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Biomedical subjects

R J Lamb

Publications and source records attributed to R J Lamb.

At least 19 recordsLinked to original sources
PubMed2000

Effects of Delta 9-tetrahydrocannabinol, (R)-methanandamide, SR 141716,and d-amphetamine before and during daily Delta 9-tetrahydrocannabinol dosing.

We examined the effects of Delta 9-tetrahydrocannabinol (Delta 9-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide, AM 356), SR 141716, and d-amphetamine on fixed-ratio (FR) responding maintained by food in rats before and during daily dosing with Delta 9-THC. Rats responded under a FR 10 schedule of food reinforcement. Cumulative dose-response curves for the various drugs were determined before and during daily Delta 9-THC administration. All four drugs dose-dependently decreased responding both before and during daily dosing with Delta 9-THC (18 mg/kg/day). The dose-response curves for both Delta 9-THC and (R)-methanandamide were shifted to the right with daily dosing with Delta 9-THC, indicating tolerance to the effects of Delta 9-THC and cross-tolerance to the effects of (R)-methanandamide. The doses of d-amphetamine examined produced similar effects both before and during daily dosing with Delta 9-THC. The effects of SR 141716 were not consistently altered by daily Delta 9-THC administration. These results indicate that tolerance develops to the effects of Delta 9-THC, when Delta 9-THC is administered repeatedly. These results also indicate that cross-tolerance to (R)-methanandamide develops with repeated Delta 9-THC administration.

Animals↗
PubMed2000

Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats: a systematic replication.

Järbe et al. (1998a) trained rats to discriminate between (-)-delta9-tetrahydrocannabinol (delta9-THC) and vehicle, using different training doses in order to create assays with different efficacy demands, to examine whether (R)-methanandamide, an analog of the endogenous ligand anandamide, had lower efficacy than delta9-THC. Rats were initially trained with 3 mg/kg delta9-THC, then tested with (R)-methanandamide and delta9-THC. Thereafter, the rats were split into two groups and retrained with either 1.8 or 5.6 mg/kg delta9-THC, followed by additional tests with the two agonists. The current study systematically replicated this study in two groups of rats, trained from the outset to discriminate between vehicle and either 1.8 or 5.6 mg/kg delta9-THC, respectively. Two-lever operant drug discrimination procedures were used. The outcomes in the two studies were similar. In tests with (R)-methanandamide, full substitution occurred in the low-dose delta9-THC training group, whereas substitution was partial in the high-dose delta9-THC training group. (R)-Methanandamide in higher doses exerted marked suppression of lever pressing. In tests with delta9-THC, full substitution occurred in both delta9-THC-trained groups, and rates of responding were comparable to those observed during regular drug training sessions. In conclusion, both sets of data indicate that cannabinoid agonists either can have varying degrees of efficacy at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both. Prevailing training-dose condition rather than prior training-dose history is the major determinant for the substitution pattern.

Animals↗
PubMed1999

Discriminated taste aversion and context: a progress report.

The research described here concerns the interaction between the environment (context), the organism, and the effects of opiates, focusing on how conditioning and contextual cues affect drug controlled behaviors. This analysis applies the powerful tool of drug discrimination to a respondent conditioning procedure (discriminated taste aversion, DTA). Data show that the use of DTA is feasible in that it is sensitive to morphine dose and saccharin concentration. Swifter control over DTA was achieved by increasing the LiCl dose (UCS magnitude). It is also clear that morphine alone can serve as a discriminative stimulus not requiring saccharin as a contextual element (which has been the case for most DTA studies to date), or saccharin being part of a compounded stimulus. Pharmacological specificity was demonstrated in substitution tests with delta-9-tetrahydrocannabinol. This research continues a systematic experimental analysis of the interaction between drug-controlled behavior and context.

Animals↗
PubMed1999

Effects of lithium dose (UCS) on the acquisition and extinction of a discriminated morphine aversion: tests with morphine and delta9-THC.

