Kratom: Mitragynine For Beginners

An organic alternative to methadone?

A disclaimer: Everything I know about kratom, I learned on the Internet and in science journals. I have no real world experience with this opiate-like plant drug, haven’t used it, don’t know very many people who have. Although it comes from a tree indigenous to Thailand and Southeast Asia, and has presumably been around forever, a recent journal article referred to kratom as “an emerging botanical agent with stimulant, analgesic and opioid-like effects.” Which makes it sound like a combination of heroin, amphetamine, and strong weed. In reality, however, it is evidently a fairly mild stimulant with additional sedative effects when the leaf is chewed. If that sounds contradictory, it is, but the overall effect is reported to be more in league with coca leaves than injected morphine. Addictive? Erowid notes that the leaves can vary widely in potency, but yes, potentially addictive. It’s not entirely surprising that kratom has been used in Asia, and increasingly in Europe and the U.S., as a self-managed treatment for pain and for opioid withdrawal. You can find kratom for sale all over the web. You will also find it in smoke shops and herbal outlets. But is any of it legal? And, as with methadone and buprenorphine: Is kratom part of the problem or part of the solution?

According to one web site maintained by kratom aficionados, the legality of kratom can be hard to determine. It is definitely illegal in Australia, Malaysia, Burma (Myanmar), and Thailand. However: “In the United States, access to county, state, and federal laws are often available online and it’s a simple matter of reading through the material (dense as it may be) to determine the actual legality of Mitragyna speciosa…. the only state where kratom is illegal in 2013 is Indiana. That’s not to say other state legislators haven’t tried to get kratom scheduled as an illicit substance. States to keep your eye on, especially if you’re a resident, are: Iowa, Hawaii, Vermont, Virginia, and Arizona. Louisiana hasn’t outright banned kratom, but they don’t allow it to be marketed as ‘for human consumption’ and thus we suggest, if you live in Louisiana, you exercise extra caution in your purchases.” In addition, you may rest assured that kratom is on the U.S. Drug Enforcement Administration (DEA) list of “Drugs and Chemicals of Concern.”

In other countries, kratom is controlled through licensing and prescription, similar in certain respects to the medical marijuana market in the United States. Nations in this category include Finland, Denmark, Romania, Germany, and New Zealand.

Kratom (Mitragyna speciosa) contains several psychoactive ingredients. The plant can be chewed, smoked, brewed into a tea—or made into an extract for sale as capsules or tablets (with accompanying arguments about “full-spectrum” extracts vs. “standardized” extracts).  According to Erowid, it is “unknown how long alkaloids retain their potency after being isolated from kratom leaves,” and furthermore, “many manufacturers are clearly exaggerating the potencies and quantities of whole leaf kratom used in their extracts.”

The leaves contain a plethora of psychoactive alkaloids, but the two primary stimulators of opioid receptors appear to be mitragynine and 7-hydroxymitragynine. These two compounds are considered to be stronger analgesics than euphorics, although users do sometimes report visual effects. Kratom is not considered toxic, but overdoses can be quite unpleasant, Erowid relates. Chronic heavy use reportedly leads to insomnia, dry mouth, constipation, and darkening of the skin.  Importantly, Erowid says they are “not aware of any cases of severe poisoning or death resulting from its use. Animal studies have found even very large doses of mitragynine (920 mg/kg) to be non-lethal.”

Last year, writer David DiSalvo, who blogs at Forbes, turned guinea pig, experimented with kratom, and blogged about the results. DiSalvo purchased an entirely legal supply of kratom—Lucky, Mayan, Nutmeg, and OnlineKratom by brand—and ran the self-experiment for a few weeks.

Here are excerpts from DiSalvo’s report: “My overall takeaway is that kratom has a two-tiered effect. Initially it provides a burst of energy very similar to a strong cup of coffee. Unlike coffee, however, the energy I derived from kratom was longer-lasting and level…. The second-tier effect was relaxing, but fell short of being sedating. I never felt sleepy while taking kratom, but I did experience a level relaxation that was pleasant, and balanced out the initial energy-boosting effects nicely.” Not surprisingly, DiSalvo’s major concern was that “it’s not easy to nail down the specific amount to take.” As for withdrawal, DiSalvo ranked it beneath caffeine withdrawal for severity.

