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Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers ( N =8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as ‘I feel a good drug effect’ and ‘I like the drug.’ In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine⩾heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of ‘I feel a bad drug effect’ and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

By 2050, 85.7 million people in the United States are projected to be 65 or older. Older adults are especially prone to the effects of substances, and a 2021 survey showed that 4 million older adults were dealing with a substance use disorder. As the country's population ages, clinicians will inevitably have to care for a greater number of older adults with substance use disorders, but the literature on the topic—and the evidence base for treatment—is limited. In Substance Use in Older Adults, more than 20 contributors translate their real-world experience in geriatric psychiatry into an accessible, evidence-based guide to screening for and assessing substance use in older adults. Early chapters discuss not only etiology and epidemiology but also comorbidities and management and subsequent sections address the problematic use of specific substances, including • Alcohol• Tobacco• Opioids• Sedatives• Stimulants• Cannabinoids Readers will find guidance on safe prescribing practices for older patients, as well as an examination of the cultural and ethical issues that may arise when working with this patient population. Rife with case examples that illustrate key points in clinical practice, Substance Use in Older Adults also features numerous tables that can be referenced time and again with information on comorbidities, screening frameworks, and interventions for specific substances; stigma-reducing language; the pharmacological implications of physiological changes in older adults; and more. Clinicians from psychiatric professionals to primary care providers will benefit from exhaustive listings of additional resources. This guide also includes resources for patients, families, and caregivers that will help to strengthen the partnership between clinician and patient.

In this 12-month randomized trial involving 251 long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity. As compared with methadone, injectable diacetylmorphine was associated with more serious adverse events, including seizures and drug overdoses. In long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity. Opioid dependence, most commonly manifested as heroin dependence, is a chronic relapsing condition 1 that is estimated to affect more than 1 million persons in North America. 2 , 3 The risks of opioid dependence include fatal overdoses, infections (including endocarditis, human immunodeficiency virus infection, and hepatitis C virus infection), social disintegration, violence, and crime. The associated burdens on communities include medical, public health, and criminal-justice costs as well as public disorder and crimes against property. Methadone, the standard opioid-substitution treatment, has been shown to reduce major risks associated with untreated opioid dependence in patients who are willing to undergo and are successfully . . .

The treatment of opioid addiction mainly involves the medical administration of methadone or other opioids, aimed at gradually reducing dependence and, consequently, the need for illicit opioid procurement. Thus, initiating opioid maintenance therapy with a lower level of dependence would be advantageous. There is compelling evidence indicating that opioids induce brain oxidative stress and associated glial activation, resulting in the dysregulation of glutamatergic homeostasis, which perpetuates drug intake. The present study aimed to determine whether inhibiting oxidative stress and/or neuroinflammation reduces morphine self-administration in an animal model of opioid dependence. Morphine dependence, assessed as voluntary morphine self-administration, was evaluated in Wistar-derived UChB rats. Following an extended period of morphine self-administration, animals were administered either the antioxidant N-acetylcysteine (NAC; 40 mg/kg/day), the anti-inflammatory ibudilast (7.5 mg/kg/day) or the combination of both agents. Oxidative stress and neuroinflammation were evaluated in the hippocampus, a region involved in drug recall that feeds into the nucleus accumbens, where the levels of the glutamate transporters GLT-1 and xCT were further assessed. Daily administration of either NAC or ibudilast led to a mild reduction in voluntary morphine intake, while the co-administration of both therapeutic agents resulted in a marked inhibition (-57%) of morphine self-administration. The administration of NAC or ibudilast markedly reduced both the oxidative stress induced by chronic morphine intake and the activation of microglia and astrocytes in the hippocampus. However, only the combined administration of NAC + ibudilast was able to restore the normal levels of the glutamate transporter GLT-1 in the nucleus accumbens. Separate or joint administration of an antioxidant and anti-inflammatory agent reduced voluntary opioid intake, which could have translational value for the treatment of opioid use disorders, particularly in settings where the continued maintenance of oral opioids is a therapeutic option.

