Proponents of legalizing marijuana have long argued that criminalization of the drug causes more problems than it solves. For instance, taxpayers spend between $7.5 billion and $10 billion a year on arresting and prosecuting Americans for marijuana-related crimes. Supporters of legalized marijuana maintain that this money would be better spent cracking down on violent criminals.

Now, pro-legalization backers have yet another point in their favor: According to a new study from the University of Colorado-Denver, the 16 states that have legalized medical marijuana have seen an average 9 percent drop in traffic deaths since their medical marijuana laws took effect. The study analyzed data from 1990 through 2009.

“We went into our research expecting the opposite effect,” says study co-author Daniel Rees, a professor of economics at the University of Colorado-Denver. “We thought medical marijuana legalization would increase traffic fatalities. We were stunned by the results.”

When it comes to traffic safety, can marijuana really save lives?

Is marijuana an alcohol substitute?

Is this a sign of the times? A new study ties legalization of medical marijuana to a decrease in fatal car crashes in 16 states. One possible reason: Motorists who are high tend to drive slowly.

It’s long been known that alcohol is a primary contributor to deadly car crashes. According to estimates from the Insurance Institute for Highway Safety, drivers with a blood-alcohol level above 0.15 percent are 385 times as likely to be involved in a fatal crash as sober drivers are. In every state, the legal limit for driving while intoxicated is 0.08 percent.

The University of Colorado-Denver study found that the increase in legal use of medical marijuana often leads to a reduction in alcohol consumption. The study cites data from the Beer Institute, an industry trade group, indicating that beer purchases go down by an average of 5 percent after medical marijuana laws are passed. In these states, the researchers theorize, some people are smoking marijuana rather than downing booze.

A 2009 study from the University of California, Berkeley, backs up that finding. Four of every 10 patients at the university’s medical marijuana dispensary said they used marijuana to curb alcohol cravings.

Are high drivers better than drunken drivers?

The differences between drivers under the influence of alcohol and those who’ve smoked weed are stark, says Mason Tvert, executive director of the marijuana legalization advocacy group SAFER (Safer Alternative for Enjoyable Recreation).

“People who abuse alcohol take more risks, drive faster and are less likely to recognize that they’re impaired,” Tvert says. “They feel like Superman when they’re drunk.”

By contrast, motorists who’ve puffed pot “drive slower, are less likely to take risks, and are more likely to recognize when they’re impaired and decide not to drive,” he says.

Studies support Tvert’s view: A clinical trial conducted in Israel compared the simulated driving skills of people who’d consumed alcohol and those who’d smoked marijuana. The researchers found that alcohol caused these people to speed up their driving, while smoking marijuana prompted the drivers to slow down. An analysis by the U.S. Department of Transportation found marijuana rarely is the only drug found in the bodies of drivers who’ve died in car crashes.

Is driving under the influence of marijuana safe?

Mothers Against Drunk Driving (MADD) advocates against impaired driving of any form, and that includes smoking marijuana and getting behind the wheel. Emily Tompkins, MADD’s executive director for Colorado, says the group is keeping tabs on marijuana legalization and how it affects traffic safety.

MADD isn’t interested in determining how much marijuana someone can consume to remain within a legal limit, but Tompkins urges people who smoke marijuana (medical or otherwise) to be aware of when their driving is impaired. Tompkins claims marijuana-impaired drivers often show their medical marijuana cards to police officers who pull them over, as though the card legally entitles them to drive under the influence of drugs — which it does not.

The U.S. Department of Transportation found that although the harm of marijuana for drivers is minimal compared with that of alcohol and other drugs, it may be dangerous in certain situations, such as when quick thinking is required or when a driver has combined marijuana with alcohol or other drugs.

No one is advocating that driving while stoned is better than being alcohol- or drug-free, but experts agree that marijuana use while driving presents far less danger than many other drugs as well as alcohol.

Meanwhile, more Americans appear to be embracing marijuana. A Gallup poll released in October 2011 found that a record-high 50 percent of Americans favor legalizing marijuana. In 2009, the National Survey on Drug Use and Health showed 16.7 million Americans age 12 and older had smoked pot at least once in the month before being surveyed.

