2018 January

Monitoring the Future University of Michigan’s annual drug abuse survey, Monitoring the Future, were released today showing that the percentage of teens using over-the-counter (OTC) cough medicine containing dextromethorphan (DXM) to get high remains at just 3 percent, the lowest level recorded for teen cough medicine abuse since 2015. When first reported in 2006, teen abuse of these OTC cough medicines was nearly 6 percent, but has declined significantly since then.

Since 2006, the rate of teen OTC cough medicine abuse has decreased by 44% (from 5.4% to 3%).

Over the past decade, the Consumer Healthcare Products Association (CHPA) has worked to help reduce teen DXM abuse by employing three strategies: increasing parent engagement in abuse awareness and prevention; heightening teen perceptions of the risks and social disapproval of medicine abuse; and limiting teen access to DXM through age-18 sales restrictions in states. In 2008, CHPA member companies voluntarily placed a “PARENTS: Learn About Teen Medicine Abuse” icon on the packaging of cough medicines containing DXM. The icon serves as a mini public service announcement for parents, making them aware of cough medicine abuse at the point-of-sale and point-of-use and directing them to StopMedicineAbuse.org – a well-established website and abuse prevention campaign aimed at engaging parents and community leaders about teen abuse of OTC cough medicine.

“Public policy and education are both vitally important to combating teen OTC cough medicine abuse,” said CHPA president and CEO Scott Melville. “This is why CHPA has long supported state efforts to limit teen access to DXM and has worked to increase parental awareness through our Stop Medicine Abuse education campaign, while at the same time, ensuring continued access for millions of families who responsibly use medicines containing DXM.” CHPA also collaborates with the Partnership for Drug-Free Kids to target teens who are most likely to abuse DXM based on their online search activity and to provide them with accurate information about the consequences of abusive behavior. Teens are directed to visit WhatIsDXM.com to learn more.

“The Partnership for Drug-Free Kids welcomes the data from this year’s Monitoring the Future Survey showing no year-to-year increases in high school students’ misuse of over-the-counter cough and cold remedies,” said Partnership president and CEO Fred Muench. “For nearly a decade now, the Partnership and CHPA have collaborated on a digital media prevention effort targeting this behavior – and we have seen steady and significant declines over this period in teens’ misuse of OTC cough medicine to get high. It’s compelling evidence that smart, strategic prevention initiatives can work, and can deliver real benefits to teens and their families.”

Additionally recognizing that retailers play a critical role in abuse prevention, this year CHPA launched a new Pharmacists & Retailers page on the StopMedicineAbuse.org site, where retailers can download or order free materials. Please visit StopMedicineAbuse.org for more information about teen DXM abuse, the retailer education materials, and other helpful resources for parents and community leaders.

The Consumer Healthcare Products Association (CHPA) is the 136-year-old national trade association representing the leading manufacturers and marketers of over-the-counter (OTC) medicines and dietary supplements. Every dollar spent by consumers on OTC medicines saves the U.S. healthcare system $6-$7, contributing a total of $102 billion in savings each year. CHPA is committed to empowering consumer self-care by preserving and expanding choice and availability of consumer healthcare products. chpa.org

Source: https://www.businesswire.com/news/home/20171214006254/en/New-Results-Annual-Survey

For more than four decades, marijuana has been synonymous with Jamaica. It was traditionally associated with the Rastafarian community in Jamaica and is regarded as a herb of religious significance by the Rastafarians and is widely used as a sacrament in their religious ceremonies.

However, the use of marijuana has transcended its traditional use from that of a sacrament for Rastafarians and it is now being used as a recreational drug in mainstream society. It has assumed both cultural and religious significance and is regarded as a harmless “holy herb” that bestows wisdom on its users.

Marijuana has permeated the society to such an extent that the taboo once associated with its use has her diminished, and this has led to it being more available. As a result of such availability, the “weed” is easily accessible and can be found in the palms of many of the countries’ youth (12 to 19 years old), especially those in the lower socioeconomic communities.

With the amendments to the Dangerous Drugs Act decriminalising the use and possession of small quantities of marijuana, it is projected that more youth will be using the drug.

Given Jamaica’s history with marijuana use and it’s so, called powers of wisdom, persons are unwilling to accept the fact that this herb can have any ill affect on one’s mental health, and persons who admit to suffering ill effects from its use are seen as weak.

This policy seeks to address the effect marijuana usage has on the mental health of adolescents and outlines options for preventing marijuana usage and reducing ganja- related harms.

THE PROBLEM FACING JAMAICA

1) Smoking marijuana increases the risk of mental disorders such as depression and schizophrenia in adolescents.

2) The decriminalising of small quantities of marijuana will only serve to increase the availability and usage of marijuana among the nation’s youth, resulting in increased ganja-related mental illnesses.

3) The focus on marijuana is largely on the criminal justice perspective. However, there is insufficient attention being placed on the issue of health, especially the mental health of young persons who consume the drug.

4) Marijuana is the most commonly used drug in Jamaica. Some of the active ingredients in marijuana have been shown to be harmful to the user. they can induce hallucinations, change thinking, and cause delusions.

5) The United Nations Office on Drugs and Crime (UNDOC) reports that the majority of marijuana users in Jamaica are between the ages of 13-25 years, implying that marijuana use is occurring in the most productive years of individuals’ lives.

6) The World Health Organisation (WHO) and (others) have reported that the most prevalent disorder in Jamaica is schizophrenia, which has been increasing yearly between 2009 and 2013. These studies have also highlighted the connection with early usage of marijuana and the increase in mental illness.

7) The National Secondary Schools Survey (2013) conducted islandwide from a sample of 3,365 grades 8, 10, 11, and 12 students, revealed the following:

a) 43.2% reported that marijuana was the easiest illicit drug to access.

b) One in five students who were current marijuana users were at high risk for marijuana misuse

c) Age of first use of marijuana was 12.9 years

d) 30.8% reported that drugs(including marijuana) were available at their school

e) 50.4% believed that drugs, including marijuana were available near school. Students who believed that drugs were available reported significantly higher use than those who did not believe drugs were available in and around school.

The American Psychiatric Association (APA) is opposed to the use of marijuana. Its position is based the following on:

i. There is no current scientific evidence that marijuana is in any way beneficial for the treatment of any psychiatric disorder. In contrast, current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders. Adolescents are particularly vulnerable to harm, given the effects of cannabis on neurological development.

ii. The use of marijuana/ganja in young people has been examined in many major studies worldwide. Results on the findings of these studies have differed. Some have found little or no association between marijuana use and mental disorders. Others have found deleterious effects of marijuana usage on mental health.

iii. Longitudinal studies conducted in New Zealand and Denmark suggest that the effects on the brain caused by marijuana probably explains higher rates of psychose.

The findings highlighted above suggest that the effects on the brain caused by marijuana usage can lead to mental disorders.

OPTIONS

a) A public education/media campaign (digital, print, radio, and TV) to develop and disseminate effective drug information for youth, parents, and caregivers. At the core of the strategy is essential information about the harmful effects of marijuana use.

i. To bring awareness to the fact that the teen brain continues to develop to age 25, therefore, it is vitally important that teens refrain from marijuana use as this use will affect brain development.

ii. Once youth perceive that marijuana use is harmful and risky, marijuana use dramatically declines.

iii. The longer a child delays drug use, addiction and substance abuse disorders are significantly reduced.

b) Teach life skills and drug-refusal skills focusing on critical thinking, communication, and social competency. This strategy will take on the following options:

i. Engaging families to strengthen these skills by setting rules, clarifying expectations, monitoring behaviour, communicating regularly, providing social support, and modelling positive behaviours.

ii. Encouraging social bonding and caring relationships, with people holding strong standards against substance abuse in families, schools, peer groups, mentoring programmes, religious and spiritual contexts, and structured recreational activities.

The campaign will have an enhanced focus on marijuana use and abuse. In addition to new national-level prevention and demand reduction messaging, the education-media campaign will work directly with communities to amplify the effects of the campaign and to encourage youth participation in the initiative through the help of on-the-ground partner organisations such as uniform groups, youth clubs, and national non-profit organisation devoted solely to the education and development of young people through policy and programme creation.

Since marijuana use has become ingrained in Jamaica’s social and cultural psyche, then any policy directed at marijuana reduction must be geared at behaviour modification.

Public education campaigns, whether they are used as a drug-prevention or health-promotion tool, tend to be based on their ability to affect behavioural change.

They have been successfully applied to the reduction of tobacco use and the promotion of road safety and have shown moderately positive results in a number of areas, including the promotion of healthier nutrition, physical activity, participation in screening for breast and cervical cancer, disease prevention, and other health related concerns.

EXPECTED OUTCOMES

i. First 12 months – 42 per cent improvement in perception of risks of marijuana use by both youth and adults; 50 per cent improvement in the disapproval rates of marijuana use by 12 to 19 year-olds;

ii.Year 3-4 – 70 per cent decrease in marijuana use by youth ages 12 to 19 years; 30 per cent decline in ganja-related mental illnesses.

iii. Year 5-7 – 91 per cent reduction in marijuana use by youth ages 12-19 years old; 75 per cent decline in ganja-related mental illnesses.

Despite the best efforts, some teens will use drugs invariably. Legislative and law enforcement methods offer an alternative to prevent and/or reduce adolescent marijuana usage. At the core of this option are the following strategies:

i. Mandatory counselling and treatment for adolescent found using marijuana.

ii. Mandated community service if adolescent continues to offend.

iii. Mandated prison sentence after the offender has done community service on two previous occasions.

Marijuana is the most widely consumed illicit (pre-decriminalisation in some nation states) drug. It is targeted in one way or another by most prevention interventions. However, few interventions have targeted marijuana specifically. Prevention is typically delivered in the context of wider informational activities and shares a platform with prevention for other substances such as other illicit drugs, alcohol, and tobacco. This policy will be geared specifically at marijuana.

The recommended option of a public education campaign marijuana prevention and reduction programme offers the best alternatives for achieving the stated objectives of the policy.

– This is a heavily edited presentation by Sophia Simpson-Wickham who recently completed an MSc in International Public and Development Management in the Department of Government, UWI, Mona. Feedback: mozzass@hotmail.com or editorial

Source: http://jamaica-gleaner.com/article/news/20171210/target-ganja-babies-urgent-focu

During the late 1970s, my colleague, Dr. Herb Kleber, and I introduced a novel neuroanatomical model to explain the pathophysiology of opioid withdrawal and put forth our contention that addiction was not simply a matter of avoiding withdrawal. Using what was then a novel new drug, clonidine, we were able to effectively detox heroin and methadone addicts in half the time, and without the surge of norepinephrine release from the locus coeruleus. This minimized the agitation and somatic anxiety that can be unbearable for some patients.

This helped prove our conviction that addictive disease was the result of numerous and largely unknown factors, and not simply to avoid withdrawal. In spite of effectively and humanely withdrawing addicts from opioids, we also discovered that something was clearly different and unique about their brain and behavior. After being clean and sober for 6-8 months in a safe and secure rehab environment, most addicts returned to using heroin as soon as the door was unlocked. This looked like Pavlovian principles on steroids. Although it was not due to avoidance of withdrawal symptoms, the answer remained unclear.

In some ways, we have travelled light years in furthering our understanding of the brain and addictive disease. Yet, relapse remains the norm and not the exception for opioid addicts. The development and use of naltrexone in the 1990s followed by buprenorphine has helped many addicts achieve a better quality of life. Yet, relapse remains the norm.

