Is Kratom the CBD of Opioids?

Another bad move by the DEA
Kratom CBD Schedule 1
By on September 23, 2016

It’s been used traditionally as both a medicine and a textile. It’s reportedly helpful for treating drug addiction, and its consumption has never resulted in a documented death from toxic overdose. But the Drug Enforcement Administration (DEA) considers it a dangerous drug with no medical value.

Sound familiar?

No, this isn’t about Cannabis. This is about the leaves of a native Southeast Asian tree commonly known as “Kratom.” Its official botanical name is Mitragyna speciosa, and it’s the only natural source of opioid alkaloids other than the poppy plant and Akuamma seeds.

Mitragyna is a small genus in the Rubiaceace family, which includes coffee. Like coffee, Kratom acts as a mild stimulant, an invigorating energy supplement, but only in low doses. At higher doses, it causes a narcotic-like effect and functions as an opiate substitute.

Smoked, chewed or steeped in tea, Kratom has a long history as a folk remedy for diarrhea, muscle pain, fever, coughing, hypertension, fatigue, depression, and other ailments. In modern times it has been used to treat opiate withdrawal, anxiety, chronic pain, and to boost the endurance of manual laborers. Despite its proscribed status in several countries, Kratom is still consumed socially during community gatherings in the Asian tropics.

The unauthorized use of this herb has spread to Western societies in recent years, much to the chagrin of the DEA and the Food and Drug Administration (FDA) officials who view Kratom as a threat to public health. On August 25, 2016, the DEA announced its intention to add Kratom to the list of illegal Schedule I drugs. While this designation, for the moment, is temporary, in all likelihood it will become a permanent ban in the months ahead. (A false story on a bogus "Boston Tribune" website claimed that public protests forced the DEA to reverse course and suspend the scheduled ban.)

Not your typical painkiller

At least 25 alkaloids have been isolated from Kratom leaves. Three of these compounds directly activate opiate receptors. Mitragynine (MG), the dominant indole alkaloid found in Kratom, is responsible for much of Kratom’s analgesic activity. MG’s painkilling potency is equal to codeine. Japanese researchers reported in 2004 that MG accounted for 66 percent of a crude Kratom extract and six percent of plant material by dry weight.

It’s worth noting that pure, single-molecule MG is actually less effective as a painkiller when compared to equal amounts of MG in a whole plant Kratom extract, which contains many biologically active components, including 7-hydroxymitragynine (7-OH-MG). A potent analgesic, this compound has a high affinity for the mu-opioid receptor, but it is structurally different from other opioids. MGs don’t bind to opiate receptors like an ordinary opiate. What’s more, these promising medicinal compounds can confer novel, beneficial effects that differ from those of pharmaceutical opioids.

Preclinical research has determined that Kratom’s physiological properties are mediated by several neurotransmitter systems -- dopamine, serotonin, GABA -- in addition to its unique interactions at the opioid receptors. But MG’s painkilling activity does not directly involve the cannabinoid CB1 receptor, according to a 2012 study by Malaysian scientists.

Much like aspirin, Kratom produces an anti-inflammatory effect by suppressing prostaglandin production in the COX-2 pathway. Cannabidiol (CBD), a potent anti-inflammatory, works through similar channels. Could Kratom be the CBD of the opiate world?

Toxicology studies

In his book Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source, Robert Raffa reports that well defined studies of MG and 7-OH-MG toxicity in humans are lacking. But data from animal studies involving different dosage regimens is reassuring and calls into question the DEA’s recent decision to ban Kratom.

In rats, there was no observed toxicity following single, huge oral doses up to 806 mg/kg of MG. (CBD is also well tolerated at very high doses.) Moreover, chronic use of MG -- 30 multiple oral doses of up to 50 mg/kg per day -- did not produce any noticeable side effects. In dogs, no side effects were seen during daily oral doses of 16 mg/kg of MG per day, plus two additional days of oral 32 mg/kg per day. Transient clinical findings, primarily blood dyscrasias (a blood cell disorder), were observed with higher doses and longer exposures. At high doses MG can also produce respiratory depression in animals, but not as potently as morphine or codeine.

Although MG activates mu-opioid receptors, human Kratom ingestion is not associated with respiratory depression, pulmonary edema, coma or death. Kratom has been consumed as a beverage for centuries in the South Pacific seemingly without adverse consequences. Regular Kratom users do not appear to experience significant impairments in their social functioning.