The effects of varying the lithium dose (unconditioned stimulus [UCS]; LiCl range 30-180 mg/kg) on the acquisition and extinction of stimulus control by 5.6 mg/kg of morphine in a discriminated taste aversion (DTA) procedure were examined in rats. In addition, pharmacological specificity was examined by substituting (-)-delta-9-tetrahydrocannabinol (delta9-THC) for morphine during a test phase intervening between acquisition and extinction. DTA acquisition was more rapid at higher LiCl doses. The lowest dose of LiCl, 30 mg/kg, did not robustly maintain a DTA. Two groups treated with 60 mg/kg LiCl, differing only in the type of drinking nozzle used (ball-bearing vs standard non-ball-bearing), behaved similarly. Suppression of drinking was related to the morphine dose, in an orderly manner (dose range 0.3-10 mg/kg), in rats for which morphine was followed by LiCl. No significant decline in drinking occurred for rats for which morphine was followed by saline, except perhaps at the 10 mg/kg test dose of morphine. The control of drinking was pharmacologically specific; both experimental and control animals were equally affected in tests with delta9-THC (0.3-10 mg/kg). Low doses of delta9-THC increased water consumption; this did not occur with morphine. During extinction the reinstitution of drinking was similar across groups that had been effectively conditioned, i.e. there was no apparent effect of lithium dose on extinction. After extinction, a much attenuated reaction occurred to morphine in tests with 3 and 10 mg/kg. These doses of morphine had significantly suppressed drinking before the extinction phase. Collectively, these data add to the formal similarities between sensory and drug discriminative stimuli.

Animals↗
PubMed1998

Lack of an effect of zolmitriptan (Zomig, 311C90) on psychometric task performance: results of a placebo-controlled study in healthy volunteers.

The novel selective 5-hydroxytryptamine (5-HT)1B/1D agonist, zolmitriptan (Zomig, formerly known as 311C90), has shown good efficacy in the acute oral treatment of migraine. Zolmitriptan acts both centrally and peripherally, therefore it is important to assess central nervous system effects. At single doses of 25-50 mg (up to 8 times the likely therapeutic dose), zolmitriptan can cause sedation; therefore, a study was designed to examine the dose-response. A double-blind, randomized, placebo-controlled, six-limb crossover study in 13 healthy volunteers compared the effects of single oral doses of zolmitriptan (5, 10, 15 or 20 mg) and lorazepam (2 mg) on various psychometric tests. Zolmitriptan doses less than 20 mg had no statistically significant effects on choice reaction time, the Stroop test, visual analog scale (VAS) assessments of physical sedation, tranquilization and other types of feelings, the logical reasoning test or the adaptive tracking test. There was a mild transient increase in the subjective assessment on VAS of mental sedation which was dose related and occurred mainly with the highest zolmitriptan dose and were not reflected in objective measures of drug effects. In contrast, lorazepam (used as a positive control) was associated with statistically significant impairment in all tests (except tranquilization) for up to 10 h after dosing. The results demonstrate that therapeutic doses of zolmitriptan are unlikely to cause clinically significant impairment in psychometric performance.

Adolescent↗
PubMed1998

Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats.

The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than delta9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg delta9-tetrahydrocannabinol (delta9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% delta9-THC responses in the two lower delta9-THC training dose conditions. However, only around 60% delta9-THC responses occurred in the 5.6 mg/kg delta9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer delta9-THC-appropriate responses in this group. Morphine did not substitute for delta9-THC. In conclusion, the data with delta9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.

Animals↗
PubMed1998

Schedule of voucher delivery influences initiation of cocaine abstinence.

This study examined whether voucher delivery arrangements affect treatment outcome. First, 90 cocaine-dependent adults were randomly assigned to behavioral counseling or counseling plus vouchers for cocaine-free urine samples. The value of each voucher was low at the beginning but increased as the patient progressed (Voucher Schedule 1). Voucher Schedule 1 produced no improvements relative to counseling only. Next, 23 patients received vouchers on either Voucher Schedule 1 or Voucher Schedule 2. Voucher Schedule 2 began with high voucher values, but requirements for earning vouchers increased as the patient progressed. Average durations of cocaine abstinence were 6.9 weeks on Voucher Schedule 2 versus 2.0 weeks on Voucher Schedule 1 (p = .02). This confirms that vouchers can assist in initiating abstinence and that voucher delivery arrangements are critical.

Adult↗
PubMed1998

First day post-operative review following uncomplicated phacoemulsification.