The potential of octreotide (OCT), an octapeptide synthetic somatostatin agonist, to mitigate addiction, specifically morphine dependence, was evaluated in a comprehensive approach involving behavioral, molecular, histological, and docking studies. OCT decreased addiction-related behaviors in Wistar rats previously exposed to morphine, normalizing their exploratory activities and reducing drug-seeking behaviors. Histological assessments revealed octreotide-induced reductions in opioid-induced neuronal damage, suggesting a neuroprotective function. Octreotide’s behavioral and histopathological effects were associated with regulation of molecular pathways known to be critical in morphine dependence processes, including TLR4, BDNF, SIRT1, and mTOR. Supplementary docking studies elucidated octreotide’s high affinity for addiction-related targets, suggesting that a biological interaction between OCT and players in pathways known to play a role in addiction could be involved in behavioral and cellular effects noted. When our results are taken together, we conclude that OCT could be a promising candidate for opioid dependence treatment and underscore the necessity for further preclinical and clinical investigations.

Methadone maintenance treatment (MMT) is widely available in China; but, high rates of illicit opiate use and dropout are problematic. The aim of this study was to test whether cognitive behavioral therapy (CBT) in conjunction with MMT can improve treatment retention and reduce opiate use. A total of 240 opiate-dependent patients in community-based MMT clinics were randomly assigned to either weekly CBT plus standard MMT (CBT group, n=120) or standard MMT (control group, n=120) for 26 weeks. The primary outcomes were treatment retention and opiate-negative urine test results at 12 weeks and 26 weeks. The secondary outcomes were composite scores on the Addiction Severity Index (ASI) and total scores on the Perceived Stress Scale (PSS) at 12 weeks and 26 weeks. Compared to the control group in standard MMT, the CBT group had higher proportion of opiate-negative urine tests at both 12 weeks (59% vs. 69%, p<0.05) and 26 weeks (63% vs. 73%, p<0.05); however, the retention rates at 12 weeks (73.3% vs. 74.2%, p=0.88) and 26 weeks were not different (55.8% vs. 64.2%, p=0.19) between the two groups. At both 12 and 26 weeks, all of the ASI component scores and PSS total scores in the CBT group and control group decreased from baseline; but the CBT group exhibited more decreases in ASI employment scores at week 26 and more decrease in the PSS total score at week 12 and week 26. CBT counselling is effective in reducing opiate use and improving employment function and in decreasing stress level for opiate-dependent patients in MMT in China. ClinicalTrials.gov NCT01144390.

The naloxone investigation (N-ALIVE) randomized trial commenced in the UK in May 2012, with the preliminary phase involving 5,600 prisoners on release. The trial is investigating whether heroin overdose deaths post-prison release can be prevented by prior provision of a take-home emergency supply of naloxone. Heroin contributes disproportionately to drug deaths through opiate-induced respiratory depression. Take-home emergency naloxone is a novel preventive measure for which there have been encouraging preliminary reports from community schemes. Overdoses are usually witnessed, and drug users themselves and also family members are a vast intervention workforce who are willing to intervene, but whose responses are currently often inefficient or wrong. Approximately 10% of provided emergency naloxone is thought to be used in subsequent emergency resuscitation but, as yet, there have been no definitive studies. The period following release from prison is a time of extraordinarily high mortality, with heroin overdose deaths increased more than sevenfold in the first fortnight after release. Of prisoners with a previous history of heroin injecting who are released from prison, 1 in 200 will die of a heroin overdose within the first 4 weeks. There are major scientific and logistical challenges to assessing the impact of take-home naloxone. Even in recently released prisoners, heroin overdose death is a relatively rare event: hence, large numbers of prisoners need to enter the trial to assess whether take-home naloxone significantly reduces the overdose death rate. The commencement of pilot phase of the N-ALIVE trial is a significant step forward, with prisoners being randomly assigned either to treatment-as-usual or to treatment-as-usual plus a supply of take-home emergency naloxone. The subsequent full N-ALIVE trial (contingent on a successful pilot) will involve 56,000 prisoners on release, and will give a definitive conclusion on lives saved in real-world application. Advocates call for implementation, while naysayers raise concerns. The issue does not need more public debate; it needs good science.