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Substance use disorders (SUDs), defined as a collection of symptoms including tolerance and withdrawal, are chronic illnesses characterized by relapse and remission. In the United States, billions of dollars have been lost due to SUDs. In the past 30 years, effective medications and behavioral interventions have played a major role in preventing relapse and facilitating longer periods of abstinence. From the late 1990s to the present, the opioid epidemic or opioid crisis in the United States has raised public awareness of SUDs. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Methadone and buprenorphine target mu opioid receptors (MORs) in the brain to treat opioid dependence by reducing withdrawal and craving, whereas naloxone is an opioid antagonist used to treat opioid overdose. Mu, kappa, and delta are opioid receptor subtypes with common analgesic effects, and each also has unique effects and distribution in the brain. MORs in distinct brain regions, such as the nucleus accumbens and basolateral amygdala, trigger the euphoria and incentive properties of rewarding stimuli. Kappa opioid receptors can trigger anti-reward effects and produce dysphoric effects. Delta opioid receptors can induce anxiolytic effects. Though effective medications are available, relapse is still common due to neurobiological changes in brain pathways and tolerance of opioid receptors with repeated abuse of substances. In this article, I summarize the biological mechanisms of opioid dependence and opioid receptors and review previous articles about medications used to treat SUDs and their clinical effects.

The US opioid epidemic has led to similar concerns about prescribed opioids in the UK. In new users, initiation of or escalation to more potent and high dose opioids may contribute to long-term use. Additionally, physician prescribing behaviour has been described as a key driver of rising opioid prescriptions and long-term opioid use. No studies to our knowledge have investigated the extent to which regions, practices, and prescribers vary in opioid prescribing whilst accounting for case mix. This study sought to (i) describe prescribing trends between 2006 and 2017, (ii) evaluate the transition of opioid dose and potency in the first 2 years from initial prescription, (iii) quantify and identify risk factors for long-term opioid use, and (iv) quantify the variation of long-term use attributed to region, practice, and prescriber, accounting for case mix and chance variation. A retrospective cohort study using UK primary care electronic health records from the Clinical Practice Research Datalink was performed. Adult patients without cancer with a new prescription of an opioid were included; 1,968,742 new users of opioids were identified. Mean age was 51 ± 19 years, and 57% were female. Codeine was the most commonly prescribed opioid, with use increasing 5-fold from 2006 to 2017, reaching 2,456 prescriptions/10,000 people/year. Morphine, buprenorphine, and oxycodone prescribing rates continued to rise steadily throughout the study period. Of those who started on high dose (120-199 morphine milligram equivalents [MME]/day) or very high dose opioids (≥200 MME/day), 10.3% and 18.7% remained in the same MME/day category or higher at 2 years, respectively. Following opioid initiation, 14.6% became long-term opioid users in the first year. In the fully adjusted model, the following were associated with the highest adjusted odds ratios (aORs) for long-term use: older age (≥75 years, aOR 4.59, 95% CI 4.48-4.70, p < 0.001; 65-74 years, aOR 3.77, 95% CI 3.68-3.85, p < 0.001, compared to <35 years), social deprivation (Townsend score quintile 5/most deprived, aOR 1.56, 95% CI 1.52-1.59, p < 0.001, compared to quintile 1/least deprived), fibromyalgia (aOR 1.81, 95% CI 1.49-2.19, p < 0.001), substance abuse (aOR 1.72, 95% CI 1.65-1.79, p < 0.001), suicide/self-harm (aOR 1.56, 95% CI 1.52-1.61, p < 0.001), rheumatological conditions (aOR 1.53, 95% CI 1.48-1.58, p < 0.001), gabapentinoid use (aOR 2.52, 95% CI 2.43-2.61, p < 0.001), and MME/day at initiation (aOR 1.08, 95% CI 1.07-1.08, p < 0.001). After adjustment for case mix, 3 of the 10 UK regions (North West [16%], Yorkshire and the Humber [15%], and South West [15%]), 103 practices (25.6%), and 540 prescribers (3.5%) had a higher proportion of patients with long-term use compared to the population average. This study was limited to patients prescribed opioids in primary care and does not include opioids available over the counter or prescribed in hospitals or drug treatment centres. Of patients commencing opioids on very high MME/day (≥200), a high proportion stayed in the same category for a subsequent 2 years. Age, deprivation, prescribing factors, comorbidities such as fibromyalgia, rheumatological conditions, recent major surgery, and history of substance abuse, alcohol abuse, and self-harm/suicide were associated with long-term opioid use. Despite adjustment for case mix, variation across regions and especially practices and prescribers in high-risk prescribing was observed. Our findings support greater calls for action for reduction in practice and prescriber variation by promoting safe practice in opioid prescribing.

