Kratom and Addiction: Is Kratom Addictive?

kratom and addiction

ETHA Co-founders, Alexander Karp and Victor Chung, discuss kratom tolerance and addiction:

Is Kratom Addictive?

While millions of people across the world for hundreds of years have safely benefited from regular kratom use, the questions still arises “is kratom addictive?”

Dr. Scott E. Hemby, Professor and Chair of the Department of Basic Pharmaceutical Sciences at the Fred Wilson School of Pharmacy at High Point University response “To answer the question if kratom is addictive, we look at its origin. Kratom is different in its origin, chemistry and biological effects.  Kratom does not show toxicity and does not cause respiratory depression issues. When you use kratom in the common, raw, natural plant form, it does not produce hyper pleasurable euphoric effects that lead to abuse and addiction.”

This is an important study that addresses the addictiveness of kratom,” says Jack E. Henningfield, Ph.D., at Pinney Associates, a health consulting firm. “It shows that the major naturally occurring constituent responsible for the health-related effects of kratom, mitragynine, is of very low abuse potential. A second substance, 7-hydroxymitragynine (7-HMG), has higher abuse potential, but which naturally occurs at such low levels in kratom that it might be of minimal health consequence. This has at least two regulatory implications. First, the findings do not support the FDA’s claim that kratom is a narcotic-like opioid. Second, in regulating kratom products, the FDA could set standards to ensure that no kratom product contain levels of 7-HMG exceeding those that are commonly present in kratom leaves and products.”

Dangers of Synthetic Opioids

Provisional data from CDC’s National Center for Health Statistics indicate that there were an estimated 100,306 drug overdose deaths in the United States during 12-month period ending in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before.  The data documents that estimated overdose deaths from opioids increased to 75,673 in the 12-month period ending in April 2021, up from 56,064 the year before. In 2015, the American Society of Addiction Medicine (ASAM) reported that individuals overdosing from prescription pain relievers like fentanyl, oxycodone, and hydrocodone accounted for 20,101 deaths during the year of 2015. The increase in the number of deaths from prescription pain relievers in the last several years is alarming.

Long-term synthetic opioid use can be very dangerous and even fatal. However, those that suffer from chronic pain could potentially benefit significantly from opioids. This is the paradox. To get the benefits while preventing the risk from synthetic opioids, the solution may be to look at plants like kratom, nature’s alternative to synthetic opioids.

What is Addiction?

The danger of opioids lies in their potential to be chemically addictive. What is addiction? According to American Society of Addiction Medicine, “addiction is characterized by the inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response.  Addiction is caused by a chronic disease of brain reward, motivation, memory and related circuitry. Addiction affects neurotransmissions and interactions within reward structures of the brain.”  In other words, when someone is addicted to a substance, they are willing to harm or compromise themselves and loved ones to use the substance again.

Don’t forget to read: How much kratom should you take

Opioids can be addictive because of their destructive influence on the brain’s reward system.  A properly functioning reward system motivates repeated behaviors  that cause a person to thrive (eating and spending time with loved ones), causing a release of dopamine. Dopamine is a neurotransmitter present in regions of the brain that regulate movement, emotion, cognition, motivation, and feelings of pleasure. Opioids can overstimulate the reward system, flooding it with dopamine producing euphoric effects and the desire for more opioids, which in turn can lead to addiction.


Tolerance Build-Up - Beta Arrestins

One of the ways our system tries to prevent our receptors from overactivation by chemicals like synthetic opioids, is by releasing arrestins.  Arrestins are proteins thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals.  In other words, arrestins bind to receptors to help prevent other chemicals from attaching to the receptors and activating them.  They are like plugs in a hole.  Opioids can recruit beta arrestins which reduce their ability to fire the receptor.  The problem is individuals who previously have used opioids, desire the same euphoria and reward, but cannot get it because of the buildup of beta arrestins.  They now have to increase their dosage to overcome the arrestins.  This is what we call drug tolerance.

This is very dangerous because the higher the use of opioids the higher the risk of respiratory depression.  In other words, the more opioids you use, the higher the chance you experience respiratory depression which means you stop breathing and can die.  Respiratory depression is the leading cause of death from opioids.