However, there have been serious problems involving adulterants. Kratom is unlikely to be tainted in South Asian countries where residents can buy fresh Kratom juice from local producers. But adulterants are not uncommon in commercialized Kratom products -- capsules, tablets, concentrates, powder and raw leaves -- that are sold over the Internet to Western consumers. Many Kratom products are spiked with caffeine, Tramadol (a synthetic opioid pain medication) or other pharmaceuticals. Ironically, the greatest danger of Kratom these days is from fake products contaminated with substances approved by the FDA.

Kratom’s image has suffered from the unregulated distribution of dubious materials that are advertised as Kratom. Marketed under names such as “Krytpon," these adulterated products have been implicated in a number of reported fatalities. Polydrug use involving Kratom and other substances is also a serious issue. Just as combining booze with benzodiazepines can have fatal consequences, Kratom can interact in harmful ways with other drugs. Kratom, or more specifically MG, can alter the metabolism of various substances by inhibiting cytochrome P450 enzymes.

Crisis mismanagement

In February 2014, the FDA issued “Import Alert 54-15,” which gave Customs and other U.S. border agencies a green light to seize Kratom products from foreign suppliers. It also set the stage for the DEA’s recent heavy-handed move against Kratom. These official maneuvers reflect an abiding institutional prejudice against botanical remedies and products that dates back to at least the 1940’s, when dozens of medicinal plants, along with Cannabis, were removed from the U.S. Pharmacopeia.

The DEA should not be in the business of defining what is medicine and what is not. And the FDA should not be in the business of blocking access to nonlethal herbal supplements or nutritive products that could help mitigate the current opioid addiction crisis in the United States. Utilized as a natural alternative to physician-supervised opioid replacement therapy, Kratom can attenuate severe opioid withdrawal. Yet cessation of Kratom administration itself appears to be associated with only modest withdrawal discomfort.

If the DEA succeeds in misclassifying Kratom as a Schedule I substance, it will be more difficult for scientists to study its compelling components and properties. It makes little sense to criminalize the consumption of an herb that could potentially replace the use of pharmaceutical opioids for many conditions, especially at a time when opioid addiction is rampant throughout the United States, resulting in hundreds of overdose deaths every week. Kratom and its derivatives may hold the key to developing safe pain medication that is more potent than morphine with fewer unwanted side effects.

Jahan Marcu is the chief scientist of Americans for Safe Access. The information in this article is not intended to diagnose or treat any disease.

Sources

  • Boyer, Edward W et al. “Self-treatment of opioid withdrawal using kratom (Mitragyna speciosa korth).” Addiction, 2008 June.
  • Cinosi et al. “Following ‘the Roots’ of Kratom (Mitragyna speciosa): The evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.” BioMed Research International, Vol. 2015, Article ID 968786.
  • Hanapi NA et al. “Inhibitory effect of mitragynine on human cytochrome P450 enzyme.” Pharmacognosy Res, 2013 Oct-Dec.
  • Khor, Beng-Siang et al. “Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish.” PLOS One, December 2011.
  • Lu Jun et al. “Evaluation of the Cardiotoxicity of Mitragynine and Its Analogues Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.” PLOS One, Dec 23, 2014.
  • Matsumoyo K et al. “Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa.” Life Sci, 2004 March.
  • Menzies JR et al. “Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae).”Eur J Pharmacol. May 1998.
  • Pantano F et al. “Hepatoxicity Induced by ‘the 3Ks’: Kava, Kratom and Khat.” Int J of Molecular Sciences. 2016, 17, 580.
  • Raffa, Robert. Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source. CRC Press, 2014.
  • Sabetghadam A et al. “The evlautation of antinociceptivce activity of alkaloid, methanolic, and aqueous extracts of Malaysian Mitragyna speciosa Korth leaves in rats.” Pharmacognosy Res, 2010 May-June.
  • Shamima, Abdul Rahman et al. “Antinociceptive Action of Isolated Mitragyna Speciosa through Activation of Opioid receptor System.” Int. J. Mol. Sci. 2012.
  • Takayama H. “Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa.” Chem Pharm Bulletin (Tokyo). 2004 August:52(8):916-28.

Find dispensaries near you

(and delivery services)