Abstract
SUMMARYDespite record-breaking numbers of opiate related deaths in the UK in 2019, pharmacological management of opiate dependence has evolved little since the advent of methadone in 1965. Along with harm minimisation and psychosocial interventions, the mainstay of pharmacological treatment remains opioid substitution therapy (OST) using methadone or buprenorphine, with many patients receiving OST for many years. Even with these treatments, opiate users continue to face mortality risks 12 times higher than the general population, and emerging evidence suggests that individuals who remain on long-term OST present with a range of physical and cognitive impairments. Therefore, with a growing ageing opiate dependent population who would benefit from detoxification from OST, this article provides an overview of the current state of opiate dependence in clinical practice, explores the reasons why availability and acceptability of detoxification pathways are declining, and discusses emerging pharmacological therapies that could provide benefit in relapse prevention.
Highlights
We briefly describe the neurobiology of the opioid system and clinical management of opiate dependence
To investigate whether endogenous opioid levels were blunted in addiction our group used [11C]-carfentanil to assess changes in levels following an oral D-amphetamine challenge. We showed that both pathological gamblers and abstinent alcoholics have blunted D-amphetamine-induced endogenous opioid release in various brain regions, including the nucleus accumbens, putamen and frontal lobe (Mick 2016; Turton 2020)
Results from a metaanalysis of randomised control trials (RCTs) examining the effect of contingency management on reducing substance use in substance dependence indicated effect sizes (Cohen’s d) of 0.46 at the end of treatment
Summary
Despite record-breaking numbers of opiate related deaths in the UK in 2019, pharmacological management of opiate dependence has evolved little since the advent of methadone in 1965. This reflects the success of our treatment of opioid dependence, in that users are staying alive for longer, the deaths of middle-aged heroin users is one of the main drivers for the spike in drug-related deaths (Public Health England 2019) This dispels a commonly held belief that opioid related deaths usually occur from overdose in inexperienced users. To maintain brain function and homeostasis in the presence of increasing circulating opioids, individuals will develop marked tolerance, namely reduced sensitivity and physical dependence, with repeated and prolonged opioid use Such neurobiological adaptation is an expected response and seen with other drugs, such as benzodiazepines and alcohol. PET studies using [11C]-diprenorphine to label MOR, KOR and DOR receptors in opioid dependent individuals during early abstinence showed higher [11C]diprenorphine binding in multiple brain regions compared with controls This higher binding reflects an increase in opioid receptor availability due to either increased numbers of receptors or reduced circulating endogenous opioids. In keeping with findings of increased MOR binding in opioid dependence, PET studies have found that recently abstinent cocaine users have higher MOR binding with [11C]-carfentanil in BOX 3 Common signs/symptoms of opioid withdrawal
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