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Is caffeine a drug of dependence? criteria and comparisons
Published in B.S. Gupta, Uma Gupta, Caffeine and Behavior, 2020
Stephen J. Heishman, Jack E. Henningfield
Drug-induced euphoria has been postulated as a predictor of a drug’s reinforcing effects and its dependence potential.74,75 As discussed, caffeine typically produces positive mood changes at low to intermediate doses (50 to 300 mg), whereas doses in the 300 to 500 mg range can produce positive or negative subjective effects. The ability of caffeine to produce euphoria and dysphoria in the same dosage range may function to limit caffeine’s dependence potential. Some studies have shown that caffeine at low to intermediate doses increased ratings of drug “liking” and scores on the MBG scale, two subjective measures of drugs of dependence.11,33,34 However, these positive mood effects of caffeine are typically less reliably observed and of lesser magnitude than those reported for known drugs of dependence, such as d-amphetamine.
The Current Status of the Incentive Sensitization Theory of Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Mike J. F. Robinson, Terry E. Robinson, Kent C. Berridge
Sensitization has also been demonstrated in the brains of ordinary people, as direct elevation of the amount of mesolimbic dopamine released in response to an addictive drug. For example, significantly greater amphetamine-induced ventral striatal dopamine release was observed two weeks and again one year after the administration of three drug doses over a one-week period (Boileau et al. 2006). Compelling evidence for neural sensitization of dopamine release has also been shown in Parkinson patients with dopamine dysregulation syndrome (DDS) (Evans et al. 2006). This leads to compulsive use of dopaminergic drug medications, with increased reports of drug wanting but not drug liking, and increased dopamine release in the ventral striatum especially in the combined presence of cues and the dopamine-stimulating drug. Consequent incentive-sensitization may also manifest itself by pathological gambling, hypersexuality, food bingeing and punding (a form of complex behavioral stereotypy). Conversely, there was no apparent sensitization to how much subjects liked amphetamine or other dopamine-stimulating drugs in the aforementioned studies.
Assessment of Moderator and Mediator Effects
Published in Gueorguieva Ralitza, Statistical Methods in Psychiatry and Related Fields, 2017
The human laboratory study of the effects of menthol on nicotine reinforcement in smokers introduced in Section 1.5.7 has a two-level cross-over experimental design with three different levels of menthol (high, low, placebo) administered on three different test days in random order. Within each test day, again in random order, three different nicotine concentrations (saline, low dose, high dose) were infused and effects of nicotine were measured using the Drug Effects Questionnaire scale. The design of the study is shown in Figure 1.12. In Chapter 5, we used these data to illustrate the non-parametric approach to the analysis of repeated measures data. We looked at menthol and nicotine effects and their interactions on drug liking effects. Herein, we focus on the entire sample of subjects and on a different outcome; namely, maximum stimulatory effects during each infusion. The sample consists of two types of individuals: those who smoke mentholated cigarettes and those who smoke non-mentholated cigarettes. The question of interest here is whether nicotine and menthol effects vary depending on the preferred type of cigarettes smoked. Thus, we are investigating whether preference for mentholated cigarettes is a moderator of nicotine and menthol effects. Note that the potential moderator in this study is pre-specified and randomization is stratified on it, thus guaranteeing that there is no relationship between the moderator and the treatments.
What is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion
Published in Expert Review of Clinical Pharmacology, 2022
Louise Carton, Romain Icick, Sébastien Weibel, Maurice Dematteis, Etienne Kammerer, Anne Batisse, Benjamin Rolland
The abuse potential of LDX has also been assessed through safety data from randomized clinical trials (RCT) evaluating the efficacy of LDX in various conditions. Among 259 patients included in the safety analysis of LDX for treatment in adults with moderate-to-severe BED, one case of death related to methamphetamine overdose was reported; however, the study investigator did not consider this death to be related to the study drug [19]. In a phase III RCT, 12-month extension safety and tolerability trial of LDX in adults with BED enrolling 604 participants, a subject with no history of drug dependence dropped out of the study due to intermittent drug craving [20]. In a clinical trial evaluating LDX as an adjunctive treatment for bipolar disorder in 25 patients, one case of suspected misuse was reported (medication tampering) [21]. A phase-II dose escalation study evaluating safety and tolerability of oral LDX in 16 adults with methamphetamine dependence found that the ‘high’ item of the Drug Effects Questionnaire 5 (DEQ5) increased from a median score of 9 (IQR: 2–35) to 28 (IQR: 5–48) (z = 2.622, p = 0.009). Other changes in the drug liking effects were not significant [22].
Human abuse potential studies of abuse-deterrent opioids: lessons from oral and intranasal studies with morphine abuse-deterrent, extended-release, injection-molded tablets
Published in Current Medical Research and Opinion, 2018
Lynn R. Webster, Eugene R. Viscusi, Colville Brown, Jeffrey M. Dayno
Blood samples were collected for analysis of plasma morphine concentrations and the calculation of PK parameters (Table 1) in both studies. The primary PD end-point of both studies was the peak effect (Emax) of Drug Liking using a 0–100 bipolar Drug Liking Visual Analog Scale (VAS; 0 = “strong disliking”; 50 = “neither like nor dislike”; 100 = “strong liking”). Drug Liking VAS scores were collected at multiple discrete time points (pre-dose through 24 h post-dose), and, therefore, provide an assessment of drug attractiveness at a particular moment in time, with Emax representing the pinnacle of a drug’s attractiveness for each participant. Secondary PD outcomes of each study are summarized in Table 1. Key secondary end-points in the HAP studies were Overall Drug Liking (0 = “strong disliking”; 50 = “neither like nor dislike”; 100 = “strong liking”) and the Take Drug Again Assessment (0 = “definitely would not”; 50 = “do not care”; 100 = “definitely would”), which were assessed at 12 and 24 h post-treatment. This is a global, retrospective assessment of the participants’ experiences after study medication administration.
Modeling the potential impact of abuse-deterrent opioids on medical resource utilization
Published in Journal of Medical Economics, 2019
Mihran A. Yenikomshian, Alan G. White, Michael E. Carson, Zitong B. Jia, Mario R. Mendoza, Carl L. Roland
Previous work by White et al.11 has estimated potential cost savings associated with a hypothetical abuse-deterrent opioid from a private-payer perspective. White et al.12 have also quantified the association between positive subjective measures from human abuse potential studies and non-medical use of abuse-deterrent opioids12. Positive subjective measures quantify the experience of drug liking and drug high from various drugs among study participants. The positive subjective measures score includes both positive and negative experiences with the drug. Reductions in the positive subjective measure of an abuse-deterrent opioid from the non-abuse-deterrent opioid have been correlated with reductions in non-medical use12.