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Cognitive enhancement supplements

Cognitive enhancement supplements
Agent name Alternative name(s) listed on supplement label Proposed mechanism of activity Potential adverse effects
Vinpocetine Lesser periwinkle, Vinca minor, Cavinton, apovincaminic acid, creeping myrtle Vasodilator Flushing, headaches, and decreased blood pressure[1,2]
Picamilon N-nicotinyl-y-aminobutyric acid, pikamilon, pikamilone, pikatropin, pycamilon GABA agonist; derived from GABA May be similar to gabapentin[3]
Phenibut B-phenyl-y-aminobutyric acid, phenigam, PhGaba, Phenigamma, Phenygam, phenyl-GABA GABA-B agonist Lethargy, agitation, tachycardia, confusion, dependence. With overdose, delirium, psychosis, and coma.[4-6]
Huperzine A Huperzia serrata extract, HupA, Huperzia selago extract, Sealgine Anticholinesterase inhibitor Similar to prescription cholinesterase inhibitors (eg, GI [nausea, diarrhea, vomiting], increased urination, muscle cramps). Avoid concomitant use of prescription cholinesterase inhibitors as this increases the risk of adverse effects.[7,8]
Piracetam Barcan, Noostan, Nootrop, Nootropil, Nootropyl, Normabraïn, pyrrolidone acetamide Antimyoclonic; modulates CNS neurotransmission (eg, cholinergic and glutamatergic) Anxiety, insomnia, agitation, sleepiness, weight gain, depression[9,10]
Omberacetam Noopept, N-phenylacetyl-L-prolylglycine ethyl ester, ethyl phenylacetyl-Pro-Gl Activation of HIF 1 Unknown[11]
Aniracetam Draganon Ampakine, potentiates neurotransmission via AMPA-type glutamate receptors Unknown[11,12]
Meclofenoxate Centrophenoxine Cholinergic agent Unknown[13,14]
Levodopa L-dopa, Mucuna pruriens extract,[15] cowhage Dopamine precursor. NOTE: Limited entrance of levodopa into CNS without co-administration of peripheral dopa-decarboxylase inhibitor (eg, carbidopa). Nausea, vomiting, sleepiness, orthostatic hypotension, confusion, hallucinations
Tianeptine Coaxil, Stablon Atypical antidepressant with various CNS receptor actions Dependence and abuse potential. Agitation, drowsiness, confusion, sweating, rapid heartbeat, high blood pressure, nausea, vomiting, slowed breathing, coma, and death.[16]
Kratom Mitragyna speciosa CNS mu-opioid receptor agonist properties Dependence and abuse potential, respiratory depression, anorexia, depression, psychosis, seizures[17]
CBD Cannabidiol Unknown; appears to inhibit CNS neurotransmission; may mimic effects of endogenous cannabinoid compounds Diarrhea, somnolence, decreased appetite, increased transaminases. Potential THC and synthetic cannabinoid exposure.[18,19]
Testing of dietary supplements often reveals drugs not declared on labeling, labeled drugs/herbs not detected in the product, inaccurate quantities, and adulteration with prescription and experimental drugs. In addition, doses contained in supplements may far exceed pharmaceutical quantities, increasing the risks of adverse effects. For review of health risks and an approach to patient counseling, refer to UpToDate topic reviews of high-risk dietary supplements.
GABA: gamma-aminobutyric acid; GI: gastrointestinal; HIF: hypoxia-inducible factor; CNS: central nervous system; CBD: cannabidiol; THC: delta-9-tetrahydrocannabinol.
References:
  1. Cohen PA. Vinpocetine: An unapproved drug sold as a dietary supplement. Mayo Clin Proc 2016; 90:1455.
  2. National Toxicology Program. Chemical information review document for vinpocetine. Available at: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/vinpocetine091613_508.pdf (Accessed on July 13, 2022).
  3. Avula B, Chittboyina AG, Sagi S, et al. Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States. Drug Test Anal 2016; 8:334.
  4. Cohen PA, Ellison RR, Travis JC, et al. Quantity of phenibut in dietary supplements before and after FDA warnings. Clin Toxicol (Phila) 2022; 60:486.
  5. Graves JM, Dilley J, Kubsad S, Liebelt E. Notes from the field: Phenibut exposures reported to poison centers - United States, 2009-2019. MMWR Morb Mortal Wkly Rep 2020; 69:1227.
  6. McCabe DJ, Bangh SA, Arens AM, Cole JB. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med 2019; 37:2066.
  7. Crawford C, Wang YH, Avula B, et al. The scoop on brain health dietary supplement products containing huperzine A. Clin Toxicol (Phila) 2020; 58:991.
  8. Alzheimer's Association. Taking control: A guide for early-stage Alzheimer's disease. Available at: https://www.alz.org/media/manh/documents/alzhiemer_s-taking-control-guide-(tcg).pdf (Accessed on July 13, 2022).
  9. Winblad B. Piracetam: A review of pharmacological properties and clinical uses. CNS Drug Rev 2005; 11:169.
  10. Cohen PA, Zakharevich I, Gerona R. Presence of piracetam in cognitive enhancement dietary supplements. JAMA Intern Med 2020; 180:458.
  11. Cohen PA, Avula B, Wang YH, et al. Five unapproved drugs found in cognitive enhancement supplements. Neurol Clin Pract 2021; 11:e303.
  12. Martin JR, Haefely WE. Pharmacology of Aniracetam. Drug Invest 1993; 5:4.
  13. Zou JJ, Ji HJ, Wu DW, et al. Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study. Clin Ther 2008; 30:1651.
  14. Cohen PA, Avula B, Khan I. The unapproved drug centrophenoxine (meclofenoxate) in cognitive enhancement dietary supplements. Clin Toxicol (Phila) 2022.
  15. Cohen PA, Avula B, Katragunta K, et al. Levodopa content of Mucuna pruriens supplements in the NIH Dietary Supplement Label Database. JAMA Neurol 2022.
  16. US Food and Drug Administration. Tianeptine products linked to serious harm, overdoses, death. February 2022. Available at: https://www.fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death (Accessed on July 13, 2022).
  17. US Food and Drug Administration. FDA and kratom. Available at: https://www.fda.gov/news-events/public-health-focus/fda-and-kratom (Accessed on July 13, 2022).
  18. Rianprakaisang T, Gerona R, Hendrickson RG. Commercial cannabidiol oil contaminated with the synthetic cannabinoid AB-FUBINACA given to a pediatric patient. Clinical Toxicol (Phila) 2020; 58:215-216.
  19. Cohen PA, Sharfstein J. Perspective: The opportunity of CBD — reforming the law. N Engl J Med 2019; 381:297.
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