Could widespread legalization boost road safety?

Dan Rees, an economics professor at the University of Colorado-Denver, says he was “stunned” by the findings of the medical marijuana study.

While the University of Colorado-Denver study presents striking evidence of marijuana’s effect on road safety, the research was limited to motorists who have access to medical marijuana. In some states, that’s a relatively significant portion of the population. In Montana, 3 percent of the state’s population has access to medical marijuana; in Colorado, it’s 2.5 percent. Actual percentages for marijuana use may be considerably higher than that, however.

“Under medical marijuana laws, caregivers and patients can grow marijuana, and there’s very little policing of this,” Rees says.

Rees believes that authorized marijuana users often sell or give pot to others for recreational use. He says many of those recreational users probably are young adults — a group who’s responsible for a disproportionately high number of alcohol-related car crashes. Marijuana advocacy group NORML says pot is the third most popular recreational “drug” in the United States, behind alcohol and tobacco.

Rees teamed up with D. Mark Anderson, assistant professor of economics at Montana State University, on the marijuana study.

For now, medical marijuana is legal in Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington, as well as the District of Columbia. In those places, doctors prescribe marijuana to ease pain and suffering for patients with conditions like cancer.

Federal law prohibits the growth and sale of marijuana for any purpose. Opponents of legalizing the drug maintain that marijuana is a “gateway” to harder drugs like cocaine and heroin, and argue that the dangers posed by stoned drivers would rise.

While widespread legalization of marijuana isn’t likely in the near future, such a move might have a dramatic effect on road safety if drivers — particularly young adults — flock to marijuana instead of alcohol to get buzzed.

“When you see fewer traffic accidents in every state that legalizes medical marijuana, that’s strong proof,” Rees says.

According to the 2010 National Survey on Drug Use and Health(NSDUH), about 2.4 million Americans use prescription drugsfor non-medical purposes (in other words, without a prescription or to get high). In November 2011, the U.S. Centers for Disease Control reported that the death toll from narcotic pain reliever overdose — about 15,000 a year, or 40 deaths a day — is now greater than that of heroin and cocaine combined.

It’s understandable, then, that critics of these new superdrugs cite the potential for addiction and abuse as a reason for caution.

Dr. Gharibo acknowledges that abuse is a concern with opioid narcotics: “The majority of the misuse out there starts out very casually. Patients may double up on their medications and then build up a certain degree of tolerance.” He also notes: “There’s a lot of misprescribing out there that pretty much started in the late ’90s, where we started overprescribing opioids. Now we’re sort of treading back from what we did. There’s a pendulum that goes back and forth.”

Critics have also noted that Zohydro can be easily crushed, a feature popular with addicts who can snort the powder for an immediate high. OxyContin, which was initially also crushable, now comes in a more tamper-resistant form. Gharibo says, “For those products that are lacking the tamper resistance, it’s sort of like lacking the seat belt on a car. It’s just too easy to abuse.” He notes that more tamper-resistant opioid formulations are expected to become available over the next decade.

According to the AP article, patients taking the new superdrugs will be more closely supervised, since under government regulations a refill of pure hydrocodone requires a new prescription. By comparison, Vicodin may be refilled up to five times within six months of the time the initial prescription was written.

Acetaminophen: Safety Concerns

There’s another advantage to the new drugs: The makers of Zohydro also claim that it will actually be safer than Vicodin, since unlike that medication it won’t contain acetaminophen. Acetaminophen is the main ingredient in the nonprescription painkiller Tylenol, and it’s also found in many over-the-counter cold drugs. But too much acetaminophen can be harmful to the liver, and because it’s in so many products, overdose is a real danger.

“Oral acetaminophen toxicity is the leading cause of liver transplantations in the country,” says Dr. Gharibo, adding that often patients are unaware of their total acetaminophen intake.

Bottom line: These new pain medications ”could be a valuable addition,” says Gharibo. “It could be useful to have a broader palette to utilize, so that we don’t have to keep going up and up on the dosing for the drugs that are available now. I wouldn’t keep this particular compound from being approved.”

