Saturday, July 27, 2013

"Glee" Star Cory Monteith

According to the British Columbia Coroner, Cory Monteith, the star of the TV show "Glee", died after taking a toxic combination of heroin and alcohol.

This is another example of how dangerous it is to combine opiates with other CNS depressants (sedatives). Opiates, by themselves, are generally safe, as are most sedatives. It is the combination that is particularly risky.

Still, others speculate that Mr. Monteith was more vulnerable to overdose after recently going through a detox program, because his body was no longer able to tolerate high doses of heroin. There is no evidence indicating he used high doses of heroin in the past or at the time of his death, making this conjecture less plausible. In addition, while it is theoretically possible to die from an overdose of heroin alone, in practical terms this is rare. Only about a quarter of the thousands of heroin-related deaths each year occur as a result of heroin alone. The vast majority of heroin-related deaths -- a whopping 70 percent or more -- are caused by combining heroin with another sedative, usually alcohol. Regrettably, Mr. Monteith too was a victim of this combination. [emphasis added - Ed] 
As a neuropsychopharmacologist who specializes in substance abuse, I find the focus on factors other than this drug combination distracting and irresponsible. Too often in these tragic cases some "experts" emphasize the failures of rehab, rather than providing the drug-using population with practical information that could prevent countless overdose deaths. We are missing an important public health education opportunity to decrease drug-related accidents. 
The Coroner concluded, "there is no evidence to suggest Mr. Monteith's death was anything other than a most-tragic accident." What was not said is that this horrible accident, and the thousands of others that occur each year, could have been prevented if our public health education message clearly focused on the potential dangers associated with the alcohol-heroin combination instead of being preoccupied with blaming rehab and vilifying heroin. 
"Glee" Star Cory Monteith's Death Proves Heroin (Alone) Is Not the Problem by Dr. Carl Hart
I agree with Dr. Hart about educating drug users in overdose prevention, but he is wrong about blaming rehab. While it is absurd to claim Monteith's death was a direct result of his going to rehab, it was almost certainly a contributing factor. 

First Monteith was coerced into rehab by his employer in an "intervention." Apparently his employer found out that Monteith was "using" again and that was sufficient evidence, not whether Monteith's work was actually impaired (which as with tobacco or alcohol should be the standard used, it matters not what drugs an individual consumes but how they behave). Second, the rehab chosen did not use evidence-based practices, but focused on abstinence and the 12-step model. Maia Szalavitz fills us in on the details:
Apparently, these “experts” suggested Eric Clapton’s Crossroads rehab in Antigua, an old-school program that does not “believe in” using medications to treat opioid addiction, despite all the data favoring them as lifesaving for people whose problems involve heroin or painkillers. Murphy implies that Monteith was in another rehab (reportedly Betty Ford) that “didn’t work”—but that after the second program, “all indications were that he’d gone through the Steps.” 
We all know what happened next. Although the intervention did get him into treatment—unlike the one conducted on [Kurt] Cobain, which was followed directly by his suicide—Monteith followed the pattern of the 90 percent of opioid addicts who are coerced into 12-step recovery and denied an adequate period of maintenance treatment: He relapsed.  
He also followed two other predictable and dangerous patterns. 
First, the risk of overdose is highest in the initial few months after being in rehab or any other situation where a period of abstinence has occurred. After a complete detoxification, a person’s tolerance drops precipitously—meaning that the dose they took before treatment without even getting very high may now be potentially fatal. The first two weeks following prison, for example, were shown by one study to carry a greater than 120-fold increased risk of overdose death; that extreme risk elevation holds for whenever the person first uses again after a period without opioids. 
Second, the vast majority of “opioid overdoses”—overdoses involving drugs like heroin or Vicodin—are not accurately characterized by that name. Instead, they are really “opioid mixture overdoses,” typically including an opioid and other depressants like alcohol and/or benzodiazepines like Xanax and Valium. Opioids are the drug that most often makes these mixes turn deadly—but only one third or fewer of so-called opioid overdoses involve those drugs by themselves. 
Monteith took the deadliest possible combination—alcohol and heroin, whose actions to slow breathing are not additive but multiple—at the deadliest possible time. He was likely not informed about the risk because abstinence-focused rehabs typically don’t provide harm reduction advice. He certainly was not provided with maintenance medication like methadone or buprenorphine that can dramatically reduce that risk; he may not even have know that maintenance was an option—just as Cobain was told he could not take any more opioids, even for his chronic pain. Nor, apparently, were Monteith or his loved ones given naloxone, which can reverse opioid overdose, or instructed on how to use it. 
How Addiction Treatment Killed Cory Monteith by Maia Szalavitz
Cory Monteith's death was due to his own actions to be sure. But that does not mean that we, as a society, have not contributed to it with our drug policies. Had heroin been legal and pure, and accurate drug information was covered in grade school in place of counterproductive anti-drug "education", perhaps it would be widely known not to mix opiates with sedatives.

