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Biomedical subjects

K L Preston

Publications and source records attributed to K L Preston.

At least 91 records · Page 5Linked to original sources
PubMed1990

Low-dose caffeine physical dependence in humans.

This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

Adult↗
PubMed1990

Low-dose caffeine discrimination in humans.

A novel drug discrimination procedure was used to study the discriminability and subjective effects of caffeine in seven human volunteers who abstained from dietary sources of caffeine. Daily sessions involved p.o. ingestion of two capsules sequentially, one of which contained caffeine and the other placebo, under double-blind conditions. Each day subjects attempted to identify and were later informed which capsule contained caffeine and which contained placebo. All subjects acquired rapidly the initial discrimination (100 or 178 mg vs. placebo). Examination of progressively lower caffeine doses showed that accuracy and ratings of confidence in accuracy were increasing functions of dose. There were individual differences in the lowest discriminable dose: three subjects discriminated 56 mg, three discriminated 18 mg and one discriminated 10 mg. Discrimination accuracy was usually higher after the second capsule than after the first capsule. All subjects indicated that they believed that they made the discrimination predominantly on the basis of central effects of caffeine vs. placebo, such as changes in mood and socializing. Compared to placebo, 100 mg of caffeine increased ratings of alertness, well-being, social disposition, motivation for work, concentration, energy and self-confidence and decreased ratings of headache and sleepiness. This dose of caffeine also produced a large increase in a measure of "euphoria." The present study documents biological activity of caffeine at lower doses than heretofore recognized. The general approach to investigating the effects of low drug doses may have broad application in human psychopharmacology research for characterizing other subtle psychotropic effects.

Adult↗
PubMed1989

Antagonist effects of nalbuphine in opioid-dependent human volunteers.

The subjective, physiological and behavioral effects of nalbuphine, an opioid mixed agonist/antagonist analgesic, naloxone and hydromorphone were studied on adult, male, methadone-dependent volunteers living on a clinical research ward. The purpose was to assess nalbuphine's agonist properties vs. antagonist properties relative to a standard agonist (hydromorphone) and a standard antagonist (naloxone) in opioid-dependent subjects. Drug conditions included saline placebo, nalbuphine hydrochloride (0.375, 0.75, 1.5, 3 and 6 mg), naloxone hydrochloride (0.1 and 0.2 mg) and hydromorphone hydrochloride (4 and 8 mg). Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5 hr experimental sessions. Physiologic measures were monitored continuously before and for 2 hr after drug administration: pupil diameter and subject- and observer-rated behavioral responses were measured intermittently over this same period. Hydromorphone increased ratings significantly on subjective measures typical of morphine-like effects. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Nalbuphine produced effects which were qualitatively similar to the effects of naloxone and showed no evidence of opioid agonist effects in these methadone-dependent subjects. The withdrawal syndrome precipitated by nalbuphine was indistinguishable from that produced by naloxone.

Adult↗
PubMed1989

Drug discrimination in human postaddicts: agonist-antagonist opioids.

To assess the stimulus properties of opioid mixed agonist-antagonist drugs in humans, postaddict volunteers were trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. given saline (4 ml), hydromorphone (3 mg/70 kg) and pentazocine (45 mg/70 kg). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were also collected. After training, subjects were tested for their ability to discriminate between the three drugs; generalization curves for the training drugs and three mixed agonist-antagonist test drugs (butorphanol, nalbuphine and buprenorphine) were then determined. In generalization testing both hydromorphone and pentazocine produced dose-related increases in drug-appropriate responses and in characteristic subjective effects measures. Butorphanol produced dose-related increases in identifications as pentazocine and in those subjective effect measures increased by pentazocine. Nalbuphine was not consistently identified as either pentazocine or hydromorphone and produced relatively flat dose-response functions on most of the subjective effect measures. At the three highest doses tested buprenorphine was identified in 50% of trials as hydromorphone and in 50% of trials as pentazocine in the discrimination measures and increased subjective effect scales which were characteristic of both hydromorphone and pentazocine. The results are most consistent with butorphanol having the stimulus properties of a kappa agonist and both nalbuphine and buprenorphine having the stimulus properties of partial mu agonists although the profiles of observed drug effects were complicated and not entirely consistent with a simple mu/kappa opioid receptor model.

Adult↗
PubMed1989

Opioid drug discrimination in humans: stability, specificity and relation to self-reported drug effect.