In a recent placebo-controlled clinical trial by Kowalczyk, et al, participants were given (0.3 mg/d) of clonidine or placebo during 18 weeks of Medication-Assisted Treatment (MAT) with buprenorphine, and documented their mood and activities via a pre-programmed smart phone.

Study participants receiving clonidine in addition to buprenorphine had increased abstinence from opioids and were able to decouple their stress from drug craving. Additionally, participants in the buprenorphine-plus-clonidine group, not only experienced longer periods of abstinence, but were also better in managing, or coping with their “unstructured” time. In other words, clonidine helped persons deal with their boredom and inability to create or engage in healthy activities, which is a strong predictor of relapse.

Why Does This Matter?

The study replicates previous research demonstrating that 1.) unstructured time, especially during early recovery is a trigger and predictor of relapse, 2.) engaging in responsible or helpful activities is associated with better outcomes among patients receiving Medication-Assisted Treatment, and 3.) clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have experienced.

From a personalized-medicine perspective, these data are a good reminder that addiction is a multifaceted disease requiring a multimodal approach. It is not treatable with any singular intervention. At best, psychopharmacology is adjunctive. And remember before any MAT, many addicted persons enjoyed sustained recovery via 12-step programs.

Source: https://www.rivermendhealth.com/resources/clonidine-plus-mat-improves-treatment-outcomes/ November 2017

Interviewed by Mark Gold, MD

FEATURED ADDICTION EXPERT: Brian Fuehrlein, MD, PhD, Assistant Professor, Yale University Director, Psychiatric Emergency Room, VA Connecticut Healthcare System

If a patient has overdosed on opioid, can you describe your approach to the emergency including the exam, medications, observation and discharge-transfer?

As the director of a psychiatric emergency room at VA Connecticut and Yale, I assume the care of patients after medical stabilization. Medical stabilization often includes Narcan administration and other possible treatments. While I am not generally directly involved in the Narcan administration, I will frequently see patients soon after a Narcan reversal (days to weeks). I have a very clear approach to these patients. My approach to a patient post Narcan reversal is aggressive and assertive. In my mind, I may be the last physician that this patient sees alive. I am very aggressive when discussing the severity of the illness and the critical need for treatment. When developing a treatment plan, I am very assertive. I will spend as much time as I can with the patient attempting to motivate them for treatment. When a patient has already required a Narcan reversal (and hence nearly died) they are high risk for this to occur again. This is as critical of a patient that I care for.

We generally refer to opioid overdoses as accidental, but do you have an idea of what percentage of the patients are depressed, wanted to die, or had passive suicidal ideation? Do you formally evaluate them for concurrent psychiatric illness at some time after you save their lives?

All patients who present to the psychiatric emergency room receive a thorough psychiatric and substance use assessment. The prevalence of co-occurring psychiatric illness with opioid use disorder (OUD) is very high. By the time the OUD has progressed to the point of intravenous use leading to Narcan reversal, there are typically many psychosocial consequences and stressors. In addition, these patients are often young (<30). These severe consequences, which often occur quickly, may lead to feelings of hopelessness, helplessness and passive suicidal ideation (SI). While I do not know firm percentages, in my experience the majority of those with severe opioid use disorder suffer from comorbid anxiety and/or depression. A lower percentage, but still significant amount, experience passive SI and will report things like “I was not trying to kill myself, but if I were to never wake up the world would be better off without me”. I would say that a small but significant percentage is actively suicidal at the time of the overdose with intent to die.

Patients will often have a history of multiple overdoses. What is your approach and ideal post rescue plan? Do you transfer them to a locked unit or give them a follow-up appointment? What happens to a person who is given Narcan and rescued by an EMT?

I tend to be as aggressive and assertive as possible while discussing the severity of the illness and the dire need for intensive treatment, especially in a patient who has had multiple overdoses. I attempt to motivate every patient who has experienced an overdose to be initiated on medication-assisted treatment (MAT). If agreeable, I will start buprenorphine in the VA/Yale psychiatric emergency room. Initiating buprenorphine in an emergency room setting is difficult in practice. Given the resources available at the VA we are able to do it. This practice is based upon a recent study at Yale that showed that initiating buprenorphine in emergency setting results in patients more likely to be connected to treatment. I also educate every patient about the need for a psychosocial support structure. I am a proponent of AA/NA programs and I discuss with all patients the importance of meetings/sponsorship. The goal for all patients who present post overdose is to initiate them on buprenorphine, transfer them to our substance use treatment program (either inpatient or IOP level of care) and then to attend 90 meetings in 90 days.

Unfortunately, many patients request discharge without willingness to engage directly in treatment. While state laws differ, in CT it is often hard to commit patients involuntarily specifically for substance use. If the patient is actively or passively suicidal or manic/psychotic, etc., we can often commit them on a psychiatric commitment. But if the risk stems primarily from ongoing substance use, we are often unable to hold the patient and force treatment upon them. We try very hard to motivate them for treatment. We will also engage their family to help with the motivation. But many patients are discharged home with outpatient follow-up only. We will prescribe a Narcan rescue kit, educate about harm reduction strategies, provide an appointment to see mental health within 7 days and place a follow-up phone call the day after discharge. But we are often unable to do more unless the patient is willing.

What is your suggestion for the role of Vivitrol post Narcan care?

I attempt to motivate all patients with opioid use disorder, particularly those post overdose, to initiate buprenorphine in the psychiatric emergency room. The first line treatment is buprenorphine, unless there is a reason/contraindication. For example, if adequate trials of buprenorphine have demonstrated its lack of efficacy in that patient, or if there was an intolerable side effect or adverse reaction. Methadone is generally the second line agent that is used following a buprenorphine failure. Following a Methadone treatment failure (side effect, etc), then Vivitrol the third line agent. Veterans at the VA will have an assigned outpatient treatment coordinator. We will collaborate with the outpatient team to determine the appropriate management of the opioid use disorder. We are able to initiate buprenorphine or Vivitrol the PER but Methadone initiation is deferred to the opioid treatment program. It is critical that patients with OUD are initiated on maintenance medication (one of the 3 mentioned) AND referred to a treatment program AND AA/NA.

Can you compare patients that you would suggest for Methadone vs. Suboxone vs. Vivitrol? How do you decide the doses? How long do you suggest MAT plus therapy and when to stop?

In general, buprenorphine is the first line, Methadone is second line and Vivitrol is third line, though this depends greatly on the individual patient. At times, Methadone is the first line agent if the patient requires the structure of the opioid treatment program or if the severity of the addiction is such that high dose Methadone is preferred. In general, buprenorphine is appropriate for the majority of the patients that I see in the psychiatric emergency room. Duration of MAT therapy remains debated. It depends on many factors and is an individual decision between the physician and the patient. In my opinion, a very important consideration when deciding whether to stop MAT is the patient’s commitment to a recovery program. If the patient is going to daily meetings, has a sponsor and is completing step work, I am more likely to endorse a plan of tapering down the buprenorphine than the same patient who is relying solely on the buprenorphine for sobriety.

Other considerations include IV use, previous OD with Narcan administration and other high risk behaviors. These would make me more likely to recommend longer term use of buprenorphine. In addition, the decision to stop MAT would depend on factors like cost, side effects, etc. Opioid use disorder is a deadly illness that requires long term treatment. When the illness is severe, high risk behaviors are present and the buprenorphine is not causing problems, I am unlikely to recommend tapering it off.

Are you seeing opioid overdose and addicts concurrently using marijuana, alcohol, cocaine, methamphetamine, other? Can you give us a sense of how many patients just use one drug or are just addicted to one drug? Do you do drug testing on all patients in the ED?

Yes, we perform urine drug screens on all patients who present to the psychiatric emergency room (PER). In my experience there are several groups of patients with opioid use disorder.

The most common group of patients with OUD also have a history of other substance use disorders. Most common would be marijuana, alcohol, cocaine and sedatives. While this group has struggled with an addiction to multiple substances, the opioids are the clear drug of choice. Many patients in this group will set all other drugs aside and only use them occasionally once opioids are discovered.

The second most common group with OUD continues to use other drugs concomitantly with the opioids. They may not identify opioids (or any of the others) as a clear drug of choice. This group will often speedball (mix opioids and cocaine). They also may unfortunately mix alcohol or sedatives with opioids, which is an unfortunate combination.

The least common group has OUD with no other history of substance use.

Methamphetamine is not as common in the northeast and hence for regional considerations I do not see it commonly. As a resident in Dallas, TX, methamphetamine use, with or without opioids, was common.

Do you have a protocol for switching someone from Suboxone to Naltrexone?

In the PER we do not generally complete an opioid detox and hence do not generally switch from buprenorphine to Naltrexone. We either initiate and titrate buprenorphine for maintenance or transfer to a local rehab or detox facility for completing detox.

Do you have an opioid detox protocol that you’d use in the hospital or ED?

First, we try hard to not detox OUD patients. Patients with OUD should be on MAT and we use the psychiatric emergency room (PER) visit as a means to initiate buprenorphine. We aggressively recommend buprenorphine initiation. If agreeable, we generally will start buprenorphine 4mg in the PER once withdrawal symptoms are moderate (COWS >8). We will then repeat the 4mg dose if indicated for a maximum dose of 8mg on day 1. The patient will then spend the night in the PER for observation.

On day 2, we titrate up to a maximum dose of 16mg if indicated. At that point the patient is ready for movement to the next level of care. Occasionally, patients will require a second night in the PER to titrate the buprenorphine up and for complete stabilization of withdrawal symptoms.

Once at a stabilizing dose the patients will generally move to our 21-day substance use treatment program. While in the program the buprenorphine is titrated as necessary. Upon completion of the program the patient is referred to the buprenorphine clinic in conjunction with a psychosocial program.

If the patient is unwilling to attend the 21-day program, and buprenorphine is initiated in the PER, the patient is discharged from the PER and seen daily in the outpatient detox/stabilization clinic until an appointment is available in the buprenorphine clinic. Given the resources at the VA we are able to initiate buprenorphine in the PER with confidence that a plan on the backend is achievable.

If the patient is unwilling to be on maintenance therapy then an opioid detox is completed. This is done with either buprenorphine or symptom-driven. Typically for detox, the patient is transferred to a local detox facility that the VA contracts with.

You have worked in both the inpatient and residential drug free drug programs and now Yale in ED and MAT, can you give me a sense of what lessons you have learned from each and how each might have a role and limitations?

Residential programs are a very important part of the recovery process but are not a cure for addiction. I often encounter patients who have completed our 21-day treatment program multiple times, each time having relapsed almost immediately after completion. When patients and/or families expect that years or decades of use will be cured after 21 days in a program they will naturally be disappointed. “Treatment begins when you leave the program” is a very important tenet of recovery. A good residential program will introduce/reinforce recovery principles and motivate the patient to continue this process after completion of the program. Without a solid aftercare program, residential programs are destined to fail.

Regarding the emergency room, many providers may not see the emergency room as an ideal environment for a discussion about recovery. Every patient that I see in the PER will hear about the importance for long term treatment and the need for a solid recovery program. I will discuss long term strategies including MAT, NA and other treatment options. Even with patients who present to the PER frequently, I always spend time discussing the importance of a solid foundation of recovery and the need for MAT. Even in the context of a busy emergency room, there is always time for a brief motivational interaction which may make a real difference and save a life.

Are you seeing meth or cocaine emergencies and/or overdoses? What is your approach?

