Abstract
Introduction: The use of psychoactive substances (PAS) represents a serious public health problem both in Colombia and worldwide. In recent years, there has been an accelerated growth in the PAS market, linked to the presence of new substances with increasingly potent and unpredictable effects. An interdisciplinary approach was carried out with the objective of identifying mechanisms of action, effects that these substances have on the Central Nervous System (CNS), compromised neurotransmission pathways, and associated neuropsychiatric alterations.
Materials and methods: A narrative review was carried out based on the 6 groups of new PAS reported by the United Nations Office on Drugs and Crime (UNODC).
Results: As of June 2025, 123 new substances have been detected, belonging to the following groups: stimulants, synthetic opioid receptor agonists, synthetic cannabinoid receptor agonists, dissociatives, classic hallucinogens, and sedatives/hypnotics.
Discussion: Alterations in neural networks related to reward, emotional regulation, memory, learning, and executive control have been reported, favoring the emergence of behavioral disorders and impairment in different spheres of human interaction.
Conclusion: Molecular detection of new substances continues to be a challenge, as they are combined with opiates or other substances to potentiate their effects, hence clinical signs of intoxication, withdrawal and behavioral changes are critical to provide timely and effective treatment.
References
United Nations Office on Drugs and Crime. United Nations: Office on Drugs and Crime [internet]. Viena: UNODC. [citado 2025 jun. 27]. https://www.unodc.org/
UNODC Laboratory and Scientific Service. Seis nuevas sustancias psicoactivas en revisión crítica por el 46º Comité de Expertos en Farmacodependencia [internet]. Viena: UNODC; 2023 [citado 2024 mzo. 8]. https://www.unodc.org/LSS/Announcement/Details/5386afdf-a42d-460a-b5c3-ab3b8ab17550
Oficina de las Naciones Unidas contra la Droga y el Delito en México. Drogas sintéticas: una carrera contra nuevas sustancias [internet]. Viena: UNODC; 2021 [citado 2024 mzo. 26]. https://www.unodc.org/lpomex/es/noticias/mayo-2021/25_05_21_drogas-sintticas_-una-carrera-contra-nuevas-sustancias.html
Ministerio de Justicia y del Derecho. Sustancias psicoactivas [internet]. Bogotá: MinJusticia. [citado 2024 mzo. 20]. https://www.minjusticia.gov.co/programas-co/ODC/Paginas/Sustancias-Psicoactivas.aspx
Ministerio de Justicia y del Derecho. Estudio Nacional de Consumo de Sustancias Psicoactivas 2019 [internet]. Bogotá: MinJusticia; 2019. [citado 2025 jun. 28]. https://www.minjusticia.gov.co/programas-co/ODC/Documents/Publicaciones/Consumo/Estudios/estudio%20Nacional%20de%20consumo%202019v2.pdf
Departamento Administrativo Nacional de Estadística. Encuesta Nacional de Consumo de Sustancias Psicoactivas (ENCSPA) [internet]. Bogotá: DANE; 2019 [citado 2025 jun. 28]. https://www.dane.gov.co/files/investigaciones/boletines/encspa/bt-encspa-2019.pdf
United Nations Office on Drugs and Crime. The challenge of new psychoactive substances: a technical update 2024 [internet]. Viena: UNODC; 2024 [citado 2025 jun. 27]. https://www.unodc.org/documents/scientific/The_Challenge_of_NPS_A_technical_update_2024.pdf
World Health Organization. Critical review report: bromazolam [internet]. Ginebra: WHO; 2024 [citado 2024 mar 1]. https://cdn.who.int/media/docs/default-source/46th-ecdd/bromazolam_46th-ecdd-critical-review_public-version.pdf
Orsolini L, Corkery JM, Chiappini S, Guirguis A, Vento A, De Berardis D, et al. “New/Designer Benzodiazepines”: An Analysis of the Literature and Psychonauts’ Trip Reports. Curr Neuropharmacol. 2020;18(9):809-37. https://doi.org/10.2174/1570159x18666200110121333
Oficina de las Naciones Unidas contra la Droga y el Delito. Drogas sintéticas y nuevas sustancias psicoactivas en América Latina y el Caribe 2021 [internet]. UNODC; 2021 [citado 2025 jun. 28]. https://www.unodc.org/documents/scientific/Synthetic_Drugs_and_NPS_in_Latin_America_and_the_Caribbean_2021_SP.pdf