“Having now experienced the product myself for a number of weeks,” he wrote “I can see no reason why it should be banned, or on what basis such a product would be banned if people can walk into a typical coffee shop and buy an enormous cup of an addictive substance that’s arguably more potent than any kratom available anywhere.”

In September, Larry Greenemeier examined the case for kratom legalization in an article for Scientific American that tracks the herb’s “strange journey from home-brewed stimulant to illegal painkiller to, possibly, a withdrawal-free treatment for opioid abuse.” Greenemeier interviewed Edward Boyer, director of medical toxicology at the University of Massachusetts Medical School, who first became familiar with kratom after a software engineer who had been using kratom tea for pain ended up at Massachusetts General Hospital after combining kratom with modafinil and suffering a seizure. (The case was reported in the June 2008 issue of Addiction).

According to Boyer, mitragynine “binds to the same mu-opioid receptor as morphine, which explains why it treats pain. It’s got kappa-opioid receptor activity as well, and it’s also got adrenergic activity so you stay alert throughout the day.” As if that weren’t enough, kratom also binds with serotonin receptors. “Some opioid medicinal chemists would suggest that kratom pharmacology might reduce cravings for opioids while at the same time providing pain relief. I don’t know how realistic that is in humans who take the drug, but that’s what some medicinal chemists would seem to suggest…. So if you want to treat depression, if you want to treat opioid pain, if you want to treat sleepiness, this compound really puts it all together.”

And again, unlike heroin and prescription painkillers, which can lead to respiratory difficulties and death, “in animal studies where rats were given mitragynine, those rats had no respiratory depression,” according to Boyer.

However, Boyer cautions that, like any other opioid, kratom has abuse liability. “Heroin was once marked as a therapeutic product and later was criminalized,” he reminds us. 

Photo Credit: https://hampedia.org/wiki/File:Kratom.jpg

Interview with Michael Farrell of Australia’s National Drug and Alcohol Research Centre.

On prisons, pot, and the DSM-V.

(The “Five-Question Interview” series.)

Our latest participant is Professor Michael Farrell, director of the National Drug and Alcohol Research Centre (NDARC) at the University of New South Wales in Sydney, Australia. Before that, he was Professor of Addiction Psychiatry at the Institute of Psychiatry at Kings College, London. He has been a member of the WHO Expert Committee on Drug and Alcohol Dependence since 1995, and chaired the Scientific Advisory Committee of the European Monitoring Centre on Drugs and Drug Abuse (EMCDDA) in 2008 for three years. The NDARC does a wide variety of research and data collection on drug abuse, including longitudinal studies of heroin dependence, studies on the prevalence of ADHD among addicts, and evaluation studies of inner city youth at risk. Professor Farrell is a recognized expert on drug abuse in Europe, and was kind enough to share some of his thoughts with Addiction Inbox.

1. Does the National Drug and Alcohol Research Centre (NDARC) of Australia have a specific research slant, or area or interest, or do you try to cover the waterfront?

Michael Farrell: The research base of NDARC is very broad. The Australian Federal Government provides a fifth of our funding under the National Drug Strategy and this includes a brief for national monitoring of drug trends among illicit drug users and improving the evidence base around effective treatment and prevention. Our projects cover the majority of illicit drugs as well as alcohol, prescription drugs and more recently tobacco, and we have a strong international presence through our collaborations with the United Nations, the World Health Organisation and the Global Burden of Disease project.

Our current research programs include prevention, treatment evaluation, policy, law enforcement, health economics and epidemiology. NDARC has two “Centres within the Centre”—NCPIC (see below) and the Drug Policy Modelling Program (DPMP). We have teams working with school-aged children, mothers and babies, and injecting drug users. So it would be fair to say that we are covering the waterfront!

2. You have been critical of proposed revisions in the Diagnostic and Statistical Manual of Mental Disorders (DSM), particularly as they relate to alcoholism. What do you think is going wrong, and what’s going right, when it comes to DSM-V changes?