Methamphetamine is not a common drug of abuse in this region of the country. Cocaine is incredibly common and it is commonly abused in the powder form or in the form of crack. It is often used in conjunction with opioids (speedballs). When cocaine overdoses occur (rarer than opioid overdoses), the patient is seen and stabilized in the medical ER prior to transfer to the PER. With patients who are using cocaine at levels so dangerous that it leads to overdose, I am aggressive and assertive the way I am with opioids. The difference with stimulants is the lack of MAT. Hence the reliance on a psychosocial treatment becomes more important. Patients are referred to the substance use treatment program to begin the recovery process. They are then referred to AA/NA, contingency management, CBT for addiction or other psychosocial support programs.

Source: https://www.rivermendhealth.com/resources/q-a-with-brian-fuehrlein-md-phd-the-opioid-epidemic-and-emergency-room-visits November 2017

As part of the U.S. Food and Drug Administration’s ongoing efforts to protect consumers from health fraud, the agency today issued warning letters to four companies illegally selling products online that claim to prevent, diagnose, treat, or cure cancer without evidence to support these outcomes. Selling these unapproved products with unsubstantiated therapeutic claims is not only a violation of the Federal Food, Drug and Cosmetic Act, but also can put patients at risk as these products have not been proven to be safe or effective. The deceptive marketing of unproven treatments may keep some patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.

The FDA has grown increasingly concerned at the proliferation of products claiming to treat or cure serious diseases like cancer. In this case, the illegally sold products allegedly contain cannabidiol (CBD), a component of the marijuana plant that is not FDA approved in any drug product for any indication. CBD is marketed in a variety of product types, such as oil drops, capsules, syrups, teas, and topical lotions and creams. The companies receiving warning letters distributed the products with unsubstantiated claims regarding preventing, reversing or curing cancer; killing/inhibiting cancer cells or tumours; or other similar anti-cancer claims. Some of the products were also marketed as an alternative or additional treatment for Alzheimer’s and other serious diseases.

“Substances that contain components of marijuana will be treated like any other products that make unproven claims to shrink cancer tumours. We don’t let companies market products that deliberately prey on sick people with baseless claims that their substance can shrink or cure cancer and we’re not going to look the other way on enforcing these principles when it comes to marijuana-containing products,” said FDA Commissioner Scott Gottlieb, M.D. “There are a growing number of effective therapies for many cancers. When people are allowed to illegally market agents that deliver no established benefit they may steer patients away from products that have proven, anti-tumour effects that could extend lives.” The FDA issued warning letters to four companies – Greenroads Health, Natural Alchemist, That’s Natural! Marketing and Consulting, and Stanley Brothers Social Enterprises LLC – citing unsubstantiated claims related to more than 25 different products spanning multiple product webpages, online stores and social media websites. The companies used these online platforms to make unfounded claims about their products’ ability to limit, treat or cure cancer and other serious diseases. Examples of claims made by these companies include:

· “Combats tumour and cancer cells;”

· “CBD makes cancer cells commit ‘suicide’ without killing other cells;”

· “CBD … [has] anti-proliferative properties that inhibit cell division and growth in certain types of cancer, not allowing the tumour to grow;” and

· “Non-psychoactive cannabinoids like CBD (cannabidiol) may be effective in treating tumours from cancer – including breast cancer.”

Unlike drugs approved by the FDA, the manufacture of these products has not been subject to FDA review as part of the drug approval process and there has been no FDA evaluation of whether they work, what the proper dosage is, how they could interact with other drugs, or whether they have dangerous side effects or other safety concerns. The FDA has requested responses from the companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure and injunction.

“We have an obligation to provide caregivers and patients with the confidence that drugs making cancer treatment claims have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they’re on the market,” Commissioner Gottlieb added. “We recognize that there’s interest in developing therapies from marijuana and its components, but the safest way for this to occur is through the drug approval process – not through unsubstantiated claims made on a website. We support sound, scientifically-based research using components derived from marijuana, and we’ll continue to work with product developers who are interested in bringing safe, effective, and quality products to market.”

This latest action builds on the more than 90 warning letters issued in the past 10 years, including more than a dozen this year, to companies marketing hundreds of fraudulent products making cancer claims on websites, social media and in stores. Additionally, the FDA recently took decisive action to prevent the use of a potentially dangerous and unproven treatment used in ‘stem cell’ centers targeting vulnerable cancer patients. The FDA encourages health care professionals and consumers to report adverse reactions associated with these or similar products to the agency’s MedWatch program.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm583295.htm

Millions of people use cannabis as a medicine. That’s not based on clinical evidence, nor do we know which of the hundreds of compounds in the plant is responsible for its supposed effects. Elizabeth Finkel reports.

LAST YEAR DEDI MEIRI, A CANNABIS RESEARCHER AT THE TECHNION, ISRAEL’S OLDEST UNIVERSITY, RECEIVED A “BEFORE AND AFTER” VIDEO OF AN AUTISTIC BOY.

The before showed the boy helmeted, hands tied behind his back, butting his head against a wall. The after showed him calmly sitting at a table, sketching. The difference: two drops of cannabis oil administered below the tongue. The video had been sent to Meiri by Abigail Dar, an Israeli champion for the use of cannabis in children with autism.

Early this year it was a different story. Over the course of a day, Meiri’s lab received a stream of phone calls from Dar: a few autistic children had gone berserk after receiving their two drops of oil.

Meiri, who is primarily a cancer researcher, received the video and the calls because he has, reluctantly, become one of Israel’s cannabis experts. “Even now I am reluctant to tell people I work on medical cannabis,” he says. “I am not pro-cannabis; I think 90% is placebo.”

But Israel is in the grip of a vast medical experiment. Cannabis has taken hold here to treat a startling range of medical conditions. Not just familiar things like anorexia and pain in cancer patients but autism, Crohn’s disease, Tourette’s syndrome, epileptic seizures, multiple sclerosis, arthritis, diabetes and more. With close to 30,000 users in a population of eight million, Meiri says “everyone knows someone who is being treated with cannabis”. While there is a semblance of orderly medicine, with doctors prescribing cannabis oil from eight registered growers, no one can say just what, exactly, is responsible for the apparent responses.

A cannabis plant is a pot-pourri of more than 500 chemicals whose abundance varies greatly across different genetic strains and according to growth conditions – they’re not cultivars so much as chemovars. The medicinal effect may depend on tetrahydrocannabinol (THC), the chemical that gives you the high, or cannabidiol (CBD), which is thought to reduce inflammation and pain, or a hundred other “cannabinoids” unique to the plant with their own medicinal profile.

Bottom line: with dozens of varieties grown under different conditions, Israeli patients are receiving quite different medicinal concoctions.

Israel’s predicament is tame by comparison to the United States. Here it is the Wild West. Federal sheriffs outlaw medical research on the plant while cannabis cowboys peddle chemovars (varying in their content of THC and CBD) for cures and profit. In the 29 US states that have legalised medical cannabis, dispensaries that resemble something out of a Harry Potter tale sell candies, cookies, oils, ointments and joints to an estimated 2.3 million Americans. As to their exact medical benefits and risks, no one knows. This is medieval medicine – akin to boiling willow bark to treat headache. It is also great business – the North American market for legal cannabis products grew 30% in 2016, with sales topping $US6.7 billion.

Israel’s medical cannabis mess is a lot easier to deal with. To help address it, Meiri’s laboratory of Cancer Biology and Cannabinoid Research is conducting a reverse clinical trial. While patients using medical cannabis fill in a monthly questionnaire, the ranks of analytical machines bursting out of Meiri’s lab create chemical fingerprints of the cannabis extracts patients are using. The idea is to try to link individual cannabis compounds to the patient response.

It is an approach that’s “two or three rungs down” from the ideal of randomised placebo-controlled clinical trials (RCTs), says Donald Abrams, an oncologist at the University of California, San Francisco, who prescribes cannabis as a palliative for patients with cancer. “But, if well done and there’s a strong effect, observational studies like these are invaluable.”

Israel is also one of the few places in the world pushing forward with gold-standard RCTs. But given that dozens of cannabis strains are already being used for a ballooning number of conditions, RCTs seem like a finger in the dyke.

Countries like Australia, where the federal government legalised medical cannabis in October 2016, are entering this brave new world with trepidation. “Because there has been no proper research, we’re now at a difficult crossroads,” says University of Melbourne pharmacologist James Angus, who chairs the federal government’s advisory council on the medical use of cannabis. “Our health workforce has no guidelines or experience in prescribing, and patients are demanding it. We’ve run out of time.”

The Promised Land may well be the world’s best bet for deliverance from the medical cannabis mess.

Anecdotes on the medical use of cannabis go back to mythical Chinese emperor Shen Neng in 2700 BCE. More piquant references can be found in ancient Roman, Greek and Indian texts. Or just google.

Thousands of years on from Shen Neng, it seems we still don’t have a great deal more than anecdotes to go on. As a report from the US National Academies of Science in January 2017 states: “Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the short- and long-term health effects – both harms and benefits – of cannabis use remains elusive.”

While the medical uses of the opium poppy, a vastly more dangerous plant, are well understood, cannabis has remained stuck in a no man’s land. It had been part of the US pharmacopeia till the 1930s, as an alcohol-based tincture, until the federal government effectively outlawed its possession and sale through the Marijuana Tax Act. More draconian penalties followed. It is still demonised by federal law as a ‘Schedule 1’ drug with no medical use, lumped in the same category as heroin, LSD and ecstasy. Yet as a quick online search will show, the plant is lauded for a seemingly inexhaustible list of curative properties.

In the past two decades the disparity between evidence and anecdotes has grown extreme. Despite a majority of states (beginning with California in 1996) having legalised cannabis to treat medical conditions, federal restrictions on research remained ironclad. So researchers have great difficulty studying whether such medical uses have any basis in science. “What we have is a perfect storm,” says Daniele Piomelli, a neurobiologist at the University of California, Irvine.

Piomelli has been researching cannabis as best as he can. To comply with the mandates of the federal Drug Enforcement Agency (DEA), his precious store of 50 milligrams of THC must be kept in a locked safe, in a locked cool room, in a locked lab. “Any person on the street can go to a dispensary and for $10 obtain cannabis,” he says. “But if we bring it into the university we risk being raided by the FBI and DEA. We live in a schizophrenic state.”

Even when researchers have gained permission to do research, the cannabis can only be supplied by one authorised lab, at the University of Mississippi. The lab has been growing the same variety for decades, one that bears little resemblance to the chemovars now available through dispensaries.

In San Francisco, Abrams tried valiantly in the 1990s to set up a clinical trial to test the claims of dying AIDS patients that smoking weed outperformed their anti-nausea drugs. After more than a year trying to get permission from the National Institute on Drug Abuse, the penny finally dropped; the agency, as he often tells journalists, sees itself as the National Institute “on” Drug Abuse, not “for” Drug Abuse. So the January report of the National Academies of Science was hardly a surprise. The document, based on reviewing 10,000 publications, found “modest” evidence for the effectiveness of cannabis to treat nausea and vomiting in adults undergoing chemotherapy, for chronic pain, and to alleviate spasms in multiple sclerosis. It did not, however, deliver a verdict for a long list of illnesses including epilepsy, inflammatory bowel disease, Parkinson’s Disease, post-traumatic stress, anxiety, insomnia and cancer. “For these conditions, the report states, “there is inadequate information to assess their effects.”

But bits of information are trickling through. In May, a report in the New England Journal of Medicine offered evidence that an oily, strawberry-flavoured formulation of pure cannabidiol (made by British company GW Pharmaceuticals) could reduce the severity of seizures in children with a rare form of epilepsy known as Dravet’s syndrome. Of the 120 youngsters recruited, 60 received cannabidiol and 60 received only a strawberry-flavoured oil, the placebo. Three of the treated group achieved complete remission from their seizures while in 40% of those treated, the frequency of seizures was reduced by half. But 27% of the placebo group also saw a halving in their seizure rate and there were significant side effects amongst the treated group. “It’s not a magical drug”, explains Ingrid Scheffer, a paediatric neurologist at the University of Melbourne and co-author of the study. But she points out the sometimes exasperated parents of her patients have a different view. “The attitude is, ‘it’s obvious you fuddy duddy, just give it to us’.”

