Codeine-induced memory changes: Nature and relationship to opiate system

Abstract

Learning and recall processes were studied in three experiments with 33 subjects, 1 and 3 h after oral administration of codeine phosphate 25 mg, 50 mg and 100 mg. Recall was measured 3 and 24 h after drug administration. Nine subjects received naloxone i.m. with the 50 mg dose of codeine. Learning and memory were assessed by using associative, serial and concept learning tasks. Flicker fusion frequency was measured to assess the general vigilance level of the subjects. Learning performance in the serial learning task was improved 3 h after administration of codeine 100 mg. Recall in the serial learning task was also improved after codeine 25 mg, but only when the material was learnt after 1 hour and was recalled 24 h after drug intake. To demonstrate the enhanced recall both learning and recall had to take place under the same drug condition. The same test showed a tendency to enhanced recall after codeine 50 mg of material learnt 1 hour after drug intake and recalled 24 h later. This effect was counteracted by naloxone. The data are consistent with the hypothesis that codeine may exert its action via opiate receptors and that this system participates in memory functions.

Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers

“…The modest e¤ects cannot be attributed to a lack of sensitivity of our subjective-e¤ects test battery because dose-dependent and robust e¤ects have been detected with intravenously administered opiates, including morphine (Zacny et al 1994a), meperidine (Zacny et al 1993), butorphanol (Zacny et al 1994b), and nalbuphine . Ratings of intensity of drug e¤ect were increased slightly by both drugs, and previous studies have also found mild increases on this measure with oral morphine (Berman et al 1993) and oral codeine (Liljequist 1981). Scores on the PCAG scale of the ARCI were increased by morphine 40 mg in the present study but not by the other drug conditions.…”

“…Mild performance decrements have been found for eye-hand coordination, visual acuity (Bradley and Nicholson 1986), and one measure of driving ability (Linnoila and Hakkinen 1973) using doses ranging from 30 to 90 mg. However, oral codeine doses up to 100 mg did not impair postural balance, information processing, perception, learning and recall, reaction time, or Þne motor control (Liljequist 1981;Redpath and Pleuvry 1982;Stacher et al 1982Stacher et al , 1987Bradley and Nicholson 1986;SaarialhoKere et al 1986), and three other measures of driving ability were una¤ected or enhanced by codeine (Linnoila and Hakkinen 1973). It appears, then, that oral morphine and codeine produce mild or no psychomotor impairment and, in some cases, may actually enhance performance (Linnoila and Hakkinen 1973;Liljequist 1986;Stacher et al 1987).…”

“…For example, oral codeine doses ranging from 60 to 120 mg have been shown to increase ratings of mentally slow (SaarialhoKere et al 1986) and decrease subjects conÞdence in their cognitive / psychomotor ability (Bellville et al 1968), but another study found increases in ratings of ability to concentrate following oral codeine 25100 mg (Liljequist 1981). Oral codeine 60 120 mg increased ratings of tiredness (Stacher et al 1982) and sleepy (Bellville et al 1968), but in another study, codeine 30 60 mg had no e¤ect on self-reported sedation (Redpath and Pleuvry 1982).…”

Effects of a mu‐opioid receptor agonist (codeine phosphate) on visuo‐ motor coordination and dynamic visual acuity in man.

“…Further, altered performance is unlikely to be related to change in pupil size. A minimal miosis with codeine (Jasinski et al, 1971;Liljequist, 1981) would only tend to reduce peripheral aberration, and this would be of no consequence as, in the present study, the task was well illuminated and targets were highly contrasted with the background.…”

Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man

“…Obviously the subjects are expected to be less attentative if treated with CNS depressant agents. Nevertheless, there are several data in the literature according to opiates facilitate learning performance in humans (Liljequist 1981) and in experimental animals (Mondadori and Wase 1978;White et al 1978). It must be added, however, that in other experimental situations (see Sz~kely 1982 for review) opiates unequivocally decrease the learning performance.…”