But, he says, Zohydro and the other super painkillers should only be used for a limited time and only for those patients who can follow their doctors’ directions and who are psychologically stable, ie, not prone to addiction. “They have to be used for the right clinical indication, in the right patient, and in the right setting.”

1. It is important that you make the decision to stop drinking.  You have to want to quit drinking, and be ready to do it. If you are thinking of quitting because your spouse, your mother, your probation officer, or some other person wants you to do so, your chances of success are diminished. The more support that you have from your family and friends will definitely be very helpful, but you must be the one that is making the decision.  You must do it for yourself and not for others.  The bottom line is that when you improve your life, the lives of everyone around you will also improve.

2. Set your quit date, and stick with it.  It could be today, tomorrow, or the day after the Special Event that you’re already committed to attend next week. It might be a good idea to set a special date that is easy to remember, like your birthday. Any day is a good day to make a new beginning. Do not pick a date too far in the future. It would be a tragedy to have made the commitment to quit, only to kill someone (or yourself) by driving drunk before that date arrives. Contact Assisted Recovery for information on enrolling in one of our Pennsylvania Model programs. Set up an appointment to come in so that we can discuss with you the evidence based treatment options offered by Assisted Recovery.

3. When the “quit” date arrives, come to Assisted Recovery for a free consultation.  When you decide to enter the Assisted Recovery Pennsylvania Model program, you will be immediately seen (in most cases) by a program physician.  The program physician will evaluate your case and prescribe safe, effective, approved anti-alcohol medications, for example naltrexone and ondansetron.  The physician may also provide a prescription to assist in the detoxification from alcohol.

4. Recovery is a process, not an event.  You will need to put effort into this process.  Plan to attend one or more meetings weekly for at least one full year. Assisted Recovery meetings are positive, informative, and fun. We stress the biological, psychological, and social components of recovery from alcohol dependence, and provide a variety of tools to help you deal with each.

5. The individual therapy sessions provided by Assisted Recovery will help you to make the adjustment in your thinking, away from irrational bad decisions. Define the goals of your personal recovery, and begin working towards them. Abstinence from alcohol is not enough; it’s only the beginning of the process of recovery. In order to achieve a happy, healthy sobriety, you’ll have to do some work. Setting and achieving your goals in life will provide you with long-term happiness and satisfaction, which the quick-fix of alcohol promises, but never delivers.

6. Get on with the rest of your life. Our goal is to help you get to the point where you don’t need us anymore. But that doesn’t mean that you’re cured forever, and all your work is done. You will have arrested your current bout with alcohol dependence, but if you start drinking again you will probably become re-addicted. Maintaining your commitment to remain abstinent requires some effort. Recovery is like climbing up the down escalator: if you’re not working to move forward, you’re automatically sliding backwards. We will assist you in developing a long-term strategy for preventing a relapse, and our meetings are always open to those who wish to return. Helping others is an excellent way to help maintain your commitment.

If you are ready to quit drinking for good, Naltrexone and
Assisted Recovery will help you to do it.

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 Pharmaceuticals 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 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 of 1971, President Richard 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. It is interesting to note that the Nixon Administration placed a priority on research and treatment rather than incarceration.

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 and opiate 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 the transit of naltrexone 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 for Heroin Treatment

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.  Naltrexone was not addicting in any way, either psychologically or physically.  It was not substituting one drug for another as is the case with methadone treatment.
Dr. Arnold Schecter, who conducted many of the early studies, reported that many opiate-dependent 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 immediate and severe withdrawal symptoms in patients with opiates in their system (Schecter 1974).  Many were unable to comply because of the psychological effects of withdrawal, including anxiety and depression.

Taking naltrexone does not provide any reinforcement or the euphoric effect (the high) associated with using opiates.  Unlike methadone, which helps suppress cravings, naltrexone only prevents an individual from using an opiate. Naltrexone blocks the ability of any opiate to produce either a high or pain relief.  Many of the potential study participant’s feared naltrexone would make them more vulnerable to cravings, and 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 psycho/social support services.  Very early, it was clear that naltrexone should be administered concurrently with therapy or counseling.

