Kratom, the controversial plant consumed for centuries for its stimulant properties, has recently been the topic of an FDA public health advisory addressing the deadly risks of its use. Kratom may help relieve pain, improve mood, combat anxiety and depression, and decrease inflammation. Read on to learn more about the potential benefits and side effects of this plant.

Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

What Is Kratom?

You may know Kratom by its street names: Thang, Kakuam, Thom, Ketum, Biak-Biak, and Krypton (this one also contains O-Desmethyltramadol).

Kratom (Mitragyna speciosa) is an evergreen deciduous tree native to Southeast Asia. It is part of the coffee (Rubiaceae) family [R].

It grows naturally in Thailand, Malaysia, Indonesia, and Papua New Guinea [R].

Kratom leaves have been used for centuries by natives of Southeast Asia for their stimulant properties. Kratom reportedly reduces fatigue during manual labor and extreme heat. It may also treat muscle pain, gut infection, coughing, and diarrhea [R, R, R, R].

In addition, it has been used for self-treatment of opiate addiction [R].

However, kratom has since transitioned to a recreational drug in both Southeast Asian and Western contexts [R].

Kratom inhibits the sensation of pain (anti-nociceptive, sensory neurons block pain stimulus) and has euphoric, anti-inflammatory, anti-depressant, and muscle relaxant properties [R].

Kratom is widely available via online stores in the form of a powder, extract, pill, or dried leaves [R].

A cross-sectional survey in the United States identified the most commonly consumed form to be kratom powder with a beverage or food [R].

Kratom is currently legal in the United States, however, the FDA released an advisory regarding the associated deadly risks in November 2017 [R].

What Are the Effects of Kratom?

Users report that euphoria can be achieved within 5 to 10 minutes of chewing the leaves and can last up to 1 hour [R, R].

Kratom functions as a depressant with reports of “morphine-like” sedation and nausea at high doses and a “cocaine-like” stimulant at low doses [R].

Mechanism of Action

Over 25 compounds have been identified in kratom extract. The active ingredients are mitragynine and 7-hydroxymitragynine [R, R].

Mitragynine is the most abundant alkaloid and a partial opioid receptor activator (agonist). It targets a portion of the brain that responds to opioids, having similar effects to morphine [R, R, R].

The minor alkaloid, 7-hydroxymitragynine, is considered to be more potent than morphine [R, R].

These active alkaloids act on the mu (MOR), delta (DOR), and kappa (KOR) opioid receptors, and the alpha 2 adrenergic and 5-HT2A receptors to produce pain relief (analgesia) and euphoria [R, R, R, R, R].

Kratom extract may also activate dopamine D1 receptors (DRD1) [R].

The activity of these receptors improves mood and lowers anxiety.

Changes in the body in response to these alkaloids include secretion of stomach acid and inhibition of contraction of a portion of the small intestine (ileum) and male reproductive system (vas deferens) [R, R].

Positive Kratom Effects

1) Kratom May Aid with Pain Management

In an online survey of kratom users, pain relief was the most reported beneficial effect of this plant [R].

Although no well-controlled human studies have been published, animal studies show that kratom extract improves various forms of pain.

Mitragynine and 7-hydroxymitragynine relieved and blocked pain (they were analgesic and anti-nociceptive) in animals, with opioid-like effects observed in organ samples [R, R].

Animals given kratom extracts demonstrated decreased (nociceptive) responses to harmful stimuli such as the hot plate, tail-flick, and acetic acid-induced writhing tests [R, R].

High doses of kratom in rats reduce muscle and nerve function by blocking the exposed sciatic nerve response to electrical stimulation at the nerve-muscle junction [R, R].

2) Kratom May Help with Anxiety and Depression

In a 2016 online sectional survey in the US, 66% of the participants used kratom for mental conditions including depression and anxiety [R].

In particular, people report that kratom helps to reduce social anxiety [R].

Both low and high doses of mitragynine in rats effectively reduced anxiety [R].

