This page is devoted to a drug called Naltrexone, which for the specific use pf alcohol or substance abuse-- is considered a "medically assisted treatment" ("MAT") under the Federal regulatory guidelines (i.e.-- it can only be prescribed by a medical doctor with the proper credentials"). It is readily available through off-shore on-line pharmacies. There is an initiative to make naltrexone available over-the-counter in the United States, however medical supervision in strongly advised. The prescribing of naltrexone as a "MAT", it is a legal requirement that a behavioral therapy must also be administered in conjunction with the application of the drug-- to deal with the psychlogical and behavioral factors that contribute to, or are inextricably linked with alcohol abuse behavior-- and that possible trigger drinking episodes-- at the least, underlying coping mechanisms that accompany the motivation or need to drink.
In all of SAMHSA's literature, they recommend an augmentation behavioral therapy to assure compliance, and a more compresensive approach of combining medical and behavioral.
Without identifying any specific "therapy" to be employed -- specific decision is left in the hands of the clinician as to what the most effective behavioral techniques or methods are.
What is unaddressed by the government or it's researchers and experts - is the reality that nasltrexone itself does nothing to prevent drinking-- it only mitigates and attenuates the euphoric effect of alcohol when imbibed. It simply blocks endorphins!
The Sinclair Method (TSM), was a heavily reasearched protocol-- proven effective, patented, and proven successful by by published clinical studies, as well as years of use now by thousands of rehabilitated adherents-- and yet this method is largely ignored and overlooked by the mainstream alcohol treatment community. TSM addresses the behavior of the brain's addiction to the euphoria derived from the endorphins created by alcohol.
Taking naltrexone as a preventative is by and large-- ineffectual, and is quite useless and untdetectable if there in no drinking associated with the action.
It is also expensive to take it as a regimen, and does nothing to cure of suppress the cravings for the high... which is the neurologic addiction itself.
The Sinclair Method utilizes naltrexone's unique effects- in conjunction as a package treatment. It is an adjunctive therapy, using naltrexone as an overall, and essential component and delivery system.
This page is devoted only to naltrexone... classified by the FDA as an orphan drug.
What Is Naltrexone?
There is a plethora of research in the late 1980's and throughout the 1990's, and effective application and impressive successful results by thousands of AUD sufferers-- that evidences that many people have more success when they combine anti-craving medications with personalized one-on-one support, and varying cognitive therapies whereby they are able to set their own goals around alcohol, rather than abide by the goals of a program. The primary medication The Sinclair Method protocols work in conjunction with to treat alcohol dependence... is Naltrexone. In a small percentage of patients, naltrexone is relatively ineffective, and other alternative similar-acting drugs are used to achieve the same result.
If you’re considering this drug, you’re probably wondering how safe it is.
In this post, we’ll outline the side effects of Naltrexone and whether it could be right for you.
Naltrexone is an anti-craving medication that’s prescribed to treat alcohol use disorder.
It’s FDA-approved for alcohol dependence, but it was first used to help prevent relapse in people dependent on opioids. When someone uses an opiate drug like heroin or oxycodone, Naltrexone stops the person from feeling the pleasure or sense of euphoria they usually do. That’s because Naltrexone is an opiate antagonist, meaning it blocks the body from responding to endorphins.
Although alcohol isn’t an opiate drug, researchers have found that Naltrexone works in a similar way with alcohol by blocking alcohol-induced pleasure. Typically, a person takes Naltrexone at the beginning of the day or when they anticipate drinking. They still feel the intoxicating effects of alcohol while taking Naltrexone, but the pleasure effects of alcohol decrease. Over time, as the brain stops making the connection between alcohol and pleasure, many people find it easier to stop drinking after the first or second drink. The drug works to gradually undo dependence.
Research on Naltrexone has shown that it effectively reduces heavy drinking and cravings. Compared to patients who took a placebo, or fake medication, those who took Naltrexone also had fewer relapse episodes.
Fortunately, Naltrexone’s side effects are mild and relatively rare. A recent review of research concluded that there were only a few safety concerns related to using the drug for alcohol use disorder. In fact, the number of people who stop using Naltrexone because of its side effects is about the same number as those who experience side effects from a placebo.