PURPOSE: To determine whether the first day review is essential in management of patients following uncomplicated phacoemulsification with intraocular lens implantation. Patients are routinely seen on the day following surgery. This can produce logistical problems in patient attendance that can necessitate an overnight stay. If the first day review were abandoned this would lead to an increased uptake of day case surgery and a reduction in health care costs. METHODS: A retrospective cohort study was performed on all cases of uncomplicated phacoemulsification with intraocular lens implant surgery over a 6 month period. Slit lamp examination findings on the first post-operative day were reviewed. Visual acuity, corneal clarity, anterior chamber activity, intraocular pressure and configuration of the pupil were recorded. Any cases that failed to meet predetermined criteria underwent full case-note review. The subsequent management of these patients was analysed. RESULTS: Of the 201 cases of uncomplicated surgery, 74 cases (37%) failed to meet the study criteria and underwent review. Of these only 12 (6%) had their management altered as a result of the first day post-operative findings. This was entirely due to raised intraocular pressure. Visual acuity, corneal oedema and activity in the anterior chamber all improved on subsequent follow-up. CONCLUSIONS: The first day review of uncomplicated phacoemulsification with lens implant surgery provides the opportunity to treat raised intraocular pressure. A prospective randomised study is needed to identify means to prevent the post-operative intraocular pressure rise before we are able to consider abandoning the first review.

Ambulatory Surgical Procedures↗
PubMed1998

Effects of delta-9-tetrahydrocannabinol and (R)-methanandamide on open-field behavior in rats.

This study compared the effects of (R)-methanandamide, an analog of the mammalian brain constituent anandamide, and delta-9-tetrahydrocannabinol on the open-field behavior of male Sprague-Dawley rats. Rats were individually housed with free access to food and water. Animals were treated with 0, 1, 3, and 5.6 mg/kg delta-9-tetrahydrocannabinol given i.p. 30 min pre-session; and 0, 3, 10, and 18 mg/kg (R)-methanandamide, 15 min pre-session. The behavioral categories recorded were ambulation (the number of squares crossed), rearing (the number of times the rat stood erect on its hind-legs), latency (the time in seconds to leave the starting area, the circle in the center of the field), circling (the number of times the animal turned around its vertical axis, 0.5 point given for each 180 degrees turn), grooming (the number of cleaning bouts), urination and defecation (the number of urination spots and fecal boli deposited during the 5 min observation period). Delta-9-tetrahydrocannabinol was more potent than (R)-methanandamide, but otherwise the effects of delta-9-tetrahydrocannabinol and (R)-methanandamide were similar, with one exception; whereas delta-9-tetrahydrocannabinol produced dose-related increases in circling, (R)-methanandamide did not increase circling over the doses examined. The delta-9-tetrahydrocannabinol-induced increase in circling was blocked by the central cannabinoid receptor CB1 antagonist SR 141716. The differential effects with regard to circling may indicate that there are qualitative behavioral differences in the effects of delta-9-tetrahydrocannabinol and (R)-methanandamide.

Analysis of Variance↗
PubMed1997

Chronic lymphocytic leukemia B cells are resistant to the apoptotic effects of transforming growth factor-beta.

Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western world and is characterized by a slowly progressing accumulation of clonal CD5+ B cells. Our laboratory has investigated the role of transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion in CLL. In vitro addition of TGF-beta did not increase spontaneous apoptosis of B cells from most CLL patients, as determined using the TUNEL method, compared with a twofold increase observed in cultures of normal B cells. There was similar expression of TGF-beta type II receptors on both CLL B cells and normal B cells. In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with addition of TGF-beta. In vitro addition of IL-4, previously reported to promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells compared with normal B cells. CLL B-cell expression of IL-4 receptors was increased compared to normal B cells. Thus, our results show aberrant apoptotic responses of CLL B cells to TGF-beta and IL-4, perhaps contributing to the relative expansion of the neoplastic clone.

Apoptosis↗
PubMed1997

Reinforcing operants other than abstinence in drug abuse treatment: an effective alternative for reducing drug use.

This study examines the effectiveness of using vouchers to reinforce either the provision of urine samples testing negative for illicit drugs (UA group) or the completion of objective, individually defined, treatment-plan-related tasks (TP group). A third group was assigned to the clinic's standard treatment (STD group). Participants were randomly assigned to groups after a 6-week baseline-stabilization period. Urine specimens were collected thrice weekly throughout the study. In the UA condition, participants earned $5 (U.S. dollars) in vouchers for each drug-free urine submitted. In the TP condition, participants earned up to $15 in vouchers per week for demonstrating completion of treatment plan tasks assigned by their counselors. Contingencies were in effect for 12 weeks, after which all participants received the clinic's standard treatment. Urinalysis results indicate that the TP intervention was significantly more effective in reducing illicit drug use than either the UA or STD interventions. These effects were maintained with a trend toward continuing improvement for the TP groups even after contingencies were discontinued.

