Sinclair Method

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The Sinclair Method is a treatment for alcoholism based on the use of opiate antagonists, such as naltrexone or nalmefene. It differs from other treatment in that patients use the drug while continuing to drink. Dr. John David Sinclair has found this treatment to be more effective in reducing overall alcohol use by addicts than in asking them to try to achieve abstinence, even when combined with naltrexone and psychosocial counseling. The Sinclair Method, specifically, has been adopted in Finland as a standard treatment protocol for alcohol dependence.[1]

Naltrexone and others have been shown to create pharmacological extinction of addiction, resulting in a decrease in the craving for alcohol over time, but is less successful in achieving abstinence. Supported by studies in the early 1990s, naltrexone was approved by the U.S. Food and Drug Administration (FDA) in 1994 in the United States for treatment of alcohol dependence.[2] Pharmacological extinction works by blocking the positive reinforcement effects of ethanol-triggered endorphin in the brain. A major study released by the National Institutes of Health in the US in 2008 found that naltrexone is markedly successful when used as treatment for alcoholics having a certain gene related to opioid reception, which is found among 25-30% of whites.[3]

Pharmacological extinction[edit]

Main article: Naltrexone

Naltrexone is an opioid competitive antagonist which has been approved in the United States by the FDA since 1994 for the treatment of Alcohol Dependence. An opioid antagonist is a drug which blocks the opioid receptors in the brain and prevents opioids from binding to them. An antagonist not only produces no high, it prevents people from getting any high from drugs such as heroin, since it prevents them from binding to the receptors in the brain.[1]

Naltrexone also prevents the endorphins, the brain's natural painkillers, from binding to the receptors in the brain, which is why it is claimed to be effective in reducing the desire for alcohol.[1] It reduces the "reward" for drinking, producing pharmacological extinction.

"A World Health Organization (1996) publication concluded that naltrexone was a ‘safe and effective treatment for alcohol dependence'. The United States Agency for Health Care Policy and Research (AHCPR), reviewing the scientific evidence for different pharmaceuticals in treating alcoholism,[4] supported both naltrexone and acamprosate, but with the evidence for naltrexone being somewhat better."[2] Proponents claim that thousands of patients have been cured of alcoholism by the Sinclair Method since the early 1990s, but it is dependent on allowing patients to continue to use alcohol in a normal range of behavior.[2]

Following the first two clinical trials in the early 1990s, which were double-blind, placebo-controlled (DBPC), six more DBPC clinical trials with naltrexone followed, with positive results: in the UK (Chick in Litten et al., 1996); Maryland (McCaul et al., 1997), Sweden (Balldin et al., 1997; Månsson et al., 1999a,b), South Carolina (Anton, 1999; Anton et al., 1999), Finland (Alho et al., 1999; Heinälä et al., 1999a,b), and Australia (Morris et al., 1999). DBPC trials showing the safety and efficacy of nalmefene have also been conducted (Mason et al., 1994, 1999).[2]

Unlike alcoholism treatments/methods such as Antabuse (disulfiram), Temposil (calcium carbimide), and Alcoholics Anonymous, which all promote abstinence from alcohol, the Sinclair Method treats alcoholism by allowing patients to continue drinking. Naltrexone is available in multiple forms, including tablet and injection. For tablet form, a patient following the Sinclair Method takes a 50 mg tablet one hour before every drinking session. Patients who achieve success with the treatment experience a reduced urge to drink over time.

The treatment has been standardized as the "Sinclair Method", named after Dr. John David Sinclair, who published results of studies in 2000 and 2001 in peer-reviewed journals related to his treatment method.[2][5] He found that giving alcoholics naltrexone daily and telling them to abstain from drinking was not effective, even with counseling. By contrast, giving alcoholics naltrexone and telling them to take it only before drinking alcohol was highly effective in reducing the amount of their drinking, and could be considered to cure Alcohol Dependence.[1]

The goal of the Sinclair Method is to reduce a person's desire for alcohol in order to allow the person to regain rational control, generally achieved during a period of three to 15 months. The individual may continue to drink based on a perception of rational benefit to drinking, but will no longer be driven to drink by uncontrollable addiction.[1] Once the patient no longer drinks daily, he/she takes naltrexone only on days in which he expects to drink, an hour before the drinking occurs. The patient needs to continue taking naltrexone before drinking for the remainder of life, or the endorphin conditioning will be re-established.


Alcohol triggers the release of endorphins into the system, reinforcing drinking behavior. Continued consumption of alcohol strengthens this reaction. The theory suggests that for those with a strong endorphin reaction (generally due to genetic factors), the pro-alcohol conditioning exaggerates the strength of arguments for drinking, and perpetually keeps drinking in the person's mind as a favorable option.

