Kratom’s Antipsychotic Potential

More Potential Benefits of Kratom Continue to Emerge

UPDATED AUGUST 17. 2020

Please see references below

Introduction

I came across an interesting article the other day from the December 6th, 2016 (volume 7) issue of Frontiers in Pharmacology. This is a peer-reviewed journal, and I try to use those as confirmation of pretty much anything I read on the internet or anywhere else really. Having a team of other published researchers in the same field approve a piece before it is published makes the data more credible. This particular study piqued my interest because, among the many other lies, our government agencies have claimed that kratom causes psychosis.

This particular study attempted to compare mitragyna speciosa to typical antipsychotics (like haloperidol) and atypical antipsychotics (like risperidone) as a potential treatment option for subjects suffering from psychosis. If effective, the big benefit would be that mainstream antipsychotic drugs are associated with lots of side effects; some of them serious and some potentially fatal. Keep in mind these drugs are approved by the FDA.

Side Effects of Traditional Antipsychotic Medications

I figure the best way to do it would probably be to start with a brief list of known adverse effects of mainstream antipsychotics (Dalpoas et al., 2018):

    • Extrapyramidal effects: dystonia (neurological condition that can leave users’ limbs literally stuck in weird positions), akathisia (uncontrollable restlessness), Parkinson’s-like symptoms, and others (Drugs.com, 2020)
    • Metabolic Syndrome, a/k/a Syndrome X: this is a collection of symptoms including elevated lipid profiles (insoluble fat in the blood that can clog arteries), insulin resistance (precursor to type 2 diabetes), increased fat around the midsection, abnormally high LDL levels (the bad type of cholesterol), high blood pressure, and low HDL levels (the good kind) (Eckel et al., 2005).
    • Anti-cholinergic effects: dysfunction of the parasympathetic nervous system (involuntary muscle movements such as in digestion or bowel motility), confusion, blurred vision, and more (Greenblatt & Shader, 1973)
    • Hyperprolactinemia: effects include loss of libido, lactation in both males and females, and infertility (Sawyers, 2018)

In The Real World

Let’s take a drug called Haloperidol for example. Haldol, which is the drug’s trade name, is known to cause tardive dyskinesia (a serious neurological condition involving uncontrollable movements all over the body) and neuroleptic malignant syndrome, which is a life threatening condition involving unstable blood pressure, stupor, and loss of autonomic function (Caroff et al., 2011).

It’s not like this is top-secret knowledge, either. This delightful excerpt was taken right from the FDA’s own database: “Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving HALDOL” (Ortho-McNeil Pharmaceutical, Inc., 2005). Atypical antipsychotic drugs are associated with transient ischemic attacks (TIAs), metabolic syndrome, tardive dyskinesia, and an increased risk of diabetes, among other things (College of Psychiatric and Neurologic Pharmacists, 2018).

Details of the Study

In the study, which was first published in the December 2016 version of Frontiers in Pharmacology, the research team created a kratom solution using methanol as the base solvent and gave it to apomorphine-induced mice to see how well the solution performed in this standard test. Apomorphine is a dopamine receptor agonist often used to treat Parkinson’s but in this case used to manufacture psychotic episodes (Zarrindast et al., 2000).

The kratom solution not only decreased the psychotic behavior of the mice, but it also improved catalepsy (muscle rigidity and limbs often being “stuck” in odd positions) in other mice that had been treated with haloperidol.

This conclusion was that mitragyna speciosa somehow regulates dopaminergic neurotransmission in the brain regions associated with psychosis. It was also shown to alleviate the symptoms of ketamine-induced social withdrawal. There was no mention of any adverse effects from the kratom concoction.

Kratom as an Antidepressant & Antipsychotic

Kratom, contains the indole alkaloids, mitragynine, which interacts with serotonin, dopamine, and alpha-2 adrenergic receptors in the human body. D2 dopamine receptors are where traditional antipsychotic medications bind in the brain. Mitragynine has been shown to bind to these receptors in the same way, acting as a dopamine antagonist.

This suggests kratom’s main alkaloid may be a potential treatment for positive symptoms of psychosis such as auditory, tactile, and visual hallucinations. One study showed that mitragynine also proposed mitragynine’s antagonism at certain serotonin receptors, also making it a potential treatment for the negative symptoms of psychosis such as lack of motivation and difficulty speaking (Vijeepallam, et al., 2016).