Farrell: The change in overall terminology is probably the most controversial with the reintroduction of “addiction” into the terminology. Personally I prefer “dependence” and think the measurement of dependence has continued to improve over the years. It is important that we use terms that we can measure carefully and be confident that we are all talking the same language. Alcohol abuse and alcohol dependence have been combined into a single disorder of graded severity, the criterion reflecting substance-related legal problems has been removed, and a new diagnostic criterion representing craving has been included. Finally, new diagnostic thresholds for alcohol use disorder (AUD) have been proposed. It seems that there is strong support for the first three changes. However, there is little published literature regarding the impact of the revised diagnostic threshold. Using data from a survey of over 10,000 people in the Australian general population, Mewton and colleagues at NDARC (2010) demonstrated that the prevalence of alcohol use disorder defined according to the DSM-5 was 60 per cent higher than the prevalence of the same disorder according to DSM-IV. A disorder which increases so dramatically in prevalence after applying a new definition is surely problematic.

3. Increasingly, the study of addiction has moved away from traditional medicine and psychiatry, becoming a recognized area of study in molecular biology and neuroscience. How do you personally view this shift in emphasis toward hard science?

Farrell: In reality, no professional groups have been jumping at the chance to handle addiction problems. In the early phases of treatment development it was often religious groups and humanitarian social activist groups who pioneered helping responses for marginalised groups. As the size of the problem and response has grown, thankfully it has been possible to get mainstream health and social care professionals more involved. There is still a need for more involvement. Modern young doctors need addiction treatment skills if they are to be properly equipped to practice in the 21st century.

Greater involvement of the biological sciences in the study of addiction holds out the possibility that we might get some exciting breakthroughs in understanding of behaviour, prevention, and treatment.  Goodness knows we could do with some new breakthroughs or advances in treatment! A focus on biological sciences does not need to be at the expense of the other social and epidemiological approaches, and ideally, with further investment in research around drugs, we might better understand the interactions between genes and environment.

4. NDARC also houses the National Cannabis Prevention and Information Centre (NCPIC). What is the mission there, and do you see marijuana as an addictive drug?

Farrell: NDARC is privileged to have NCPIC funded by the Federal Government as a “Centre within a Centre” and to the best of my knowledge there is nowhere like it anywhere else in the world. The mission of NCPIC is to reduce the use of cannabis in Australia. Cannabis is the most commonly consumed illicit drug in the country, with one in three (33.5%, 5.8 million) Australians aged 14 years and older reporting having used it in their lifetime. Just over one in ten (10.3%, 1.9 million) had used it in the previous twelve months. The burden of disease associated with cannabis is substantial. I have no doubt that cannabis can result in dependence, and that the stronger, more potent forms of cannabis give rise to more physical and mental health problems. Cannabis dependence seems to occur at rates similar to alcohol, but the effects of cannabis dependence can be mild, and may be associated with otherwise high levels of social function. Equally, dependence at the severe end is associated with significant harms, including poor social functioning and reduced participation in the education and the workforce.

5. You have a long-standing interest in the question of substance abuse in the prison system. Why can’t prison officials eliminate the drug trade behind bars?

Farrell: The prison authorities cannot eliminate drugs from behind bars because nearly half of all prisoners have a history of serious drug involvement. It is no more likely that we will have a drug free prison than it is that we will have a drug free society. The serious gaps in response in prisons are often quite shocking. The near complete absence of methadone or buprenorphine treatment in American prisons is hard to understand, when you see what a great contribution US research and treatment with methadone and buprenorphine has had globally. Now there are over 300,000 people on methadone in China as part of HIV and AIDS prevention.  Most countries in Europe have methadone in their prisons, and many emerging countries have developed prison methadone programmes. But in the US there are only a handful of programmes. There is a need for real change in this area as it is an incredible gap that could be readily addressed.

Overall we still have a long way to go in building an evidenced-based approach to drug prevention and treatment. We have come a fair distance in the past twenty years, but the road remains long and winding.

Photo Credit:  http://ndarc.med.unsw.edu.au/ 

Why are Treatment Centers Afraid of Anti-Craving Medications?

Using What Works

Why do so many drug treatment centers continue to shun science by ignoring medications that ease the burden of withdrawal for many addicts? That’s the question posed in an article by Alison Knopf in the May-June issue of Addiction Professional, titled “The Medication Holdouts.”

