Emerging Pharmaceutical Use To Control Abusive Alcohol and Cannabis Use
Certainly, twelve step approaches to treatment for alcohol and other drug abuse and addiction have been the most successful to date. These programs (AA, NA, GA et al) promote strict adherence to abstinence generating much debate about whether or not that approach limits the scalability to a broader population. There are estimates that of the 40 million people who suffer from alcohol or other drug abuse issues, less than 10% achieve successful recovery if measured by one year of continuous abstinence.
In their book Alcoholics Anonymous the founders discussed how their focus was solely on those who had traveled far down the curve of economic, physical, emotional, spiritual and social decline. New adherents had to “hit bottom”. At that time there were few successful approaches to treatment and the founders believed that their approach was sufficiently demanding that only the most desperate were likely to persist in this new program of recovery. The long held moralistic view of drunkenness and drug use were sufficiently prevalent at that time that they insisted on strict anonymity as well.
Today thinking about alcohol and other drug use has evolved to include a focus not just about the addict but also the substance abuser. Estimates are that there are more than 50 million Americans who are binge drinkers (several drinks in a sitting) or heavy drinkers (several drinks in a typical week). Similarly there are likely near 37 million Americans who use cannabis recreationally and perhaps 9 million who have become dependent (admittedly the research on cannabis is nowhere near as far developed as that for alcohol). The term “substance use disorder” recognizes abuse as well as addiction although the bright line between abuse and addiction is at present less well defined.
Certainly, twelve step programs have been a godsend to millions of Americans over the past 90 years. It is appropriate, though, to pursue additional approaches given the current success rate. The founders themselves recognized limitations to success in their program of recovery noting that, “there are those with severe emotional or mental disorders but many of them do recover if they have the capacity to be honest” (“Alcoholics Anonymous”, AA World Services, 2017). A bit self-serving to accuse those not successful in their new program with emotional or mental disorders, or self-deception, but this does indicate their awareness that this will not work for everybody.
We have discussed several different approaches and their current efficacy in previous articles. Given the increasing promotion of programs involving naltrexone as a pharmaceutical intervention alone or with other support, we thought it important to discuss those approaches. We won’t name them here. Turn on the television – you will see them.
Medical Assisted Treatment (MAT) is over 70 years old. The first, broad based approach involved methadone for the treatment of heroin addiction. In 1966 Rockefeller University researcher Mary Jane Creek and colleagues published a paper introducing methadone as a treatment for heroin addiction (“Fifty years after landmark methadone discovery, stigmas and misunderstandings persist”, Rockefeller University News and Highlights, 2016). When a subsequent study established that methadone could be administered once daily, “methadone maintenance” became a standard “treatment” for heroin addiction. The U.S. Food and Drug Administration approved methadone as a component of treatment for heroin and other opioid addiction in 1973 and by 2016 1.3 million people worldwide were on methadone maintenance. The quotation marks are because this is not treatment strictly speaking but a drug substitution that also has its negative effects.
Previously, Danish researchers studying compounds to treat parasitic stomach infections self-administered (before modern clinical trials this was not uncommon) a small dose of disulfiram to check its side effects. Later they became very ill after ingesting alcohol. They concluded that an interaction of disulfiram and alcohol was responsible and licensed the new drug Antabuse. Antabuse causes severe, unpleasant outcomes when combined with alcohol in the system and is used as part of aversion therapy. It was administered to patients with extreme resistance to treatment which at that time was, mostly, abstinence through Alcoholics Anonymous. In the 1950s the FDA approved Antabuse for treatment but after several severe, negative outcomes including deaths Antabuse was scaled back as treatment and then administered only in much lower doses.
Subsequently naltrexone (1994) and acamprosate (2024) were approved by the FDA as a means of easing withdrawal. FDA advisories and NIH studies recommended these MAT pharmaceuticals be administered to reduce the negative impacts of withdrawal which are a barrier to many seeking recovery. The idea was to administer these drugs combined with cognitive behavioral therapy (CBT) and to gradually reduce the dosage over time. Abstinence was still the goal.
