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Harry R Sumnall

Publications and source records attributed to Harry R Sumnall.

9 recordsLinked to original sources
PubMed2007

Olanzapine and JL13 induce cross-tolerance to the clozapine discriminative stimulus in rats.

We have previously shown that chronic treatment with clozapine induces tolerance to the clozapine discriminative stimulus in rats. The studies reported here extended this work to assess whether chronic treatment with the clozapine-like antipsychotics olanzapine and 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate (JL13) induced cross-tolerance to clozapine. Two groups of rats were trained to discriminate clozapine (5 mg/kg, intraperitoneal). Training was suspended and the rats were treated with either olanzapine or JL13 at high doses (5 and 20 mg/kg, respectively). These doses were administered twice daily. The clozapine generalization curve was computed three times - before chronic drug treatment, after 10 days of chronic treatment, and after 16 drug-free days. Both olanzapine and JL13 induced cross-tolerance to the clozapine stimulus, shown by significant 3.4 and 3.9 fold parallel shifts to the right in the clozapine generalization curves. Cross-tolerance was lost spontaneously during the drug-free days after treatment as clozapine sensitivity returned to baseline. We interpret these findings as indicative of the development of pharmacodynamic cross-tolerance to clozapine. Possible neuroadaptive mechanisms involved in such cross-tolerance are discussed. The paradigm outlined here allows refinement of antipsychotic drug discrimination assays to identify common chronic effects of such drugs.

Animals↗
PubMed2006

The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy.

Previous investigations of the subjective effects of MDMA (material sold as ecstasy) have conducted interviews and surveys of various groups of ecstasy users within particular sub-populations. This study examined subjective drug effects reported by different sub-populations of ecstasy users and explored whether the function or purpose served by using ecstasy influenced the nature of the drug experience. Drawing on previous measures of alterations in consciousness, psychedelic drugs and cannabis, and informal interviews with ecstasy users and MDMA researchers, a 130-item survey assessing subjective effects of ecstasy/MDMA was developed. Principal components analysis of responses of ecstasy users revealed six components; perceptual alterations, entactogenic effects, prosocial effects, aesthetic effects, negative effects and sexual effects. The derived scale was used to predict ecstasy use behaviours, and functions and experiences of use. A variety of component scores were related to ecstasy use parameters; in particular, heavier users expected fewer negative, perceptual and aesthetic effects from taking the drug. The reasons given for using ecstasy (use function) also influenced reported drug effects. Abstainers expected greater negative, perceptual, aesthetic and sexual effects than users. These data indicate that the subjective ecstasy experience is influenced by a variety of extra-psychopharmacological factors. Drug intervention strategies may be made more effective by targeting particular user groups defined by reasons given for substance use, as it is likely that their experiences of ecstasy effects will differ. Future research into ecstasy may be improved by recognizing user diversity.

Adolescent↗
PubMed2005

Is ecstasy perceived to be safe? A critical survey.

Recent publications claim that the recreational drug ecstasy is considered to be safe by many or most ecstasy users, or by young people or the general public. Unfortunately, there are no references that provide any support for this claim. Previous studies of various populations, including drug users and adolescents in several nations, also failed to support claims of the perceived safety of ecstasy. Epidemiological surveys from the USA and UK consistently report high proportions of young people who perceive great risk in using ecstasy. Studies in ecstasy users show that they are aware of a number of short- and long-term risks of ecstasy use, although, in the absence of actual problems, they evaluate the personal significance of these risks as low. This study further investigated the perceived harmfulness of ecstasy, drawing on an online survey of over 900 drug users. Little support for the claim was found. Seventy-three percent of the participants in the online survey viewed ecstasy as carrying at least 'some risk'. The claim of ecstasy's perceived safety is plausibly based on researchers' assumptions that the continued widespread use of the drug indicates that users are unaware of the associated risks, and that informing them about these risks would lead to a reduction in drug use. We argue that these assumptions are inadequate and that drug information and harm reduction strategies should focus on more affective and personally significant aspects of risk perception.

Adolescent↗
PubMed2005

Self-reported depressive symptomatology in community samples of polysubstance misusers who report Ecstasy use: a meta-analysis.

National drugs information strategies convey the message that use of Ecstasy is associated with an increase in both the incidence and severity of major depressive disorder. However, very little primary research supports this. Unlike apparent deficits in higher cognitive functions, most published studies have found no difference in self-reported depressive symptomatology between Ecstasy users and controls. To investigate this further, we conducted a meta-analysis of studies investigating depressive symptomatology in recreational users of Ecstasy. According to selection criteria, we identified 25 relevant studies. A statistically significant effect size (ES) of 0.31 (95% confidence interval 0.17-0.37, p < 0.001) was calculated. Significance remained after examining the small number of studies that controlled for cannabis use (n = 9, p < 0.001) but, in general, drug histories were poorly reported. There was an association between ES and lifetime Ecstasy exposure (p < 0.001), but not for other use parameters or abstention (p > 0.05). These data indicate that there is an association between Ecstasy use and depressive symptomatology, but this is small and unlikely to be clinically relevant. In addition, the self-report scales used may be heavily confounded by the somatic effects of substance misuse. Public health strategies derived from psychopharmacological investigations should acknowledge the potential negative effects of substance misuse but qualify the difficulties in interpreting research studies.

Depressive Disorder↗
PubMed2004

A behavioural economic analysis of alcohol, amphetamine, cocaine and ecstasy purchases by polysubstance misusers.

