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

Spiced: Synthetic Cannabis Keeps Getting Stronger

Case reports of seizures in Germany from 2008 to 2011.

I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic.  I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic cannabinoids like JWH-122 and JWH-210. I wish talented chemists didn’t have to spend precious time and lab resources laboriously characterizing the various metabolic pathways of these drugs, in an effort to understand their clinical consequences. I wish Spice drugs didn’t make regular cannabis look so good by comparison, and serve as an argument in favor of more widespread legalization of organic marijuana.

A German study, published in Addiction, seems to demonstrate that “from 2008 to 2011 a shift to the extremely potent synthetic cannabinoids JWH-122 and JWH-210 occurred…. Symptoms were mostly similar to adverse effects after high-dose cannabis. However, agitation, seizures, hypertension, emesis, and hypokalemia  [low blood potassium] also occurred—symptoms which are usually not seen even after high doses of cannabis.”

The German patients in the study were located through the Poison Information Center, and toxicological analysis was performed in the Institute of Forensic Medicine at the University Medical Center Freiburg. Only two study subjects had appreciable levels of actual THC in their blood. Alcohol and other confounders were factored out. First-time consumers were at elevated risk for unintended overdose consequences, since tolerance to Spice drug side effects does develop, as it does with marijuana.

Clinically, the common symptom was tachycardia, with hearts rates as high as 170 beats per minute. Blurred vision, hallucinations and agitation were also reported, but this cluster of symptoms is also seen in high-dose THC cases that turn up in emergency rooms. The same with nausea, the most common gastrointestinal complaint logged by the researchers.

But in 29 patients in whom the presence of synthetic cannabinoids was verified, some of the symptoms seem unique to the Spice drugs. The synthetic cannabinoids caused, in at least one case, an epileptic seizure. Hypertension and low potassium were also seen more often with the synthetics. After the introduction of the more potent forms, JWH-122 and JWH-210, the symptom set expanded to include “generalized seizures, myocloni [muscle spasms] and muscle pain, elevation of creatine kinase and hypokalemia.” The researchers note that seizures induced by marijuana are almost unheard of. In fact, studies have shown that marijuana has anticonvulsive properties, one of the reason it is popular with cancer patients being treated with radiation therapy.

And there are literally hundreds of other synthetic cannabinoid chemicals waiting in the wings. What is going on? Two things. First, synthetic cannabinoids, unlike THC itself, are full agonists at CB1 receptors. THC is only a partial agonist. What this means is that, because of the greater affinity for cannabinoid receptors, synthetic cannabinoids are, in general, stronger than marijuana—strong enough, in fact, to be toxic, possibly even lethal. Secondly, CB1 receptors are everywhere in the brain and body. The human cannabinoid type-1 receptor is one of the most abundant receptors in the central nervous system and is found in particularly high density in brain areas involving cognition and memory.

The Addiction paper by Maren Hermanns-Clausen and colleagues at the Freiburg University Medical Center in Germany is titled “Acute toxicity due to the confirmed consumption of synthetic cannabinoids,” and is worth quoting at some length:

The central nervous excitation with the symptoms agitation, panic attack, aggressiveness and seizure in our case series is remarkable, and may be typical for these novel synthetic cannabinoids. It is somewhat unlikely that co-consumption of amphetamine-like drugs was responsible for the excitation, because such co-consumption occurred in only two of our cases. The appearance of myocloni and generalized tonic-clonic seizures is worrying. These effects are also unexpected because phytocannabinoids [marijuana] show anticonvulsive actions in humans and in animal models of epilepsy.

The reason for all this may be related to the fact that low potassium was observed “in about one-third of the patients of our case series.” Low potassium levels in the blood can cause muscle spasms, abnormal heart rhythms, and other unpleasant side effects.

