Interest in psychedelic therapies for adults is rapidly growing, with substances like 3,4-methylenedioxymethamphetamine for posttraumatic stress disorder, psilocybin for treatment-resistant depression, and lysergic acid diethylamide for generalized anxiety disorder showing promise. However, research on these therapies in children and adolescents is limited, with no recent trials. Despite this lack of scientific exploration, adolescents may still experiment with these substances for both recreational and therapeutic purposes as accessibility continues to increase. This raises significant concerns, as adolescents are a vulnerable population requiring heightened caution and safety measures. Therefore, we advocate for structured, safe, and well-controlled exploration of psychedelic therapies in adolescents.
Get full access to this article
View all access options for this article.
References
1.
AdayJS, HeifetsBD, PratscherSD, et al.Great expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology (Berl), 2022; 239(6):1989–2010; doi: 10.1007/s00213-022-06123-7
BaraA, FerlandJ-MN, RompalaG, et al.Cannabis and synaptic reprogramming of the developing brain. Nat Rev Neurosci, 2021; 22(7):423–438; doi: 10.1038/s41583-021-00465-5
5.
Blest-HopleyG, ColizziM, GiampietroV, et al.Is the adolescent brain at greater vulnerability to the effects of cannabis? A narrative review of the evidence. Front Psychiatry, 2020; 11:859; doi: 10.3389/fpsyt.2020.00859
6.
BreeksemaJJ, KuinBW, KamphuisJ, et al.Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review. J Psychopharmacol, 2022; 36(10):1100–1117; doi: 10.1177/02698811221116926
7.
Carhart-HarrisR, GiribaldiB, WattsR, et al.Trial of psilocybin versus escitalopram for depression. N Engl J Med, 2021; 384(15):1402–1411; doi: 10.1056/NEJMoa2032994
FuentesJJ, FonsecaF, ElicesM, et al.Therapeutic use of LSD in psychiatry: A systematic review of randomized-controlled clinical trials. Front Psychiatry, 2019; 10:943; doi: 10.3389/fpsyt.2019.00943
14.
GoodwinGM, AaronsonST, AlvarezO, et al.Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med, 2022; 387(18):1637–1648; doi: 10.1056/NEJMoa2206443
15.
GreenSM, RobackMG, KennedyRM, et al.Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Annals of Emergency Medicine, 2011; 57(5):449–461; doi: 10.1016/j.annemergmed.2010.11.030
16.
GukasyanN, DavisAK, BarrettFS, et al.Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. J Psychopharmacol, 2022; 36(2):151–158; doi: 10.1177/02698811211073759
17.
HoTC, KingLS. Mechanisms of neuroplasticity linking early adversity to depression: Developmental considerations. Transl Psychiatry, 2021; 11(1):517; doi: 10.1038/s41398-021-01639-6
JeromeL, FeducciaAA, WangJB, et al.Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: A longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl), 2020; 237(8):2485–2497; doi: 10.1007/s00213-020-05548-2
20.
KannikeswaranN, Lieh-LaiM, MalianM, et al.Optimal dosing of intravenous ketamine for procedural sedation in children in the ED-a Randomized Controlled Trial. Am J Emerg Med, 2016; 34(8):1347–1353; doi: 10.1016/j.ajem.2016.03.064
21.
KesslerRC, AvenevoliDS, CostelloDJ, et al.Severity of 12-month DSM-IV disorders in the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry, 2012a;69(4):381–389; doi: 10.1001/archgenpsychiatry.2011.1603
22.
KesslerRC, AvenevoliS, CostelloEJ, et al.Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry, 2012b;69(4):372–380; doi: 10.1001/archgenpsychiatry.2011.160
23.
LarsenB and LunaB. Adolescence as a neurobiological critical period for the development of higher-order cognition. Neuroscience & Biobehavioral Reviews, 2018; 94:179–195; doi: 10.1016/j.neubiorev.2018.09.005
MitchellJM, Ot’aloraG M, van der KolkB, et al.MAPP2 Study Collaborator Group. MDMA-assisted therapy for moderate to severe PTSD: A randomized, placebo-controlled phase 3 trial. Nat Med, 2023; 29(10):2473–2480; doi: 10.1038/s41591-023-02565-4
28.