Naltrexone is an “antagonist” that works by reducing dopamine release effectively blocking the pleasure receptors in the brain that provides the relief from withdrawal and by extension reduce the pleasurable feelings from consumption. The approaches one will find on television, online and print advertisements focus on alcohol consumption and will offer naltrexone prescriptions online. CBT is offered as well but not usually required for the prescription. In some programs there is no limit on “refills”. To be clear, there is nothing about any of these components that are, in themselves, problematic. As we will detail, naltrexone has been shown to reduce cravings and alcohol consumption, telehealth has extended care to millions of Americans, and CBT is a proven, effective means of therapy. Acamprosate works slightly differently to reduce pleasurable signaling in the brain but is not as often prescribed by these approaches.
The use of targeted naltrexone often comes to patients’ and clinicians’ attention through a provocative 2015 Atlantic article entitled “The Irrationality of Alcoholics Anonymous”. The article highlighted the story of neuroscientist John Sinclair and his program that prescribing naltrexone 1 hour before drinking improves drinking outcomes by decreasing the reward of and cravings for alcohol.
Reviews of naltrexone’s effectiveness in reducing alcohol consumption are nascent, sometimes contradictory, but generally positive. Several studies indicate that properly administered, naltrexone can minimize cravings, reduce frequency and amounts of consumption, and greatly minimize the return to binge drinking. One limitation of the existing evidence for medications is that most studies on problematic alcohol use and medications for Alcohol Use Disorder (AUD, including addictive and abusive alcohol consumption) focus on severe AUD, often addicted drinking and ignore binge-drinking and heavy drinking populations which may not (yet) be addictive.
A review in the Journal of Psychiatry (Naltrexone and Alcohol Use, Jonathan Avery, M.D.et al, December 2022) offered a generally favorable review. The review notes that among approved medications daily and long-acting injectable naltrexone have the strongest evidence for their use as they have been shown to improve drinking outcomes, including the frequency and amounts of consumption as well as a return to any drinking including binge drinking and heavy drinking. As an opioid antagonist that alters dopamine release following alcohol use, naltrexone is thought to help with craving and alcohol-related euphoria. The authors also note the limitation of existing evidence focused primarily on addictive alcohol use. They suggest that prescribing naltrexone 1 hour before drinking as contemplated in the Sinclair Method may be especially helpful for binge drinkers.
In 2023 a meta-analysis of over 200 studies comparing pharmaceutical use in AUD treatment was published in the Journal of the American Medical Association (“Pharmacotherapy for Alcohol Use Disorder, A Systematic Review and Meta-Analysis”, Melissa McPheeters, PhD, MPH; Elizabeth A. O’Connor, PhD; Sean Riley, MSc, MA, JAMA Online, November 2023). Data from 118 clinical trials and 20,976 participants were included. The authors conclude, “In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.” The authors found moderately strong correlation for use of naltrexone and acamprosate often when combined with other forms of treatment for reducing return to any drinking, return to heavy drinking, percentage of drinking days, and percentage of heavy drinking days. They note that oral naltrexone is more convenient than acamprosate and the contraindications for use with other medications and with certain medical conditions.
The authors also reported on studies about use of disulfiram (Antabuse) that as previously noted has been FDA approved for alcohol use disorder since the 1950s. They found limited evidence to support the efficacy of disulfiram compared with placebo for preventing any return to alcohol use.
A 2019 study prepared for the Veterans Administration similarly reviewed several studies on the use of pharmaceuticals for treatment of cannabis use disorder (CUD) (“Pharmacotherapy for the Treatment of Cannabis Use Disorder: A Systematic Review”, Department of Veterans Affairs Veterans Health Administration Health Services Research & Development Service, Washington, DC, Karli Kondo, Ph.D., MA, February 2019). The authors conclude, “There is limited research examining the effectiveness of pharmacotherapies for CUD, and many of the existing studies are hampered by poor methodological quality or reporting. There is moderate strength evidence that antidepressants do not reduce cannabis use or improve treatment retention and may be associated with lower rates of abstinence. Although we found that cannabinoids do not improve retention, increase rate of abstinence, or reduce cannabis use, we did find low strength evidence that they may reduce withdrawal symptoms. We found insufficient evidence to comment on effects of all other drug classes.”
While there are other studies to report they generally complement these reviews. As we noted, these studies are relatively nascent. What might we conclude at this stage of the deployment of pharmaceutical to treat alcohol and/or cannabis use disorder?
