buprenorphine and Cognition-Disorders

Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood.. Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin.. The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients.. Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

Topics: Adult; Buprenorphine; Cognition Disorders; Female; Heroin Dependence; Humans; Male; Mental Recall; Middle Aged; Naltrexone; Narcotic Antagonists; Neuropsychological Tests; Psychomotor Performance; Verbal Learning

In the present study, we investigated whether buprenorphine as a partial mu-opioid receptor agonist is associated with less cognitive impairment than methadone.. Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated.. MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task.. In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Middle Aged; Neuropsychological Tests; Opioid-Related Disorders; Receptors, Opioid, mu; Young Adult

Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence.. To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2).. Residential laboratory study; subjects (N=16) maintained on 100mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32mg/8mg), intramuscular naloxone (0.2mg), oral methadone (100mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels.. Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32mg/8mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses.. There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2mg/0.5mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cognition Disorders; Double-Blind Method; Drug Combinations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders; Substance Withdrawal Syndrome

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects of repeated administration of the buprenorphine/naloxone combination product (8/2, 16/4, 32/8 mg, sublingual tablets) in eight opioid-dependent volunteers on performance of a broad range of tasks, following a period of 7-10 days of dosing at each level, in a double-blind, within-subject, crossover design. The testing battery included measures of psychomotor speed, time perception, conceptual flexibility, focused attention, working memory, long-term/episodic memory, and metamemory. Supporting the hypothesis of limited impairment with buprenorphine, results revealed minimal impairment in performance as buprenorphine/naloxone dose was increased four-fold. The only significant effect of dose was an impairment in episodic/long-term memory (recognition memory) performance at the highest dose (32/8 mg) relative to the two lower doses. Future studies incorporating larger sample sizes and non-drug controls, as well as directly comparing buprenorphine to methadone and LAAM are needed to further test the hypothesis of limited impairment with buprenorphine.

Topics: Adult; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory Disorders; Naloxone; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders

To describe neurocognitive function among opioid-dependent adults seeking buprenorphine treatment and to explore the impact of lifetime psychiatric conditions on neurocognitive function. To explore the additive interaction of patient-based characteristics that may help to inform treatment.. Cross-sectional assessment of neurocognitive function, substance use, and psychiatric characteristics of adults seeking buprenorphine treatment within substance use treatment centers in New York City.. Thirty-eight opioid-dependent adults seeking buprenorphine treatment.. A comprehensive battery, which included measures of executive functioning, learning, memory, verbal fluency, attention, processing speed, and motor functioning were administered. The Wide Range Achievement Test-Third Edition, the Composite International Diagnostic Interview, and an audio computer assisted structured interview were also completed. Correlations and independent sample t-tests were used to ascertain group differences.. Thirty-nine percent of participants were impaired in global neurocognitive function (n=15). Over one third were impaired in either: learning (n=28), memory (n=26), executive functioning (n=17), motor functioning (n=17), attention/working memory (n=14) or verbal fluency (n=12). Lifetime history of alcohol dependence was associated with impairment in global neurocognitive, executive functioning, and motor functioning. Lifetime history of cocaine dependence was associated with impairment in executive functioning and motor functioning (all p's<0.05). Major depressive disorder history was not associated with neurocognitive impairment.. Among this sample of opioid-dependent adults, there were high rates of global and domain-specific neurocognitive impairment, with severe impairment in learning and memory. Lifetime alcohol and cocaine dependence were associated with greater neurocognitive impairment, particularly in executive functioning. Because executive functioning is critical for decision-making and learning/memory dysfunction may interfere with information encoding, these findings suggest that opioid-dependent adults may require enhanced support for medical decision-making.