Had opiates been legal, I highly doubt his employer would have been able to coerce Monteith into rehab. The very notion of staging an "intervention" over non-problematic opiate use would seem as absurd as staging an intervention over occasional alcohol drinking. If Monteith's opiate use did indeed become problematic and interfere with his work, he should have at least have been given the option of maintenance medicines. Szalavitz also addresses this in the same article cited above:
In no other type of treatment are FDA-approved medications seen as appropriate to withhold—without even informing the patient of their existence. No cancer center in the US provides only chemo while refusing to inform patients about radiation treatment or putting it down as something “we don’t believe in here” because it is “cheating” rather than “real recovery.” But the equivalent is done in addiction treatment—even for celebrities—every day. If we don’t want to keep losing patients, we’ve got to actually treat addiction like a disease, by providing evidence-based treatment, not just repeating faith-based philosophies.
Monteith's death, like thousands of others, could have been prevented if our drug policies approached drugs in a rational way. Instead we get vilification of drugs and the people who use them. Meanwhile the body count grows ever higher.

Saturday, July 20, 2013

Opioid Antagonists: Naloxone and Naltrexone

The effects of opioids are primarily due to their action on the mu opioid receptor. Molecules that interact with this receptor can be classified into three primary types, full agonists, partial agonists and antagonists. Full agonists such as morphine or methadone activate the receptor in a dose dependent manner. Partial agonists also activate the receptor, but the activation reaches a plateau and will not respond to increases in dosage. Finally antagonists such as naloxone bind to the receptor, but do not activate it at all.

The two most commonly used opioid antagonists are naloxone and naltrexone. Both are competitive antagonists, which means they work by competing for the receptor's binding site. The strength of the bond between the ligand (drug) and the receptor is known as the affinity. Molecules with higher affinity for the receptor will replace those with lower affinity. Naloxone has a higher affinity for the mu opioid receptor than morphine, when administered it will replace the morphine bound to the receptor. Because naloxone is an antagonist, the receptor will deactivate completely reversing the effects of the morphine.

Both naltrexone and naloxone can be described as substituted derivatives of oxymorphone. The tertiary amine methyl-substituent is replaced with a longer chain of carbon atoms (an allyl group). With naloxone the N-methyl group of oxymorphone is substituted with an N-prop-2-enyl group, with naltrexone this substitution is with an N-cyclopropylmethyl group. The name naloxone has been derived from N-allyl and oxymorphone.

While both antagonists have high oral bioavailability, they both undergo extensive first-pass metabolism. Up to 98% of naloxone is metabolized to an inactive metabolite, and for this reason it must be administered as an injection or intranasal spray. Naltrexone is metabolized to 6-β-naltrexol, which is an active metabolite also acting as an antagonist at the mu receptor. While naloxone is used primarily as an emergency antidote to opioid overdoses, naltrexone has been used as a medication to treat alcoholism and opioid addiction.