Operant conditioning suggests that gaining rewards for behavior increases the desire to perform that behavior. Without rewards, the urge to perform that behavior gets weaker. This effect is referred to as the extinction of that behavior. This was demonstrated in the research by Edward L. Thorndike and later, B. F. Skinner.

In the case of alcoholism, the behavior is the consumption of alcohol, and the reward is the flush of endorphins in the brain related to drinking. By this theory, if the drinking behavior occurs, and the neurons do not receive their flush of endorphins, then the pro-alcohol conditioning should be extinguished. In practical terms, if the individual drinks but the endorphins are blocked from stimulating the neurons, the desire to drink is reduced. By this means, the urge to drink, that drives alcoholism, is reduced, provided the alcoholic continues to take the endorphin-blocking medication as recommended, prior to every occasion on which alcohol is consumed.

Evidence of efficacy[edit]

Sinclair published evidence for this treatment in 2000[2] and 2001, the latter an article entitled "Targeted Use of Naltrexone Without Prior Detoxification in the Treatment of Alcohol Dependence: A Factorial Double-Blind, Placebo-Controlled Trial"].[5][6] In this study, patients were divided into four groups. The first received naltrexone and was given counseling to encourage moderate drinking. The second received a placebo and was given counseling to encourage moderate drinking. The third received naltrexone and was given counseling to support abstinence. The fourth received placebo and was given counseling to support abstinence.

Although all groups in the study achieved a decrease in drinking, the group who received naltrexone in combination with a goal of moderate drinking were far less likely to relapse into heavy drinking than the other three groups. In the 32-week run of the study, 27% of those who combined naltrexone with drinking never had a relapse to heavy drinking, compared to 3% for those who combined naltrexone with abstinence.

Roughly a quarter of the participants of the study became completely abstinent and stayed that way. Overall, four-fifths of the participants reduced their drinking to healthy drinking levels or below. In three- and five-year follow up studies, roughly half of those who had benefited from the program continued to take a dose of naltrexone before drinking. For all those who continued the program, there was zero incidence of relapse.

The Sinclair Method is used extensively as an outpatient treatment at the Contral Clinic in Finland. By 2000, they had treated tens of thousands of patients with a claimed success rate around 78%, with 25% reducing their drinking to complete abstinence[7] with little or no craving.[2]

Related evidence[edit]

In a different take on the issue, a review of the literature was made in 2006 to determine how naltrexone could be used most effectively. They found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo. Only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo.[8] These did not evaluate results of the Sinclair Method per se.

In a major study released by the National Institutes of Health in 2008, another factor was evaluated in the use of naltrexone in achieving reductions in alcohol use among alcoholics. Published in the Archives of General Psychiatry, the report of the study showed that alcoholics having a certain variant of the opioid receptor gene (G polymorphism of SNP Rs1799971 in the gene OPRM1) demonstrated strong response to naltrexone and were far more likely to experience success at cutting back or discontinuing their alcohol intake altogether, while in those lacking the gene variant, naltrexone appeared to have no effect significantly different from placebo.[3]

See also[edit]


  1. ^ a b c d e Kenneth Anderson, "Drink Your Way Sober with Naltrexone", Overcoming Addiction Blog, Psychology Today, 27 July 2013, accessed 10 August 2014
  2. ^ a b c d e f g Sinclair, J.D. (January 14, 2000). "Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism". Alcohol and Alcoholism (Oxford Journal of Medicine) 36 (1): 2–10. doi:10.1093/alcalc/36.1.2. PMID 11139409. 
  3. ^ a b Anton R, Oroszi G, O’Malley S, Couper D, Swift R, Pettinati H, Goldman D (2008). "An Evaluation of Opioid Receptor (OPRM1) as a Predictor of Naltrexone Response in the Treatment of Alcohol Dependence". Archives of General Psychiatry 65 (2): 135–144. doi:10.1001/archpsyc.65.2.135. PMC 2666924. PMID 18250251. 
  4. ^ Garbutt et al., 1999;
  5. ^ a b Sinclair, John David (June 2001). "Targeted Use of Naltrexone Without Prior Detoxification in the Treatment of Alcohol Dependence: A Factorial Double-Blind, Placebo-Controlled Trial". Journal of Clinical Pharmacology (Oxford Journal of Medicine) 21 (3): 287–292. doi:10.1097/00004714-200106000-00006. PMID 11386491. 
  6. ^ Alternate link to full text of JoCP study on Erowid
  7. ^ Contral Clinic treatment FAQ[dead link]
  8. ^ Pettinati, H. M.; O'Brien, C. P.; Rabinowitz, A. R.; Wortman, S. P.; Oslin, D. W.; Kampman, K. M.; Dackis, C. A. (2006). "The Status of Naltrexone in the Treatment of Alcohol Dependence". Journal of Clinical Psychopharmacology 26 (6): 610–625. doi:10.1097/ PMID 17110818.  edit

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