One happier possibility that arises from the research is that the fierce affinity of synthetic cannabinoids for CB1 receptors could be used against them. “A selective CB1 receptor antagonist,” Hermanns-Clausen and colleagues write, “for example rimonabant, would immediately reverse the acute toxic effects of the synthetic cannabinoids.”

The total number of cases in the study was low, and we can’t assume that everyone who smokes a Spice joint will suffer from epileptic seizures. But we can say that synthetic cannabinoids in the recreational drug market are becoming stronger, are appearing in ever more baffling combinations, and have made the matter of not taking too much a central issue, unlike marijuana, where taking too much leads to nausea, overeating, and sleep.

(See my post “Spiceophrenia” for a discussion of the less-compelling evidence for synthetic cannabinoids and psychosis).

Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B. & Auwärter V. (2013). Acute intoxication by synthetic cannabinoids - Four case reports, Drug Testing and Analysis,   n/a-n/a. DOI: 10.1002/dta.1483

Graphics Credit: http://www.aacc.org/

State Marijuana Legalization: The Opposing Voices

Repeating Our Alcohol Mistakes?

A recent article in the always insightful Alcoholism and Drug Abuse Weekly, edited by Alison Knopf, concerns itself with the voices speaking out against Attorney General Holder’s announcement that federal authorities would not interfere with state efforts to legalize marijuana. It’s no secret that we here at Addiction Inbox have been longtime advocates for decriminalization along Dutch lines. So it’s high time we heard from some prominent dissenters on this issue.

Kevin A. Sabet, Ph.D., director of Project SAM (Smart Approaches to Marijuana) and former White House advisor on marijuana policy: “It’s the same thing with alcohol:  The marijuana industry is giving lip service, saying that they don’t want kids to use.”

Sue Thau, public policy consultant for Community Anti-Drug Coalitions of America (CADCA): “This is the start of Big Marijuana the way we have Big Alcohol and Big Tobacco…. Anyone who cares about addiction has to care about this.”

Rafael Lemaitre, spokesman for the Office of National Drug Control Policy: “We know that marijuana use, particularly long-term, chronic use that began at a young age, can lead to dependence and addiction. Marijuana is not a benign drug, and we continue to oppose marijuana legalization because it runs counter to a public health approach to drug policy.”

Gen. Arthur T. Dean, CEO of Community Anti-Drug Coalitions of America (CADCA): "This decision sends a message to our citizens, youth, communities, states, and the international community at large that the enforcement of federal law related to marijuana is not a priority."

The article is entitled “Advocates dismayed as legalization moves forward.”

Here are a few I have come across recently from other sources:

Citizens Against Legalizing Marijuana (CALM): "After decades of study the FDA continues to reaffirm that there is no medical benefit provided by the use of smoked marijuana and that, in fact, considerable harm can be caused by such use. We affirm the 2006 FDA finding and vast scientific evidence that marijuana causes harm. The normalization, expanded use, and increased availability of marijuana in our communities are detrimental to our youth, to public health, and to the safety of our society."

Office of National Drug Control Policy: "The Office of National Drug Control Policy is working to reduce the use of marijuana and other illicit drugs through development of strategies that fully integrate the principles of prevention, treatment, recovery, and effective supply reduction efforts. Proposals such as legalization that would promote marijuana use are inconsistent with this public health and safety approach.... Marijuana use is associated with dependence, respiratory and mental illness, poor motor performance, and impaired cognitive and immune system functioning, among other negative effects."

CNBC: "Contrary to the beliefs of those who advocate the legalization of marijuana, the current balanced, restrictive, and bipartisan drug policies of the United States are working reasonably well and they have contributed to reductions in the rate of marijuana use in our nation.... The rate of current, past 30-day use of marijuana by Americans aged 12 and older in 1979 was 13.2 percent. In 2008 that figure stood at 6.1 percent. This 54-percent reduction in marijuana use over that 29-year period is a major public health triumph, not a failure."


Photo Credit: LARRY MAYER/Billings Gazette Staff