Most of the 400 pages in the hefty NAS tome report on the adverse effects of cannabis, like a raised risk of schizophrenia or road accidents or chronic cough. This, says Piomelli, reflects what researchers obtained funding for: “There is a bias towards the null hypothesis – that cannabis causes harm.” Those harms exist, he agrees. “But society is asking for answers about its benefits, and that’s not a question that researchers have been able to answer.”

Israel staked its claim in the field of cannabis research back in the 1960s. It was the beginning of the pot-smoking hippy revolution. But no one actually knew what the psychoactive ingredient of pot was.

Raphael Mechoulam, a chemist at the Hebrew University of Jerusalem, saw an opportunity. In 1964 he was the first to link pot’s mind-altering effects to THC. His research flourished in a regulated but permissive environment: his chief source of cannabis was the local police station. His group also isolated the natural equivalents of cannabis made by the brain, using pigs (with great difficulty, given the researchers were in Jerusalem). In 1992 they identified anandamide, the so-called bliss molecule, and in 1995 its more prosaically named partner, 2-arachidonoyl glycerol or 2 AG. These brain-made counterparts of THC are known as endocannabinoids.

Meanwhile the Israeli public began to clamour for medical cannabis. Just as in San Francisco, the AIDS epidemic had put medical cannabis on the radar. Mirroring the experience of Donald Abrams, immunologist Zvi Bentwich also witnessed the anti-nausea and pain-relieving effects that smoking cannabis had on his AIDS patients. While anti-retroviral drugs would mercifully bring the raging AIDS epidemic in both countries under control, the clamour for the palliative use of cannabis by cancer patients grew, aided by the internet.

Israel’s government obliged but with strict regulation. Patients, supported by a letter from a physician, could obtain a medical cannabis permit from the ministry of health. Growers needed a licence. One of the first companies to gain one, in 2007, was Tikun Olam. As patient numbers grew, it began to collect information about their responses. In 2015 Bentwich, who also heads the Centre for Emerging Tropical Diseases and AIDS at Ben Gurion University, joined Tikun Olam to lead a formal clinical trials program. “If the medical community is to accept cannabis, that depends on carrying out large reliable clinical trials,” he says. “In the US, as well as in most European countries, that is still extremely difficult.”

So far Israel is leading the pack. It is the only country, for instance, to have published the results of a randomised double blind study on the use of cannabis by Crohn’s disease patients. Timna Naftali, a gastroenterologist at Meir Medical Centre, carried out the trial after discovering several patients were self-medicating with cannabis. “They had reduced their medication and not suffered flare ups,” she says. “It was very intriguing.”

In her trial, 21 patients were assigned randomly to a group that smoked THC-rich cannabis cigarettes twice a day for eight weeks or to a group that smoked cannabis free of THC and other cannabinoids. The results, published in Clinical Gastroenterology and Hepatology, showed that in 10 of 11 patients with Crohn’s disease who smoked the THC-rich cigarettes, there were “significant clinical benefits”. One criticism was that perhaps patients merely felt better due to the euphoric effects of cannabis, so Naftali is repeating the trial, leaving it to an endoscopist to decide. This time 50 patients are receiving an oil, containing a 4:1 ratio of cannabidiol to THC. “As a doctor, I’m not happy about telling patients to smoke,” Naftali says. Another trial that tested a pure extract of cannabidiol was ineffective. “Perhaps it was the low dose,” Naftali muses. “There’s also a claim you have to have it in combination.” Perhaps it is a case of what Mechoulam has dubbed the “entourage effect” – the consequence of a mysterious biological synergy between cannabis compounds.

Another world-first trial under way in Israel is testing the effects of cannabis on youngsters with autism. Given cannabis can trigger psychotic behaviour, it is surprising to think it would be a candidate for a condition where psychotic behaviour is often part of the problem. But a third of autistic children also suffer from seizures.

When paediatric neurologist Adi Aran, at Jerusalem’s Shaare Zedek Medical Centre, prescribed cannabis for the seizures of autistic children, their parents reported dramatic results. Children who never spoke began speaking, and writing for the first time. To verify these anecdotal results, he is running a trial on 120 youngsters, aged 5 to 21 years. Some receive whole cannabis oil containing, amongst other things, a 20:1 ratio of cannabidiol to THC; others receive a purified extract containing only cannabidiol and THC; a final group receive a placebo, an identically flavoured oil. All will undergo a ‘washout’ period, where they are gradually weaned off their oil.

In principle, most doctors would like to see the results of numerous such trials before prescribing cannabis. However, parents like Abigail Dar disagree with this approach. “A parent like me with a complicated child doesn’t have the luxury of principles,” she says. Her son, Yuval, now in his early twenties, is severely autistic, and was once so prone to violent outbreaks she could not be alone with him. “Yuval tried over a dozen anti-psychotic medications since he was 12 years old to treat symptoms

like endless anxiety, restlessness, violent outbreaks or, as we call it, ‘life in the shadow of hell’. They only made him more agitated and aggressive.”

Dar managed to get a medical cannabis prescription for Yuval in 2015. Though autism did not count as one of Israel’s qualifying conditions, the health ministry finally granted permission as a ‘mercy treatment’. “It was a life-changer from the very first day,” according to Dar. “He hasn’t exhibited a single self-injurious behaviour or outburst in the last 14 months. He is calmer, more attentive and communicative. He smiles more.”

Dar has carried out her own careful experimentation for what works for her son, using chemovars that vary in their CBD-to-THC ratio. As far as she is concerned, placing Yuval in a randomised, placebo-controlled, washout trial would be immoral. “With suffering kids you don’t take it away,” she says. “I tell parents to stay away; it’s not in favour of kids.”

Instead, through a collaboration with Meiri’s lab, she is pushing to gather the data already being generated. “We have 200 kids and adults with severe autism we are guiding through strains and dosages to find out what works. We track them with questionnaires: we look at things like violent outbreaks, sleep and appetite. The idea eventually is to go global. It will give us some small amount of knowledge on how to treat autism.”

It’s not just desperate cases like Dar that make cannabis a poor fit for the box of a RCT. Abrams sees no need for more trials when it comes to treating pain or nausea in patients with cancer. Nor is he alarmed by the range of products sold in dispensaries. “I don’t consider it to be that dangerous, compared to the pharmaceutical agents we already prescribe,” he says. “I have many patients that were weaned off opiates thanks to cannabis.” He points out that in the US, 90 people die each day from overdoses of opiates, in many cases prescribed to treat chronic pain [LINK: https://www.cdc.gov/drugoverdose/epidemic/index.html].

Mieri never imagined his CV would one day include heading a laboratory for cannabis research. In early 2015, after four years at the Ontario Cancer Institute, he was all set to return to cancer research.

Then he noticed a curious publication from a Japanese research group that reported a cannabis extract blocked the ability of human breast cancer cells to spread in a culture dish. What pricked Meiri’s interest was that the extracts appeared to be scrambling the cell’s internal scaffolding – his particular area of expertise.

Meiri repeated the experiment on different types of cancer cells. He found the cannabis extract was just as potent as some chemotherapy drugs. But it was another finding that really captured his interest: the effectiveness of the extract depended on the cannabis variety and the grower.

As the son of a strawberry farmer, he understood exactly what he was seeing. “Strawberries taste different in the morning and afternoon,” he explains. He was seeing the effects of a cocktail of different chemicals.

Which of these chemicals were responsible for the anti-cancer effect? To find out, Meiri bought a machine for high-performance liquid chromatography, a technique to separate and identify parts of a mixture. Soon he was a de facto guru. A grant from a philanthropist in 2016 marked a point of no return.

‘The plural of anecdote is not data’ is an oft-quoted medical aphorism. But anecdotes can’t be ignored either. Meiri is acquiring quite a collection. On one occasion, he was contacted by the father of a seven-year-old whose seizures had returned after being free of them for nearly a year. The father, wanting to know why the oil had stopped working, sent samples to Meiri. When the scientist analysed them, he found they were just olive oil. “It was a data point,” he says, “showing that the effects of cannabis extract were real.”

Then there was the disastrous day he learned that several autistic kids taking cannabis oil had gone berserk. “Tali, we have a situation,” he recalls telling the head of the project. All the extracts the children were taking had the same 20:1 ratio of CBD to THC. But looking at the chemical profiles, it was clear the offending medication carried at least five different compounds. “It doesn’t provide the answers,” he says. “It shows where to begin searching.”

There is no simple way out of the cannabis mess. With much of the world clamouring to use cannabis as a cure for all manner of ailments, and an exploding cannabis industry that is happy to push that demand along, it is crucial to establish just how real its clinical benefits and harms are – especially for children.

The medical establishment ideally needs randomised clinical trials, such as those Israel is admirably pushing ahead with. “I would say the Israelis have taken the lead,” Abrams says.

But 30,000 users in Israel and millions in the US aren’t waiting for such results. Some, like Abigail Dar, are too desperate. Others are wedded to their own trial-and-error experiments with different chemovars.

Another complicating factor is that the diabolically complex chemistry of the cannabis plant is too overwhelming to sort out through individual RCTs. Researchers are still scratching at the surface of a potential treasure trove of medicines that appear to act synergistically. The list of conditions to try them against appears never-ending. The number of trials needed to test each combination against each condition seems mindboggling.

The database collated by Meiri and his clinical collaborators is now being prepared for publication. It should help link the pot-pourri of chemicals inside cannabis to its clinical effects. It may be second-tier science, but it appears to be one of the best strategies for navigating a path out of the haze that still envelops medical cannabis.

Conflict of interest statement. Elizabeth Finkel is a member of the scientific advisory board of AUSiMED, which raises funds to support scientific collaborations between Australia and Israel.

Source: Cosmos 76 – Spring 2017

The use of buprenorphine and other Medically-Assisted Treatments (MAT) for opioid use disorder has increased rapidly in response to the opioid epidemic in the United States. From the clinician’s perspective, buprenorphine seemed like a panacea. I remember feeling the same way about methadone in the 70s and Naltrexone in the 80s.

Buprenorphine’s unique chemistry, being a partial agonist and antagonist medication, meant patients were able to detox from heroin or powerfully addictive prescription pain medications using Suboxone (a trade name for buprenorphine) and then taper off with relative ease, compared to heroin or oxycodone. In some cases, patients were not able to come off of Suboxone and remained on a small maintenance dose for months, and even years, but had attained a quality of life they never believed was possible when addicted to illicit opioids.

However, a large study by the Johns Hopkins Bloomberg School of Public Health (2017) reports that a significant proportion of patients on Suboxone therapy, or shortly after the conclusion of their therapy, were attaining and filling prescriptions for other opioid medications. Outcome measures matter. Different treatments work if your outcome measure is one month of adherence to the treatment versus five years of drug-free outcome and return to work.

The methodology in the Johns Hopkins study reviewed pharmacy claims for over 38,000 persons who had been prescribed Suboxone between 2006 and 2013. The results were shocking. Two-thirds of these patients had filled a prescription for an opioid painkiller in the first 12 months following Suboxone treatment—while 43 percent had received a prescription for an opioid during Suboxone therapy. In addition, approximately two-thirds of the patients who received Suboxone therapy stopped filling prescriptions for it after just three months.