“Nowhere else in medicine,” Knopf writes, “are the people who treat a condition so suspicious of the very medications designed to help the condition in which they specialize.”

Acamprosate, a drug used to treat alcoholism, is a good case in point. A dozen European studies examining thousands of alcohol test subjects found that the drug increased the number of days that most subjects were able to remain abstinent. But when a German drug maker decided to market the drug in the U.S., fierce advocates for drug-free addiction therapy came out in force, even though the drug was ultimately approved for use.

Disulfiram, naltrexone, acamprosate, methadone, buprenorphine—the evidence for all of them is solid. Knopf cites the case of buprenorphine:

“‘There are scores of peer-reviewed journal articles that evaluate the success of buprenorphine,’ says Nicholas Reuter, MPH, senior public health adviser in the Division of Pharmacologic Therapies at the federal Center for Substance Abuse Treatment (CSAT). ‘It's well established that the data and the evidence are there. Not treating patients with a medication consigns most of them to relapse, adds Reuter. While some opioid-addicted patients, as many as 20 percent, do respond to abstinence-based therapy, ‘That still leaves us with the 80 percent who don't,’ he says.”

Dr. Charles O'Brien, one the nation’s most respected addiction professionals and a Professor of Psychiatry at the University of Pennsylvania, is incensed that anti-craving medications are not more widely used. “It's unethical not to use medications,” he says. “This is a subject that I feel very strongly about.” O’Brien told Addiction Professional he no longer cares who he offends on the subject. “If you're discouraging people from taking medications, you are behaving in an unethical way; you are depriving your patients of a way to turn themselves around. Just because you don't like it doesn't mean you have to keep your patients away from it.”

And at the Association for Addiction Professionals, “the prevailing philosophy is pro-medication,” Knopf writes. Misti Storie, education and training consultant for the group, told Knopf that the “disconnect” at treatment centers is due to a “lack of education about the connection between biology and addiction.” Counselors working in centers that do not allow anti-craving medications are in a tough spot, Storie acknowledged.

It is continually astonishing that treatment centers--where the primary goal is supposed to be the prevention of relapse, even though the success rate remains abysmal--would spurn medications that often help to accomplish precisely that goal. Relapse rates hover around 80%, by an amalgam of estimates, so it’s not like rehabs are wildly successful at what they do. What’s really behind the resistance?

What stands between many addicts and the new forms of treatment is “pharmacological Calvinism.” I would love to claim this term as my own, but it was coined by Cornell University researcher Gerald Klerman. Pharmacological Calvinism may be defined as the belief that treating any psychological symptoms with a pill is tantamount to ethical surrender, or, at the very least, a serious failure of will. As Peter Kramer quoted Klerman in Listening to Prozac: If a drug makes you feel better, then by definition “somehow it is morally wrong and the user is likely to suffer retribution with either dependence, liver damage, or chromosomal change, or some other form of medical-theological damnation.”

Photo credit: www.life123.com

Addicted to Bad Reporting

How should we cover drug dependence?

Journalists usually learn it early: Drug stories are crime stories. Articles about alcoholism and assorted “hard” drug addictions are typically sourced by law enforcement, and the frequently lurid results tend to dump recreational, illegal, and prescription drugs into the same stew.

This is a particular problem for patients on opioid substitution therapy, who take maintenance drugs such as methadone and buprenorphine (Suboxone). Both drugs are the subject of black markets the size of which is difficult to pin down, but the vast majority of users take the drugs under medical supervision in government-supervised health and social programs.

According to the World Health Organization (WHO), it is in everybody’s interest to get this straight. The U.N. agency reports that every dollar spent on drug treatment results in a savings of $7 in health and social costs. Treatment of opioid addiction with methadone or buprenorphine is now possible in 63 countries. “Substitution maintenance therapy is one of the most effective treatment options for opioid dependence,” says WHO. Such therapies reduce “heroin use, associated deaths, HIV risk behaviors and criminal activity.”

