The effects of methamphetamine and secobarbital on the contingent negative variation amplitude

-upon-Tyne NE2 4AB 1 The effects in five normal subjects of a single dose of clonidine (300 Ag), 304 (750 Ag) and placebo on a subjective rating scale for alertness/sleepiness, the contingent negative variation (CNV), reaction time, blood pressure and heart rate were compared over 6 h in a double-blind study. 2 After both drugs there was a fall in systolic and diastolic blood pressure and in heart rate. These changes were maximal between 2 and 4 h and were greater after clonidine than after UK-14,304. 3 There was a progressive increase in subjective ratings of sleepiness after both drugs, commencing at 1 h and maximal between 2 and 4 h. This effect was more pronounced after clonidine than after UK-14,304. There was a close correlation between the fall in blood pressure and the change in subjective rating for sleepiness after both drugs. Behavioural sleep also occurred after both drugs. 4 Compared with placebo there was a decrease in CNV magnitude at 2 and 4 h after both drugs, associated with a lengthening of reaction time and consistent with the subjective and behavioural changes. Depression of CNV magnitude was more pronounced after clonidine than after UK-14,304. 5 In some subjects after both drugs there was an initial increase in CNV magnitude at 1.5 h, occurring at the same time as behavioural sleep and subjective ratings of sleepiness. Such a dissociation between CNV magnitude and subjective and behavioural effects of drugs in man has not previously been reported. 6 It was concluded that UK-14,304 causes less central nervous system depression than clonidine at this dosage, but also has a less marked hypotensive effect.

Section: Discussionmentioning

confidence: 99%

Central nervous system depressant actions of clonidine and UK‐14,304: partial dissociation of EEG and behavioural effects.

Ashton¹,

Rawlins²

1978

“…In this respect, cannabis does not differ from many other commonly used psychotropic drugs such as nicotine, benzodiazepines and amphetamines for which dosedependent, biphasic, stimulant and depressant effects on various measures of central nervous system activity have been described (Ashton et al, 1974(Ashton et al, , 1976Ashton et al, 1978a;Kopell et al, 1974). Interactions of centrally acting drugs with personality (Eysenck, 1967;Eysenck & O'Connor, 1979) and with environmental setting (Schachter, 1971;Bem, 1972) are also well known.…”

Section: Introductionmentioning

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

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.

“…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.