What These Data Cannot Tell Us

At first glance these data are disappointing. Just looking at patient return to the program over a short time like six months, it is very clear that most methadone patients come back and many Suboxone patients do not. However, there is much the study results don’t tell us.

In a clinical and policy environment where the number of prescribers, the volume and nature of opioid prescriptions, overdoses, prescribing policies, laws and regulations are changing frequently and dramatically, data loses some of their value. In Florida, for example, the legislature, in response to the “Pill Mills,” enacted a monitoring program whereby all prescribed scheduled medications were on a single database, accessible by any licensed physician.

Twelve months after implementation, the outcomes were evaluated. Overall opioid prescriptions decreased by 1.4%. Opioid volume decreased by 2.5%, and a decrease of 5.6% in MME per transaction was observed. These data were limited to prescribers and patients with the highest baseline opioid prescribing and usage. The findings also accounted for potential confounding variables including sensitivity analyses, varying time windows and dynamic enrolment criteria. The opioid landscape in Florida continues to improve, and the pill mills are virtually gone. This is just one example of how a state’s policies impact the data and the outcome in longitudinal research.

In addition, prescription drug monitoring programs (PDMPs) are associated with reductions in all drug use (including opioids). Data culled from adult Medicare beneficiaries in states that utilize PDMPs compared with states that do not have PDMPs show significant reductions in prescription opioid transactions. Moreover, the top treatment centers may prescribe buprenorphine but also set up voluntary drug monitoring and continuing care programs for their patients, much as the programs do for impaired physicians, nurses and pilots who mandate random and for-cause drug testing for five years.

Most heroin addicts have multiple drug dependencies and problems. They also have multiple medical co-morbidities. It is not as simple as switching the patient’s heroin for buprenorphine. But street heroin is more than a drug, it is many drugs and dangerous adulterants. Over 80 percent of the Physician Health Program participants are treated effectively, monitored and never had a positive drug test throughout the five years of post-treatment outpatient monitoring.

Lastly, the Institute of Medicine released their exhaustive report on Pain in America, revealing that 100 million Americans currently suffer from chronic or intractable pain syndromes. The Johns Hopkins study does not indicate what percent of the study participants have a pain syndrome, requiring treatment with opioid medication, hopefully under the supervision of a specialist in pain managements and addiction medicine.

Why Does This Matter?

The findings certainly raise questions about the effectiveness and the appropriateness of Suboxone for addiction treatment. Clearly, if we were to adopt an oncology standard of five years, Suboxone is not likely to be considered an effective treatment. But it is a viable and important option and part of an arsenal of treatment modalities used to individualize treatment for our patients.

The study researchers noted, and I agree, that the continued use of pain medication during and after addiction treatment indicates that too many patients did not receive a multimodal, integrated treatment plan for their addiction or concurrent chronic pain or co-occurring mental illness, which approximately 50-65% of those with Substance Use Disorder (SUD) have.

Dr. Alexander, the lead author of the study noted: “There are high rates of chronic pain among patients receiving opioid agonist therapy, and thus concomitant use of buprenorphine and other opioids may be justified clinically. This is especially true as the absence of pain management among patients with opioid use disorders may result in problematic behaviors such as illicit drug use and misuse of other prescription medications.”

Addicts are quick to discover the probabilities of attaining a “high” from just about any drug they come across. Buprenorphine, while not commonly abused or sold on the streets, can be used to get high or to ease the pangs of withdrawal when heroin and other opioids are scarce.

The efficacy of treatment for SUD, regardless of the drug, is largely dependent upon non-medical factors. Yes, monitoring is important, but only if the potential for losing something one values is at stake. Surrendering, which cannot be described in medical or psychological language, is the single most important factor in determining recovery. Adjunctive treatments such as Suboxone, Methadone, N.A., A.A., CBT, yoga, meditation, diet and exercise can help a highly motivated individual. When treatment is

individualized and a bond of trust is established between a counselor and patient, good and even improbable things happen, and lives are restored.

MATs are not a replacement for the traditional foundations of treatment and recovery. At best, they can provide a specific need for a specific patient. They are not for everyone. When people ask me what the elements of success are in treatment, I often start with long-term. If a person has been abusing and addicted for years, it is difficult to imagine treatment in weeks. But, as a shortcut to what works, I tell them the 3 M’s: treatment that is high-dose, intense multimodal, multidisciplinary and multifaceted, staffed by dedicated professionals who are experienced and really do care about the patients.

Suboxone and the similar medications that will be developed are inherently not good or bad and certainly don’t work for every opioid addict. But I am thankful we have them. I believe they have saved thousands of lives. The real trick of successful treatment is to know your patients and collaborate with him or her in developing a plan that gives them the best shot at recovery.

Source: https://www.rivermendhealth.com/resources/buprenorphine-saves-lives-but-its-far-from-a-panacea/? Author: Mark Gold, MD

By Christopher Glazek

You’re aware America is under siege, fighting an opioid crisis that has exploded into a public-health emergency. You’ve heard of OxyContin, the pain medication to which countless patients have become addicted. But do you know that the company that makes Oxy and reaps the billions of dollars in profits it generates is owned by one family?

The newly installed Sackler Courtyard at London’s Victoria and Albert Museum is one of the most glittering places in the developed world. Eleven thousand white porcelain tiles, inlaid like a shattered backgammon board, cover a surface the size of six tennis courts. According to the V&A’s director, the regal setting is intended to serve as a “living room for London,” by which he presumably means a living room for Kensington, the museum’s neighborhood, which is among the world’s wealthiest. In late June, Kate Middleton, the Duchess of Cambridge, was summoned to consecrate the courtyard, said to be the earth’s first outdoor space made of porcelain; stepping onto the ceramic expanse, she silently mouthed, “Wow.”

The Sackler Courtyard is the latest addition to an impressive portfolio. There’s the Sackler Wing at New York’s Metropolitan Museum of Art, which houses the majestic Temple of Dendur, a sandstone shrine from ancient Egypt; additional Sackler wings at the Louvre and the Royal Academy; stand-alone Sackler museums at Harvard and Peking Universities; and named Sackler galleries at the Smithsonian, the Serpentine, and Oxford’s Ashmolean. The Guggenheim in New York has a Sackler Center, and the American Museum of Natural History has a Sackler Educational Lab. Members of the family, legendary in museum circles for their pursuit of naming rights, have also underwritten projects of a more modest caliber—a Sackler Staircase at Berlin’s Jewish Museum; a Sackler Escalator at the Tate Modern; a Sackler Crossing in Kew Gardens. A popular species of pink rose is named after a Sackler. So is an asteroid.

The Sackler name is no less prominent among the emerald quads of higher education, where it’s possible to receive degrees from Sackler schools, participate in Sackler colloquiums, take courses from professors with endowed Sackler chairs, and attend annual Sackler lectures on topics such as theoretical astrophysics and human rights. The Sackler Institute for Nutrition Science supports research on obesity and micronutrient deficiencies. Meanwhile, the Sackler institutes at Cornell, Columbia, McGill, Edinburgh, Glasgow, Sussex, and King’s College London tackle psychobiology, with an emphasis on early childhood development.

The Sacklers’ philanthropy differs from that of civic populists like Andrew Carnegie, who built hundreds of libraries in small towns, and Bill Gates, whose foundation ministers to global masses. Instead, the family has donated its fortune to blue-chip brands, braiding the family name into the patronage network of the world’s most prestigious, well-endowed institutions. The Sackler name is everywhere, evoking automatic reverence; the Sacklers themselves, however, are rarely seen. [In 1974, when the Sackler brothers made a large gift to the Met—$3.5 million, to erect the Temple of Dendur—they stipulated that all museum signage, catalog entries, and bulletins referring to objects in the newly opened Sackler Wing had to include the names of all three brothers, each followed by “M.D.”]

The descendants of Mortimer and Raymond Sackler, a pair of psychiatrist brothers from Brooklyn, are members of a billionaire clan with homes scattered across Connecticut, London, Utah, Gstaad, the Hamptons, and, especially, New York City. It was not until 2015 that they were noticed by Forbes, which added them to the list of America’s richest families.

The magazine pegged their wealth, shared among twenty heirs, at a conservative $14 billion. (Descendants of Arthur Sackler, Mortimer and Raymond’s older brother, split off decades ago and are mere multi-millionaires.) To a remarkable degree, those who share in the billions appear to have abided by an oath of omertà: Never comment publicly on the source of the family’s wealth.

That may be because the greatest part of that $14 billion fortune tallied by Forbes came from OxyContin, the narcotic painkiller regarded by many public-health experts as among the most dangerous products ever sold on a mass scale. Since 1996, when the drug was brought to market by Purdue Pharma, the American branch of the Sacklers’ pharmaceutical empire, more than two hundred thousand people in the United States have died from overdoses of OxyContin and other prescription painkillers. Thousands more have died after starting on a prescription opioid and then switching to a drug with a cheaper street price, such as heroin. Not all of these deaths are related to OxyContin—dozens of other painkillers, including generics, have flooded the market in the past thirty years. Nevertheless, Purdue Pharma was the first to achieve a dominant share of the market for long-acting opioids, accounting for more than half of prescriptions by 2001.

According to the Centers for Disease Control, fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year. This past July, Donald Trump’s Commission on Combating Drug Addiction and the Opioid Crisis, led by New Jersey governor Chris Christie, declared that opioids were killing roughly 142 Americans each day, a tally vividly described as “September 11th every three weeks.” The epidemic has also exacted a crushing financial toll: According to a study published by the American Public Health Association, using data from 2013—before the epidemic entered its current, more virulent phase—the total economic burden from opioid use stood at about $80 billion, adding together health costs, criminal-justice costs, and GDP loss from drug-dependent Americans leaving the workforce. Tobacco remains, by a significant multiple, the country’s most lethal product, responsible for some 480,000 deaths per year. But although billions have been made from tobacco, cars, and firearms, it’s not clear that any of those enterprises has generated a family fortune from a single product that approaches the Sacklers’ haul from OxyContin.

Even so, hardly anyone associates the Sackler name with their company’s lone blockbuster drug. “The Fords, Hewletts, Packards, Johnsons—all those families put their name on their product because they were proud,” said Keith Humphreys, a professor of psychiatry at Stanford University School of Medicine who has written extensively about the opioid crisis. “The Sacklers have hidden their connection to their product. They don’t call it ‘Sackler Pharma.’ They don’t call their pills ‘Sackler pills.’ And when they’re questioned, they say, ‘Well, it’s a privately held firm, we’re a family, we like to keep our privacy, you understand.’ ”

To the extent that the Sacklers have cultivated a reputation, it’s for being earnest healers, judicious stewards of scientific progress, and connoisseurs of old and beautiful things. Few are aware that during the crucial period of OxyContin’s development and promotion, Sackler family members actively led Purdue’s day-to-day affairs, filling the majority of its board slots and supplying top executives. By any assessment, the family’s leaders have pulled off three of the great marketing triumphs of the modern era: The first is selling OxyContin; the second is promoting the Sackler name; and the third is ensuring that, as far as the public is aware, the first and the second have nothing to do with one another.

