FORWARDS 1 study

Treatment of opiate addiction with opiate substitute treatment (eg methadone) is beneficial. However some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues of baclofen administration to opiate dependent individuals receiving methadone.

Opiate dependent individuals maintained on methadone will be recruited from addiction services in northwest London. Participants will be medically healthy with no severe chronic obstructive pulmonary disease or Type 2 respiratory failure, not currently dependent on other substances (excluding nicotine), have no current severe DSM-5 psychiatric disorder, and able to take baclofen or 4800IU vitamin D (placebo).

Medical, psychiatric (eg depression, anxiety) and dependence history and current status will be obtained using validated questionnaires and examinations. Participants will be randomised in a 3:1 ratio to baclofen or placebo. A Bayesian dose-escalation adaptive model will inform the baclofen dose (10, 30, 60 or 90mg) based on the prior incidence of ‘dose-limiting toxicity’ (DLT) and participant-specific methadone dose.