With that being said, there are a few side effects you may experience while your body is adjusting to the medication. These include:
The most commonly reported side effects are headaches and nausea. Women taking Naltrexone may be more susceptible to nausea, but it usually subsides as they get into the routine of taking the medication. To prevent this side effect, you can take your medication with food or ask your doctor if they can start you at a lower dose and gradually increase it.
Naltrexone is also a good option for people who are concerned about experiencing alcohol withdrawal symptoms if they stop drinking. Because Naltrexone works by helping a person to gradually decrease their drinking over an extended period of time, this process can minimize or even eliminate the impacts of alcohol withdrawal.
If side effects are severe or prolonged, you should tell your doctor.
Like most drugs, it’s possible to overdose on naltrexone, possibly leading to coma or death. Do not take more than the recommended dose.
Naltrexone is effective but it isn’t a one-time magic pill. When you take it using the Sinclair Method, you’ll notice results over time. Even after you’ve cut back, your coach may still suggest taking it every time before you drink to keep yourself on track or further minimize your consumption. For this reason, you may be wondering if naltrexone has any long-term side effects.
There are no known side effects or problems caused by long-term use when used as directed. With that being said, your doctor may recommend avoiding high doses of acetaminophen (ex. Tylenol). This is because it may increase your chances of liver damage while taking naltrexone.
Women who are struggling to quit alcohol before or during pregnancy may wonder if Naltrexone is a safe option.
How Naltrexone may affect a fetus is unknown. Experts believe that it crosses the placenta, meaning that the drug could be transferred to the baby. A review of research on animals showed that Naltrexone may cause developmental abnormalities, such as higher birth and organ weights and longer body lengths. It may also have developmental effects later on.
Although it hasn’t been shown to cause birth defects, studies on rats and rabbits show that high doses may cause miscarriage. It’s important to understand that these results may not translate to humans. Also, the doses used on animals are much higher in comparison.
If you are pregnant or planning on becoming pregnant while taking Naltrexone, you should talk to your doctor. If you are expecting and considering Naltrexone, your doctor may still recommend it. He or she will weigh the benefits and risks to assess whether it’s the best option. For example, alcohol has well-known adverse effects on a fetus. Even though Naltrexone also has risks, the consequences of binge drinking could affect a fetus more. In these cases, a healthcare provider will determine which treatment is less likely to harm the baby.
Some people are afraid that their addiction to alcohol may morph into a dependence on their medication. The concern is valid since some alcohol withdrawal medications, such as benzodiazepines, are highly addictive. However, it’s not possible to become addicted to Naltrexone, according to the National Institute on Alcohol Abuse and Alcoholism.
The medication isn’t habit-forming and doesn’t cause physical or psychological dependence. You won’t feel any sort of buzz, high, or sense of euphoria. In fact, when someone takes the drug, they usually don’t feel anything other than a decreased desire to drink.
Being an anti-craving medication, naltrexone works by stopping you from feeling the endorphins alcohol releases. Some people wonder if the drug also blocks healthy endorphins, impacting your mood. Endorphins can be released from normal activities, such as:
The current evidence suggests that naltrexone only impacts endorphins released by alcohol.
One theory is that alcohol elevates hormones in a different way. While drinking activates the gabaergic system, other behaviors don’t. Because of this, the medication seems to specifically target alcohol reward.
Naltrexone also does not directly affect serotonin or dopamine—two chemicals that help regulate emotions. Since it works in the body’s opioid system, it doesn’t impact neurotransmitters. A 2006 study concluded that even though depression is cited as a naltrexone side effect, it shouldn’t be considered common. In fact, they found that adhering to naltrexone treatment may be associated with fewer depressive symptoms.
In general, people don’t lose pleasure from other enjoyable activities while taking Naltrexone. With that being said, in rare cases, a patient will report emotional changes. These should always be discussed with your doctor.
While mood may not be impacted, the bad news is that some evidence suggests Naltrexone may change the way we process social situations. In a 2016 study, 34 volunteers received a placebo or Naltrexone. Researchers found that the medication:
There is also some evidence that the medication may affect social attachment. A 2016 study on healthy adults concluded that naltrexone reduced feelings of connection, suggesting that it may affect their ability to bond with others.
