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      The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research

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          Abstract

          Rationale

          Consideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health.

          Objective

          The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA.

          Results

          Kratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems.

          Conclusions

          Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist. Furthermore, appropriate regulation by FDA is vital to ensure appropriate and safe use.

          Electronic supplementary material

          The online version of this article (10.1007/s00213-017-4813-4) contains supplementary material, which is available to authorized users.

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          Most cited references76

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          International society of sports nutrition position stand: caffeine and performance

          Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance.
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            Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?

            Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.
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              Emergency Department Visits for Adverse Events Related to Dietary Supplements.

              Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited.
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                Author and article information

                Contributors
                301-718-8440 , jhenning@pinneyassociates.com
                rfant@pinneyassociates.com
                dwang@pinneyassociates.com
                Journal
                Psychopharmacology (Berl)
                Psychopharmacology (Berl.)
                Psychopharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0033-3158
                1432-2072
                23 December 2017
                23 December 2017
                2018
                : 235
                : 2
                : 573-589
                Affiliations
                [1 ]Research, Health Policy and Abuse Liability, Pinney Associates, 4800 Montgomery Lane, Suite 400, Bethesda, MD 20814 USA
                [2 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Psychiatry and Behavioral Sciences, , The Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                Article
                4813
                10.1007/s00213-017-4813-4
                5813050
                29273821
                23613a4c-03c4-41c2-a696-ed1e77d487e2
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 19 July 2017
                : 6 December 2017
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Pharmacology & Pharmaceutical medicine
                kratom,mitragynine,abuse potential,controlled substances act,food and drug administration,analgesic,opioid,withdrawal,dependence,dietary ingredient

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