Elsevier

Biological Psychiatry

Volume 45, Issue 10, 15 May 1999, Pages 1307-1312
Biological Psychiatry

Original Articles
Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study

https://doi.org/10.1016/S0006-3223(98)00155-3Get rights and content

Abstract

Background: Neurophysiological studies of marihuana (THC) often contain uncontrolled confounds [psychiatric diagnoses, polydrug use, central nervous system (CNS)-relevant injury, etc.] that can alter electrophysiological measures. This P50 sensory gating report is part of a larger neurophysiological and neurocognitive investigation of chronic THC exposure using rigorously screened medically and psychiatrically normal individuals without concurrent use of non-THC substances.

Methods: Following medical and psychiatric screening, including serial urine drug screens, technically adequate P50 paired auditory recovery tests were obtained on 19 chronic THC users and 14 control subjects. Fifty pairs of 80-dB auditory clicks (1 pair per 10 sec, 500-msec interclick separation) were delivered through earphones. The sensory gating measure was the ratio between the P50 amplitudes at the vertex elicited by the conditioning (first) and test (second) click.

Results: THC subjects had significantly higher sensory gating ratios (i.e., reduced suppression) than did control subjects. Among THC users, sensory gating ratios did not correlate with duration or frequency of THC use, although subjects with ratios above 40 had nearly twice the number of “joint-years” of THC exposure than did those with lower ratios.

Conclusions: Reduced P50 suppression in the sensory gating paradigm may be a possible neurophysiological CNS sequela of long-term cumulative exposure to THC.

Introduction

Our previous studies Struve et al 1989, Struve et al 1994, Struve et al 1995, Struve et al in submission have demonstrated and replicated a significant association between chronic marihuana (THC) use and topographic quantitative electroencephalographic (EEG) patterns of persistent “alpha hyperfrontality” (i.e., elevations of alpha absolute power, relative power, and interhemispheric coherence over frontal cortex) as well as reductions of alpha mean frequency. These findings from chronic users are consistent with both nontopographic Rodin et al 1970, Dornbush et al 1971, Dornbush et al 1972, Hockman et al 1971, Galanter et al 1973, Tassinari et al 1976, Volavka et al 1971, Volavka et al 1973, Volavka et al 1977 and topographic Manno et al 1993, Struve et al 1993, Struve et al 1996, Lukas et al 1995 transient EEG effects of acute THC administration; however, our attempts to demonstrate evoked potential sequelae of chronic marihuana use have been less successful. Although our initial pilot studies involving psychiatric patient chronic THC users and nonuser control subjects suggested that significant alterations of several evoked potential measures might be associated with chronic THC exposure (Straumanis et al 1991), subsequent work from our laboratory, using rigorously screened normal subjects Patrick and Struve 1994, Patrick et al 1995, Patrick et al 1997, failed to confirm these evoked potential findings.

This report presents pilot findings relating the P50 auditory sensory gating response to chronic cumulative THC exposure using a population of medically and psychiatrically screened normal subjects. In this evoked potential paradigm two auditory stimuli are presented very close together with the result that the amplitude of the second (“test”) stimulus evoked P50 wave is normally attenuated by the effects of the first (“conditioned”) stimulus (Davis et al 1966), a phenomenon first used by Adler et al (1982) to explore auditory evoked response differences between normal and clinical populations. The diminished P50 amplitude to the second stimulus constitutes sensory gating. A robust inhibitory gating mechanism can completely suppress the response to the test stimulus, whereas a total absence of gating would result in identical P50 amplitude response to both conditioning and test stimuli.

Section snippets

Subjects

The P50 sensory gating paradigm was introduced as a dependent measure late in an ongoing neurophysiological study of chronic THC exposure in normal subjects, and because of this, data were only available on a relatively small subsample of subjects still being entered into the parent project. Twenty-four chronic marihuana users and 19 nonuser control subjects were initially entered into a pilot P50 sensory gating study. Of these, data from 5 THC subjects and 5 control subjects had to be omitted

Results

Chronic THC use had no measurable effect on the P50 response to the first, or conditioning, click stimulus (THC group: mean latency = 56.7 msec, σ = 4.7 msec, range = 24 msec, control group: mean latency = 56.8 msec, σ = 4.9 msec, range = 20 msec, t = 0.028, df = 31, p = ns; mean amplitude: THC = 4.08 μV, control = 3.38 μV, t = 1.16, df = 31, p = ns). Thus both groups were found to be entirely comparable on the primary auditory P50 evoked response.