A 2019 study investigated this impact further by looking at how the drug affects social warmth (the feeling of being connected to others). Social and physical warmth leads to increased activity in two parts of the brain: ventral striatum and middle-insula. Researchers also established that brain activity caused by social warmth was related to social connection. What’s interesting is that Naltrexone disrupted this; brain activity in those two areas decreased. The results suggest that physical and social warmth may be dependent on opioid receptors. Since Naltrexone blocks these receptors, social connection may be affected.
If you have a Naltrexone prescription for alcohol dependence, you’ll probably notice a warning label about hepatotoxicity, or drug-induced liver damage. However, research shows that it’s only unsafe if it’s taken for extended periods in doses of 300mg or higher. Doctors usually prescribe Naltrexone for alcohol use disorder at much lower doses, typically 50mg. If a patient is already suffering from liver damage or disease, their doctor may recommend an anti-craving drug that’s not metabolized in the liver, such as baclofen.
While the drug is safe to take for most people, it does not get rid of the risks of alcohol. Naltrexone might block the pleasure effects of alcohol, but you can still get drunk while taking the medication. This means that you still need to be aware of how much you’re drinking because you could still experience bad coordination, impaired judgment, or blackouts.
Before prescribing you Naltrexone, your doctor will assess if it’s the right anti-craving medication for you.
Naltrexone is considered a non-addictive, safe drug but some people may experience mild side effects when they begin taking it. Prolonged or severe side effects are rare and should be reported to your doctor. Naltrexone works by blocking endorphins released by alcohol but doesn’t seem to affect those released by other activities. It also does not interact with neurotransmitters, meaning that it shouldn’t affect your mood. On the other hand, some research suggests it may affect how we perceive social situations or connections
Naltrexone was originally synthesized in 1963 and patented in 1967 as “Endo 1639A” (US patent no. 3332950) by Endo Laboratories, a small pharmaceutical company in Long Island, NY, a company with extensive experience in narcotics.
In 1969, DuPont purchased Endo Labs. DuPont had been struggling to develop its drug business since the late 1950s, and the acquisition of Endo provided DuPont with valuable expertise in drug manufacturing and marketing.
In the purchase, DuPont acquired the rights to several successful Endo drugs, including: Coumadin (warfarin), an anticoagulant; Percodan, a prescription narcotic; and Naloxone, a drug used for narcotic overdose.
Naltrexone, still in its early development phase, came to DuPont as part of the overall purchase of Endo.
At the time it seemed unlikely that DuPont would develop naltrexone, because at the time, naltrexone seemed to have relatively low market potential, and its patent would probably expire before the completion of any clinical trials.
The Federal Government Steps In
In June 1971, President Nixon created the Special Action Office for Drug Abuse Prevention (SAODAP). The first director of SAODAP, Dr. Jerome Taffe, was determined to improve access to drug abuse treatment by shifting services from prisons and hospitals to community-based services. “I regarded the development of naltrexone as one of my high priorities,” said Dr. Taffe.
SAODAP recognized that the development of naltrexone was of no burning interest to the private pharmaceutical industry, and that governmental funding would be necessary to bring it to market.
In March 1972, Congress passed the Drug Abuse Office and Treatment Act, calling for development of "long-lasting, non-addictive, blocking and antagonist drugs or other pharmacological substances for the treatment of heroin addiction." This Act provided substantial financial support for research.
By mid-1974, as SAODAP began to phase out of existence, the narcotic antagonist development project fell to the newly formed National Institute on Drug Abuse (NIDA). That same year, NIDA approached DuPont with the idea of developing naltrexone as a drug addiction therapy, and asked for DuPont's assistance in facilitating naltrexone's transit through the FDA approval process. DuPont agreed to assist NIDA with the development of naltrexone. In return, NIDA agreed to pay for the bulk of clinical development costs.
When asked later, DuPont representatives said that the primary reason for helping the government was Dupont’s "public spirit", and that naltrexone would probably not have been developed without the government's clinical and financial support.
The clinical trials for naltrexone as a treatment for heroin addiction began in 1973 (Schecter 1974, O'Brien 1978).
Difficulties in Clinical Trials
Early trials of naltrexone in rats, rabbits, dogs and monkeys had determined that the drug was nontoxic at therapeutic levels, with very few side effects. The subsequent human trials confirmed that the drug was safe for humans, but the efficacy trials ran into some unexpected problems.