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 opiate or 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”. In other words, it was not the “magic bullet” or a cure in the bottle, and that in order for it to be effective an individual had to make the rational decision to take the naltrexone.

The final results of the clinical trials showed that naltrexone was modestly successful in the reduction of opiate use.

OnDecember 30, 1984, the FDA approved naltrexone in a 50 mg dose as a treatment for heroin and opiate dependence.  DuPont named the new anti-opiate medication Trexan.  At the same time DuPont’s naltrexone patent expired.  OnMarch 11, 1985, the FDA designated naltrexone as 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 not only to a lay audience, but to the medical community. 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 opiate dependent individuals (Scrip 1993).

Naltrexone as a Treatment for Alcoholism

Dr. Joseph Volpicelli, MD, Ph.D of theUniversity ofPennsylvania,School ofMedicine first recognized the potential of naltrexone to treat alcoholism while experimenting and doing research with laboratory rats as a graduate student at UPenn.   While doing research on opiate dependence Volpicelli realized that he had additional naltrexone available, and there was also available alcohol dependent rats that were not currently employed (part of a study).

Dr. Volpicelli wanted to see what kind of reaction the alcohol dependent rats would have while on naltrexone.  Because alcohol and opiates are very different chemically, he had no idea of what to expect.  The result of the experiment was that the rats became sober.  This intrigued him and he continued with the research.  In 1981, he began to publish his findings.

In 1985, Volpicelli and Dr. Charles O’Brien, a professor at UPenn 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.  Sadly, this is still the case in 2011.  One of the problems is that alcohol dependence is still considered primarily a “spiritual” disease, and how can you treat a physical disease with a medication.

Dr. Volpicelli and Dr. O’Brien tracked 70 men for 12 weeks in an outpatient detox program. Half of the men received naltrexone, and half a placebo. In the study 54% of the volunteers who received a placebo reverted to drinking, while only 23% of those who took naltrexone experienced a relapse.

In 1991, researchers at the 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 (NIAAA).  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.

The Phase IV trial is also known as a Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may or may not be required by the FDA. The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-IIIclinical trials.
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  

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).  Again, naltrexone is a tool, not a cure.  It should always be used in conjunction with therapy.

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.

On December 30, 1994 the FDA approved naltrexone in a 50 mg 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.  With the approval by the FDA, DuPont/Merck changed the brand name from Trexan to ReVia.

Marketing Strategy for ReVia

In 1991 in an effort to improve marketing and sales, DuPont joined with Merck Pharmaceuticals to create DuPont/Merck.  Due to the fact that the alcohol treatment system is less regulated than the opiate treatment system, DuPont/Merck had more flexibility in marketing ReVia directly to clinics and treatment providers.  Despite ReVia’s clinical efficacy and less restrictive distribution channels DuPont/Merck’s sales force encountered enormous marketing problems.  Like Trexan, it was thought that ReVia would be most successful in highly motivated patients who had access to a strong psychosocial support and counseling services.

One of the numerous impediments to successfully marketing ReVia was the lack of training and experience by medical doctors as regards treating alcohol dependence.  Most doctors were trained to refer their patients to AA.  It has been estimated that the average physician gets less than two hours of formal training regarding addiction.  In July 2011 the American medical establishment took the first step to rectify this problem.  Ten major medical schools for the first time created Residency Programs for Addiction Science.

DuPont/Merck was not successful in selling ReVia, except to comprehensive alcohol treatment programs such as Assisted Recovery Centers of America (ARCA), located In Phoenix, Arizona.  The difficult task of creating acceptance of the new medication is illustrated by the experience of Lloyd Vacovsky, Director of ARCA who in 1995 was a social worker at Central Arizona Shelter Services (CASS), which is the largest provider of services to the homeless inArizona.  Alcohol directly impacted many if not most of his clients atCASS.  Traditional 12 Step treatment was all that was available and it just was not working for the vast majority of his clients.  Vacovsky became very frustrated with the fact that despite a lot of work, people were not getting sober.