All-Natural Bio-Active Alkaloids

Unlike opioids, kratom is a plant that receives its incredible benefits from several bio-active alkaloids. Bio-active alkaloids are nitrogenous organic compounds originating in plants that have pronounced physiological actions on humans.  Laboratory research has been able to identify over 40 different alkaloids within the kratom plant. 

One of the most well known alkaloid in kratom is mitragynine. Mitragynine is a partial opioid-receptor agonist.  An agonist is a chemical that binds to a receptor to activate it.  In this case, mitragynine is a partial agonist to the µ-opioid (Mu) receptor which can produce analgesic properties also known as pain relief.  This is one of the main reasons people can experience significant pain relief with kratom.  There are other active alkaloids within kratom such as 7-hydroxymitragynine, speciogynine, and paynantheine. These alkaloids are being researched for their role in relieving pain, increasing blood flow, improving the immune system, inflammation reduction, muscle relaxation and supporting healthy responses to stress.†


Different from Opiates

How are kratom’s bio-active alkaloids different from opiates?  The answer lies in the chemistry and science. There are three opioid receptors that help manage pain: µ (Mu), δ (Delta), and κ (Kappa) opioid receptors. Opiates can be agonist on all three receptors which means they activate all of them.  When all three receptors are activated, dopamine is released creating euphoria and reinforcing the need for more of the same chemical that activated the receptors. The increase in dopamine and resulting euphoria can create addiction.

Kratom is different in that the known alkaloids are only partial agonist on the Mu receptor.  This means that kratom activates the receptor to create analgesic effects or pain relief, but does not aggressively bind to the receptor.  Also, some of kratom’s alkaloids may be antagonist to the Delta and Kappa receptors which means they block those receptors.  The Kappa receptor manages dopamine and serotonin.  Kratom alkaloids’ ability to block the Kappa receptor can limit the chemical reward of using kratom and thereby prevent addiction.  The Delta receptor rewards the use of the Mu receptor. So again, blocking it prevents dopamine and serotonin from flooding your system.

Another way opiates are different from kratom’s alkaloids is the way they impact tolerance buildup. Opiates can recruit beta arrestins to the opioid receptors. This makes it harder and harder to activate them unless you use more of the drug.  The known alkaloids in kratom do not recruit beta arrestins.  This means kratom does not have the same issues of tolerance buildup as you would with pharmaceutical pain relievers.  


Is there an amount of Kratom Tablets you can use where the reward system is activated and chemical reinforcement happens in the brain?  Yes.  According to Pinney Associates’ Assessment of Kratom under the CSA Eight Factors and Scheduling Recommendation study, “a human would need to consume over 1,200 grams of kratom leaves (or extract) to obtain a reinforcing effect (typical dose is 2-3 grams). Kratom leaves also contain smaller quantities of other alkaloids including 7OH-MG, which is more potent at the Mu opioid receptor. However, you have to consume very large quantities of kratom to even see the levels of withdrawal seen in rats in this study.”

In other words, addiction and withdraw, which we commonly associate with opioids, are not typically associated with all-natural kratom use. Kratom can become an issue when used in abnormal, very large quantities, combined with other drugs known to be addictive and dangerous, is adulterated, or certain kratom alkaloids are extracted and used at large quantities.

What makes kratom so special is the low to non-existent potential for abuse. Users who take too much kratom often experience diminishing returns after exceeding certain usage threshold further reducing kratom’s abuse potential. In fact, taking too much kratom can lead to temporary nausea, irritability, and sometimes dysphoria. For this reason, there is little reward for purposefully choosing to take more kratom than what is advisable.


Is Kratom Addictive?

When you use kratom in its natural form, the likelihood of addiction is very minimal. However, the potential for benefits is very high.  When looking at the likelihood of abuse, the scientific mechanism of kratom’s alkaloids and the diminishing returns of higher quantities of use minimize the possibility of abuse.  The potential for improvements in health and general well-being reinforce more long-term use of kratom.  Like exercise, meditating, and a proper diet, kratom can be a positive habit.  

As always, ETHA encourages you to do your own research, connect with others experienced with natural medicines, and stay informed about your health.


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