Addiction-related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects.

The gabapentinoid pregabalin is a rapid-acting anxiolytic and analgesic, possibly suitable in supervised opioid detoxification. However, clinicians have been cautious in using it because of its unknown addictive risk and rising number of mortalities after pregabalin self-medication in opioid abusers. Here, we studied interactions of pregabalin and morphine on reward functions of the dopamine system in mice and the efficacy of pregabalin on withdrawal in opioid addicts. After the treatment of mice with pregabalin and morphine, we used electrophysiology to study neuroplasticity in midbrain slices, self-administration and conditioned place preference tests to investigate the rewarding potential of pregabalin and naloxone-precipitated morphine withdrawal to evaluate opioid withdrawal symptoms. Further, we ran a pilot single-blind, randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin alone did not induce glutamate receptor neuroplasticity of dopamine neurons in the ventral tegmental area, but pre-treatment with pregabalin suppressed morphine-induced neuroplasticity, hyperlocomotion and morphine self-administration. Pregabalin administration after chronic morphine exposure failed to induce any rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both morphine-treated mice and opioid addicts and was well tolerated. Intriguingly, pregabalin administration after a low dose of morphine strongly facilitated ventral tegmental area neuroplasticity and led to increased conditioned place preference. Pregabalin appears to have the efficacy to counteract both reinforcing and withdrawal effects of opioids, but it also has a potentiating effect when given to mice with existing opioid levels.

Psychosocial and contextual correlates of opioid overdose risk among drug users in St. Petersburg, Russia.

BACKGROUND: Opioid overdose in Russia is a problem that has grown more severe as heroin abuse expanded over the past decade, yet few studies have explored it in detail. In order to gain a clearer understanding of the situation, 60 drug users, both in and out of drug treatment in St. Petersburg, were interviewed concerning their overdose experience and knowledge about overdose recognition and prevention. METHODS: Using a semi-structured interview, we sought to identify and describe local attitudes, knowledge and experience (both self-sustained and witnessed) of opioid overdose. Bi-variate and multiple logistic regressions were performed in order to identify the relationship between overdose experience and sociodemographic factors, risk behaviors, and clinical psychiatric measures. RESULTS: We found that having experienced or witnessed an opioid overdose within the previous year was common, overdose knowledge was generally high, but nearly half the participants reported low self-efficacy for effectively intervening in an overdose situation. In bivariate analyses, self-reported family problems (i.e., perceived problematic family interactions) were positively associated with both experiencing (t56 = 2.49; p < 0.05) and with witnessing a greater number of overdoses in the previous year (rhos = 0.31; p < 0.05). Having previously overdosed [Adjusted Risk Ratio (ARR) 1.7, 95% Confidence Interval (CI) 1.1-2.6] and higher SCL-90-R somatization scores (ARR 1.2, 95% CI 0.96 - 1.5) were independently associated in multivariable analyses with self-sustained overdose experience in the past year. Greater perceived likelihood of experiencing a future overdose and concern about medical problems were independently associated with witnessing a higher number of overdoses within the previous year. Over two thirds of the participants expressed interest in receiving training in overdose prevention and response. CONCLUSION: Opioid overdose experience is very common among drug users in St. Petersburg, Russia, and interest in receiving training for overdose recognition and prevention was high. Future research should target the development of effective overdose recognition and prevention interventions, especially ones that include naloxone distribution and involve drug users' families.

Social and structural aspects of the overdose risk environment in St. Petersburg, Russia.

BACKGROUND: While overdose is a common cause of mortality among opioid injectors worldwide, little information exists on opioid overdoses or how context may influence overdose risk in Russia. This study sought to uncover social and structural aspects contributing to fatal overdose risk in St. Petersburg and assess prevention intervention feasibility. METHODS: Twenty-one key informant interviews were conducted with drug users, treatment providers, toxicologists, police, and ambulance staff. Thematic coding of interview content was conducted to elucidate elements of the overdose risk environment. RESULTS: Several factors within St. Petersburg's environment were identified as shaping illicit drug users' risk behaviours and contributing to conditions of suboptimal response to overdose in the community. Most drug users live and experience overdoses at home, where family and home environment may mediate or moderate risk behaviours. The overdose risk environment is also worsened by inefficient emergency response infrastructure, insufficient cardiopulmonary or naloxone training resources, and the preponderance of abstinence-based treatment approaches to the exclusion of other treatment modalities. However, attitudes of drug users and law enforcement officials generally support overdose prevention intervention feasibility. Modifiable aspects of the risk environment suggest community-based and structural interventions, including overdose response training for drug users and professionals that encompasses naloxone distribution to the users and equipping more ambulances with naloxone. CONCLUSION: Local social and structural elements influence risk environments for overdose. Interventions at the community and structural levels to prevent and respond to opioid overdoses are needed for and integral to reducing overdose mortality in St. Petersburg.