"When naloxone hydrochloride is administered intravenously the onset of action is generally apparent within two minutes; the onset of action is only slightly less rapid when it is administered subcutaneously or intramuscularly. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. Intramuscular administration produces a more prolonged effect than intravenous administration. The requirement for repeat doses of naloxone hydrochloride, however, will also be dependent upon the amount, type and route of administration of the narcotic being antagonised. Following parenteral administration naloxone hydrochloride is rapidly distributed in the body. It is metabolised in the liver, primarily by glucuronide conjugation and excreted in the urine. In one study the serum half-life in adults ranged from 30 to 81 minutes (mean 64 ± 12 minutes). In a neonatal study the mean plasma half-life was observed to be 3.1 ± 0.5 hours."
-Naloxone Data Sheet (New Zealand)

"Naltrexone Hydrochloride is a pure opioid receptor antagonist. Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%. The activity of naltrexone is believed to be due to both parent and the 6-β-naltrexol metabolite. Both parent drug and metabolites are excreted primarily by the kidney (53% to 79% of the dose), however, urinary excretion of unchanged naltrexone accounts for less than 2% of an oral dose and faecal excretion is a minor elimination pathway. The mean elimination half-life (T-1/2) values for naltrexone and 6-β-naltrexol are 4 hours and 13  hours, respectively. The elimination half-life and time to maximum concentration are dose-independent.  Naltrexone and 6-β-naltrexol are dose proportional in terms of AUC and Cmax over the range of 50 to 200 mg and there is no significant accumulation after 100 mg daily doses."
-Naltrexone Data Sheet (New Zealand)

Responding to an opiate overdose

Most overdoses are the result of mixing opiates with central nervous system depressants. Although naloxone only works on opioids, it is the synergism of the drug combo that causes the overdose. Removing the opioid component only will usually restore respiratory function. Opiate users should practice assembling the naloxone kit so as to be efficient in case of an emergency. If someone has stopped breathing every minute matters, combined with the stress and adrenaline of the emergency you don't want to have to take time out to read an instruction manual. Since naloxone overdose kits have been introduced in the US, over 10,000 lives have been saved by non-emergency persons (the friends and family of drug users).

If the individual has stopped breathing:

Do rescue breathing for a few quick breaths, then administer the naloxone. Depending on if the naloxone is administered as an injection or intranasally, it may take a few minutes to take effect. If there is no effect after 3-5 minutes, administer another dose of naloxone.

If the naloxone does not work after the second application, something is wrong. Naloxone may not work if:

1. The overdose is not due to opioids.
2. The opioid causing the overdose has a higher affinity for the mu receptor than naloxone, which can happen with some synthetic opioids (such as buprenorphine or fentanyl and its analogs).
3. Too much time has lapsed and the heart has stopped.

"Naloxone only lasts between 30 – 90 minutes, while the effects of the opioids may last much longer. It is possible that after the naloxone wears off the overdose could recur. It is very important that someone stay with the person and wait out the risk period just in case another dose of naloxone is necessary. Also, naloxone can cause uncomfortable withdrawal feelings since it blocks the action of opioids in the brain. Sometimes people want to use again immediately to stop the withdrawal feelings. This could result in another overdose. Try to support the person during this time period and encourage him or her not to use for a couple of hours."
Administer Naloxone Overdose Response from Harm Reduction Coalition 

Further Reading:

Community-Based Opioid Overdose Prevention Programs Providing Naloxone — United States, 2010
Morbidity and Mortality Weekly Report (MMWR)
February 17, 2012 / 61(06);101-105 [Link]

Understanding Naloxone, Harm Reduction Coalition

Tuesday, July 16, 2013

Drug Prohibition and Human Rights

The War on Drugs is causing human rights violations on a global scale.

All over the world, people are subjected to police mistreatment, harassment and arbitrarily arrest simply for their choice of intoxicant. Many are subject to involuntary "treatment", which amounts to little more than prison labor camps. The "patients" (inmates) are either unpaid, or paid below the minimum wage and then nickel-and-dimed with administrative fees. Resistance is met with savage beatings, torture, sexual abuse and increased time added to their "rehabilitation". Most "patients" are forced into treatment without judicial overview or opportunity for appeal. Drug treatment, when present at all, is not evidence-based. (One example includes having the "patients" chant "Healthy!Healthy!Healthy!").

One product of these labor camps is shelled cashews and the US is an importer. If you buy shelled cashews in the US it is quite possible they were shelled by a fellow opiate user enslaved by the state. As part of their "treatment", the drug users are given quotas to fill. Failure to meet the quotas are met with severe punishment.