MithoeferMC, WagnerMT, MithoeferAT, et al.The safety and efficacy of {+/-}3,4-Methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: The First Randomized Controlled Pilot Study. J Psychopharmacol, 2011; 25(4):439–452; doi: 10.1177/0269881110378371
29.
MithoeferMC, MithoeferAT, FeducciaAA, et al.3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy for Post-Traumatic Stress Disorder in Military Veterans, Firefighters, and Police Officers: A Randomised, Double-Blind, Dose-Response, Phase 2 Clinical Trial. Lancet Psychiatry, 2018; 5(6):486–497; doi: 10.1016/S2215-0366(18)30135-4
30.
OehenP, TraberR, WidmerV, et al.A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic post-traumatic stress disorder (PTSD). J Psychopharmacol, 2013; 27(1):40–52; doi: 10.1177/0269881112464827
31.
Ot’aloraG M, GrigsbyJ, PoulterB, et al.3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. J Psychopharmacol, 2018; 32(12):1295–1307; doi: 10.1177/0269881118806297
32.
Psilocybin for Major Depressive Disorder (MDD) (uAspire). ClinicalTrials.gov identifier: NCT06308653. August 20, 2024. Available from: https://clinicaltrials.gov/study/NCT06308653 [Last accessed: August30, 2024].
33.
Psychopharmacologic Drugs Advisory Committee Meeting (PDAC). Food and Drug Administration Center for Drug Evaluation and Research; June 4, 2024. Available from: https://www.fda.gov/media/180703/download [Last accessed: August10, 2024].
34.
RaisonCL, SanacoraG, WoolleyJ, et al.Single-dose psilocybin treatment for major depressive disorder: A randomized clinical trial. JAMA, 2023; 330(9):843–853; doi: 10.1001/jama.2023.14530
35.
ReiffCM, RichmanEE, NemeroffCB, et al.the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry, 2020; 177(5):391–410; doi: 10.1176/appi.ajp.2019.19010035
36.
ReinblattSP, dosReisS, WalkupJT, et al.Activation adverse events induced by the selective serotonin reuptake inhibitor fluvoxamine in children and adolescents. J Child Adolesc Psychopharmacol, 2009; 19(2):119–126; doi: 10.1089/cap.2008.040
37.
RheadJC. The use of psychedelic drugs in the treatment of severely disturbed children: A review. Journal of Psychedelic Drugs, 1977; 9(2):93–101; doi: 10.1080/02791072.1977.10472034
SelemonLD. A role for synaptic plasticity in the adolescent development of executive function. Transl Psychiatry, 2013; 3(3):e238–e238; doi: 10.1038/tp.2013.7
40.
SimonssonO, MosingMA, OsikaW, et al.Adolescent psychedelic use and psychotic or manic symptoms. JAMA Psychiatry, 2024; 81(6):579–585; doi: 10.1001/jamapsychiatry.2024.0047
41.
StrawnJR, MillsJA, PoweleitEA, et al.Adverse effects of antidepressant medications and their management in children and adolescents. Pharmacotherapy, 2023; 43(7):675–690; doi: 10.1002/phar.2767
von RotzR, SchindowskiEM, JungwirthJ, et al.Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine, 2023; 56:101809; doi: 10.1016/j.eclinm.2022.101809
44.
YadenDB, YadenME, GriffithsRR. Psychedelics in psychiatry—keeping the renaissance from going off the rails. JAMA Psychiatry, 2021; 78(5):469–470; doi: 10.1001/jamapsychiatry.2020.3672
45.
2022 National Healthcare Quality and Disparities Report. Rockville, MD: Agency for Healthcare Research and Quality; October 2022. AHRQ Pub. No. 22(23)-0030.