Regarding kratom for depression, there have been comparisons drawn between kratom and fluoxetine (Prozac) and amitriptyline (Elavil) due in part to the former’s performance on forced swimming and tail suspension tests carried out in rats. These popular experiments place rats in a forced state of despair and monitor their perseverance, put simply.

In both tests, rats dosed with mitragynine showed the same drive and persistence as those given the prescription medications. There was also a decrease in blood levels of cortisol (Idayu, et al., 2011), a major stress hormone also present in humans.

These findings were repeated in another animal study in 2006, which showed similar results on the forced swimming test. The rats showed less time in a state of immobility when faced with the challenge – a typical anti-depressive indicator. There was also no effect on locomotive behavior, which is a key property of stimulants.

NOTE: THIS IS AN ONGOING ARTICLE BEING UPDATED SPORADICALLY. CHECK BACK FOR MORE STUDY DATA

Further studies would be great to further qualify kratom’s antipsychotic and antidepressant potential. Research will go on as long as kratom remains decriminalized. Even if they do take away our right to use kratom, perhaps by turning its components into controlled, profitable, prescription medications, it’s safe to say that we will continue learning about it moving forward. The venue may just change a bit, that’s all.

So what’s the moral of the story? Your morning Green Malay your evening Red Maeng Da, or your Friday night Yellow Thai kratom is not going to make you go crazy, no matter how hard they try to convince you. In fact, it will probably help you if you’re already crazy :)!

Don’t stop following the science. Google Scholar is one source of credible information, though you need to pay attention to who funds studies and who is to benefit from the potential results as these things create an automatic bias. There’s also the Directory of Open Access Journals, which can give you a good starting point. Remember: think critically!

References

Caroff, S. N., Hurford, I., Lybrand, J., & Campbell, E. C. (2011). Movement Disorders Induced by Antipsychotic Drugs: Implications of the CATIE Schizophrenia Trial. Neurologic Clinics, 29(1), 127–viii. Retreived March 24, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018852/

Dalpoas, S. E., Peters, M. E., & Marano, C. (2018, December 3). Antipsychotics | Johns Hopkins Diabetes Guide. https://www.hopkinsguides.com/hopkins/.//view/Johns_Hopkins_Diabetes_Guide/547011/all/Antipsychotics?refer=true

Eckel, R. H., Grundy, S. M., & Zimmet, P. Z. (2005). The metabolic syndrome. The Lancet, 365(9468), 1415–1428. https://doi.org/10.1016/S0140-6736(05)66378-7

Greenblatt, D. J., & Shader, R. I. (1973). Anticholinergics. New England Journal of Medicine, 288(23), 1215–1219. https://doi.org/10.1056/NEJM197306072882306

Idayu, N. F., Hidayat, M. T., Moklas, M. a. M., Sharida, F., Raudzah, A. R. N., Shamima, A. R., & Apryani, E. (2011). Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 18(5), 402–407. https://doi.org/10.1016/j.phymed.2010.08.011

Macallis. (2013, November 13). 2.1: Extrapyramidal symptoms | Antipsychotic Agents. UNC Eshelman School of Pharmacy. https://learn.pharmacy.unc.edu/antipsy/node/39

Mayo Clinic Staff. (2017, July 11). Orthostatic hypotension (postural hypotension)—Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/orthostatic-hypotension/symptoms-causes/syc-20352548

National Alliance on Mental Illness. (2020, February). Risperidone (Risperdal). https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Risperidone-(Risperdal)

Ortho-McNeil Pharmaceutical, Inc. (2005). HALDOL ® brand of haloperidol injection (For Immediate Release). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/015923s082,018701s057lbl.pdf

Vijeepallam, K., Pandy, V., Kunasegaran, T., Murugan, D. D., & Naidu, M. (2016). Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice. Frontiers in Pharmacology, 7, 464. https://doi.org/10.3389/fphar.2016.00464

What is Hyperprolactinemia: Pituitary Tumor Center at Johns Hopkins in Baltimore, MD. (2015, October 05). Retrieved December 02, 2020, from https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/pituitary_center/conditions/hyperprolactinemia.html

Zarrindast, M.-R., Fazli-Tabaei, S., Semnanian, S., Fathollahi, Y., & Yahyavi, S. H. (2000). Effects of Adrenoceptor Agents on Apomorphine-Induced Licking Behavior in Rats. Pharmacology Biochemistry and Behavior, 65(2), 275–279. https://doi.org/10.1016/S0091-3057(99)00198-7

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