Non-dependent volunteers with histories of opioid use were trained in a three-choice drug-discrimination procedure to discriminate the effects of i.m. saline, hydromorphone hydrochloride (3 mg/70 kg) and pentazocine lactate (45 mg/70 kg). In daily sessions, monetary reinforcement was contingent upon correctly identifying by letter code, the drug administered; measures of drug discrimination included an operant procedure and a qualitative and a quantitative choice procedure. Drug effects were assessed concurrently on self reports and physiological indices. After acquisition of the discrimination, subjects were tested for generalization to: 1) a range of doses of the training drugs, 2) p.o. doses of the training drugs and 3) novel drugs. The discrimination was readily learned and all three discrimination measures were comparable. Discrimination performance, as well as self reports and physiological effects, remained stable over the course of the study, suggesting that tolerance did not develop in the daily session procedure. Testing with a range of doses of the training drugs resulted in dose-related effects in discrimination performance, physiological effects and self-reported drug effect. Oral doses of the training drugs resulted in partial generalization to the i.m. training doses, compatible with the attenuated subjective effects of the p.o. doses. Novel drugs (d-amphetamine, 10-20 mg p.o.; Lorazepam, 2-4 mg p.o.; and secobarbital, 100-200 mg p.o.) did not generalize to hydromorphone, but showed partial generalization to both pentazocine and saline. In general, drug-discrimination performance paralleled the patterns of self reports.

Adult↗
PubMed1989

Heat retention in varieties of warm compresses: a comparison between warm soaks, hard-boiled eggs and the re-heater.

Warm compresses are the most common form of treatment for chalazia and other inflammatory conditions of the eyelids. We compared the heat retention characteristics of warm washcloths, hard-boiled eggs, and a heat-generating product called the Re-Heater when used for delivering heat to the eyelids. Skin temperature was measured during 20-minute applications of each "device." The Re-Heater had the best total heat delivery, followed closely by the hard-boiled egg. Both of these methods are reusable, easy, and cause no discomfort. We recommend that physicians instruct their patients in the use of either of these techniques when heat application to the eyelids is desired.

Bandages↗
PubMed1989

Evaluation of the abuse potential of methocarbamol.

The subjective and behavioral effects of p.o. administered methocarbamol, lorazepam and placebo were studied in a nonresidential group of adult male volunteers with histories of recreational substance abuse including sedative/hypnotics. In the first phase of the investigation, a dose run-up of methocarbamol (up to 12 g) was conducted in six subjects to determine appropriate doses. In the second phase, a randomized block cross-over study using 14 subjects was conducted. The following drug conditions were tested in the cross-over phase: placebo, lorazepam 1, 2 and 4 mg, and methocarbamol 2.25, 4.5 and 9 g. Drug conditions were tested under double-blind conditions. Psychomotor and cognitive performance measures and subject- and observer-rated behavioral responses were measured daily before dosing and for 5.5 hr after drug administration. The results showed that both lorazepam and methocarbamol produced statistically significant dose-related increases in subjects' ratings of drug effect and liking, although only lorazepam increased morphine-benzedrine group (MGB) scale scores. Methocarbamol also increased ratings on measures indicating the emergence of dysphoric and other side effects at high doses. Both drugs impaired psychomotor and cognitive performance, with lorazepam generally producing greater effects than methocarbamol. The results indicate that methocarbamol, at doses well above those used therapeutically, has some potential to be abused by persons with histories of sedative/hypnotic abuse; however, this potential for abuse is probably decreased by the accompanying side effects at high doses and is probably less than that of lorazepam.

Adolescent↗
PubMed1988

Buprenorphine and naloxone alone and in combination in opioid-dependent humans.

Subjective, physiological and behavioral effects of subcutaneously administered hydromorphone (6 mg), naloxone (0.2 mg), buprenorphine (0.2 and 0.3 mg), and two buprenorphine-naloxone combinations (buprenorphine 0.2 mg plus naloxone 0.2 mg and buprenorphine 0.3 mg plus naloxone 0.2 mg) were assessed under double-blind conditions in six opioid-dependent volunteers. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 120 min after drug administration. Hydromorphone decreased pupil diameter and respiration, increased blood pressure and increased scores on subjective measures indicating opioid-like effects. Buprenorphine given alone had no significant effect on any variable measured. Naloxone given alone produced opioid abstinence-like effects which were measurable on subject- and observer-rated behavioral measures and physiological measures. Buprenorphine in combination with naloxone somewhat attenuated the naloxone-precipitated withdrawal response. Overall, the naloxone-buprenorphine combinations produced effects which were qualitatively similar to the effects of naloxone alone, suggesting a low potential for abuse of the combination product by opioid-dependent individuals.