Antidepressant-like effects are seen in numerous animal models of depression. These are primarily based on kratom’s action on opioid receptors [R, R, R].

Both animal and cell-based experiments show mitragynine also interacting with adrenergic and serotonergic receptors. These non-opioid receptors are common targets of antidepressant drugs and may contribute to the antidepressant effects of kratom [R].

No well-controlled human clinical trials have confirmed these findings.

3) Kratom May Boost Energy (in Low Doses)

In a cross-sectional survey of 293 northern Malaysian users, kratom was used to enhance physical energy by 27 to 28% of medium- and long-term users [R].

Many of these people used kratom to enhance work performance and consumed it as an “energy-boosting drink” [R].

In addition, an online survey identified increased energy as one of the most reported benefits of the substance [R].

According to a review of animal and human studies, kratom causes stimulant effects and holds off fatigue [R].

In rats, a low dose of mitragynine caused non-stop movement (hyperactivity), characteristic of increased physical energy [R].

4) Kratom May Cause Euphoria

In an analysis of 120 journal articles ranging from animal to human studies, euphoria was one of the kratom’s more reported effects [R].

However, only 6% to 12% of 136 active users in northern Malaysia reported euphoria as a reason they use kratom [R].

Euphoria is also connected to kratom’s addiction potential.

In a case report, a 44-year-old patient required a dose increase from 4 g to 8 g twice daily to experience the desired euphoria [R].

5) Kratom May Help in Opiate Withdrawal

Kratom has been used as an opium substitute since the 19th century [R].

At high doses, kratom induces a “morphine-like” effect of calmness (sedation) [R].

Opioid abusers resort to kratom for self-treatment of addiction and to relieve symptoms of withdrawal. For now, kratom is easy to buy, requires no medical prescription, and is less expensive than other opioid replacement treatments (e.g., buprenorphine, methadone) [R].

Mechanistically, kratom (mitragynine and 7-hydroxymitragynine) may reduce symptoms of opiate withdrawal by interacting with opioid receptors (MOR and DOR); descending serotonin, norepinephrine, dopamine (monoaminergic) projections, primarily in the brain stem; and by blocking neuron calcium channels [R, R].

6) Kratom May Promote Relaxation (in High Doses)

Users report feelings of relaxation and tiredness after consumption of a higher dose of kratom [R].

Multiple animal studies show that kratom extract and mitragynine both decrease muscle twitch, highlighting their direct effect on muscle relaxation [R, R].

7) Kratom May Decrease Inflammation

Mitragynine, the main active ingredient of kratom, decreased inflammation (by inhibiting the bacterial endotoxin/LPS-stimulated production of COX-2 and PGE2) in response to an immune stimulant [R, R].

Negative Effects of Kratom

1) Kratom May Impair Learning and Memory

Although no well-controlled human studies have been published, animal studies show that chronic mitragynine treatment impairs learning and memory [R, R].

In mice and rat models, mitragynine caused cognitive impairments. It hindered the ability to avoid a response that routinely leads to punishment (passive avoidance learning), and memory maintenance and retrieval [R].

2) Kratom May Cause Liver Damage

In a case report, a young male kratom user developed jaundice and pruritus and had alkaloids in his urine sample after 2 weeks of use. These clinical signs indicate an inability of the liver to cleanse the body of the alkaloids and correlate with liver damage (intrahepatic cholestasis) [R].

Kratom use may be linked to cholestatic liver injury. In another case report, a middle-aged man who used a low dose of kratom for 3 months developed jaundice and liver abnormalities. Interestingly, his jaundice reversed upon withdrawal and reappeared upon resuming consumption of kratom [R].

Mitragynine inhibits three liver cytochrome P450 enzymes (CYP2C9, CYP2D6, and CYP3A4) necessary for the breakdown of drugs and toxins. Without these, the liver’s alternate detoxification pathways can become overtaxed [R].

Other Side Effects

Side effects of kratom use can include:

With the exception of diarrhea, an online survey of American users shows that all negative effects are dose-dependent. Therefore, lower doses (< 5 g) are less likely to cause negative effects [R].