The distribution of auditory P50 gating ratios

Discussion

Evoked potential techniques have not been widely used to study the acute and chronic effects of THC exposure, and attempts to demonstrate changes in auditory, visual, and somatosensory early and middle latency evoked potentials have been variable, with no replicable findings clearly emerging Kopell et al 1978, Lewis et al 1973, Low et al 1973, Panayiotopoulos and Stefanis 1977, Rodin et al 1970, Roth et al 1973, Roth et al 1977, Straumanis et al 1991, Tassinari et al 1974, Tinklenberg 1972.

Acknowledgements

Supported in part by NIDA grant DA06643.

References (61)

  • W.T. Roth et al.

    Ethanol and marihuana effects on event-related potentials in memory retrieval paradigm

    Electroencephalogr Clin Neurophysiol

    (1977)
  • N. Solowij

    Do cognitive impairments recover following cessation of cannabis use

    Life Sci

    (1995)
  • N. Solowij et al.

    Effects of long-term cannabis use on selective attentionAn event-related potential study

    Pharmacol Biochem Behav

    (1991)
  • N. Solowij et al.

    Differential impairments of selective attention due to frequency and duration of cannabis use

    Biol Psychiatry

    (1995)
  • D.J. Weisz et al.

    Changes in hippocampal CA1 population spikes following administration of delta-9-THC

    Brain Res Bull

    (1982)
  • D.L. Woods et al.

    Generators of middle and long-latency auditory evoked potentialsImplications from studies of patients with bitemporal lesions

    Electroencephalogr Clin Neurophysiol

    (1987)
  • L.E. Adler et al.

    Neurophysiological evidence for a deficit in neuronal mechanisms involved in sensory gating in schizophrenia

    Biol Psychiatry

    (1982)
  • K.A. Campbell et al.

    Δ9-tetrahydrocannabinol differentially affects sensory-evoked potentials in the rat dentate gyrus

    J Pharmacol Exp Ther

    (1986)
  • K.A. Campbell et al.

    Effects of Δ9-tetrahydrocannabinol on sensory-evoked discharges of granule cells in the dentate gyrus of behaving rats

    J Pharmacol Exp Ther

    (1986)
  • Deadwyler A, Heyser C, Michaelis R, Hampson R, Breese C (1988): Behavioral and electrophysiological effects of...
  • Deadwyler SA, Heyser CJ, Michaelis RC, Hampson RE (1990): The effects of delta-9-THC on mechanisms of learning and...
  • W.A. Devane et al.

    Determination and characterization of a cannabinoid receptor in rat brain

    Mol Pharmacol

    (1988)
  • R.L. Dornbush et al.

    Marihuana, memory and perception

    Am J Psychiatry

    (1971)
  • R.L. Dornbush et al.

    Twenty-one day administration of marihuana in male volunteers

  • M. Galanter et al.

    Delta-9-transtetrahydrocannabinol and natural marihuanaA controlled comparison

    Arch Gen Psychiatry

    (1973)
  • W.R. Goff et al.

    Neural origins of long latency evoked potentials recorded from the depth and from the cortical surface of the brain in man

    Prog Clin Neurophysiol

    (1980)
  • M. Herkenham et al.

    Cannabinoid receptor localization in brain

    Pro Natl Acad Sci USA

    (1990)
  • M. Herkenham et al.

    Characterization and localization of cannabinoid receptors in rat brainA quantitative in vitro autoradiographic study

    J Neurosci

    (1991)
  • C.J. Heyser et al.

    Effects of delta-9-tetrahydrocannabinol on delayed match to sample performance in ratsAlterations in short-term memory associated with changes in task specific firing of hippocampal cells

    J Pharmacol Exp Ther

    (1993)
  • C.H. Hockman et al.

    Electroencephalographic and behavioral alterations produced by delta-9-tetrahydrocannabinol

    Science

    (1971)
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