Maintenance therapy with buprenorphine and methadone is the gold standard pharmacological treatment for opioid use disorder (OUD). Despite these compounds demonstrating substantial efficacy, a ...significant number of patients do not show optimal therapeutic responses. The abuse liability of these medications is also a concern. Here we used rats to explore the therapeutic potential of the new long-acting pan-opioid agonist Cebranopadol in OUD. We tested the effect of cebranopadol on heroin self-administration and yohimbine-induced reinstatement of heroin seeking. In addition, we evaluated the abuse liability potential of cebranopadol in comparison to that of heroin under fixed ratio 1 (FR1) and progressive ratio (PR) operant self-administration contingencies. Oral administration of cebranopadol (0, 25, 50 μg/kg) significantly attenuated drug self-administration independent of heroin dose (1, 7, 20, 60μg/inf). Cebranopadol also reduced the break point for heroin (20 μg/inf). Finally, pretreatment with cebranopadol significantly attenuated yohimbine-induced reinstatement of drug seeking. In abuse liability experiments under FR1 contingency, rats maintained responding for heroin (1, 7, 20, 60μg/inf) to a larger extent than cebranopadol (0.03, 0.1, 0.3, 1.0, 6.0μg/inf). Under PR contingency, heroin maintained responding at high levels at all except the lowest dose, while the break point (BP) for cebranopadol did not differ from that of saline. Together, these data indicate that cebranopadol is highly efficacious in attenuating opioid self-administration and stress-induced reinstatement, while having limited abuse liability properties. Overall, the data suggest clinical potential of this compound for OUD treatment.
•Methadone and buprenorphine are the goldstandard therapies in OUD. Their abuse liability is a concern.•Cebranopadol, a first-in-class opioid agonist that also activates the NOP receptor, is in phase-III for pain.•Cebranopadol reduces the motivation for heroin self-administration and heroin seeking.•Results demonstrate a low abuse liability of cebranopadol in rat self-administration experiments.•Cebranopadol is candidate for immediate clinical investigation in OUD disorder patients.
IntroductionNHS England funding of Alcohol Care Teams (ACT) within acute hospitals targets the increased identification of alcohol dependence (AD). Previous research1 estimates that our centre ...experiences ~11,000 AD admissions annually, yet just 1367 were coded with AD in 2021, suggesting significant under-detection of AD, limiting opportunities to support clinical needs and access to specialist treatment. Universal screening (US) of admissions can increase detection of alcohol use disorders (AUD), including AD, allowing ACTs to provide specialist care during an individual’s hospital admission. As one of few Trusts using US, we report our initial experience.MethodThe Fast Alcohol Screening Tool (FAST2) is a validated, 4 question screening tool with a score of ≥3 indicating possible AUD. A recent study3 examining the utility of FAST cut-scores versus full AUDIT ≥20 (i.e. AD) identified FAST≥5 as the optimal score for probable AD requiring clinical assessment. In 2022 FAST was added to the electronic assessment system allowing nurses across the Trust to screen all adult emergency and elective admissions (excluding maternity). Scores and ward location are visible to ACT via electronic dashboard, allowing ACT staff to respond proactively to those FAST≥5. We reviewed referral data to ACT before and after implementation of US using FAST.ResultsIn 2 years prior to US, 1620 patients with suspected AUD were referred to ACT (mean 68/month). In 6 months after US introduction we identified 2,344 patients with possible AUD (FAST 3–4; mean 391/month) and 737 with AD (FAST≥5; mean 123/month) – a doubling of referrals to the ACT and together comprising 9% of all admissions. 44 wards utilised FAST with only 2 reporting no FAST+ve cases. The majority of FAST≥5 scores were identified on the acute assessment unit. We also found large increases in screening in elective surgery, ENT and cardiology wards, all of which generated few referrals pre-US. Following ACT review we identified 82 patients (11.1%) who were incorrectly scored, potentially leading to both inappropriate referrals and missed intervention opportunities. An ongoing ACT-led, pan-Trust nurse education programme should mitigate this in future.ConclusionUS has increased the number of ACT referrals and revealed a broader distribution of AUD/AD across the Trust, often in areas with historically few referrals or ACT in-reach. US has allowed the Trust to increase identification of people at risk, intervene in their care, and better utilise resources. The ACT-led education programme will maintain and improve US.ReferencesRoberts E, Morse R, Epstein S, Hotopf M, Leon D, Drummond C. The prevalence of wholly attributable alcohol conditions in the United Kingdom hospital system: a systematic review, meta-analysis and meta-regression. Addiction. 2019;114(10):1726–37.Hodgson R, Alwyn T, John B, Thom B, Smith A. The Fast Alcohol Screening Test. Alcohol and Alcoholism. 2002;37(1):61–6.Phillips T, et al. FASTER Access to Alcohol Treatment Study (IRAS: 275280, CPMS: 44867) funded by the Office of Police and Crime Commissioner and NIHR Yorkshire and The Humber Clinical Research Network.
PDF