If you head north on I-95 through Stamford, Connecticut, you will spot, on the left, a giant misshapen glass cube. Along the building’s top edge, white lettering spells out ONE STAMFORD FORUM. No markings visible from the highway indicate the presence of the building’s owner and chief occupant, Purdue Pharma. Originally known as Purdue Frederick, the first iteration of the company was founded in 1892 on New York’s Lower East Side as a peddler of patent medicines. For decades, it sustained itself with sales of Gray’s Glycerine Tonic, a sherry-based liquid of “broad application” marketed as a remedy for everything from anemia to tuberculosis. The company was purchased in 1952 by Arthur Sackler, thirty-nine, and was run by his brothers, Mortimer, thirty- six, and Raymond, thirty-two. The Sackler brothers came from a family of Jewish immigrants in Flatbush, Brooklyn. Arthur was a headstrong and ambitious provider, setting the tone—and often choosing the path—for his younger brothers. After attending medical school on Arthur’s dime, Mortimer and Raymond followed him to jobs at the Creedmoor psychiatric hospital in Queens. There, they coauthored more than one hundred studies on the biochemical roots of mental illness. The brothers’ research was promising—they were among the first to identify a link between psychosis and the hormone cortisone—but their findings were mostly ignored by their professional peers, who, in keeping with the era, favored a Freudian model of mental illness.

Concurrent with his psychiatric work, Arthur Sackler made his name in pharmaceutical advertising, which at the time consisted almost exclusively of pitches from so-called “detail men” who sold drugs to doctors door-to-door. Arthur intuited that print ads in medical journals could have a revolutionary effect on pharmaceutical sales, especially given the excitement surrounding the “miracle drugs” of the 1950s—steroids, antibiotics, antihistamines, and psychotropics. In 1952, the same year that he and his brothers acquired Purdue, Arthur became the first adman to convince The Journal of the American Medical Association, one of the profession’s most august publications, to include a color advertorial brochure.

In the 1960s, Arthur was contracted by Roche to develop an advertising strategy for a new antianxiety medication called Valium. This posed a challenge, because the effects of the medication were nearly indistinguishable from those of Librium, another Roche tranquilizer that was already on the market. Arthur differentiated Valium by audaciously inflating its range of indications. Whereas Librium was sold as a treatment for garden- variety anxiety, Valium was positioned as an elixir for a problem Arthur christened “psychic tension.” According to his ads, psychic tension, the forebear of today’s “stress,” was the secret culprit behind a host of somatic conditions, including heartburn, gastrointestinal issues, insomnia, and restless-leg syndrome. The campaign was such a success that for a time Valium became America’s most widely prescribed medication—the first to reach more than $100 million in sales. Arthur, whose compensation depended on the volume of pills sold, was richly rewarded, and he later became one of the first inductees into the Medical Advertising Hall of Fame.

As Arthur’s fortune grew, he turned his acquisitive instincts to the art market, quickly amassing the world’s largest private collection of ancient Chinese artifacts. According to a memoir by Marietta Lutze, his second wife, collecting, exhibiting, owning, and donating art fed Arthur’s “driving necessity for prestige and recognition.” Rewarding at first, collecting soon became a mania that took over his life. “Boxes of artifacts of tremendous value piled up in numerous storage locations,” she wrote, “there was too much to open, too much to appreciate; some objects known only by a packing list.” Under an avalanche of “ritual bronzes and weapons, mirrors and ceramics, inscribed bones and archaic jades,” their lives were “often in chaos.” “Addiction is a curse,” Lutze noted, “be it drugs, women, or collecting.”

When Arthur donated his art and money to museums, he often imposed onerous terms. According to a memoir written by Thomas Hoving, the Met director from 1967 to 1977, when Arthur established the Sackler Gallery at the Metropolitan Museum of Art to house Chinese antiquities, in 1963, he required the museum to collaborate on a byzantine tax-avoidance maneuver. In accordance with the scheme, the museum first sold Arthur a large quantity of ancient artifacts at the deflated 1920s prices for which they had originally been acquired. Arthur then donated back the artifacts at 1960s prices, in the process taking a tax deduction so hefty that it likely exceeded the value of his initial donation. Three years later, in connection with another donation, Arthur negotiated an even more unusual arrangement. This time, the Met opened a secret chamber above the museum’s auditorium to provide Arthur with free storage for some five thousand objects from his private collection, relieving him of the substantial burden of fire protection and other insurance costs. (In an email exchange, Jillian Sackler, Arthur’s third wife, called Hoving’s tax-deduction story “fake news.” She also noted that New York’s attorney general conducted an investigation into Arthur’s dealings with the Met and cleared him of wrongdoing.)

In 1974, when Arthur and his brothers made a large gift to the Met—$3.5 million, to erect the Temple of Dendur—they stipulated that all museum signage, catalog entries, and bulletins referring to objects in the newly opened Sackler Wing had to include the names of all three brothers, each followed by “M.D.” (One museum official quipped, “All that was missing was a note of their office hours.”)

Hoving said that the Met hoped that Arthur would eventually donate his collection to the museum, but over time Arthur grew disgruntled over a series of rankling slights. For one, the Temple of Dendur was being rented out for parties, including a dinner for the designer Valentino, which Arthur called “disgusting.” According to Met chronicler Michael Gross, he was also denied that coveted ticket of arrival, a board seat. (Jillian Sackler said it was Arthur who rejected the board seat, after repeated offers by the museum.) In 1982, in a bad breakup with the Met, Arthur donated the best parts of his collection, plus $4 million, to the Smithsonian in Washington, D. C.

Arthur’s younger brothers, Mortimer and Raymond, looked so much alike that when they worked together at Creedmoor, they fooled the staff by pretending to be one another. Their physical similarities did not extend to their personalities, however. Tage Honore, Purdue’s vice-president of discovery of research from 2000 to 2005, described them as “like day and night.” Mortimer, said Honore, was “extroverted—a ‘world man,’ I would call it.” He acquired a reputation as a big-spending, transatlantic playboy, living most of the year in opulent homes in England, Switzerland, and France. (In 1974, he renounced his U. S. citizenship to become a citizen of Austria, which infuriated his patriotic older brother.) Like Arthur, Mortimer became a major museum donor and married three wives over the course of his life.

Mortimer had his own feuds with the Met. On his seventieth birthday, in 1986, the museum agreed to make the Temple of Dendur available to him for a party but refused to allow him to redecorate the ancient shrine: Together with other improvements, Mortimer and his interior designer, flown in from Europe, had hoped to spiff up the temple by adding extra pillars. Also galling to Mortimer was the sale of naming rights for one of the Sackler Wing’s balconies to a donor from Japan. “They sold it twice,” Mortimer fumed to a reporter from New York magazine. Raymond, the youngest brother, cut a different figure—“a family man,” said Honore. Kind and mild-mannered, he stayed with the same woman his entire life. Lutze concluded that Raymond owed his comparatively serene nature to having missed the worst years of the Depression. “He had summer vacations in camp, which Arthur never had,” she

wrote. “The feeling of the two older brothers about the youngest was, ‘Let the kid enjoy himself.’ ”

Raymond led Purdue Frederick as its top executive for several decades, while Mortimer led Napp Pharmaceuticals, the family’s drug company in the UK. (In practice, a family spokesperson said, “the brothers worked closely together leading both companies.”) Arthur, the adman, had no official role in the family’s pharmaceutical operations. According to Barry Meier’s Pain Killer, a prescient account of the rise of OxyContin published in 2003, Raymond and Mortimer bought Arthur’s share in Purdue from his estate for $22.4 million after he died in 1987. In an email exchange, Arthur’s daughter Elizabeth Sackler, a historian of feminist art who sits on the board of the Brooklyn Museum and supports a variety of progressive causes, emphatically distanced her branch of the family from her cousins’ businesses. “Neither I, nor my siblings, nor my children have ever had ownership in or any benefit whatsoever from Purdue Pharma or OxyContin,” she wrote, while also praising “the breadth of my father’s brilliance and important works.” Jillian, Arthur’s widow, said her husband had died too soon: “His enemies have gotten the last word.”

The Sacklers have been millionaires for decades, but their real money—the painkiller money—is of comparatively recent vintage. The vehicle of that fortune was OxyContin, but its engine, the driving power that made them so many billions, was not so much the drug itself as it was Arthur’s original marketing insight, rehabbed for the era of chronic-pain management. That simple but profitable idea was to take a substance with addictive properties—in Arthur’s case, a benzo; in Raymond and Mortimer’s case, an opioid—and market it as a salve for a vast range of indications.

In the years before it swooped into the pain-management business, Purdue had been a small industry player, specializing in over-the-counter remedies like ear-wax remover and laxatives. Its most successful product, acquired in 1966, was Betadine, a powerful antiseptic purchased in industrial quantities by the U. S. government to prevent infection among wounded soldiers in Vietnam. The turning point, according to company lore, came in 1972, when a London doctor working for Cicely Saunders, the Florence Nightingale of the modern hospice movement, approached Napp with the idea of creating a timed-release morphine pill. A long-acting morphine pill, the doctor reasoned, would allow dying cancer patients to sleep through the night without an IV. At the time, treatment with opioids was stigmatized in the United States, owing in part to a heroin epidemic fueled by returning Vietnam veterans. “Opiophobia,” as it came to be called, prevented skittish doctors from treating most patients, including nearly all infants, with strong pain medication of any kind. In hospice care, though, addiction was not a concern: It didn’t matter whether terminal patients became hooked in their final days. Over the course of the seventies, building on a slow-release technology the company had already developed for an asthma medication, Napp created what came to be known as the “Contin” system. In 1981, Napp introduced a timed-release morphine pill in the UK; six years later, Purdue brought the same drug to market in the U. S. as MS Contin.

MS Contin quickly became the gold standard for pain relief in cancer care. At the same time, a number of clinicians associated with the burgeoning chronic-pain movement started advocating the use of powerful opioids for noncancer conditions like back pain and neuropathic pain, afflictions that at their worst could be debilitating. In 1986, two doctors from Memorial Sloan Kettering hospital in New York published a fateful article in a medical journal that purported to show, based on a study of thirty-eight patients, that long-term opioid treatment was safe and

effective so long as patients had no history of drug abuse. Soon enough, opioid advocates dredged up a letter to the editor published in The New England Journal of Medicine in 1980 that suggested, based on a highly unrepresentative cohort, that the risk of addiction from long-term opioid use was less than 1 percent. Though ultimately disavowed by its author, the letter ended up getting cited in medical journals more than six hundred times.

As the country was reexamining pain, Raymond’s eldest son, Richard Sackler, was searching for new applications for Purdue’s timed-release Contin system. “At all the meetings, that was a constant source of discussion—‘What else can we use the Contin system for?’ ” said Peter Lacouture, a senior director of clinical research at Purdue from 1991 to 2001. “And that’s where Richard would fire some ideas—maybe antibiotics, maybe chemotherapy—he was always out there digging.” Richard’s spitballing wasn’t idle blather. A trained physician, he treasured his role as a research scientist and appeared as an inventor on dozens of the company’s patents (though not on the patents for OxyContin). In the tradition of his uncle Arthur, Richard was also fascinated by sales messaging. “He was very interested in the commercial side and also very interested in marketing approaches,” said Sally Allen Riddle, Purdue’s former executive director for product management. “He didn’t always wait for the research results.” (A Purdue spokesperson said that Richard “always considered relevant scientific information when making decisions.”)

