches to crossing the bridge from the Decade of the Brain to the Decade of Behavior. Dr. De Wit's paper describes her research on the neurobiological basis for individual differences in sensitivity to the stimulant and sedative effects of alcohol. Evidence suggests that activity of the dopaminergic and GABAergic neurotransmitters underlie these stimulant and sedative effects, respectively. Both Drs. Hutchison's and Corbin's papers describe their research on polymorphisms for the serotonin transporter (SLC6A4) as a determinant of the subjective effects of alcohol challenge. Dr. Hutchinson's and Ms. Ray's findings indicate that individuals with the short form of the SLC6A4 alleles (S) demonstrated a low level of response to alcohol, thus supporting previous research that the S allele may be associated with increased risk for alcohol dependence. In contrast, Dr. Corbin did not find a reliable association between the SLC6A4 genotype and subjective response to alcohol. Mr. Cook's and Dr. Wall's paper adds another dimension to this article by presenting research on both the aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH2) genetic variants and their association with the alcohol-related flushing response that is prevalent in Asian populations. Dr. David Goldman provides concluding remarks.