Vacovsky contacted DuPont/Merck in January 1995 after reading an article in theARIZONAREPUBLICannouncing the approval of ReVia by the FDA.  DuPont/Merck sent product information to Vacovsky.  He remembers thinking at the time, after he read the DuPont/Merck materials that naltrexone should be “put in the water, like fluoride”

Armed with information on naltrexone Lloyd went to the Director of the Shelter Mary Orton, wanting to start a naltrexone based program for shelter clients.  He was told thatCASSprovided housing and was not an alcohol treatment program.  Vacovsky was told however that if he could get another outside agency to run the program,CASSwould provide the meeting room.

Vacovsky approached several outside agencies expecting them to be excited at the prospect of a new and hopefully effective treatment option.  He states “I was confronted with a stone wall.  I was told that naltrexone was voodoo medicine and that the only effective treatment was 12 Step based.”  Vacovsky was shocked at the resistance to even learn information about naltrexone.  What bothered him was the fact that it was crystal clear that traditional treatment methods simply were not effective for the vast majority of people, yet there was no desire to improve treatment methods and outcomes.

Instead of giving up, Vacovsky went back to Shelter Director Orton and asked if he could start a group on his own time.  It was agreed that he could start a naltrexone based group, but again it would be on his own time.  There remained numerous hurdles including who would write the prescriptions for the naltrexone and how to pay for it.

Vacovsky went to the Maricopa County Homeless Clinic, which provided medical services toCASSclients.   It was quickly agreed that the clinic psychiatrist would write the prescriptions but they had no funding to purchase the naltrexone.

While Lloyd was trying to find a funding source for the naltrexone, in February 1995 the first client, Kurt was put on naltrexone.  He was a 30 year old male who had tried on numerous occasions to stop drinking.  He had several treatment experiences ranging from expensive 30 day residential to simply attending 12 Step meetings.  Armed with a prescription from the Homeless Clinic, Vacovsky and Kurt went to Walgreen’s.  Since it was a new medication, they were told that it would take Walgreen’s two days to get the naltrexone.

After only one day the pharmacist called and said the naltrexone had arrived and they could come and pick it up.  The night before, Kurt had gone on a mini-binge drinking everything he could get his hands on including mouthwash.  Arriving at Walgreen’s they proceeded through the store having to pass the fully stocked liquor department.  Lloyd could sense Kurt wanting to linger in the liquor aisle surrounded by his old friends, having doubts about this medication which he hoped would completely change his life.  Finally they got to the pharmacist window and Vacovsky paid for the naltrexone with his own money.  Kurt swallowed the 50 mg tablet and said “now what.”  Lloyd said let’s wait and see.

Fifteen minutes after taking the naltrexone, Lloyd asked, “do you want a drink?” Previously Kurt had been anxious and stressed.  Lloyd noticed a calmness that had not been present just minutes before.  The client said that he didn’t understand why, but that he did not want a drink.   It was at that moment that Vacovsky realized that science had finally provided an effective tool to help people who previously had little or no hope for a happy life without alcohol.

One of the first contacts that Vacovsky made was with Dr. Volpicelli inPhiladelphia.  Lloyd had read that Volpicelli had played a pivotal role in the development of naltrexone, especially for his research on its effect on alcohol. “Joe” was especially gracious and immediately offered to help Lloyd put together a program at the shelter that would include naltrexone and pharmacotherapy.  He explained to Lloyd that treatment was like a three legged stool.  With all three legs, you have a working piece of furniture.  You take away one of the legs and you now have something of far less value.  Treatment for alcohol dependence was similar.  The Biological, the Psychological and the Social components all had to be addressed in order to have an effective treatment protocol.  Over a period of time Dr. Volpicelli helped Vacovsky create one of the first Bio/Psycho/Social treatment programs in the country utilizing naltrexone at a homeless shelter in thedesertofArizona.

