Time-dependent neuronal changes associated with craving in opioid dependence: an fMRI study.

Relapse after initially successful treatment is a significant problem facing the treatment of opioid dependence. Evidence suggests craving elicited by re-exposure to drug cues may precipitate relapse. Attempts to identify neural biomarkers of cue-elicited craving have yielded inconsistent findings. We aimed to apply a novel continuous functional magnetic resonance imaging technique to follow the minute-to-minute evolution of brain responses, which correlate with the waxing and waning of craving. Newly detoxified male opioid-dependent patients and healthy control participants attended two separate, counterbalanced, functional magnetic resonance imaging scanning sessions during which they viewed a 10-minute video (drug cue or neutral cue) followed by 5 minutes of fixation. Participants rated the intensity of their craving throughout each session. We hypothesized that subcortical/ventral prefrontal cortex (PFC) regions and dorsal PFC regions would show different associations with craving reflecting their putative roles in appetitive processing versus cognitive control. Compared with controls, drug cue (minus neutral cue) video recruited the left amygdala and was temporally correlated with craving. In contrast, dorsal anterior cingulate blood-oxygen-level-dependent signal time course was higher than controls only during a period after cue exposure when craving levels were declining. Against expectations, neither the ventral striatum nor ventral PFC was significantly recruited by drug cue exposure. Findings suggest that the amygdala has a central role in craving, whereas the dorsal anterior cingulate may control craving in treatment-seeking patients. Time course analysis yielded new insights into the neural substrates of craving that could objectively validate development of psychological and pharmacological approaches to sustained abstinence.

The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 men.

BACKGROUND: Anabolic-androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. METHODS: An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. RESULTS: The majority of respondents were white, aged 18-30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. CONCLUSIONS: Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use.

Using a pragmatically adapted, low-cost contingency management intervention to promote heroin abstinence in individuals undergoing treatment for heroin use disorder in UK drug services (PRAISE): a cluster randomised trial.

INTRODUCTION: Most individuals treated for heroin use disorder receive opioid agonist treatment (OAT)(methadone or buprenorphine). However, OAT is associated with high attrition and persistent, occasional heroin use. There is some evidence for the effectiveness of contingency management (CM), a behavioural intervention involving modest financial incentives, in encouraging drug abstinence when applied adjunctively with OAT. UK drug services have a minimal track record of applying CM and limited resources to implement it. We assessed a CM intervention pragmatically adapted for ease of implementation in UK drug services to promote heroin abstinence among individuals receiving OAT. DESIGN: Cluster randomised controlled trial. SETTING AND PARTICIPANTS: 552 adults with heroin use disorder (target 660) enrolled from 34 clusters (drug treatment clinics) in England between November 2012 and October 2015. INTERVENTIONS: Clusters were randomly allocated 1:1:1 to OAT plus 12× weekly appointments with: (1) CM targeted at opiate abstinence at appointments (CM Abstinence); (2) CM targeted at on-time attendance at appointments (CM Attendance); or (3) no CM (treatment as usual; TAU). Modifications included monitoring behaviour weekly and fixed incentives schedule. MEASUREMENTS: Primary outcome: heroin abstinence measured by heroin-free urines (weeks 9-12). SECONDARY OUTCOMES: heroin abstinence 12 weeks after discontinuation of CM (weeks 21-24); attendance; self-reported drug use, physical and mental health. RESULTS: CM Attendance was superior to TAU in encouraging heroin abstinence. Odds of a heroin-negative urine in weeks 9-12 was statistically significantly greater in CM Attendance compared with TAU (OR=2.1; 95% CI 1.1 to 3.9; p=0.030). CM Abstinence was not superior to TAU (OR=1.6; 95% CI 0.9 to 3.0; p=0.146) or CM Attendance (OR=1.3; 95% CI 0.7 to 2.4; p=0.438) (not statistically significant differences). Reductions in heroin use were not sustained at 21-24 weeks. No differences between groups in self-reported heroin use. CONCLUSIONS: A pragmatically adapted CM intervention for routine use in UK drug services was moderately effective in encouraging heroin abstinence compared with no CM only when targeted at attendance. CM targeted at abstinence was not effective. TRIAL REGISTRATION NUMBER: ISRCTN 01591254.

Telephone delivered incentives for encouraging adherence to supervised methadone consumption (TIES): Study protocol for a feasibility study for an RCT of clinical and cost effectiveness.

The majority of people receiving treatment for their heroin addiction, are prescribed methadone; for which there is an extensive evidence base. When treatment starts, people take their daily dose of methadone under supervision at a community pharmacy. Supervision guarantees methadone is taken as directed by the individual for whom it has been prescribed, helps to ensure individuals take their correct dose every day, and safeguards against diversion and overdose. However, individuals often fail to attend the pharmacy to take their methadone. Each missed dose is of concern. If a patient misses their daily dose of methadone, they will start to experience opiate withdrawal and cravings and are more likely to use heroin. If they miss three days dose, there are concerns that they may lose tolerance to the drug and may be at risk of overdose when the next dose is taken. Hence there is an urgent need to develop effective interventions for medication adherence. Research suggests that incentive-based medication adherence interventions may be very effective, but there are few controlled trials and the provision of incentives requires time and organisational systems which can be challenging in pharmacies. The investigators have developed the technology to deliver incentives by mobile telephone. This cluster randomised trial will test the feasibility of conducting a future trial evaluating the clinical and cost effectiveness of using telephone delivered incentives (praise and modest financial rewards via text messaging) to encourage adherence with supervised consumption of methadone in community pharmacies. Three drug services (each with two or three community pharmacies supervising methadone consumption that will enrol 20 individuals, a total of 60 participants) will be recruited and randomly allocated to deliver either i) telephone delivered incentives, ii) telephone delivered reminders or iii) no telephone system. Acceptability, recruitment, follow-up, and suitable measures of clinical and cost effectiveness will be assessed. Findings from this feasibility study will be assessed against stated progression criteria and used to inform a future confirmatory trial of the clinical and cost effectiveness of telephone delivered incentives to encourage medication adherence. TRIAL REGISTRATION: ISRCTN58958179 (retrospectively registered).

Prevalence of recent fentanyl use among treated users of illicit opioids in England: based on piloted urine drug screens.

OBJECTIVE: To use a pilot of national fentanyl screening to establish the current prevalence of recent fentanyl use among treated users of illicit opioids in the English treatment system and inform the design of a full study. DESIGN: Cross-sectional fentanyl metabolite urine screening in randomly-selected study sites, stratified to cover all nine geographical regions of England, supplemented with self-report subsequent to a positive fentanyl test. PATIENTS: 468 adult (18 years of age and above) patients receiving treatment for opioid use disorder, screened December 2017 to May 2018. RESULTS: The fentanyl-positive rate in patients receiving treatment for opioid use disorder in the English treatment system was 3% (15/468, 95% CI 1.8% to 5.2%) with a per-site range (for the 10 sites in 9 regions where fentanyl was detected) of between 2% (1/57) and 15% (4/27). Self-report data indicated that the majority of fentanyl-positives (12/15, 80%) was unaware of having purchased fentanyl. CONCLUSIONS: Despite alerts already in place, patients receiving treatment for opioid use disorder, who were fentanyl-positive, were unwittingly purchasing and consuming fentanyl.