Suicide is one of the leading causes of death worldwide and rates within the United States have risen over the past two decades. Hence, there is a critical need for novel tools to treat suicidal ideation and related mental health conditions. 3,4-Methylenedioxymethamphetamine (MDMA)/ecstasy and classic psychedelics may be two such tools.
Aims:
The aim of this study was to assess non-causal associations between MDMA/ecstasy and classic psychedelic use and psychological distress and suicide risk.
Methods:
In this study, we examined the aforementioned associations among 484,732 adult participants in the National Survey on Drug Use and Health (2008–2019).
Results:
Lifetime MDMA/ecstasy use was associated with reduced odds of past year suicidal thinking (10% reduced odds; odds ratio (OR) = 0.90; 95% confidence interval, CI = (0.84–0.97); p < 0.01) and past year suicidal planning (OR = 0.88; 95% CI = (0.78–0.99); p < 0.05). Furthermore, lifetime psilocybin use was associated with reduced odds of past month psychological distress (OR = 0.78; 95% CI = (0.73–0.84); p < 0.001) and past year suicidal thinking (OR = 0.90; 95% CI = (0.83–0.96); p < 0.01). Finally, lysergic acid diethylamide (LSD) was associated with increased odds of past year suicidal thinking (OR = 1.07; 95% CI = (1.00–1.15); p < 0.05).
Conclusion:
MDMA/ecstasy and psilocybin use are associated with reduced odds of suicidal thinking and related outcomes—though experimental studies are needed to determine whether these associations are causal. These findings call for more research into the efficacy of MDMA/ecstasy and classic psychedelics for treating psychological distress and suicidal thoughts and behaviors, and for updated drug legislation that allows for further investigation into these substances.
Agin-LiebesGIMaloneTYalchMM, et al. (2020) Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology (Oxford, England)34(2): 155–166.
2.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders : DSM-IV. Washington, DC.
3.
BaumeisterDBarnesGGiaroliG, et al. (2014) Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Therapeutic Advances in Psychopharmacology4(4): 156–169.
4.
BentleyKHFranklinJCRibeiroJD, et al. (2016) Anxiety and its disorders as risk factors for suicidal thoughts and behaviors: A meta-analytic review. Clinical Psychology Review43: 30–46.
5.
BogenschutzMPJohnsonMW (2016) Classic hallucinogens in the treatment of addictions. Progress in Neuro-Psychopharmacology and Biological Psychiatry64: 250–258.
6.
BogenschutzMPForcehimesAAPommyJA, et al. (2015) Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology29(3): 289–299.
7.
BohnertKMIlgenMALouzonS, et al. (2017) Substance use disorders and the risk of suicide mortality among men and women in the US veterans health administration. Addiction112(7): 1193–1201.
8.
ClemensKJMcGregorISHuntGE, et al. (2007) MDMA, methamphetamine and their combination: Possible lessons for party drug users from recent preclinical research. Drug and Alcohol Review26(1): 9–15.
9.
ColeJCBaileyMSumnallHR, et al. (2002) The content of ecstasy tablets: Implications for the study of their long-term effects. Addiction97(12): 1531–1536.
10.
CougleJRKeoughMERiccardiCJ, et al. (2009) Anxiety disorders and suicidality in the national comorbidity survey-replication. Journal of Psychiatric Research43(9): 825–829.
11.
DanforthALGrobCSStrubleC, et al. (2018) Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: A randomized, double-blind, placebo-controlled pilot study. Psychopharmacology235(11): 3137–3148.
12.
DavisonDParrottAC (1997) Ecstasy (MDMA) in recreational users: Self-reported psychological and physiological effects. Human Psychopharmacology: Clinical and Experimental12(3): 221–226.
13.
DoblinRGreerGHollandJ, et al. (2014) A reconsideration and response to Parrott AC (2013) “human psychobiology of MDMA or ‘ecstasy’: An overview of 25 years of empirical research.”Human Psychopharmacology: Clinical and Experimental29(2): 105–108.
14.
DwivediY (2010) Brain-derived neurotrophic factor and suicide pathogenesis. Annals of Medicine42(2): 87–96.
15.
DwivediYRizaviHSConleyRR, et al. (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Archives of General Psychiatry60(8): 804–815.
16.
DyckE (2015) LSD: A new treatment emerging from the past. CMAJ : Canadian Medical Association Journal = Journal De L’association Medicale Canadienne187(14): 1079–1080.
17.
FarréMAbanadesSRosetPN, et al. (2007) Pharmacological interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: Pharmacological effects and pharmacokinetics. Journal of Pharmacology and Experimental Therapeutics323(3): 954–962.
18.
FlanaganTWNicholsCD (2018) Psychedelics as anti-inflammatory agents. International Review of Psychiatry30(4): 363–375.
19.
GasserPHolsteinDMichelY, et al. (2014) Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of Nervous and Mental Disease202(7): 513–520.
20.
GaynesBNWestSLFordCA, et al. (2004) Screening for suicide risk in adults: A summary of the evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine140(10): 822–835.