Topics: Buprenorphine; Cognition Disorders; Comorbidity; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Neuropsychological Tests; New York City; Opiate Substitution Treatment; Opioid-Related Disorders

Surgery induces learning and memory impairment. Neuroinflammation may contribute to this impairment. Nuclear factor κB (NF-κB) is an important transcription factor to regulate the expression of inflammatory cytokines. We hypothesize that inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC) reduces neuroinflammation and the impairment of learning and memory. To test this hypothesis, four-month-old male Fischer 344 rats were subjected to right carotid exploration under propofol and buprenorphine anesthesia. Some rats received two doses of 50mg/kg PDTC given intraperitoneally 30min before and 6h after the surgery. Rats were tested in the Barnes maze and fear conditioning paradigm begun 6days after the surgery. Expression of various proteins related to inflammation was examined in the hippocampus at 24h or 21days after the surgery. Here, surgery, but not anesthesia alone, had a significant effect on prolonging the time needed to identify the target hole during the training sessions of the Barnes maze. Surgery also increased the time for identifying the target hole in the long-term memory test and decreased context-related learning and memory in fear conditioning test. Also, surgery increased nuclear expression of p65, a NF-κB component, decreased cytoplasmic amount of inhibitor of NF-κB, and increased the expression of interleukin-1β, interleukin-6, ionized calcium binding adaptor molecule 1 and active matrix metalloproteinase 9 (MMP-9). Finally, surgery enhanced IgG extravasation in the hippocampus. These surgical effects were attenuated by PDTC. These results suggest that surgery, but not propofol-based anesthesia, induces neuroinflammation and impairment of learning and memory. PDTC attenuates these effects possibly by inhibiting NF-κB activation and the downstream MMP-9 activity.

Topics: Anesthetics; Animals; Buprenorphine; Carotid Arteries; Cognition Disorders; Conditioning, Psychological; Encephalitis; Fear; Hippocampus; Male; Matrix Metalloproteinase 9; Maze Learning; Neuroprotective Agents; NF-kappa B; Postoperative Complications; Propofol; Pyrrolidines; Rats; Rats, Inbred F344; Thiocarbamates

This study aimed to compare emotion perception and social inference in opioid maintenance patients with abstinent ex-users and non-heroin-using controls, and determine whether any deficits in could be accounted for by cognitive deficits and/or risk factors for brain damage.. Case-control.. Sydney, Australia.. A total of 125 maintenance patients (MAIN), 50 abstinent opiate users (ABST) and 50 matched controls (CON).. The Awareness of Social Inference Test (TASIT) was used to measure emotion perception and social inference. Measures were also taken of executive function, working memory, information processing speed, verbal/non-verbal learning and psychological distress.. After adjusting for age, sex, pre-morbid IQ and psychological distress, the MAIN group was impaired relative to CON (β = -0.19, P < 0.05) and ABST (β = -0.19, P < 0.05) on emotion perception and relative to CON (β = -0.25, P < 0.001) and ABST (β = -0.24, P < 0.01) on social inference. In neither case did the CON and ABST groups differ. For both emotion perception (P < 0.001) and social inference (P < 0.001), pre-morbid IQ was a significant independent predictor. Cognitive function was a major predictor of poor emotion perception (β = -0.44, P < 0.001) and social inference (β = -0.48, P < 0.001). Poor emotion recognition was also predicted by number of heroin overdoses (β = -0.14, P < 0.05). Neither time in treatment or type of maintenance medication (methadone or buprenorphine) were related to performance.. People in opioid maintenance treatment may have an impaired capacity for emotion perception and ability to make inferences about social situations.

Topics: Adult; Analysis of Variance; Buprenorphine; Case-Control Studies; Cognition Disorders; Emotions; Female; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Social Perception

Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST) is associated with their drug treatment variables.. Opioid-dependent patients (N = 104) who were treated either with buprenorphine or methadone (n = 52 in both groups) were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis.. Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD) and frequent substance abuse during the past month predicted about 20% of verbal memory performance.. Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

Topics: Adult; Analgesics, Opioid; Attention; Buprenorphine; Cognition Disorders; Drug Therapy, Combination; Female; Humans; Male; Memory, Short-Term; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Reaction Time; Regression Analysis; United States; Young Adult

Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls.. The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate. Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8).. Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect.

Topics: Adult; Buprenorphine; Cognition; Cognition Disorders; Drug Therapy, Combination; Female; Humans; Male; Methadone; Naloxone; Opioid-Related Disorders; Reaction Time

Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist.

Topics: Adult; Buprenorphine; Cognition Disorders; Decision Making; Female; Gambling; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Severity of Illness Index