Adult↗
PubMed1988

Butorphanol-precipitated withdrawal in opioid-dependent human volunteers.

The subjective, physiological and behavioral effects of hydromorphone, naloxone and butorphanol, an opioid agonist/antagonist analgesic, were studied in adult, male, methadone-dependent volunteers living on a clinical research ward. Drug conditions included saline placebo, 4 and 8 mg of hydromorphone HCl, 0.375, 0.75, 1.5, 3 and 6 mg of butorphanol tartrate and 0.1 and 0.2 mg of naloxone HCl. Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5-hr experimental sessions. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 2 hr after drug administration. Hydromorphone decreased pupil diameter, and significantly increased ratings of "Good Effects" on the subjective measures. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Butorphanol produced effects which were generally similar to the effects of naloxone, indicating that butorphanol doses precipitate withdrawal signs and symptoms when administered to methadone-dependent humans. There were some differences in the withdrawal syndromes precipitated by naloxone vs. butorphanol, suggesting that multiple mechanisms may be involved in opioid withdrawal precipitation.

Adult↗
PubMed1987

A comparative assay of nefopam, morphine and d-amphetamine.

Nefopam is a non-opioid analgesic reported to have some stimulant properties. The subjective, behavioral and physiological effects of nefopam, morphine and d-amphetamine were compared in seven non-dependent substance abusers to assess the abuse potential of nefopam. Morphine and d-amphetamine had significant effects on a number of measures generally consistent with the effects of drugs of the opioid and psychomotor stimulant drug classes. Subjects correctly discriminated between morphine and d-amphetamine. Nefopam was most frequently identified by subjects as being amphetamine-like, though several measures indicated that nefopam produced some sedation. Little or no "liking" of the effects of nefopam was reported by subjects. Overall, nefopam was one fifth as potent as morphine and one quarter as potent as d-amphetamine in producing subjective and physiological effects. The results indicate that nefopam is neither entirely morphine-like nor d-amphetamine-like. In our opinion, nefopam has a lesser potential to be abused than morphine or d-amphetamine.

Behavior↗
PubMed1987

Validation of the acuity card procedure for assessment of infants with ocular disorders.

The acuity card procedure has been shown to be a rapid method for the assessment of monocular and binocular grating acuity in normal infants from birth through 36 months of age. The current study seeks to validate the procedure further by using the acuity cards to assess 20 2- to 8-month-old infant patients with ocular disorders, including aphakia, strabismus, ptosis, and orbital hemangioma. Assessments were made with the acuity cards by two different observers, both blind to the infant's diagnosis, and by a third observer using a traditional forced-choice preferential looking (FPL) procedure. One hundred percent of the infant patients completed both binocular and monocular acuity card testing in an average time of 8 minutes per test. Interobserver agreement between acuity card observers and inter-technique agreement were high, and were sustained in individual cases in which the infant's acuity was not predictable from its visible signs. These results help to establish the potential clinical utility of the acuity card procedure for the assessment of infant patients.

Evaluation Studies as Topic↗
PubMed1987

Three-choice drug discrimination in opioid-dependent humans: hydromorphone, naloxone and saline.

Opioid-dependent volunteers were trained in a three-choice drug discrimination procedure to discriminate between the effects of i.m. administered saline (0.5 ml), hydromorphone hydrochloride (10 mg) and naloxone hydrochloride (0.15 mg). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Subjects received a single drug administration in each daily experimental session. During each session, subjective and physiological effects and three behavioral measures of discrimination (including an operant response, a qualitative response and a quantitative response) were collected. The study was done in three phases: a training phase in which training drugs were identified to subjects by letter code before the session, a test of acquisition phase in which the subject's ability to identify the training drug by letter code was tested and a generalization phase in which dose-response curves for the two active training drugs were tested. Results of acquisition testing of the training drug doses were similar in all three discrimination measures. The two active drugs produced contrasting effects on the various subjective report measures (opioid agonist-like effects vs. opioid withdrawal-like effects). In generalization testing, hydromorphone produced dose-related hydromorphone-appropriate responding, and naloxone produced dose-related naloxone-appropriate responding. Lowest doses of each drug produced saline-appropriate responding; there was no cross-generalization between either active drug. Similarly, hydromorphone and naloxone produced orderly dose-dependent effects on subjective effect scales similar to those produced by the training doses.

Adult↗