A five-sentence letter published in the Journal in 1980 has been heavily cited as evidence that long-term opioid therapy has seldom been associated with addiction. Of the 608 citations, 72.2% used the letter uncritically as evidence that such addiction was rare. To the Editor: The prescribing of strong opioids such as oxycodone has increased dramatically in the United States and Canada over the past two decades. 1 From 1999 through 2015, more than 183,000 deaths from prescription opioids were reported in the United States, 2 and millions of Americans are now addicted to opioids. The crisis arose in part because physicians were told that the risk of addiction was low when opioids were prescribed for chronic pain. A one-paragraph letter that was published in the Journal in 1980 3 was widely invoked in support of this claim, even though no evidence was provided by . . .

A century after the Harrison Narcotic Act took effect in the United States, its bias against maintenance therapy continues to hinder medical efforts to ameliorate the effects of our country's latest narcotic-addiction epidemic. Just over a century ago, in March 1915, the Harrison Narcotic Act took effect, requiring anyone who imported, produced, sold, or dispensed “narcotics” (at that time meaning coca- as well as opium-based drugs) to register, pay a nominal tax, and keep detailed records (see figure). With such records, officials could better enforce existing laws, such as those requiring sale by prescription only. They could also prosecute unregistered narcotics distributors such as saloonkeepers and street peddlers. The intent was to keep narcotic transactions within legitimate medical channels. For more than a decade, U.S. reformers and diplomats had been urging this course . . .

Methadone maintenance therapy (MMT), a pharmacological treatment for opioid use disorder for the past 50 years, continues to remain controversial. Despite consistent and overwhelming evidence confirming the effectiveness and safety of MMT, misconceptions and myths persist regarding its legitimacy as a treatment for opioid addiction. This often results in the underutilization and limited availability of this treatment modality. Despite successful outcomes, the controversial nature of MMT, and the stigma experienced by the patients on methadone, has been a particularly difficult obstacle to overcome. We present the history of MMT, review the evidence for its efficacy in the treatment of opioid dependence, and explore the origins of the stigma and misconceptions related to MMT.

Prescription-opioid misus e continues to be a significant health concern in the United States. The relationship between marijuana use and prescription-opioid misuse is not clear from the extant literature. This study examined national trends in prescription-opioid misuse among marijuana users and non-users using the 2007-2017 National Survey on Drug Use and Health. Cochran-Armitage tests were used to assess the statistical significance of changes in the yearly prevalence of prescription-opioid misuse and marijuana use. Multivariable logistic regression was used to examine the association between prescription-opioid and marijuana use adjusting for sociodemographic characteristics. From 2007 to 2017, marijuana use increased, while prescription-opioid misuse declined. Larger declines in prescription-opioid misuse were found among marijuana users than non-users. Marijuana ever-use was significantly associated with prescription-opioid misuse. Specifically, marijuana ever-users had higher odds of prescription-opioid misuse (ever-misuse [OR: 3.04; 95% CI, 2.68-3.43]; past-year misuse [OR: 3.44; 95% CI, 3.00-3.94]; and past-month misuse [OR: 4.50; 95% CI, 3.35-6.05]) compared to marijuana never-users. Similar results were found for the association of past-year and past-month marijuana use with prescription-opioid misuse. This study provides data on trends and associations about opioid misuse among marijuana users and non-users in a changing social environment of drug use in the United States. Future research should consider whether there is a causal relationship between marijuana use and prescription opioid misuse.

Over the 75‐year lifetime of the British Pharmacological Society there has been an enormous expansion in our understanding of how opioid drugs act on the nervous system, with much of this effort aimed at developing powerful analgesic drugs devoid of the side effects associated with morphine – the Holy Grail of opioid research. At the molecular and cellular level multiple opioid receptors have been cloned and characterised, their potential for oligomerisation determined, a large family of endogenous opioid agonists has been discovered, multiple second messengers identified and our understanding of the adaptive changes to prolonged exposure to opioid drugs (tolerance and physical dependence) enhanced. In addition, we now have greater understanding of the processes by which opioids produce the euphoria that gives rise to the intense craving for these drugs in opioid addicts. In this article, we review the historical pathway of opioid research that has led to our current state of knowledge. British Journal of Pharmacology (2006) 147, S153–S162. doi:10.1038/sj.bjp.0706435