Opiophobia and the war on drugs is also the driving force behind the inhumane treatment of pain. Third world countries are especially hard hit, the supply does not come anywhere near the levels necessary to meet the demand. This is inexcusable, morphine is cheap and easy to produce. It is also remarkably safe when used properly. There is no maximum dose. It is also relatively safe, if one was to accidentally take double the expected dose, death or organic damage would be very unlikely. Whereas if one was on the highest recommended daily dosage of acetaminophen, and accidentally doubled the dosage serious liver damage may result. Addiction in patients taking opiates for pain is actually uncommon. Even young children and terminal patients are not excepted from their torments. And really, even if aggressive treatment with opiates did result in addiction, does it really matter when the person is dying? Is the risk of addiction sufficient to justify forcing someone to live in agony?

Criminalizing drug use itself undermines our basic human right to autonomy and privacy, according to Human Rights Watch. I would also add that it violates our freedom of medicine, and the right to self-medicate. Since the US incarcerates more of its citizens than any other country in the world, largely for drug "crimes", the US itself is one of the world's greatest human rights violators. Government intransigence on the issue of harm reduction is causing an epidemic of HIV and hepatitis infections among injection drugs users, violating their right to a high standard of health.

From Human Right's Watch
(Antigua) – National drug control policies that impose criminal penalties for personal drug use undermine basic human rights, Human Rights Watch said today. To deter harmful drug use, governments should rely instead on non-penal regulatory and public health policies. The 43rd General Assembly of the Organization of American States, taking place in Antigua, Guatemala from June 4 to 6, 2013, will focus on drug control policy in the Americas.

Governments should also take steps to reduce the human rights costs of current drug production and distribution policies, Human Rights Watch said. Among the steps should be reforming law enforcement practices and exploring alternatives for legal regulation that would reduce the power of violent criminal groups.
Subjecting people to criminal sanctions for the personal use of drugs, or for possession of drugs for personal use, infringes on their autonomy and right to privacy, Human Rights Watch said. The right to privacy is broadly recognized under international law, including in the International Covenant on Civil and Political Rights and the American Convention on Human Rights. Limitations on autonomy and privacy cannot be justified unless they meet the criteria for any restriction of a basic right, namely legitimate purpose, proportionality, necessity, and non-discrimination.

While protecting health is a legitimate government purpose, criminalizing drug use to protect people from harming themselves does not meet the criteria of necessity or proportionality. Governments have many non-penal options to reduce harm to people who use drugs, including offering substance abuse treatment and social support.

Human Rights Watch research around the world has found that the criminalization of drug use has undermined the right to health. Fear of criminal penalties deters people who use drugs from using health services and treatment, and increases their risk of violence, discrimination, and serious illness. Criminal prohibitions have also impeded the use of drugs for legitimate medical research, and have prevented patients from accessing drugs for palliative care and pain treatment.

“There are many steps that governments can and should take to deter, prevent and remedy the harmful use of drugs,” Vivanco said. “But they shouldn’t do it by punishing the people whose health they are trying to protect.”

Governments have a legitimate interest in protecting third parties from harm resulting from drug use, such as driving under the influence, Human Rights Watch said. They may impose, consistent with human rights, proportionate criminal penalties on behavior that occurs in conjunction with drug use if that behavior causes or seriously risks harm to others.

With respect to drug use by children, governments have obligations to take appropriate legislative, administrative, social, and educational measures to protect children from the illicit use of drugs. Governments should not impose criminal penalties on children for drug use or possession, Human Rights Watch said.

“When someone under the influence of drugs does something that could harm others, whether it’s driving a car or endangering a child through neglect, criminal sanctions may be entirely appropriate, just as they are when people use alcohol in a way that endangers others,” said Vivanco. “However, the penalty is not for drug use alone but for engaging in activity that could endanger others while under the influence of drugs.”
Americas: Decriminalize Personal Use of Drugs
The article goes on to discuss human rights violations caused by the production and distribution of illicit drugs, and the reactionary role of the UN International Narcotics Control Board.