Risk of Kratom Addiction and Withdrawal

The euphoric feeling of being “high” can urge users to continuously consume kratom, leading to potential addiction [R, R, R].

In animal studies where kratom was administered for 5 days or longer, the animals developed a physical dependence –  addiction. Withdrawal symptoms similar to opioid withdrawal were also observed [R, R, R].

Animals withdrawing from chronic mitragynine treatment had symptoms of opioid-like withdrawal, including movement hypersensitivity to other drugs or stimulation, and enhanced anxiety [R].

Severe human side effects associated with withdrawal may occur with chronic use. These side effects include aggression, hostility, anxiety, loss of libido, muscle aches, severe weight loss, and insomnia [R, R].

Confusion and delusion were also reported [R].

Hyperpigmentation of the face and cheeks can occur after chronic kratom use because mitragynine can increase the melanocyte-stimulating substance, melanin [R].

Long-term users appear thin with swollen stomachs, unhealthy complexions, dark lips, and dry skin [R, R].

Drug Interactions

There is potential for drug interaction when mitragynine and 7-hydroxymitragynine are co-administered with drugs that get broken down by P-glycoprotein (e.g. colchicine, tacrolimus, and quinidine) or UG72B7 [R, R].

Lab experiments show that kratom extracts block select CYP enzymes (CYP3A4, CYP2D6, CYP1A2) necessary for drug metabolism, which may result in interactions with prescription and over-the-counter medications [R].

These drug interactions can result in a build-up of the active constituents of kratom and other drugs, contributing to liver damage [R].

Sources

Kratom leaves and smaller stems can be consumed fresh by chewing, or dried and smoked, steeped in water, prepared as an extract or a crushed powder in the form of an herbal supplement [R].

Two different leaf varieties are common, the red vein and white vein variety [R].

Originating in Bali, the red variety is recommended to alleviate pain, while white veined varieties originating from Malaysia are reported to generate a strong stimulant effect.

The chemically-based potency of different variants is unknown, given that they are not regulated by the FDA, thus need not be documented.

Dosage

Kratom effects are dose-dependent [R, R]:

  • Low to moderate (1 to 5 g) doses result in mild stimulant effects
  • Moderate to high (5 to 15 g) doses cause opioid-like effects (analgesia, euphoria)
  • Very high (> 15 g) doses result in sedating effects

Can You Overdose on Kratom?

Kratom is on the DEA’s list of drugs of concern due to its potential toxicity and risk of overdose. An increase from 26 to 263 calls to poison centers associated with kratom use occurred between 2010 and 2015, with more than 40% of the calls ranked as serious or life-threatening cases [R, R, R].

Signs and symptoms of kratom overdose include [R, R]:

The risk of overdose is increased with co-consumption of alcohol and other drugs (ex.: benzodiazepines, narcotics) [R].

Additional substances were present in the blood and urine samples and contributed to the deaths of 9 kratom overdose victims in a study between 2009 and 2010 [R].

An animal toxicity study demonstrated that mitragynine had relatively low toxicity [R].

However, two rat studies that orally administered a high dose of 200 mg/kg of kratom extract resulted in death [R, R].

User Experiences

A qualitative analysis of kratom user’s first-hand experiences highlighted themes of pain relief, better mood, reduced anxiety, and potential for management of opioid withdrawal. Negative response themes were also noted, such as vomiting and kratom dependency [R].

User experiences from online blogs note that kratom is great for pain relief without feeling spacey, and helps maintain a clear head for a few hours. If too large a dose is taken, nausea, vomiting, and sleepiness are common side effects. One user highly recommended kratom for those self-treating opiate withdrawal.

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

HOW WOULD YOU RATE THIS ARTICLE?

1 Star2 Stars3 Stars4 Stars5 Stars (22 votes, average: 4.64 out of 5)
Loading...

Why did you dislike this article?

TWEET
0