Adult↗
PubMed1997

Natural classes of treatment response.

This study examines an approach to identifying patterns of treatment response over time. Treatment response profiles are identified by cluster analyzing a repeated measure of patient performance collected at intervals during treatment. The procedure is demonstrated in Study 1 using monthly urinalysis results of 103 patients entering methadone maintenance treatment. The internal, external, and face validities of derived treatment response profiles are evaluated. A logistic regression model predicting treatment response is then constructed from intake variables found to correspond with the treatment response profiles. Study 2 replicates the procedures on an independent sample. Treatment response profiles facilitate the analysis of treatment response offering advantages over common measures of treatment outcome, such as performance at follow-up, change in performance from treatment entry to follow-up, or performance summed across treatment.

Adult↗
PubMed1997

Stages and processes of change as predictors of drug use among methadone maintenance patients.

In this study the authors evaluated the predictive validity of stages-of-change and processes-of- change measures among methadone maintenance patients. One month after treatment entry, participants completed questionnaires providing stage and process scale scores regarding readiness to discontinue polydrug use. Participants also completed an algorithm assigning them to a stage category on the basis of their stated intentions regarding quitting. The algorithm predicted urinalysis results during a 12-week posttest period; however, only 1 stage scale (contemplation) and no process scales correlated significantly with outcome. In a hierarchical regression, stage and process scale scores significantly improved prediction of posttest abstinence beyond that afforded by baseline drug-free urine rates, but this effect was attributable to the contemplation scale alone. Despite their widespread use, stage and process scales have yet to demonstrate clearly predictive validity.

Adult↗
PubMed1997

Multielemental stimulus control: effects of saccharin concentration on a discriminated morphine-saccharin taste aversion.

The effects of saccharin concentration on the stimulus control by a compound stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure were examined in rats (Rattus norvegicus). In paired rats injections of lithium followed presentation of this compound stimulus, whereas in unpaired rats saline injections followed this stimulus. DTA acquisition was more rapid at higher saccharin concentrations. In testing with each individual stimulus element, stimulus control was clearly exerted by all 3 stimulus elements. When another stimulus element was presented jointly with saccharin, behavioral control was similar to that of saccharin alone. Behavioral control by saccharin increased with saccharin concentration. However, behavioral control by the 2 other stimulus elements was relatively unaffected when the saliency of the saccharin element was increased.

Animals↗
PubMed1996

Decline in self-reported dysphoria after treatment entry in inner-city cocaine addicts.

This study examined self-reported dysphoria in 82 consecutive admissions to intensive outpatient treatment for cocaine abuse on whom data for the Beck scales for depression, anxiety, and hopelessness were available for intake and 4 subsequent weeks with no more than 1 missing data point. Mean scores on the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) decreased significantly between intake and Week 1, with no further significant changes from Weeks 1-4. Similar drops in the rate of clinically significant BDI and BAI scores also were observed. Scores on the Beck Hopelessness Scale (BHS) showed no significant changes. By Week 4, rates of clinically significant depression, anxiety, and hopelessness were similar (17%, 13%, and 16%, respectively). These findings suggest that assessing depression and anxiety using the BDI and BAI in this population should be postponed for at least 1 week after intake and that intake levels of self-reported mood may be inappropriate baseline measures for evaluating treatment effects.

Adult↗
PubMed1996

The accelerated intake: a method for increasing initial attendance to outpatient cocaine treatment.

We examined whether offering an accelerated (same-day) versus a standard (1- to 7-day delay) intake appointment increased initial attendance at an outpatient cocaine treatment program. Significantly more of the subjects who were offered an accelerated intake (59%) attended than those who were given a standard intake (33%), chi 2 (2, N = 78) = 4.198, p < .05. The accelerated intake procedure appears to be useful for enhancing enrollment in outpatient addiction treatment.

Adolescent↗
PubMed1995

Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease.

Base Sequence↗