Below are specific reports from Human Rights Watch. I have grouped them into three categories: pain medicine access, abuse in the name of drug treatment, and general policy and HIV response.

Pain Treatment and Access to Medicine

Global State of Pain Treatment Access to Medicines and Palliative Care. June 3, 2011

This 128-page report details the failure of many governments to take even basic steps to ensure that people with severe pain due to cancer, HIV, and other serious illnesses have access to palliative care, a health service that seeks to improve quality of life. As a result, millions of patients live and die in great agony that could easily be prevented, Human Rights Watch said.

“Please, do not make us suffer any more…” Access to Pain Treatment as a Human Right. March 3, 2009
In this 47-page report Human Rights Watch said that countries could significantly improve access to pain medications by addressing the causes of their poor availability. These often include the failure to put in place functioning supply and distribution systems; absence of government policies to ensure their availability; insufficient instruction for healthcare workers; excessively strict drug-control regulations; and fear of legal sanctions among healthcare workers.

Human Rights Abuses in the Name of Treatment

Torture in the Name of Treatment Human Rights Abuses in Vietnam, China, Cambodia, and Lao PDR. July 24, 2012
More than 350,000 people identified as drug users are held in compulsory drug "treatment" centers in China and Southeast Asia. Detainees are held without due process for periods of months or years and may be subjected to physical and sexual abuse, torture, and forced labor. International donors and UN agencies have supported and funded drug detention centers, while centers have systematically denied detainees access to evidence-based drug dependency treatment and HIV prevention services. "Torture in the Name of Treatment," summarizes Human Rights Watch’s findings over five years of research in China, Cambodia, Vietnam, and Lao PDR.

“Skin on the Cable” The Illegal Arrest, Arbitrary Detention and Torture of People Who Use Drugs in Cambodia. January 25, 2010
In this 93-page report Human Rights Watch documents detainees being beaten, raped, forced to donate blood, and subjected to painful physical punishments such as "rolling like a barrel" and being chained while standing in the sun. Human Rights Watch also reported that a large number of detainees told of receiving rotten or insect-ridden food and symptoms of diseases consistent with nutritional deficiencies.

“Where Darkness Knows No Limits” Incarceration, Ill-Treatment and Forced Labor as Drug Rehabilitation in China. January 7, 2010
This 37-page report based on research in Yunnan and Guangxi provinces, documents how China's June 2008 Anti-Drug Law compounds the health risks of suspected illicit drug users by allowing government officials and security forces to incarcerate them for up to six years. The incarceration is without trial or judicial oversight. The law fails to clearly define mechanisms for legal appeals or the reporting of abusive conduct, and does not ensure evidence-based drug dependency treatment.

The Rehab Archipelago Forced Labor and Other Abuses in Drug Detention Centers in Southern Vietnam. September 7, 2011
The 121-page report documents the experiences of people confined to 14 detention centers under the authority of the Ho Chi Minh City government. Refusing to work, or violating center rules, results in punishment that in some cases is torture. Quynh Luu, a former detainee who was caught trying to escape from one center, described his punishment: "First they beat my legs so that I couldn't run off again... [Then] they shocked me with an electric baton [and] kept me in the punishment room for a month."

Somsanga’s Secrets Arbitrary Detention, Physical Abuse, and Suicide inside a Lao Drug Detention Center. October 11, 2011
This report examines conditions in the Somsanga Treatment and Rehabilitation Center, which has received a decade of international support from the United States, the United Nations, and other donors. Detainees are held without due process, and many are locked in cells inside barbed wire compounds. Former detainees told Human Rights Watch that they had been held for periods of three months to more than a year. Police and guards are a constant presence, and those who try to escape may be brutally beaten.

An Unbreakable Cycle Drug Dependency Treatment, Mandatory Confinement, and HIV/AIDS in China’s Guangxi Province December 9, 2008
In China, illicit drug use is an administrative offense and Chinese law dictates that drug users “must be rehabilitated.” In reality, police raids on drug users often drive them underground, away from methadone clinics, needle exchange sites, and other proven HIV prevention services. And every year Chinese police send tens of thousands of drug users to mandatory drug treatment centers, often for years, without trial or due process.
This report finds that most mandatory treatment centers, while ostensibly meant to provide drug treatment, do not actually offer forms of drug dependence treatment internationally recognized as effective. Mostly, drug users are forced to work or to spend their days in crowded cells little different from prisons.