21.
GorskaAMKamińskaKWawrzczak-BargiełaA, et al. (2018) Neurochemical and neurotoxic effects of MDMA (ecstasy) and caffeine after chronic combined administration in mice. Neurotoxicity Research33(3): 532–548.
22.
GreerGTolbertR (1986) Subjective reports of the effects of MDMA in a clinical setting. Journal of Psychoactive Drugs18(4): 319–327.
23.
GreerGRTolbertR (1998) A method of conducting therapeutic sessions with MDMA. Journal of Psychoactive Drugs30(4): 371–379.
24.
GriffithsRRJohnsonMWCarducciMA, et al. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology (Oxford, England)30(12): 1181–1197.
25.
GriffithsRRRichardsWAMcCannU, et al. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology187(3): 268–283.
26.
GrobCSDanforthALChopraGS, et al. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry68(1): 71–78.
27.
HarrisECBarracloughB (1997) Suicide as an outcome for mental disorders: A meta-analysis. British Journal of Psychiatry170(3): 205–228.
28.
HedegaardHCurtinSCWarnerM (2018a) Suicide mortality in the United States, 1999–2017. NCHS Data Brief (330): 1–8.
29.
HedegaardHCurtinSCWarnerM (2018b) Suicide rates in the United States continue to increase. NCHS Data Brief (330): 1–8.
30.
HedegaardHCurtinSCWarnerM (2020) Increase in Suicide Mortality in the United States, 1999–2018 NCHS Data Brief (362): 1–8.
31.
HendricksPSCrawfordMSCropseyKL, et al. (2018) The relationships of classic psychedelic use with criminal behavior in the United States adult population. Journal of Psychopharmacology32(1): 37–48.
32.
HendricksPSJohnsonMWGriffithsRR (2015a) Psilocybin, psychological distress, and suicidality. Journal of Psychopharmacology (Oxford, England)29(9): 1041–1043.
33.
HendricksPSThorneCBClarkCB, et al. (2015b) Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology29(3): 280–288.
34.
HillAB (1965) The environment and disease: Association or causation?Proceedings of the Royal Society of Medicine58(5): 295–300.
35.
HollandJ (2001) Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA. Rochester, VT: Park Street Press.
36.
HysekCMSchmidYSimmlerLD, et al. (2014) MDMA enhances emotional empathy and prosocial behavior. Social Cognitive and Affective Neuroscience9(11): 1645–1652.
37.
InagakiMKawashimaYKawanishiC, et al. (2015) Interventions to prevent repeat suicidal behavior in patients admitted to an emergency department for a suicide attempt: A meta-analysis. Journal of Affective Disorders175: 66–78.
38.
JohnsonMWGriffithsRR (2017) Potential therapeutic effects of psilocybin. Neurotherapeutics14(3): 734–740.
39.
JohnsonMWGarcia-RomeuACosimanoMP, et al. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology (Oxford, England)28(11): 983–992.
40.
JonesTBaxterMKhandujaV (2013) A quick guide to survey research. Annals of the Royal College of Surgeons of England95(1): 5–7.
41.
Kamilar-BrittPBediG (2015) The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals. Neuroscience and Biobehavioral Reviews57: 433–446.
42.
KesslerRCBrometEJ (2013) The epidemiology of depression across cultures. Annual Review of Public Health34: 119–138.
43.
KesslerRCBerglundPBorgesG, et al. (2005) Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990–1992 to 2001–2003. JAMA : The Journal of the American Medical Association293(20): 2487–2495.
44.
KothgassnerODRobinsonKGoreisA, et al. (2020) Does treatment method matter? A meta-analysis of the past 20 years of research on therapeutic interventions for self-harm and suicidal ideation in adolescents. Borderline Personality Disorder and Emotion Dysregulation7(1): 9.
45.
KrebsTSJohansenP-Ø (2013) Psychedelics and mental health: A population study. PLoS ONE8(8): e63972.
46.
LiechtiMEGammaAVollenweiderFX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology154(2): 161–168.
47.
LumleyT (2020) Survey: Analysis of complex survey samples. R package version 4.0. Available at: https://CRAN.R-project.org/package=survey (accessed 24 September 2020).
48.
LyCGrebACCameronLP, et al. (2018) Psychedelics promote structural and functional neural plasticity. Cell Reports23(11): 3170–3182.
49.
MahapatraAGuptaR (2017) Role of psilocybin in the treatment of depression. Therapeutic Advances in Psychopharmacology7(1): 54–56.
50.
MitchellJMBogenschutzMLiliensteinA, et al. (2021) MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine27: 1025–1033.
51.
MithoeferMCFeducciaAAJeromeL, et al. (2019) MDMA-assisted psychotherapy for treatment of PTSD: Study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology236(9): 2735–2745.
52.
MithoeferMCWagnerMTMithoeferAT, et al. (2011) 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. Journal of Psychopharmacology25(4): 439–452.
53.
MithoeferMCWagnerMTMithoeferAT, et al. (2013) Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: A prospective long-term follow-up study. Journal of Psychopharmacology27(1): 28–39.