Behavioural economic models of substance choice describe the relationship between changes in unit price and consumption. As the majority of UK non-dependent substance misusers are polysubstance misusers, we investigated the influence of price upon hypothetical purchases of alcohol, amphetamine, cocaine and ecstasy. Forty-three current polysubstance misusers (25 males, 18 females; mean age 21.3 +/- 2.8) were recruited into the study. As the price of alcohol rose, demand was inelastic. Amphetamine was a substitute for alcohol, cocaine was a compliment drug and ecstasy was independent. Demand for amphetamine was elastic as its price rose, but only alcohol was identified as a substitute drug and other drug purchases were independent of amphetamine price. As the price of cocaine increased, demand was elastic. Alcohol and ecstasy were substitute drugs but amphetamine purchase was independent, indicating asymmetrical substitution of alcohol and cocaine. Finally, demand for ecstasy was also elastic, but only cocaine substituted as ecstasy price rose. These results extend previous findings in substance dependent populations using behavioural economic models and support the opinion that purchasing substances is a complex process, involving both socio-economic and psychopharmacological factors. Whilst subjects expressed a preference for ecstasy, these behavioural findings indicated that alcohol was their drug of choice when economic considerations were brought into play. Self-reported drug preference, although facilitating between subjects experimental design, may therefore not accurately represent real world polysubstance misuse.

Adolescent↗
PubMed2004

Self-reported psychopathology in polydrug users.

There is a large body of work investigating concurrent associations between polysubstance use and psychopathology, but much of this work has either pre-dated or failed to account for the complex and culturally specific patterns of contemporary drug use. In particular, attendees of dance music events report a greater drug history than their peers and engage in a unique lifestyle. To further investigate the consequences of this type of drug use, 100 subjects who regularly attended dance music events were administered a battery of self-report psychiatric symptom scales. This battery contained the Anxiety Sensitivity Index, the Beck Anxiety Inventory (BAI), the Center for Epidemiologic Studies Depression scale (CES-D), the Dissociative Experiences Scale, the Padua Inventory Revised and additional questions about substance use. Our study population included abstainers and drug users with a wide history of use. We demonstrated strong associations between use of many different drugs, suggesting that polydrug use is the norm in this type of population. We found weak, but statistically significant, correlations between use of alcohol (p < 0.05), amphetamine (p < 0.01) and ecstasy (p < 0.01) with self-reported score on the BAI. There were also positive associations between dissociative symptomatology and the use of amphetamine (p < 0.05) and cocaine (p < 0.05). Furthermore, weekly unit intake of alcohol positively correlated with score on the CES-D (p < 0.05). As polydrug use was the norm in this sample, we performed regression analysis to investigate the contribution of multiple drug use on self-report. This showed that weekly use of alcohol, and frequency of use of amyl nitrate and cigarettes were significant predictors of BAI score. However, the majority of subjects reported being unworried by these symptoms, which may represent a lack of self-awareness, or acceptance of them as the subacute effects of substance use. It remains to be determined at what point adverse effects of drug use begin to interfere with day-to-day life.

Adolescent↗
PubMed2003

The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine (MDMA).

3,4-Methylenedioxymethamphetamine (MDMA) is a relatively novel drug of abuse and as such little is currently known of its behavioural pharmacology. This review aims to examine whether MDMA represents a novel class of abused drug. MDMA is known as a selective serotonergic neurotoxin in a variety of animal species but acutely it is a potent releaser and/or reuptake inhibitor of presynaptic serotonin, dopamine, noradrenaline, and acetylcholine. Interaction of these effects contributes to its behavioural pharmacology, in particular its effects on body temperature. Drug discrimination studies indicate that MDMA and related drugs produce unique interoceptive effects which have led to their classification as entactogens. This is supported by results from other behavioural paradigms although there is evidence for dose dependency of MDMA-specific effects. MDMA also produces conditioned place preference but is not a potent reinforcer in self-administration studies. These unique behavioural effects probably underlie its current popularity. MDMA is found in the street drug ecstasy but it may not be appropriate to equate the two as other drugs are routinely found in ecstasy tablets

Animals↗
PubMed2002

The content of ecstasy tablets: implications for the study of their long-term effects.

AIMS: To examine the variation in the content of ecstasy tablets seized in the north-west of England during 2001 and to compare it to the UK average from 1991 to 2001. MEASUREMENTS: All tablets submitted to the Forensic Science Service in the north-west of England during 2001 were analysed by high performance liquid chromatography with diode array detection (HPLC-DAD). The mean MDMA content of these tablets are reported and compared to results from all Forensic Science Service laboratories in the United Kingdom from 1991 to 2001. Multiple samples (n= 80) from a single large seizure of White Dove tablets were analysed to determine the variation due to manufacturing. FINDINGS: All tablets submitted from the north-west of England to the Forensic Science Service in 2001 were found to contain 3,4-methylenedioxymethamphetamine (MDMA) and some also contained 3,4-methylenedioxyethamphetamine (MDEA). The MDMA content of these tablets ranged from 20 to 109 mg and the mean was in the 60-69 mg range. Mitsubishi tablets were the most common type and they were found across the whole range. The low variation of MDMA content in the White Dove tablets suggests that these tablets were well manufactured. The data from the north-west of England in 2001 are in agreement with tablet analyses over the past 10 years which show that the average MDMA content is falling. CONCLUSIONS: The amount of MDMA in ecstasy tablets is axiomatic to the discussion of their long-term effects. In order for the observed differences in ecstasy users to be the result of MDMA-induced neurotoxicity it is necessary for them to have ingested one or more neurotoxic doses. These data indicate that the amount of MDMA in ecstasy tablets is dropping and that dose-effect relationships need to take this into account.

Chromatography, High Pressure Liquid↗