Dr. Arnold Schecter, who conducted many of the early studies, reported that many opiate-addicted patients feared a new drug, lacked a desire to become drug free, were unwilling to possibly receive a placebo, and disliked the rigid protocols associated with the clinical trials (Schecter 1980).
Patients had to remain opiate-free for a minimum of 5 to 10 days prior to treatment because naltrexone causes severe withdrawal symptoms in patients with opioids in their system (Schecter 1974). Many addicts were unable to comply, due to the physiological effects of withdrawal.
Taking naltrexone does not provide any drug reinforcement (“high”), and produces no negative consequences (withdrawal) when discontinued. Unlike methadone, which helps suppress cravings, naltrexone has no effect until the addict attempts to use heroin. Some patients feared naltrexone would make them more vulnerable to these cravings, and felt that methadone was more effective in controlling them.
Because of these recruiting difficulties, researchers made no effort to screen out patients who might be difficult to manage in clinical trials -- e.g., patients who were poorly compliant -- and this may have compromised the results of the trials (Schecter 1980).
Since naltrexone is non-addictive and lacks the reinforcing effect of methadone, it requires more extensive psychosocial support services than methadone. Support services are expensive. Schecter estimated that total clinical treatment with naltrexone was almost twice as expensive as methadone -- not because of the medication itself, but because of the more intensive support services.
Early trial results showed that, compared with the methadone patients, the patients who were attracted to naltrexone therapy were relatively "more motivated and emotionally stable." Other studies showed that although naltrexone was an effective opiate block, clinical success (a reduction in heroin use), was limited to fully compliant patients.
As a result of these findings, the product labeling for naltrexone reads, "[Naltrexone]… does not reinforce medication compliance and is expected to have a therapeutic effect only when given under external conditions that support continued use of the medication". The final results of the clinical trials showed that naltrexone was modestly successful in the reduction of heroin use.
In 1984, the FDA approved naltrexone in a 50mg dose as a treatment for heroin addiction. Dupont brand-named the drug Trexan. The same year, DuPont’s naltrexone patent expired.
On March 11, 1985, the FDA designated naltrexone a an orphan drug,** which provided seven additional years of market exclusivity for naltrexone for DuPont.
Marketing Strategy for Trexan
The DuPont sales force had trouble explaining the mechanism of naltrexone and its benefits to a lay audience. The consumer marketplace had many misunderstandings and negative perceptions about naltrexone. One former member of the DuPont sales force said these misunderstandings were a great barrier to the use of Trexan.
DuPont also had an extremely difficult time trying to convince methadone clinic personnel to use Trexan. Most facilities could not afford to implement naltrexone therapy due to the combined price of the drug, the drug treatment program, and the additional time and staff necessary for psychosocial counseling.
Methadone clinics were also reluctant to refer patients for Trexan because of their need to keep their own censuses high enough to receive funding (Schecter 1980).
Pro-methadone treatment providers argued that because methadone was dependence-producing, it was easier to maintain a patient on methadone, and thus more likely that treatment would be successful.
As a result of these problems, Trexan failed to penetrate the highly regulated federal treatment market for opioid addiction.
By 1995, Trexan sales were approximately $5-8 million annually, which represented approximately 15-25,000 patients per year, or less than 5% of the estimated number of heroin addicts (Scrip 1993).
Naltexone as a Treatment for Alcoholism
Dr. Joseph Volpicelli first recognized naltrexone's potential to treat alcoholism while experimenting with rats as a graduate student in University of Pennsylvania. In 1981, he began to publish his findings.
In 1985, Volpicelli and Dr. Charles O'Brien, a professor at Penn and chief of psychiatry at Philadelphia's Veterans Administration Center, began a naltrexone study using volunteers at the Veterans Administration Hospital.
"We did it without any outside funding," says O'Brien. "We got it started against pretty great odds." According to O'Brien, the researchers had difficulty recruiting subjects because the idea of treating alcoholism with medication was not commonly accepted in the 1980’s.
They tracked 70 men for 12 weeks in an outpatient detox program. Half received naltrexone, half a placebo. While 54% of the volunteers who received a placebo reverted to drinking, only 23% of those who took naltrexone experienced a relapse.
In 1991, researchers at Yale University School of Medicine tested the effects of naltrexone in conjunction with psychological therapy in 104 alcohol-dependent men and women. Patients who took naltrexone were nearly twice as successful in their clinical outcomes as those who took a placebo.