Barred from Treatment Punishment of Drug Users in New York State Prisons. March 24, 2009
In this 53-page report, Human Rights Watch found that New York prison officials sentenced inmates to a collective total of 2,516 years in disciplinary segregation from 2005 to 2007 for drug-related charges. At the same time, inmates seeking drug treatment face major delays because treatment programs are filled to capacity. When sentenced to segregation, known as "the box," inmates are not allowed to get or continue to receive treatment. Conditions in the box are harsh, with prisoners locked down 23 hours a day and contact with the outside through visitors, packages, and telephone calls severely restricted.

Public Policy and HIV

Rehabilitation Required Russia’s Human Rights Obligation to Provide Evidence-based Drug Dependence Treatment. November 8, 2007
In this 110-page study, Human Rights Watch found that the treatment offered at state drug treatment clinics in Russia was so poor as to constitute a violation of the right to health. The report concluded that drug dependent people in Russia who want to overcome their dependence are left virtually to their own devices in their battle with this serious and chronic disease.

Injecting Reason Human Rights and HIV Prevention for Injection Drug Users. September 9, 2003
Government interference with sterile syringe programs is thwarting HIV prevention efforts in California. State laws and local enforcement are preventing drug users from obtaining the sterile syringes they need to protect themselves from HIV. This 61-page report documents police stopping, arresting, and harassing participants in needle exchange programs established by some California counties under state law. Even where needle exchange programs are legal, police remain authorized to arrest program participants under an antiquated law prohibiting the possession of “drug paraphernalia.” Over a quarter of new AIDS cases in the United States can be traced to infected syringes. Sharing syringes is also a major risk factor in the spread of hepatitis B and C. California is home to nearly one eighth of reported AIDS cases in the United States. The Human Rights Watch report recommends legalization of needle exchange programs and nonprescription pharmacy sales of syringes. It also calls on police departments to cease stops and seizures of participants in clean needle programs, a practice courts have recently prohibited in Connecticut, Massachusetts and New York.

Not Enough Graves The War on Drugs, HIV/AIDS, and Violations of Human Rights. July 8, 2004
This 60-page report provides fresh evidence of extrajudicial killings, arbitrary arrests and other human rights violations by Thai authorities. The report contains first-hand testimony from relatives of people killed during the drug war, as well as drug users who endured beatings, forced confessions and arbitrary arrests at the hands of Royal Thai Police. The government's anti-drug campaign has resulted in as many as 3,000 killings and has driven drug users underground and away from lifesaving HIV prevention services.

Abusing the User: Police Misconduct, Harm Reduction and HIV/AIDS in Vancouver. May 7, 2003
An anti-drug crackdown by the Vancouver Police Department has driven injection drug users away from life-saving HIV prevention services, raising fears of a new wave of HIV transmission in the city that is already home to the worst AIDS crisis in the developed world, said Human Rights Watch. In a 25-page report released today, “Abusing the User: Police Misconduct, Harm Reduction and HIV/AIDS in Vancouver,” Human Rights Watch documents instances of unnecessary force and mistreatment, arbitrary arrest, and other intimidation and harassment of drug users as part of a campaign commonly referred to as Operation Torpedo. The crackdown began on April 7 in the city’s impoverished Downtown Eastside neighborhood. Though drug traffickers are the ostensible target, drug users not charged with selling drugs have been driven to places where health workers cannot reach them to ensure access to sterile syringes and other HIV prevention services.

Courage in the Face of Death: The Thai Drug Users’ Network. July 13, 2004
Thailand enjoys an international reputation as a “best practice” model in the fight against AIDS principally because of its “100 percent condom” campaign in the 1990s. This campaign engaged sex workers with the clear recognition that they were part of the solution to a growing AIDS epidemic. Drug users have not enjoyed the same recognition in Thailand.