Perhaps the most private member of a generally secretive family, Richard appears nowhere on Purdue’s website. From public records and conversations with former employees, though, a rough portrait emerges of a testy eccentric with ardent, relentless ambitions. Born in 1945, he holds degrees from Columbia University and NYU Medical School. According to a bio on the website of the Koch Institute for Integrative Cancer Research at MIT, where Richard serves on the advisory board, he started working at Purdue as his father’s assistant at age twenty-six before eventually leading the firm’s R&D division and, separately, its sales and marketing division. In 1999, while Mortimer and Raymond remained Purdue’s co-CEOs, Richard joined them at the top of the company as president, a position he relinquished in 2003 to become cochairman of the board. The few publicly available pictures of him are generic and sphinxlike—a white guy with a receding hairline. He is one of the few Sacklers to consistently smile for the camera. In a photo on what appears to be his Facebook profile, Richard is wearing a tan suit and a pink tie, his right hand casually scrunched into his pocket, projecting a jaunty charm. Divorced in 2013, he lists his relationship status on the profile as “It’s complicated.” WHEN PURDUE EVENTUALLY PLEADED GUILTY TO FELONY CHARGES IN 2007 FOR CRIMINALLY “MISBRANDING” OXYCONTIN, IT ACKNOWLEDGED EXPLOITING DOCTORS’ MISCONCEPTIONS ABOUT OXYCODONE’S STRENGTH.

Richard’s political contributions have gone mostly to Republicans—including Strom Thurmond and Herman Cain—though at times he has also given to Democrats. (His ex-wife, Beth Sackler, has given almost exclusively to Democrats.) In 2008, he wrote a letter to the editor of The Wall Street Journal denouncing Muslim support for suicide bombing, a concern that seems to persist: Since 2014, his charitable organization, the Richard and Beth Sackler Foundation, has donated to several anti-Muslim groups, including three organizations classified as hate groups by the Southern Poverty Law Center. (The family spokesperson said, “It was never Richard Sackler’s intention to donate to an anti-Muslim or hate group.”) The foundation has also donated to True the Vote, the “voter-fraud watchdog” that was the original source for Donald Trump’s inaccurate claim that three million illegal immigrants voted in the 2016 election.

Former employees describe Richard as a man with an unnerving intelligence, alternately detached and pouncing. In meetings, his face was often glued to his laptop. “This was pre-

smartphone days,” said Riddle. “He’d be typing away and you would think he wasn’t even listening, and then all of the sudden his head would pop up and he’d be asking a very pointed question.” He was notorious for peppering subordinates with unexpected, rapid-fire queries, sometimes in the middle of the night. “Richard had the mind of someone who’s going two hundred miles an hour,” said Lacouture. “He could be a little bit disconnected in the way he would communicate. Whether it was on the weekend or a holiday or a Christmas party, you could always expect the unexpected.”

Richard also had an appetite for micromanagement. “I remember one time he mailed out a rambling sales bulletin,” said Shelby Sherman, a Purdue sales rep from 1974 to 1998. “And right in the middle, he put in, ‘If you’re reading this, then you must call my secretary at this number and give her this secret password.’ He wanted to check and see if the reps were reading this shit. We called it ‘Playin’ Passwords.’ ” According to Sherman, Richard started taking a more prominent role in the company during the early 1980s. “The shift was abrupt,” he said. “Raymond was just so nice and down-to-earth and calm and gentle.” When Richard came, “things got a lot harder. Richard really wanted Purdue to be big—I mean really big.”

To effectively capitalize on the chronic-pain movement, Purdue knew it needed to move beyond MS Contin. “Morphine had a stigma,” said Riddle. “People hear the word and say, ‘Wait a minute, I’m not dying or anything.’ ” Aside from its terminal aura, MS Contin had a further handicap: Its patent was set to expire in the late nineties. In a 1990 memo addressed to Richard and other executives, Purdue’s VP of clinical research, Robert Kaiko, suggested that the company work on a pill containing oxycodone, a chemical similar to morphine that was also derived from the opium poppy. When it came to branding, oxycodone had a key advantage: Although it was 50 percent stronger than morphine, many doctors believed—wrongly—that it was substantially less powerful. They were deceived about its potency in part because oxycodone was widely known as one of the active ingredients in Percocet, a relatively weak opioid- acetaminophen combination that doctors often prescribed for painful injuries. “It really didn’t have the same connotation that morphine did in people’s minds,” said Riddle.

A common malapropism led to further advantage for Purdue. “Some people would call it oxy-codeine” instead of oxycodone, recalled Lacouture. “Codeine is very weak.” When Purdue eventually pleaded guilty to felony charges in 2007 for criminally “misbranding” OxyContin, it acknowledged exploiting doctors’ misconceptions about oxycodone’s strength. In court documents, the company said it was “well aware of the incorrect view held by many physicians that oxycodone was weaker than morphine” and “did not want to do anything ‘to make physicians think that oxycodone was stronger or equal to morphine’ or to ‘take any steps . . . that would affect the unique position that OxyContin’ ” held among physicians.

Purdue did not merely neglect to clear up confusion about the strength of OxyContin. As the company later admitted, it misleadingly promoted OxyContin as less addictive than older opioids on the market. In this deception, Purdue had a big assist from the FDA, which allowed the company to include an astonishing labeling claim in OxyContin’s package insert: “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug.”

The theory was that addicts would shy away from timed-released drugs, preferring an immediate rush. In practice, OxyContin, which crammed a huge amount of pure narcotic into a single pill, became a lusted-after target for addicts, who quickly discovered that the timed-release mechanism in OxyContin was easy

to circumvent—you could simply crush a pill and snort it to get most of the narcotic payload in a single inhalation. This wasn’t exactly news to the manufacturer: OxyContin’s own packaging warned that consuming broken pills would thwart the timed-release system and subject patients to a potentially fatal overdose. MS Contin had contended with similar vulnerabilities, and as a result commanded a hefty premium on the street. But the “reduced abuse liability” claim that added wings to the sales of OxyContin had not been approved for MS Contin. It was removed from OxyContin in 2001 and would never be approved again for any other opioid.

The year after OxyContin’s release, Curtis Wright, the FDA examiner who approved the pharmaceutical’s original application, quit. After a stint at another pharmaceutical company, he began working for Purdue. In an interview with Esquire, Wright defended his work at the FDA and at Purdue. “At the time, it was believed that extended-release formulations were intrinsically less abusable,” he insisted. “It came as a rather big shock to everybody—the government and Purdue—that people found ways to grind up, chew up, snort, dissolve, and inject the pills.” Preventing abuse, he said, had to be balanced against providing relief to chronic-pain sufferers. “In the mid-nineties,” he recalled, “the very best pain specialists told the medical community they were not prescribing opioids enough. That was not something generated by Purdue—that was not a secret plan, that was not a plot,that was not a clever marketing ploy. Chronic pain is horrible. In the right circumstances, opioid therapy is nothing short of miraculous; you give people their lives back.” In Wright’s account, the Sacklers were not just great employers, they were great people. “No company in the history of pharmaceuticals,” he said, “has worked harder to try to prevent abuse of their product than Purdue.”

Purdue did not invent the chronic-pain movement, but it used that movement to engineer a crucial shift. Wright is correct that in the nineties patients suffering from chronic pain often received inadequate treatment. But the call for clinical reforms also became a flexible alibi for overly aggressive prescribing practices. By the end of the decade, clinical proponents of opioid treatment, supported by millions in funding from Purdue and other pharmaceutical companies, had organized themselves into advocacy groups with names like the American Pain Society and the American Academy of Pain Medicine. (Purdue also launched its own group, called Partners Against Pain.) As the decade wore on, these organizations, which critics have characterized as front groups for the pharmaceutical industry, began pressuring health regulators to make pain “the fifth vital sign”—a number, measured on a subjective ten-point scale, to be asked and recorded at every doctor’s visit. As an internal strategy document put it, Purdue’s ambition was to “attach an emotional aspect to non cancer pain” so that doctors would feel pressure to “treat it more seriously and aggressively.” The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American.

The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American. By 2001, annual OxyContin sales had surged past $1 billion.

OxyContin’s sales started out small in 1996, in part because Purdue first focused on the cancer market to gain formulary acceptance from HMOs and state Medicaid programs. Over the next several years, though, the company doubled its sales force to six hundred—equal to the total number of DEA diversion agents employed to combat the sale of prescription drugs on the black market—and began targeting general practitioners, dentists, OB/GYNs, physician assistants, nurses, and residents. By 2001, annual OxyContin sales had surged past $1 billion. Sales reps were encouraged to downplay addiction risks. “It was sell, sell,

sell,” recalled Sherman. “We were directed to lie. Why mince words about it? Greed took hold and overruled everything. They saw that potential for billions of dollars and just went after it.” Flush with cash, Purdue pioneered a high-cost promotion strategy, effectively providing kickbacks—which were legal under American law—to each part of the distribution chain. Wholesalers got rebates in exchange for keeping OxyContin off prior authorization lists. Pharmacists got refunds on their initial orders. Patients got coupons for thirty- day starter supplies. Academics got grants. Medical journals got millions in advertising. Senators and members of Congress on key committees got donations from Purdue and from members of the Sackler family.

It was doctors, though, who received the most attention. “We used to fly doctors to these ‘seminars,’ ” said Sherman, which were, in practice, “just golf trips to Pebble Beach. It was graft.” Though offering perks and freebies to doctors was hardly uncommon in the industry, it was unprecedented in the marketing of a Schedule II narcotic. For some physicians, the junkets to sunny locales weren’t enough to persuade them to prescribe. To entice the holdouts—a group the company referred to internally as “problem doctors”—the reps would dangle the lure of Purdue’s lucrative speakers’ bureau. “Everybody was automatically approved,” said Sherman. “We would set up these little dinners, and they’d make their little fifteen-minute talk, and they’d get $500.”

Between 1996 and 2001, the number of OxyContin prescriptions in the United States surged from about three hundred thousand to nearly six million, and reports of abuse started to bubble up in places like West Virginia, Florida, and Maine. (Research would later show a direct correlation between prescription volume in an area and rates of abuse and overdose.) Hundreds of doctors were eventually arrested for running pill mills. According to an investigation in the Los Angeles Times, even though Purdue kept an internal list of doctors it suspected of criminal diversion, it didn’t volunteer this information to law enforcement until years later. As criticism of OxyContin mounted through the aughts, Purdue responded with symbolic concessions while retaining its volume-driven business model. To prevent addicts from forging prescriptions, the company gave doctors tamper-resistant prescription pads; to mollify pharmacists worried about robberies, Purdue offered to replace, free of charge, any stolen drugs; to gather data on drug abuse and diversion, the company launched a national monitoring program called RADARS.

Critics were not impressed. In a letter to Richard Sackler in July 2001, Richard Blumenthal, then Connecticut’s attorney general and now a U. S. senator, called the company’s efforts “cosmetic.” As Blumenthal had deduced, the root problem of the prescription-opioid epidemic was the high volume of prescriptions written for powerful opioids. “It is time for Purdue Pharma to change its practices,” Blumenthal warned Richard, “not just its public-relations strategy.”

It wasn’t just that doctors were writing huge numbers of prescriptions; it was also that the prescriptions were often for extraordinarily high doses. A single dose of Percocet contains between 2.5 and 10mg of oxycodone. OxyContin came in 10-, 20-, 30-, 40-, and 80mg formulations and, for a time, even 160mg. Purdue’s greatest competitive advantage in dominating the pain market, it had determined early on, was that OxyContin lasted twelve hours, enough to sleep through the night. But for many patients, the drug lasted only six or eight hours, creating a cycle of crash and euphoria that one academic called “a perfect recipe for addiction.” When confronted with complaints about “breakthrough pain”—meaning that the pills weren’t working as long as advertised—Purdue’s sales reps were given strict instructions to tell doctors to strengthen the dose rather than increase dosing frequency.

Sales reps were encouraged to downplay addiction risks. “It was sell, sell, sell,” recalled Sherman. “We were directed to lie. Why mince words about it?”