After the Penn and Yale studies were published in the Archives of General Psychiatry in November 1992, DuPont showed interest in marketing naltrexone specifically as an alcoholism treatment.
Governmental funding for the development of naltrexone as a therapy for alcoholism was provided by the National Institute on Alcohol Abuse and Alcoholism.
The FDA modified existing regulatory requirements to encourage DuPont to develop naltrexone as an alcoholism therapy. They offered DuPont three additional years of post-approval market exclusivity for naltrexone as an alcohol therapy.
Marketing exclusivity allows a pharmaceutical company to sell its drug for a certain length of time free of competition from generic versions of the drug. This type of marketing exclusivity is often granted to encourage pharmaceutical companies to develop a use for a drug whose patent has expired or to encourage a company to develop an already approved drug for a new use. With market exclusivity, the expected returns are higher, thus improving the profitability of the drug.
The FDA also linked phase IV clinical trial requirements to annual sales. No phase IV trials would be required if naltrexone as an alcoholism therapy did not meet certain sales thresholds. If the drug did well in the alcohol-abuse market, DuPont would have to conduct phase IV trials based on the level of sales.
By allowing for flexible phase IV studies, the federal government lowered post-marketing costs, improved profitability projections, and made investment in naltrexone as an alcoholism therapy more attractive to DuPont.
Clinical trials for naltrexone as an alcoholism therapy encountered familiar problems -- difficulties with patient recruitment and compliance, high cost of clinical support services, and low funding of treatment centers.
Because researchers had difficulty recruiting patients, they accepted all patients who agreed to participate, and didn’t reject any unsuitable patients. This may have negatively affected the results of the clinical trials by including a high proportion of high-risk patients, who may have been motivated more by payment for participating in the trial than a desire for treatment, which led to poorer compliance and higher drop-out rates (Schecter 1980).
The study found that naltrexone as an alcoholism therapy did not perform significantly better than a placebo unless it was administered as part of a comprehensive, multidisciplinary treatment program (O'Malley 1995).
Although the government funded and supported the clinical trials, the funding fell short of the amount necessary to provide the necessary intensive psychosocial support. As a result, the labeling for ReVia (the brand-name eventually chosen by DuPont) includes the following stipulation, "ReVia should be considered as only one of many factors determining the success of treatment of alcoholism." Understandably, this labeling had a profoundly negative effect on marketing strategy and sales.
In 1995, the FDA approved naltrexone in a 50mg dose as a treatment for alcohol abuse.
The FDA surprised the researchers by authorizing naltrexone's use in alcoholism treatment in just six months. According to Volpicelli, the FDA was "pretty confident" that the drug was safe: It had been researched for 20 years and was on the market for 10 as a treatment for heroin addiction.
At this point, Dupont changed the brand name from Trexan to ReVia.
Marketing Strategy for ReVia
Because the alcohol treatment system is less regulated than the heroin treatment system, DuPont had more flexibility in marketing ReVia directly to clinics and treatment providers. Despite ReVia's clinical effectiveness and less restrictive distribution channels, however, DuPont's sales force encountered marketing problems.
Like Trexan, ReVia is most successful in highly motivated patients who have a strong psychosocial support and access to counseling services.
DuPont was not successful in selling ReVia, except in comprehensive alcohol treatment programs such as VA hospitals and "white collar" treatment centers. These patients tended to be more highly motivated and have a stronger support network. ReVia became the treatment of choice for more upscale patients, such as physicians, nurses, pharmacists and attorneys (O'Brien).
Another roadblock to naltrexone’s wider acceptance was insurance regulations. "Insurance companies often don't allow naltrexone to be prescribed by a primary care physician," said Tania Graves, spokeswoman for the Arizona Medical Association.
"Their point of view is that drug or addiction problems should be sent to a specialist."
Some insurance companies do not accept naltrexone at all. For example, a chain of California treatment centers using naltrexone as the primary treatment had to suspend operations after only six months, citing managed care companies' unwillingness to cover the treatment (Behavioral Health Treatment 1996).
Some physicians were reluctant to prescribe naltrexone due to the "black box" warning of liver toxicity in the package insert. The warning was included based on liver enzyme elevations reported with the100 - 300 mg/day dose (the recommended dose is 50mg) that was given during a study of naltrexone treatment for obesity.