Vacovsky again contacted DuPont/Merck and was referred to Percy Menzies, who was a DuPont/Merck product representative based inDenver,Colorado.  Vacovsky detailed to Menzies his frustration in helping his clients and how traditional treatment just did not seem to work. He told Menzies about Kurt, who by that time had been sober for several weeks.  Menzies agreed to fly toPhoenixand meet with Lloyd atCASS.  Remember, it was thought that naltrexone would be only effective for highly motivated professional people who had a lot to lose, for example airline pilots, doctors and lawyers.  If a naltrexone based pharmacotherapy program could work at a homeless shelter, it would work anywhere.

Menzies recognized the passion and the desire by Vacovsky to find effective, state of the art treatment for his clients.  Menzies agreed to help and asked DuPont/Merck to provide the naltrexone to enable Vacovsky to start a pilot program atCASS.  DuPont/Merck agreed to provide ReVia to the Maricopa County Homeless Clinic and one of the first pharmacotherapy programs utilizing naltrexone (ReVia) was born.

Vacovsky recruited David Heward, a close friend and himself a recovering alcoholic to help with his project.  Together they created a Bio/Psycho/Social treatment protocol.  Heward had come across a new, non 12 Step support system called SMART Recovery.  SMART has since become the leading secular alternative to the traditional 12 Step approach.  The psycho/social support was delivered via SMART meetings facilitated by David and Lloyd, while the bio component was delivered by the ReVia.  The success of the program at Central Arizona Shelter Services led to the creation of Assisted Recovery Centers of Americain 1997.

The Bio/Psycho/Social treatment protocol that was created was named The Pennsylvania Model of Recovery in honor of the research in the field by theUniversity ofPennsylvania and in particular Dr. Volpicelli and Dr. O’Brien.  The protocol combines safe, effective, approved medications, for example naltrexone and counseling, for example cognitive behavioral therapy.  This approach is supported by the U.S. Department of Health Services, in its publication HELPING PATIENTS WHO DRINKTOOMUCH, A Clinician’s Guide, Updated 2005 Edition.
Another roadblock to naltrexone’s wider acceptance was insurance coverage.  “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.”  The only problem with that is again, until just recently in July 2011, American medical schools were not training doctors to be “addiction specialists”.

Some insurance companies did 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. Researchers conducting the naltrexone clinical trials had noticed that many individuals taking naltrexone had lost weight.  This created a stir among the research team in that perhaps they had a medication that not only combated alcohol and drug abuse, but also obesity.

DuPont backed a study that would document this effect.  It was a very small study, with a total of 12 participants.  Six were given naltrexone and six were given a placebo.  None of the participants had a history of alcohol abuse and were not drinking alcohol at the time of the study.  The study participants were given up to 300 mg of naltrexone per day. The naltrexone group actually gained more weight than the placebo group.

At the end of two years there was no significant weight loss.  The warning was included based on elevated liver enzymes  in one of the six of the naltrexone group. One in six is statistically significant, even in a very small study group. The results were reported to the FDA, which resulted in the warning.

A review of literature and adverse effect reports from DuPont/Merck demonstrated that a 50 mg/day dose poses no risk for liver damage, but the warning remains.  People lost weight because they had altered their life style.  They were not drinking alcohol and otherwise took better care of themselves, for example better nutrition and exercise. This alone has probably prevented thousands of people not being prescribed naltrexone due to largely unfounded fear created by the warning.

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 ‘pharmacopoeia’ 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

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).

OnDecember 30, 1997, DuPont/Merck’s ReVia market exclusivity agreement expired. 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 inPomonaNY. At this time, ReVia had annual sales of approximately $20 million.

In 2001, Bristol Myers Squibb acquired DuPont/Merck Pharmaceuticals.   In April 2002, Bristol Myers Squibb sold the ReViabrand-name rights in the U.S. and Canada to Barr Laboratories.

As of February 2005, Barr manufactures ReVia in 50 mg 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 100 mg naltrexone pills in the U.S. under the trade name Depade.

Other 50 mg 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: Vivitrol

Researchers continued to explore the potential of naltrexone as a drug and alcohol therapy.   Attempts to address compliance issues resulted in the introduction of a naltrexone implant in 2003.  This was a very controversial use of naltrexone and never did receive FDA approval.