Nonetheless, the tendency among news writers to use phrases like “fake heroin,” “drug-using criminals,” and “giving drugs to drug users” led the International Harm Reduction Association (IHRA), with sponsorship from Schering-Plough, makers of the addiction treatment drug Suboxone, to suggest media reporting guidelines in a white paper issued earlier this year. In “Addicted to News: A Guide to Responsible Reporting on Opioid Dependence and its Treatment,” the authors reviewed 53 English-language articles about substitution therapy and discovered a continuing trend toward “sensationalist ‘tabloid’ stories’” leading to a “backlash against people with the condition, or an increase or exacerbation of the problem if it is glorified or publicized by a celebrity.”

Specifically, the IHRA identifies the following problems:

--Exaggerated terminology (“magic bullet,” “junkies,” “pharmaceutical narcotics”).

--Depiction of patients as criminals rather than people with a serious condition often requiring medical treatment.

--Undue emphasis on criminal activity related to substitution therapies.

--Assumption that the treatment has failed unless the patient is drug free.

--Portrayal of medical anti-craving drugs as indistinguishable from recreational drugs.

So what can a serious journalist do about it? IHRA is glad to provide some suggestions:

DO:

--Ask yourself, “what if this was me or someone close to me?’

--Use factual and correct terminology.

--Include balanced, up-to-date local statistics on treatment programs.

DON’T:

--Depend entirely on law enforcement as story sources.

--Use exaggerated or derogatory descriptions of patients in treatment.

--Try to localize a national or international story without close attention to its relevance to the local community.

--Allow celebrity news to warp the reporting of treatments available for this serious condition.

As the IHRA tirelessly points out, when patients are effectively treated, everybody benefits.

Graphics Credit: http://asp.cumc.columbia.edu

The Perils of Polydrug Abuse

Methadone and benzodiazepines.

For patients in opiate treatment programs, benzodiazepine use represents both a barrier to recovery and a potentially life threatening situation. The combination of benzodiazepines and methadone can lead to fatal overdose.

The five most commonly prescribed benzodiazepines fall into two major categories. High potency medications include Xanax (Alprazolam), with a short half-life of six to 12 hours, and Ativan (Lorazepam), with a slightly longer half-life. The low-potency benzodiazepines are represented by the short-lived Restoril (Temazepam), and the longer-lasting Valium (Diazepam), with a half-life of 20 to 100 hours. The fifth popular benzodiazepine, Klonopin (Clonazepam) is a high-potency drug with a half-life of 18 to 50, the highest in its class. Their primary clinical uses include the treatment of anxiety disorders, insomnia, convulsions, and muscle spasms. They also find use in the treatment of acute mania, catatonia, and detoxification from alcohol.

While some patients are able to use benzodiazepines safely at low dosage for years, patients with a history of opiate addiction are a high-risk category for these medications. Tolerance develops quickly in patients who use benzodiazepines to “boost” the effect of methadone, or as a sedative during opioid withdrawal. Since high doses of benzodiazepines cause respiratory depression, even among opioid users who have developed a high tolerance to such effects, the combination increases the risk of severe intoxication, injuries, or fatal overdose.

In addition, benzodiazepines and methadone interact pharmacologically through the actions of the CYP450 liver enzyme, which detoxifies both substances. If the work load for CYP450 becomes too great, the result can be an accumulation of high levels of methadone in the body.

It has been estimated that “80 percent of benzodiazepine abuse is part of polydrug abuse, most commonly with opioids.” In a two-year study by the National Institute of Drug Abuse (NIDA), 73 per cent of heroin users also used benzodiazepines more often than weekly.

According to a recent Canadian study of 172 subjects, the reported lifetime prevalence of benzodiazepine abuse in methadone maintenance patients ranged from 67 to 94 percent, with two-thirds of the patients reporting benzodiazepine use during the past 6 months. Patients who took benzodiazepines also reported more previous opioid overdoses, according to the study. And women are more likely than men to abuse benzodiazepines. In a study by Australia’s National Drug and Alcohol Research Centre (NDARC), researchers conducting a five-year study of heroin overdoses in New South Wales found that attempted suicide by benzodiazepine overdose was more common than attempted suicide by heroin overdose.

Methadone maintenance patients need to be questioned carefully about benzodiazepine use. By doing so, physicians and other caregivers can work toward actively decreasing the likelihood of treatment failure or fatal methadone overdose.

Photo Credit: www.drug.uz