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. Also check out SelfDecode, all you need is your ancestry DNA from 23andMe and a subscription to SelfDecode to discover the genes that may be affecting your health and well-being.
- What Is Kratom?
- Mechanism of Action
- Positive Kratom Effects
- Negative Effects of Kratom
- Risk of Kratom Addiction and Withdrawal
- Drug Interactions
- Can You Overdose on Kratom?
- User Experiences
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).
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 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?
Mechanism of Action
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].
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.
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 reduce social anxiety [R].
Both low and high doses of mitragynine in rats effectively reduced anxiety [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)
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
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 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:
- Headache [R]
- Nausea [R]
- Chills/sweats [R]
- Dizziness [R]
- Vomiting [R]
- Anorexia [R]
- Dry-mouth [R]
- Increased production of urine (diuresis) [R]
- Increased heart rate and blood pressure [R]
- Respiratory depression [R]
- Posterior reversible leukoencephalopathy syndrome (headache, confusion, seizures, and visual loss) [R]
- Liver toxicity [R]
- Constipation [R]
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
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].
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].
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.
- 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].
- Rapid heart rate (tachycardia)
- Agitation or irritability
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].
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.
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