Chlorpromazine effects on brain activity (contingent negative variation) and reaction time in normal women

University of Newcastle-upon-Tyne, 1 The effects of two doses of A9THC (2.5 and 10 mg), delivered by paced smoking of herbal cigarettes, on CNV magnitude, subjective mood ratings and heart rate were studied in 20 subjects. 2 There were highly significant interactions between drug dosage and Extraversion and Neuroticism scores, so that the direction and degree of response to the different doses of /VTHC depended on the personality characteristics of the subjects. 3 The effects of 8 mg zV9THC and placebo, delivered in herbal cigarettes smoked naturally, on smoking behaviour, subjective mood ratings, measures of autonomic activity and auditory and visual cortical evoked responses were compared in 12 subjects. 4 Smoking behaviour, subjective 'high' rating and elevation of heart rates were the most significant discriminators between drug and placebo. The latency of some of the components of the visual evoked responses was also increased by A9THC. 5 There was a significant correlation between the effects of Q9THC on skin conductance reactivity and the basal (pre-drug) level, reactivity increasing after drug in subjects with low basal reactivity and decreasing in those with high basal levels. 6 Both experiments provided clear evidence of dose-dependent biphasic stimulant and depressant actions of A9THC on both subjective and objective measures, and these effects were influenced by the personality and the starting state of the subjects.

Section: Discussionmentioning

confidence: 99%

The seed and the soil: effect of dosage, personality and starting state on the response to delta 9 tetrahydrocannabinol in man.

Ashton¹,

Golding²,

Marsh³

et al. 1981

“…Drugs which increase the size of the CNV in normal subjects include LSD (Walter, 1964), cannabis (Kopell, Tinklenberg & Hollister, 1972;Low, Klonoff & Marcus, 1973), caffeine (Ashton, Millman, Telford & Thompson, 1974), and methylamphetamine (Kopell, Wittner, Lunde, Wolcott & Tinklenberg, 1974). Drugs which increase the size of the CNV in normal subjects include carbon monoxide (Groll-Knapp, Wagner, Hanck & Haider, 1972), ethanol (Kopell, Tinklenberg & Hollister, 1972), nitrazepam (Ashton et al, 1974), diazepam (Ashton, Millman, Telford & Thompson, 1976, flurazepam (Hablitz & Borda, 1973), quinalbarbitone (Kopell, et al, 1974), chlorpromazine (Tecce, Cole & Savignano-Bowman, 1975), atropine and metoclopramide (Thompson, Newton, Pocock, Cooper, Crow, McCallum & Papakostopoulos, 1976). Cigarette smoking appears to have a biphasic effect on the human brain and may produce both stimulant and depressant effects on CNV magnitude (Ashton, Millman, Telford & Thompson, 1973;Ashton etal., 1974).…”

Section: Introductionmentioning

confidence: 99%

Biphasic dose‐related responses of the CNV (contingent negative variation) to I.V. nicotine in man.

Ashton¹,

Marsh²,

Millman³

et al. 1980

-upon-Tyne NE2 4AB1 The effects of intravenous injections of nicotine bitartrate, given as intermittent 'shots', on the magnitude of the contingent negative variation (CNV) were studied in twelve male volunteers. 2 In one series of experiments in five subjects, a fixed dose of nicotine was used. In three of these subjects nicotine 500 ,ug or 750 ,ug produced a reproducible increase in magnitude of the CNV. In two subjects nictone 750 ug produced a reproducible decrease in magnitude of the CNV. 'The direction and magnitude of the CNV changes could be reproduced by cigarette smoking. 3 In another series of experiments in eight subjects, dose-response relationships for the effect of nicotine on the CNV were measured using a range of doses from 12.5 to 800 ,ug. Individual and mean dose-response curves were found to be biphasic so that whilst smaller doses produced an increase of CNV magnitude (stimulant effect), larger doses produced a decrease of the CNV (depressant effect). 4 The results are discussed in relation to the possible mechanism of action on the brain of nicotine as obtained by inhaling cigarette smokers.

“…By contrast, the anxiolytic effects of diazepam, as well as other benzodiazepines and barbiturates, undoubtedly result from central depressant actions as shown by the reduction in subjective symptoms of anxiety and EEG changes characteristic of drug-induced sedation (Tyrer & Lader, 1974a, b and c). An objective measure which has been shown to be of value in the investigation of central effects of drugs (Ashton, Millman, Telford & Thompson, 1974Tecce, Cole & Savignano-Bowman, 1975) is the electroencephalographic response known as the contingent negative variation (CNV) (Walter, Cooper, Aldridge, McCallum & Winter, 1964). This consists of a slow electronegative potential which develops at the vertex relative to the mastoid between a warning signal and an imperative signal requiring a response from the subject.…”

Section: Introductionmentioning

confidence: 99%

“…The CNV probably arises in subcortical regions, including the reticular activating system and possibly the limbic system, which through neural connections, elicit potential changes in the cortex that can be measured from scalp electrodes (Haider, Ganglberger & Groll-Knapp, 1968;Rebert, 1972;Rebert & Knott, 1970;McCallum, Papakostopoulos, Gombi, Winter, Cooper & Griffith, 1973). The nervous regions involved in the genesis of the CNV are known to be sensitive to many centrally acting drugs, and CNV magnitude is consistently increased by central stimulant drugs such as caffeine, pemoline and amphetamine and decreased by central depressant drugs such as nitrazepam, flurazepam, alcohol, chlorpromazine and barbiturates (Ashton et al, 1974;Ashton et al, 1975;Hablitz & Borda, 1973;Tecce & Cole, 1974;Kopell, Tinklenberg & Hollister, 1972;Kopell, Wittner, Lande, Wolcott & Tinklenberg, 1974;Tecce et al, 1975 (Ashton et al, 1974;, it seemed likely that a central effect of propranolol, whether stimulant or depressant, would be reflected by a change in CNV magnitude. The effects of propranolol on the CNV have not been investigated previously.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Some Physiological and Psychological Effects of Propranolol and Diazepam in Normal Subjects

Ashton

Millman

Telford

et al. 1976

1Some central and peripheral effects of orally administered propranolol (60 mg), diazepam (5 mg) and placebo were compared in normal subjects. 2 The central effects measured were changes in magnitude of the contingent negative variation (CNV) and subjective anxiety ratings; the peripheral effects were changes in heart rate, blood pressure, galvanic skin response and hand steadiness. 3 After diazepam there was a decrease in CNV magnitude and in the level of subjective anxiety; there was a slight fall in blood pressure but little change in heart rate. 4 After propranolol, on the other hand, there was no significant change in CNV magnitude or anxiety rating, but a significant fall in heart rate and systolic blood pressure. 5 It is concluded that, at the dosage used, propranolol, unlike diazepam, does not affect the central mechanisms determining CNV magnitude or subjective anxiety. The relationship of this finding to the use of f-adrenergic receptor blockers in clinical anxiety states is discussed.