A milestone in the history and development of naltrexone came when Alkermes, Inc. a pharmaceutical company based in Cambridge, Massachusettsbecame interested in naltrexone.  Alkermes developed products based on sophisticated drug delivery technologies to enhance therapeutic outcomes and compliance. Alkermes wanted to develop a long lasting form of naltrexone.  The Company’s primary medical product, Risperdal Consta ((risperidone) is a long-acting injection, and was the first long-acting atypical anti-psychotic medication approved for use in schizophrenia.

OnApril 1, 2005 Alkermes announced that it has submitted a New Drug Application (NDA) to the FDA.  Initially the medication was named Vivitrex and it would be naltrexone in a long-acting injection. Vivitrex was developed as a once-monthly injection for the treatment of alcohol dependence.

The Company had a pipeline of extended-release injectable products and pulmonary drug products based on its proprietary technology and expertise. Alkermes’ product development strategy had it partner its proprietary technology systems and drug delivery expertise with several of the world’s finest pharmaceutical companies.  It also develops novel, proprietary drug candidates for its own account for example naltrexone.   If approved, Vivitrex would be the first medication available for the treatment of alcohol dependence in a formulation that is administered once-monthly by injection.

“This NDA submission is a major milestone in our Vivitrex development program, which comprises a comprehensiveU.S.clinical trials program, manufacturing infrastructure and extensive regulatory and research expertise,” commented Richard Pops, chief executive officer of Alkermes. “I’d like to take this opportunity to congratulate the many employees at Alkermes who built and integrated these capabilities and made this regulatory filing possible.”

Vivitrex, an injectable, long-acting formulation of the currently approved drug naltrexone, was designed utilizing Alkermes’ proprietary Medisorb(R) drug-delivery technology. Using the Medisorb technology, naltrexone is encapsulated in micro-spheres made of a biodegradable polymer that dissolve slowly and release drug at a controlled rate following intramuscular injection.

On December 28, 2005 - Alkermes, Inc. announced that the U.S. Food and Drug Administration (FDA) issued an approval letter for Vivitrol(TM) (naltrexone for extended-release injectable suspension), which is under review for the treatment of alcohol dependence in combination with a treatment program that includes psychosocial support. Alkermes changed the name of its injectable naltrexone from Vivitrex to Vivitrol in response to issues raised by the FDA.

OnApril 13, 2006, Vivitrol was formally approved by the FDA for use in the treatment of alcohol dependence.  This was a major new weapon in the fight against alcohol and opiate dependence.  While fully approved as an anti-alcohol medication, Vivitrol was utilized “off label by opiate treatment providers untilOctober 13, 2010, when it was further formally approved for opiate treatment.

On going research documents the effectiveness of combining medications such as Vivitrol with psycho/social support like cognitive behavioral therapy.  Alcohol dependent individuals suffered fewer drinking days and fewer heavy drinking days according to Steven Lamm, M.D. who is an internist and clinical assistant professor of medicine at the New York University School of Medicine, and is a nationally recognized expert on alcohol and opiate dependence and their treatment options. He says, “Advances in research have furthered the understanding of addiction as a serious brain disease with both physical and psychological components.”

Lamm continues, “Research shows that the combination of medication, such as Vivitrol, and psychosocial support, such as counseling, is a safe and effective approach and has helped many who struggle with alcoholism to stop drinking, stay sober and rebuild their lives.”

“I have witnessed every complication from alcoholism – from suicide to cirrhosis to dementia,” Dr. Lamm further continued. “Many of my patients have been able to remain sober with medication and counseling; these people had tried other options in the past, but it wasn’t until they used Vivitrol that they were able to remain sober or dramatically reduce their number of drinking days per month.”

