Diana J. Walker

Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers

Abstract The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included to test this assumption. Codeine and morphine increased ratings of “feel drug effect” but had little effect on other subjective measures, including the Addiction Research Center Inventory, visual analog scales, and adjective checklists. The few subjective effects that were observed were modest and were dose-related for morphine but not for codeine. The drugs did not affect performance on Maddox-Wing, digit-symbol substitution, coordination, auditory reaction, reasoning, and memory tests. Dose-related decreases in pupil size (miosis) were observed following codeine and morphine. Ratings of pain intensity decreased in a dose-related manner for morphine but not for codeine. Plasma codeine and morphine levels varied as an orderly function of dose. These results suggest that oral codeine and morphine are appropriate drugs for outpatient pain relief because they are effective analgesics at doses that have only modest effects on mood, produce few side effects, and do not impair performance. The results also suggest a possible ceiling effect of codeine on analgesia and subjective effects.

Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers

Valerian is the common name given to the genus Valeriana, an odiferous, herbaceous perennial plant widely distributed in the temperate regions of Asia, Europe, and North America. It is among the most widely used herbal medicines in the world. Numerous clinical studies have demonstrated valerians ability to improve sleep; however, to the best of our knowledge, no study has systematically assessed subjective and psychomotor/cognitive effects of valerian in young healthy adults across a range of doses. In the present study, we sought to determine whether valerian extract (Valeriana officinalis) altered mood and/or impaired psychomotor/cognitive performance in young healthy volunteers. We examined the effects of valerian extract (600, 1200, and 1800 mg) and 10 mg diazepam (positive control) compared to placebo in 10 young healthy volunteers. Dependent measures included subjective and psychomotor variables. The valerian extract had no significant effects on any of the dependent measures. Diazepam, though, produced subjective effects as measured by four different rating scales, and impaired psychomotor/cognitive performance. The data suggest that acute administration of valerian does not have mood-altering or psychomotor/cognitive effects in young healthy volunteers.

Measures of IMplIcIt and explIcIt attItudes toward MaInstreaM and BdsM sexual terMs usIng the Irap and QuestIonnaIre wIth BdsM/fetIsh and student partIcIpants

The Implicit Relational Assessment Procedure (IRAP) examines implicit attitudes through the measurement of response latencies. In this study, the IRAP was used to assess implicit attitudes toward “mainstream” sexual terms (e.g., Kissing) and “BDSM” terms (e.g., Bondage) among individuals reporting BDSM interests and among students who did not report such interests. A questionnaire was used to measure explicit attitudes toward the same sexual terms as well as self-reported sexual behaviors. Results showed that the Student group generally displayed pro-mainstream attitudes, while the BDSM group displayed pro-BDSM attitudes. These effects were mirrored in the questionnaire results, which provides support for the IRAP as a potentially useful tool in measuring participant attitudes toward complex sexual stimuli.

Attenuation of cocaine-induced response-rate increases during repeated administration despite increases in rate of reinforcement

Abstract Repeated administration of cocaine often results in tolerance to its effects on operant behavior. The tolerance is often associated with an initial drug effect that results in loss of reinforcement. Cocaine can also produce effects that result in a gain of reinforcement, and it is not known if tolerance will be observed in such a circumstance. The present experiments investigated whether tolerance would develop when cocaine was administered repeatedly to subjects who experienced an increase in the frequency of reinforcement when cocaine was administered acutely. Pigeons were trained to peck a response key under fixed-ratio schedules of food presentation. The ratio value for each pigeon was chosen such that performance indicated that the ratio was relatively large, and produced ”ratio strain.”. Cocaine was administered acutely (once per week), and then subsequently a dose was chosen and administered before each session. Once performance under the daily drug regimen was stable, other doses occasionally were substituted for the usual daily dose. Acute administration of cocaine (0.3–10.0 mg/kg) revealed substantial increases of 100% or more in response rate, and therefore equivalent increases in rate of food presentation, at some doses. That finding permitted examination of the role of drug-induced increases in rate of reinforcement during repeated administration of a response-rate-increasing dose. Repeated, daily administration of a rate-increasing dose resulted in attenuation of the effects of that dose, and subsequent administration of other doses that previously had increased response rates revealed that these doses, too, had lost their ability to increase rates. That is, ”tolerance” developed to the rate-increasing effects, even though the rate increases were associated with more frequent access to food. These findings suggest that ”reinforcement gain” may not be sufficient to prevent tolerance from developing to effects of cocaine on operant behavior.

An adjusting-dose procedure for assessing the reinforcing effects of nitrous oxide with humans ☆

Despite continued abuse, there is a paucity of empirical investigations on inhalants as reinforcers. The present study attempted to derive a method for studying the reinforcing effects of nitrous oxide (N2O) with human participants. An adjusting-dose procedure was employed to assess choice allocation for inhalation periods of varying doses of N2O. After experiencing the experimental parameters in forced-choice trials, participants made choices between a fixed dose of 0% N2O (i.e., 100% O2) and an adjusting dose of N2O (0-50% N2O in O2). The adjusting dose titrated as a function of the participants choices. Conditions were run to stability and systematically replicated within-subject. Stable choice allocation served as both the chief dependent variable and an indication of the optimal reinforcing dose of N2O for that participant. Consistent with previous research on N2O, there was between-subject variability in the reinforcing effects of N2O; however, stable within-subject choice allocation was observed for 6 out of 8 participants. This method of assessing drug choice in humans allows for the testing of multiple doses within-subject, which is imperative, given that the reinforcing effects of drugs are known to vary across subjects and as a function of dose.