Double-blind placebo-controlled evaluation of the PROMETA (TM) protocol for methamphetamine dependence.
Ling W., Shoptaw S., Hillhouse M. et al. Addiction: 2012, 107(2), p. 361–369.
The US company which owns and markets the controversial PROMETA proprietary combination of drugs for methamphetamine dependence funded a rigorous trial by independent researchers; the result was a no-better-than-placebo verdict, another negative in the search for drugs to counter stimulant dependence.

Summary
After cannabis, the powerful stimulant methamphetamine is the most abused illicit drug worldwide, with 15–16 million regular users, yet there are no approved medications for the treatment of methamphetamine dependence.

A proprietary system of treatment for methamphetamine dependence, the PROMETATM protocol, combines medications purported to normalise brain systems altered by chronic stimulant use along with psychosocial treatment designed to minimise withdrawal symptoms, prevent relapse and reduce cravings. Of the three medications in the protocol, flumazenil is the principal element. Among other effects, the drug works via the GABA neurotransmitter system to block the action of benzodiazepine tranquilisers and sleeping pills. Medically it is used to reverse deep sedation and as an antidote to benzodiazepine overdose. A second element is gabapentin, an anti-convulsant which also acts on the GABA system and which has been used as an analgesic. It has been reported to reduce craving and other subjective effects of cocaine. Last is hydroxyzine hydrochloride, an anti-anxiety drug which has been widely used in the management of withdrawal from substance dependence.

The featured study was conducted when this protocol was being heavily publicised and was subject to a great deal of debate and controversy in drug abuse, investment and news media circles. Proponents were buoyed by anecdotal reports and uncontrolled studies, while opponents cited the lack of data from placebo-controlled trials. In just such a trial, the study aimed to evaluate the efficacy and safety of this protocol in the treatment of methamphetamine dependence. It was funded by the company which owns the protocol, which also referred people seeking treatment via its call centre to the researchers and trained the researchers in the protocol to ensure their implementation matched the company's specification. The company played no other part in the study.

The study recruited adults seeking treatment for methamphetamine abuse or dependence and who had used the drug on at least four of the last 30 days. The 120 eligible for and who agreed to join the study were allocated to one of three clinics which offered a 40-day medication regimen beginning with five infusions (at two clinics on an inpatient basis) plus 14 weekly sessions of cognitive-behavioural therapy over the roughly 15 weeks of the trial. For a randomly selected half of the patients, the medication was the PROMETATM protocol; the other half were given identical but inactive placebo preparations (except that they too were offered the anti-anxiety agent hydroxyzine hydrochloride, not considered a key element of the protocol). The study based its findings on the 111 patients who at least began the medication/placebo regimens. Typically they were white single men in employment who on average had used methamphetamine more than every other day and had used for about 10 years. Over 8 in 10 were on probation or parole and most had a history of physical and sexual abuse.