54.
MüllerFJohnsonMWBorgwardtS (2020) Editorial: Hallucinogens and entactogens: Establishing a new class of psychotherapeutic drugs?Frontiers in Psychiatry11: 497.
55.
Multidisciplinary Association for Psychedelic Studies (2020) A randomized, double-blind, placebo-controlled phase 2 pilot study of MDMA-assisted psychotherapy for anxiety associated with a life-threatening illness. NCT number: NCT02427568. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02427568 (accessed 23 September 2020).
56.
NeponJBelikS-LBoltonJ, et al. (2010) The relationship between anxiety disorders and suicide attempts: Findings from the national epidemiologic survey on alcohol and related conditions. Depression and Anxiety27(9): 791–798.
NuttDJKingLANicholsDE (2013) Effects of schedule I drug laws on neuroscience research and treatment innovation. Nature Reviews Neuroscience14: 577–585.
60.
OehenPTraberRWidmerV, et al. (2013) A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic post-traumatic stress disorder (PTSD). Journal of Psychopharmacology27(1): 40–52.
61.
Ot’aloraGMGrigsbyJPoulterB, et al. (2018) 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. Journal of Psychopharmacology32(12): 1295–1307.
62.
Palhano-FontesFBarretoDOniasH, et al. (2019) Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomized placebo-controlled trial. Psychological Medicine49(4): 655–663.
63.
PisanoVDPutnamNPKramerHM, et al. (2017) The association of psychedelic use and opioid use disorders among illicit users in the United States. Journal of Psychopharmacology31(5): 606–613.
64.
SaleemiSPennybakerSJWooldridgeM, et al. (2017) Who is ‘Molly’? MDMA adulterants by product name and the impact of harm-reduction services at raves. Journal of Psychopharmacology31(8): 1056–1060.
65.
SessaBHigbedLNuttD (2019) A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. Frontiers in Psychiatry10: 138.
66.
SextonJDNicholsCDHendricksPS (2020) Population survey data informing the therapeutic potential of classic and novel phenethylamine, tryptamine, and lysergamide psychedelics. Frontiers in Psychiatry10: 896.
67.
TarrierNTaylorKGoodingP (2008) Cognitive-behavioral interventions to reduce suicide behavior: A systematic review and meta-analysis. Behavior Modification32(1): 77–108.
68.
ter BogtTFMEngelsRCMEDubasJS (2006) Party people: Personality and MDMA use of house party visitors. Addictive Behaviors31(7): 1240–1244.
69.
ThompsonMRCallaghanPDHuntGE, et al. (2007) A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”). Neuroscience146(2): 509–514.
70.
United States Department of Health Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2008) National survey on drug use and health, 2008. Available at: https://datafiles.samhsa.gov/
71.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2009) National survey on drug use and health, 2009. Available at: https://datafiles.samhsa.gov/
72.
United States Department of Health and Human United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2010) National survey on drug use and health, 2010. Available at: https://datafiles.samhsa.gov/
73.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2011) National survey on drug use and health, 2011. Available at: https://datafiles.samhsa.gov/
74.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2012) National survey on drug use and health, 2012. Available at: https://datafiles.samhsa.gov/
75.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2013) National survey on drug use and health, 2013. Available at: https://datafiles.samhsa.gov/
76.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2014) National survey on drug use and health, 2014. Available at: https://datafiles.samhsa.gov/
77.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2015) National survey on drug use and health, 2015. Available at: https://datafiles.samhsa.gov/
78.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2016) National survey on drug use and health, 2016. Available at: https://datafiles.samhsa.gov/
79.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2017) National survey on drug use and health, 2017. Available at: https://datafiles.samhsa.gov/
80.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2018) National survey on drug use and health, 2018. Available at: https://datafiles.samhsa.gov/
81.
United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality (2019) National survey on drug use and health, 2019. Available at: https://datafiles.samhsa.gov/
82.
Van OekelenDLuytenWHMLLeysenJE (2003) 5-HT2A and 5-HT2C receptors and their atypical regulation properties. Life Sciences72(22): 2429–2449.
83.
Vanattou-SaïfoudineNMcNamaraRHarkinA (2012) Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ’ecstasy’) and related psychostimulants: Mechanisms and mediators. British Journal of Pharmacology167(5): 946–959.
84.
VollenweiderFXKometerM (2010) The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders. Nature Reviews Neuroscience11(9): 642–651.
85.
WilcoxHCConnerKRCaineED (2004) Association of alcohol and drug use disorders and completed suicide: An empirical review of cohort studies. Drug Abuse and Suicidal Behavior76: S11–S19.
Yazar KlosinskiBBMithoeferM (2017) Potential psychiatric uses for MDMA. Clinical Pharmacology and Therapeutics101(2): 194–196.
88.
ZeifmanRJPalhano-FontesFHallakJ, et al. (2019) The impact of Ayahuasca on suicidality: Results from a randomized controlled trial. Frontiers in Pharmacology10: 1325.