Zawilska JB, Wojcieszak J. An expanding world of new psychoactive substances-designer benzodiazepines. Neurotoxicology. 2019;73:8-16. https://doi.org/10.1016/j.neuro.2019.02.015
Salud y Fármacos. Boletín Fármacos: Farmacovigilancia. 2024;27(1). [citado 2024 mzo. 3]. https://zenodo.org/doi/10.5281/zenodo.10637795
Koch K, Auwärter V, Hermanns-Clausen M, Wilde M, Neukamm MA. Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: pharmacokinetic data. Drug Test Anal. 2018. https://doi.org/10.1002/dta.2391
Graddy R, Buresh ME, Rastegar DA. New and emerging illicit psychoactive substances. Med Clin North Am. 2018;102(4):697-714. https://doi.org/10.1016/j.mcna.2018.02.010
National Institute on Drug Abuse. Catinonas sintéticas (“sales de baño”) [internet]. Maryland: NIDA. [citado 2024 mzo. 15]. https://nida.nih.gov/es/areas-de-investigacion/catinonas-sinteticas-sales-de-bano
Walther D, Shalabi AR, Baumann MH, Glennon RA. Systematic structure-activity studies on selected monosubstituted synthetic methcathinone analogs as monoamine transporter releasing agents. ACS Chem Neurosci. 2019;10(1):740-5. https://doi.org/10.1021/acschemneuro.8b00524
Wojcieszak J, Kuczy?ska K, Zawilska JB. Four synthetic cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-?-Pyrrolidinopentiophenone, and 4-Methoxy-?-Pyrrolidinopentiophenone produce changes in the spontaneous locomotor activity and motor performance in mice with varied profiles. Neurotox Res. 2020;38(2):536-51. https://doi.org/10.1007/s12640-020-00227-8
PubChem. Dipentylone [internet]. Maryland: National Center for Biotechnology Information. [citado 2024 mzo. 9]. https://pubchem.ncbi.nlm.nih.gov/compound/119057570
Wang PF, Neiner A, Lane TR, Zorn KM, Ekins S, Kharasch ED. Halogen substitution influences ketamine metabolism by cytochrome P450 2B6: in vitro and computational approaches. Mol Pharm. 2019;16(2):898-906. https://doi.org/10.1021/acs.molpharmaceut.8b01214
Agualongo Amangandi JD, Robalino Robayo DI. Consecuencias del consumo de drogas en las funciones ejecutivas en adolescentes y jóvenes adultos. Rev Scientific. 2020;5:127-45. https://doi.org/10.29394/Scientific.issn.2542-2987.2020.5.E.6.127-145
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5.a ed. Arlington: APA; 2014.
Antón-Galindo E, Cabana-Domínguez J, Torrico B, Corominas R, Cormand B, Fernàndez-Castillo N. The pleiotropic contribution of genes in dopaminergic and serotonergic pathways to addiction. Front Psychiatry. 2023;14:1293663. https://doi.org/10.3389/fpsyt.2023.1293663
Taracha E. The role of serotoninergic system in psychostimulant effects. Postep Psychiatr Neurol. 2021;30(4):258-69. https://doi.org/10.5114/ppn.2021.111939
Manchester KR, Lomas EC, Waters L, Dempsey FC, Maskell PD. The emergence of new psychoactive substance (NPS) benzodiazepines: a review. Drug Test Anal. 2018;10(1):37-53. https://doi.org/10.1002/dta.2211
National Institute on Drug Abuse. National Institute on Drug Abuse [internet]. Maryland: NIDA. [citado 2024 mzo. 10]. https://www.drugabuse.gov
Marland V, Reid R, Brandon AM, Hill K, Cruickshanks F, McKenzie C, et al. Changing trends in novel benzodiazepine use within Scottish prisons: detection, quantitation, prevalence, and modes of use. Drug Test Anal. 2024;16(5):457-72. https://doi.org/10.1002/dta.3560
Schmitz A. Benzodiazepine use, misuse, and abuse: a review. Ment Health Clin. 2016;6(3):120-6. https://doi.org/10.9740/mhc.2016.05.120
Albores-García D, Cruz SL. Fentanyl and other new psychoactive synthetic opioids: challenges to prevention and treatment. Rev Invest Clin. 2023;75(3):93-104. https://doi.org/10.24875/ric.23000109
Baumann MH, Walters HM, Niello M, Sitte HH. Neuropharmacology of synthetic cathinones. Handb Exp Pharmacol. 2018;252:113-42. https://doi.org/10.1007/164_2018_178
Daziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, et al. Synthetic cathinones and neurotoxicity risks: a systematic review. Int J Mol Sci. 2023;24(7):6230. https://doi.org/10.3390/ijms24076230

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