First, the clinical evidence is relatively new. A body of evidence is building but further studies that reinforce, discredit or further parse the conditions presented by study participants is needed before firm conclusions are drawn.
Second, the evidence supports that the best outcomes occur when these pharmaceuticals are used in combination with other forms of support including cognitive behavioral therapy (CBT) and self-help such as in twelve step programs. This finding has been consistent in all reviews we have seen regardless of what SUD treatment is under study. A hallmark of abusive alcohol and drug use is isolation, and it is abundantly clear that engagement with other people, counselors and those who share these issues makes a very real difference in outcomes. To be clear, these studies do not report that use of naltrexone alone is always unsuccessful but that combining with other modalities is more effective and more often effective. This is similarly true of non-pharmacological approaches. People did become clean and sober through the pledge though at much lesser rates of success than other approaches.
This need for engagement raises the question of what group the client trying naltrexone or acamprosate for reducing use might access. Since those twelve step programs continue to stress continuing abstinence, they are not the likely source of engagement. An individual counselor, well chosen, will be a source to avoid isolation. As of this writing we are not aware of a gathering for people trying to continue using alcohol or cannabis for recreational purposes but to temper their use.
Third, there may be a result emerging that is encouraging to those who are drinking abusively but have not achieved an addicted status. In “Theory and Foundation” (Theory and Foundation | Prime For Life, www.primeforlife.org) the Prevention Research Institute proposes that abusive drinking will evolve to an addictive condition in most people. If so, then the opportunity to arrest binge drinking and heavy drinking exists before addiction develops. Further, it seems evident that abusive alcohol and cannabis use occurs occasionally or as a pattern in early adulthood and oftentimes dissipates with age. If this is the case, then intervention with naltrexone can be used, in conjunction with other supports, to reduce or eliminate this abusive behavior.
Fourth, we have previously reported studies that indicate that strength of motivation is a key element in recovery where abstinence is the recommended course. The studies we found about naltrexone and acamprosate have not controlled for motivation. We strongly suspect that motivation has been a factor in those cases where success has been evidenced by the participant.
Finally, these studies do not make the case that intervention with naltrexone to continue alcohol use is indicated when addictive alcohol use has evolved. That is not to say that there will never be such an approach but that the evidence to date does not support that treatment modality. Rather, these studies do not refute the long-held view that the only effective approach to addiction, as opposed to abuse, is abstinence.
Admittedly, we are closely parsing this difference between abusive and addictive use to some extent beyond our credential and, likely, beyond the available data. While the evidence from the Prevention Research Institute about the progression from abusive drinking to addiction is compelling, we have not found research beyond their citations that corroborates that thinking. Perhaps we should state our case differently. Our point might be that there comes a point when the use of pharmaceuticals to continue drinking or cannabis use is likely ineffective and certainly not worth the risk.
We have spent time in previous articles dispelling the myth that not using alcohol and cannabis is somehow antisocial or sets one apart. We reported on the Gallup Poll recently published that alcohol use by Americans has reached a new low where in 2025 46% of Americans did not have even one drink. We also note NIH reports that about 16% of Americans use cannabis recreationally. Using cannabis is the unusual behavior and it is to the point where alcohol use or refraining is about even. Allowing us a step beyond the data, if one continues to use these drugs while trying to control it through pharmaceuticals with or without other supports, and one fails, then it would be important to examine what it is that is driving that goal.
In “Old Timers For A Change” we described how twelve step members who achieved recovery through strict adherence to abstinence actively resist further research into treatment. This is no surprise given the dramatic change in their fortunes that AA, NA et al have produced. However, this heterodoxy has proven effective for too small a portion of the afflicted population to restrict further investigation into treatment. Further yet, the welcomed evolution of thinking about approaches to include binge drinkers and heavy drinkers who may not have the brain disease addiction would indicate that there are other categories of users that may benefit from approaches other than strict abstinence. We should not retard that progress.
All that said, however, there is not yet evidence that the intervention of naltrexone or other drugs for alcohol addiction, or any drug for cannabis dependence, has proven a better or more effective approach than abstinence. Of course, abstinence may be the goal to be achieved while relapse is common in early stages, or these pharmaceuticals may be used effectively to moderate withdrawal. That is not the purpose indicated in advertisements as noted.