A review of literature and adverse effect reports from Dupont demonstrates that a 50 mg/day dose poses no risk for liver damage, but the warning remains (Galloway).
From the American Council on Alcoholism website, 2005:
"Many physicians and non-physicians in treatment programs are unaware of the usefulness of naltrexone or how to use it. In other areas of medicine, it is highly probable that the development of such an efficacious medication would prompt physicians to use it readily. The biggest obstacle to using naltrexone for the treatment of alcoholism is the 'pharmacophobia' of many alcoholism-treatment professionals. This near-hysterical resistance to medication for treating alcoholism (or other substance-abuse disorders) has deep and tangled roots. Many recovering professionals learned in their recoveries that MDs and their prescription pads were evil purveyors of pharmacological lies and temptations. This attitude is often accompanied by a deeply rooted and strongly held belief that recovery has only one successful formula (usually the 12-step program) and that any modification to that approach is unethical."
Scientific evidence is irrelevant to these individuals. They believe they have the 'truth' about recovery and don't want to be bothered with other points of view. [http://www.aca-usa.org/pharm2. htm]
Poor Sales Performance
DuPont never expected either Trexan or ReVia to become major revenue generators, but sales fell far short of even DuPont's modest expectations. In 1994, just prior to the launch of ReVia, Trexan sales were approximately $5-8 million annually, which represented approximately 15-25,000 patients per year, or less than 5% of the estimated number of heroin addicts in the US (Scrip 1993).
When ReVia was launched in January 1995, DuPont expected US sales of ReVia to rise to $15-25 million annually. As of October 1996, however, ReVia had not even reached the FDA's threshold of the 200,000 prescriptions required to trigger phase IV clinical trials (Pink Sheet 1996).
In 1997, ReVia’s market exclusivity agreement lapsed. Other companies were now free to manufacture and market generic naltrexone. In May 1998, the first generic version of ReVia was produced by Barr Laboratories in Pomona NY. At this time, ReVia had annual sales of approximately $20 million.
In 2001, Bristol Myers Squibb acquired DuPont Pharmaceuticals. In April 2002, Bristol Myers Squibb sold the ReVia brand-name rights in the U.S. and Canada to Barr Laboratories, which manufactures ReVia in 50mg pills in the U.S and Canada. Bristol Myers Squibb continues to market ReVia in countries outside of the U.S. and Canada.
Other versions of naltrexone are currently manufactured in the U.S. by Eon Labs and Amide Pharmaceutical; Mallinckrodt Pharmaceuticals manufactures 50mg and 100mg naltrexone pills in the U.S. under the trade name Depade.
Other 50mg versions of naltrexone are named Nalorex (manufactured by Bristol-Myers Squibb in the UK); Nodict (manufactured by Sun Pharma in India); Naltima (manufactured by INTAS in India), Narpan (by Duopharma in Malaysia), Antaxone (by Pharmazam in Spain), Celupan (by Lacer in Spain), Narcoral (by Siton in Italy), Nemexin (Bristol Myers Squibb in Germany), as well as Revez, Naltrexona, and Naltrexonum.
The Future of Naltrexone
Researchers continue to explore the potential of naltrexone as a drug and alcohol therapy.
Attempts to address compliance issues have resulted in the introduction of a ReVia implant (2003). In addition, Alkermes, Inc. recently developed Vivitrex, a naltrexone injection which lasts a month. (Phase III clinical studies are set to begin in 2005.)
Over the years, researchers have tested naltrexone for a wide variety of medical conditions, including obesity, schizophrenia, and chronic obstructive pulmonary disease. In March 2005, Yale researchers began investigating the use of the naltrexone to help men and women quit smoking without gaining weight.
The FDA has awarded orphan drug** status to naltrexone to treat symptoms of childhood autism. Another orphan grant has been issued to naltrexone as a therapy for self-injurious behaviors. (Naltrexone therapy for self-injurious behavior is already used extensively in veterinary medicine.)
In addition, researchers have used derivatives of naltrexone to treat other conditions. For example, the FDA granted orphan drug status to methyl-naltrexone as a drug that blocks the side effects of morphine without interfering with pain relief in cancer treatment. (Oncology 1996)
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