Over the next several years, dozens of class-action lawsuits were brought against Purdue. Many were dismissed, but in some cases Purdue wrote big checks to avoid going to trial. Several plaintiffs’ lawyers found that the company was willing to go to great lengths to prevent Richard Sackler from having to testify under oath. “They didn’t want him deposed, I can tell you that much,” recalled Marvin Masters, a lawyer who brought a class-action suit against Purdue in the early 2000s in West Virginia. “They were willing to sit down and settle the case to keep from doing that.” Purdue tried to get Richard removed from the suit, but when that didn’t work, the company settled with the plaintiffs for more than $20 million. Paul Hanly, a New York class-action lawyer who won a large settlement from Purdue in 2007, had a similar recollection. “We were attempting to take Richard Sackler’s deposition,” he said, “around the time that they agreed to a settlement.” (A spokesperson for the company said, “Purdue did not settle any cases to avoid the deposition of Dr. Richard Sackler, or any other individual.”)

When the federal government finally stepped in, in 2007, it extracted historic terms of surrender from the company. Purdue pleaded guilty to felony charges, admitting that it had lied to doctors about OxyContin’s abuse potential. (The technical charge was “misbranding a drug with intent to defraud or mislead.”) Under the agreement, the company paid $600 million in fines and its three top executives at the time—its medical director, general counsel, and Richard’s successor as president—pleaded guilty to misdemeanor charges. The executives paid $34.5 million out of their own pockets and performed four hundred hours of community service. It was one of the harshest penalties ever imposed on a pharmaceutical company. (In a statement to Esquire, Purdue said that it “abides by the highest ethical standards and legal requirements.” The statement went on: “We want physicians to use their professional judgment, and we were not trying to pressure them.”)

Fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year.

No Sacklers were named in the 2007 suit. Indeed, the Sackler name appeared nowhere in the plea agreement, even though Richard had been one of the company’s top executives during most of the period covered by the settlement. He did eventually have to give a deposition in 2015, in a case brought by Kentucky’s attorney general. Richard’s testimony—the only known record of a Sackler speaking about the crisis the family’s company helped create—was promptly sealed. (In 2016, STAT, an online magazine owned by Boston Globe Media that covers health and medicine, asked a court in Kentucky to unseal the deposition, which is said to have lasted several hours. STAT won a lower-court ruling in May 2016. As of press time, the matter was before an appeals court.)

In 2010, Purdue executed a breathtaking pivot: Embracing the arguments critics had been making for years about OxyContin’s susceptibility to abuse, the company released a new formulation of the medication that was harder to snort or inject. Purdue seized the occasion to rebrand itself as an industry leader in abuse-deterrent technology. The change of heart coincided with two developments: First, an increasing number of addicts, unable to afford OxyContin’s high street price, were turning to cheaper alternatives like heroin; second, OxyContin was nearing the end of its patents. Purdue suddenly argued that the drug it had been selling for nearly fifteen years was so prone to abuse that generic manufacturers should not be allowed to copy it.

On April 16, 2013, the day some of the key patents for OxyContin were scheduled to expire, the FDA followed Purdue’s lead, declaring that no generic versions of the original OxyContin formulation could be sold. The company had effectively won several additional years of patent protection for its golden goose.

Opioid withdrawal, which causes aches, vomiting, and restless anxiety, is a gruesome process to experience as an adult. It’s considerably worse for the twenty thousand or so American babies who emerge each year from opioid-soaked wombs. These infants, suddenly cut off from their supply, cry uncontrollably. Their skin is mottled. They cannot fall asleep. Their bodies are shaken by tremors and, in the worst cases, seizures. Bottles of milk leave them distraught, because they cannot maneuver their lips with enough precision to create suction. Treatment comes in the form of drops of morphine pushed from a syringe into the babies’ mouths. Weaning sometimes takes a week but can last as long as twelve. It’s a heartrending, expensive process, typically carried out in the neonatal ICU, where newborns have limited access to their mothers.

But the children of OxyContin, its heirs and legatees, are many and various. The second- and third-generation descendants of Raymond and Mortimer Sackler spend their money in the ways we have come to expect from the not-so-idle rich. Notably, several have made children a focus of their business and philanthropic endeavors. One Sackler heir helped start an iPhone app called Red Rover, which generates ideas for child-friendly activities for urban parents; another runs a child- development center near Central Park; another is a donor to charter-school causes, as well as an investor in an education start-up called AltSchool. Yet another is the founder of Beespace, an “incubator for emerging nonprofits,” which provides resources and mentoring for initiatives like the Malala Fund, which invests in education programs for women in the developing world, and Yoga Foster, whose objective is to bring “accessible, sustainable yoga programs into schools across the country.” Other Sackler heirs get to do the fun stuff: One helps finance small, interesting films like The Witch; a second married a famous cricket player; a third is a sound artist; a fourth started a production company with Boyd Holbrook, star of the Netflix series Narcos; a fifth founded a small chain of gastropubs in New York called the Smith.

Holding fast to family tradition, Raymond’s and Mortimer’s heirs declined to be interviewed for this article. Instead, through a spokesperson, they put forward two decorated academics who have been on the receiving end of the family’s largesse: Phillip Sharp, the Nobel-prize-winning MIT geneticist, and Herbert Pardes, formerly the dean of faculty at Columbia University’s medical school and CEO of New York-Presbyterian Hospital. Both men effusively praised the Sacklers’ donations to the arts and sciences, marveling at their loyalty to academic excellence. “Once you were on that exalted list of philanthropic projects,” Pardes told Esquire, “you were there and you were in a position to secure additional philanthropy. It was like a family acquisition.” Pardes called the Sacklers “the nicest, most gentle people you could imagine.” As for the family’s connection to OxyContin, he said that it had never come up as an issue in the faculty lounge or the hospital break room. “I have never heard one inch about that,” he said.

Pardes’s ostrich like avoidance is not unusual. In 2008, Raymond and his wife donated an undisclosed amount to Yale to start the Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences. Lynne Regan, its current director, told me that neither students nor faculty have ever brought up the OxyContin connection. “Most people don’t know about that,” she said. “I think people are mainly oblivious.” A spokesperson for the university added, “Yale does not vet donors for controversies that may or may not arise.”

In May, a dozen lawmakers in Congress sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics.

The controversy surrounding OxyContin shows little sign of receding. In 2016, the CDC issued a startling warning: There was no good evidence that opioids were an effective treatment for chronic pain beyond six weeks. There was, on the other hand, an abundance of evidence that long-term treatment with opioids had harmful effects. (A recent paper by Princeton economist Alan Krueger suggests that chronic opioid use may account for more than 20 percent of the decline in American labor-force participation from 1999 to 2015.) Millions of opioid prescriptions for chronic pain had been written in the preceding two decades, and the CDC was calling into question whether many of them should have been written at all. At least twenty-five government entities, ranging from states to small cities, have recently filed lawsuits against Purdue to recover damages associated with the opioid epidemic.

The Sacklers, though, will likely emerge untouched: Because of a sweeping non-prosecution agreement negotiated during the 2007 settlement, most new criminal litigation against Purdue can only address activity that occurred after that date. Neither Richard nor any other family members have occupied an executive position at the company since 2003.

The American market for OxyContin is dwindling. According to Purdue, prescriptions fell 33 percent between 2012 and 2016. But while the company’s primary product may be in eclipse in the United States, international markets for pain medications are expanding. According to an investigation last year in the Los Angeles Times, Mundipharma, the Sackler-owned company charged with developing new markets, is employing a suite of familiar tactics in countries like Mexico, Brazil, and China to stoke concern for as-yet-unheralded “silent epidemics” of untreated pain. In Colombia, according to the L.A. Times, the company went so far as to circulate a press release suggesting that 47 percent of the population suffered from chronic pain. [Napp is the family’s drug company in the UK. Mundipharma is their company charged with developing new markets.]

In May, a dozen lawmakers in Congress, inspired by the L.A. Times investigation, sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics. “Purdue began the opioid crisis that has devastated American communities,” the letter reads. “Today, Mundipharma is using many of the same deceptive and reckless practices to sell OxyContin abroad.” Significantly, the letter calls out the Sackler family by name, leaving no room for the public to wonder about the identities of the people who stood behind Mundipharma.

The final assessment of the Sacklers’ global impact will take years to work out. In some places, though, they have already left their mark. In July, Raymond, the last remaining of the original Sackler brothers, died at ninety-seven. Over the years, he had won a British knighthood, been made an Officer of France’s Légion d’Honneur, and received one of the highest possible honors from the royal house of the Netherlands. One of his final accolades came in June 2013, when Anthony Monaco, the president of Tufts University, traveled to Purdue Pharma’s headquarters in Stamford to bestow an honorary doctorate. The Sacklers had made a number of transformational donations to the university over the years—endowing, among other things, the Sackler School of Graduate Biomedical Sciences. At

Tufts, as at most schools, honorary degrees are traditionally awarded on campus during commencement, but in consideration of Raymond’s advanced age, Monaco trekked to Purdue for a special ceremony. The audience that day was limited to family members, select university officials, and a scrum of employees. Addressing the crowd of intimates, Monaco praised his benefactor. “It would be impossible to calculate how many lives you have saved, how many scientific fields you have redefined, and how many new physicians, scientists, mathematicians, and engineers are doing important work as a result of your entrepreneurial spirit.” He concluded, “You are a world changer.”

Source: This article appears in the November ’17 issue of Esquire.

MEDS Act promotes FDA-compliant medical research of marijuana

 (Alexandria, VA)– Smart Approaches to Marijuana (SAM) applauds U.S. Senators Brian Schatz (D-HI), Orrin Hatch (R-UT), Thom Tillis (R-NC), and Chris Coons (D-DE) for introducing the Marijuana Effective Drug Studies (MEDS) Act of 2016. Once passed, it would make it easier for researchers to perform legitimate research on the medical effectiveness and safety of marijuana’s components.

Rather than rescheduling marijuana, the MEDS Act comprehensively identifies barriers to legitimate research and offers comprehensive, responsible solutions instead of “medicine by ballot initiative.” More specifically, the bill:

  • Enables more research on marijuana by creating a faster, more streamlined process for obtaining approval from the Drug Enforcement Agency (DEA) to conduct research, including the ability to amend and supplement research proposals without reapplying.  Currently, researchers who want to conduct research on marijuana must interface with several federal agencies and engage in a complex application process that can take a year or longer must start from scratch if they make any changes to their research proposal;
  • Eliminates the burdensome requirement of some DEA field offices that marijuana be kept in bolted safes – a requirement not possible in many research and clinical settings – and codifies current DEA regulations that allow marijuana to be stored in securely locked, substantially constructed cabinets; and
  • Requires the licensing of marijuana manufacturers for the purpose of valid scientific and clinical research and drug development and establishes manufacturing licenses for the commercial production of FDA-approved medical marijuana products.

“These steps are important because despite state laws, raw marijuana (smoked or ingested) is not medicine, and has never passed through the rigorous FDA approval process to ensure the health and safety of patients,” said Dr. Kevin Sabet, President of SAM.  “The plant’s components should be studied so those in need can access any therapeutic benefits while knowing dosage, side effects, and contraindications.  And more broadly speaking, the MEDS Act upholds the important, basic principle that all medications-including marijuana-based drugs-should go through the scientific process and accessed through legitimate doctors.”

SAM is proud to join the American Medical Association, American Academy of Pediatrics, American Cancer Society Cancer Action Network, American Society of Addiction Medicine, American Preventive Medical Association, American Pain Society, American Society of Anesthesiologists, and the American Academy of Pain Medicine in support of the MEDS Act.

Source:  https://learnaboutsam.org/sam-applauds-bi-partisan-legislation-legitimate-medical-marijuana-research/   

20th June 2016

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