“With Vivitrol patients don’t have to remember to take a pill. Especially when first starting treatment, patients lack clarity that they achieve later on in the process. It’s during these first few days when it can be hard for them to think of taking a daily pill. They might miss it the first day, miss it the second day, and then be paying the consequences on the third day. ”

According to the American Council on Alcoholism, “Vivitrol will play a major and ever expanding role in the fight against alcoholism and opiate abuse. It is the goal and mission of the American Council on Alcoholism to educate not only the general public but also medical and alcohol/drug treatment providers about the value of science based pharmacotherapy.”

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)

Low Dose Naltrexone

Naltrexone in substantially lower doses (Low Dose Naltrexone) is showing great promise as a treatment for multiple sclerosis, Crohn’s disease, AIDS, rheumatoid arthritis, celiac disease, CFIDS, lupus, and certain forms of cancer.

Unfortunately, obtaining FDA approval for LDN will not be a straightforward process.  Since naltrexone is now a generic drug, no pharmaceutical company currently holds exclusive manufacturing rights.  No company is eager to fund an expensive clinical trial for a drug that will make them so little profit.

However, even without governmental approval or corporate support, LDN is gaining significant grass-roots attention among patients and doctors.   The exchange of research information over the internet has greatly accelerated the recognition of the off-label use of LDN.

In the past, the federal government and the pharmaceutical corporations cooperated to create an environment where naltrexone was tested, approved and made available to patients who needed it.  Perhaps someday soon they will find a way to do the same for Low Dose Naltrexone.

In January of 1995, the ARIZONA REPUBLIC published a short news item that detailed the approval of a medication which the Director of the United States Food & Drug Administration stated would revolutionize treatment for alcohol dependence. The article announced that ReVia® (naltrexone) had been approved by the FDA on December 30, 1994.  Lloyd Vacovsky, now Director of Assisted Recovery, at the time was a Social Worker employed by Central Arizona Shelter Services in Phoenix, Arizona.  The article stated that studies had demonstrated the ability of ReVia to suppress cravings for alcohol. Vacovsky remembers thinking; “we should put this in the municipal water system, just like fluoride”.

As a social worker at the largest shelter in Arizona, Lloyd was confronted daily with clients suffering from alcohol dependence.  Even as a trained professional, it was difficult for Lloyd to understand why a human being, despite all logic and despite all consequences, continued to drink.  Up to that point, Lloyd held the view that alcohol dependence was primarily a lack of character and will power.  One thing he did know however was that his clients were not able to stop drinking.  Intrigued by the article on ReVia, Lloyd contacted DuPont/Merck, the manufacturer of ReVia.  Within days, he received information that not only changed his life, but the lives of many people suffering from alcohol dependence.

Research clearly pointed to the fact that alcohol dependence is a very complex disease, having far more to do with brain biochemistry and genetics than lack of character and will power.  In February of 1995, Vacovsky convinced the psychiatrist at the Maricopa County Homeless Clinic to prescribe ReVia to a client who had been struggling for years, and had failed numerous treatment attempts.  Within minutes of taking the first tablet of ReVia, the client reported an inner calm and the absence of wanting or even thinking about drinking.  As the days, weeks and months passed, he was able to maintain sobriety and move on in life.  Based on that initial success, a pilot program was created at Central Arizona Shelter Services in November of 1995.  In developing the program, clients were asked what would be effective, and what would be counterproductive. Virtually all responded by asking for a non 12-step approach.

Lloyd contacted Dr. Joseph Volpicelli, MD, PhD of the University of Pennsylvania School of Medicine, Treatment Research Center in Philadelphia, and who is generally recognized as the “father” of naltrexone.  He agreed that non 12-step options needed to be developed and offered.  Dr. Volpicelli emphasized that naltrexone was a tool rather than a “cure” and that counseling was a critical component of the recovery process.  Cognitive Behavioral Therapy, combined with effective medications became the foundation of what has now become known as the Pennsylvania Model of Recovery.

In April of 1997, Assisted Recovery Centers ofAmericawas born in response for the need for evidence based, non 12-step treatment option.  Assisted Recovery was the first non-academic, non-institutional program in the United States to fully embrace the Pennsylvania Model of Recovery.  Assisted Recovery is proud to be a pioneer in the development of pharmacotherapy and the Pennsylvania Model of Recovery.