Novel psychedelics approximate classic psychedelics, but unlike classic psychedelics, novel psychedelics have been used by humans for a shorter period of time, with fewer data available on these substances.
Aims:
The purpose of this study was to determine the prevalence of novel psychedelic use and the associations of novel psychedelic use with mental health outcomes.
Methods:
We estimated the prevalence of self-reported, write-in lifetime novel psychedelic use and evaluated the associations of novel psychedelic use with psychosocial characteristics, past month psychological distress, and past year suicidality among adult respondents pooled from years 2008–2016 of the National Survey on Drug Use and Health (weighted n=234,914,788).
Results:
A fraction (weighted n=273,720; 0.12%) reported lifetime novel psychedelic use. This cohort tended to be younger, male, and White, have greater educational attainment but less income, be more likely to have never been married, engage in self-reported risky behavior, and report lifetime illicit use of other drugs, particularly classic psychedelics (96.9%). (2-(4-Bromo-2,5-dimethoxyphenyl)ethanamine) (2C-B) (30.01%), (2,5-dimethoxy-4-iodophenethylamine) (2C-I) (23.9%), and (1-(2,5-dimethoxy-4-ethylphenyl)-2-aminoethane) (2C-E) (14.8%) accounted for the majority of lifetime novel psychedelic use. Although lifetime novel psychedelic use was not associated with psychological distress or suicidality compared to no lifetime novel psychedelic use or classic psychedelic use, relative to lifetime use of classic psychedelics but not novel psychedelics, lifetime novel psychedelic use was associated with a greater likelihood of past year suicidal thinking (adjusted Odds Ratio (aOR)=1.4 (1.1–1.9)) and past year suicidal planning (aOR=1.6 (1.1–2.4)).
Conclusion:
Novel psychedelics may differ from classic psychedelics in meaningful ways, though additional, directed research is needed.
AddoFR (2014) Debt, cohabitation, and marriage in young adulthood. Demography51: 1667–1701.
2.
BaumeisterDBarnesGGiaroliG, et al. (2014) Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Therap Adv Psychopharmacol4: 156–169.
3.
Brandt SimonD.KavanaghPV.WestphalF, et al. (2016) Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). Drug Test Anal8: 891–902.
4.
Brandt SimonDKavanaghPVWestphalF, et al. (2017) Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ). Drug Test Anal9: 38–50.
5.
CanalCEDa SilvaUBOGreschPJ, et al. (2010) The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology209: 163–174.
6.
Carhart-HarrisRLBolstridgeMRuckerJ, et al. (2016) Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. Lancet Psychiatry3: 619–627.
7.
Carhart-HarrisRLLeechRHellyerP, et al. (2014) The entropic brain: A theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci 8: 20.
8.
CheethamSCYamaguchiYHortonRW (1989) [3H]5-hydroxytryptamine binding sites in postmortem human brain. Neuropharmacology28: 1055–1060.
CouttsRTMalickyJL (1973) The synthesis of some analogs of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Canadian J Chem51: 1402–1409.
12.
CozziNVDaleyPF (2016) Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines. Bioorg Med Chem Lett26: 959–964.
13.
CurtisBKempPHartyL, et al. (2003) Postmortem identification and quantitation of 2,5-dimethoxy-4-n-propylthiophenethylamine using GC-MSD and GC-NPD. J Anal Toxicol27: 493–498.
14.
Drug Abuse Warning Network (2011) National Estimates of Drug-Related Emergency Department Visits. Rockville, MD: Substance Abuse and Mental Health Services Administration.
15.
De BoerDBosmanI (2004) A new trend in drugs-of-abuse; the 2C-series of phenethylamine designer drugs. Pharm World Sci26: 110–113.
16.
DeanBVStellpflugSJBurnettAM, et al. (2013) 2C or not 2C: Phenethylamine designer drug review. J Med Tox9: 172–178.
17.
EshlemanAJForsterMJWolfrumKM, et al. (2014) Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: Mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function. Psychopharmacology231: 875–888.
18.
FantegrossiWEReissigCJKatzEB, et al. (2008) Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT(1A) and 5-HT(2A) receptors in rodents. Pharmacol Biochem Behav88: 358–365.
19.
FoxMAFrenchHTLaporteJL, et al. (2010) The serotonin 5-HT2Areceptor agonist TCB-2: A behavioral and neurophysiological analysis. Psychopharmacology212: 13–23.
20.
GasserPHolsteinDMichelY, et al. (2014) Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis202: 513–520.
21.
GasserPKirchnerKPassieT (2015) LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. J Psychopharmacol29: 57–68.
GlennonRATitelerMMcKenneyJD (1984) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci35: 2505–2511.
24.
Guerra DoceE (2015) Psychoactive substances in prehistoric times: Examining the archaeological evidence. Time and Mind8: 91–112.
25.
HalpernJHPopeJ (2001) Hallucinogens on the internet: A vast new source of underground drug information. Am J Psychiatry158: 481–483.
26.
HansenMPhonekeoKPaineJS, et al. (2014) Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists. ACS Chem Neurosci5: 243–249.
27.
HendricksPSCrawfordMSCropseyKL, et al. (2017) The relationships of classic psychedelic use with criminal behavior in the United States adult population. J Psychopharmacol32: 37–48.
28.
HendricksPSThorneCBClarkCB, et al. (2015) Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol29: 280–288.
29.
JohnsonMWGarcia-RomeuACosimanoMP, et al. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol28: 983–992.
30.
KesslerRCAndrewsGColpeLJ, et al. (2002) Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychol Med32: 959–976.
31.
KhanAChienC-WBurtonNW (2014) A new look at the construct validity of the K6 using Rasch analysis. Int J Met Psychiatr Res23: 1–8.
32.
KrebsTSJohansenPØr (2012) Lysergic acid diethylamide (LSD) for alcoholism: Meta-analysis of randomized controlled trials. J Psychopharmacol26: 994–1002.
33.
KroutilLAVorburgerMAldworthJ, et al. (2010) Estimated drug use based on direct questioning and open-ended questions: Responses in the 2006 National Survey on Drug Use and Health. Int J Met Psychiatr Res19: 74–87.
34.
LawnWBarrattMWilliamsM, et al. (2014) The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample. J Psychopharmacology28: 780–788.
35.
LinGGlennonRA (2003) Hallucinogens: An update. Curr Psychiatry Rep5: 347–354.
36.
MartinsDBarrattMJPiresCV, et al. (2017) The detection and prevention of unintentional consumption of DOx and 25x-NBOMe at Portugal’s boom festival. Hum Psychopharm Clin Exp32: e2608.
37.
McIntyreIMTrochtaAGaryRD, et al. (2015) A fatality related to two novel hallucinogenic compounds: 4-methoxyphencyclidine and 4-hydroxy-N-methyl-N-ethyltryptamine. J Anal Toxicol39: 751–755.
38.
MeyerMRCasparABrandtSD, et al. (2014) A qualitative/quantitative approach for the detection of 37 tryptamine-derived designer drugs, 5 β-carbolines, ibogaine, and yohimbine in human urine and plasma using standard urine screening and multi-analyte approaches. Anal Bioanal Chem406: 225–237.
39.
MontgomeryCFiskJENewcombeR, et al. (2005) The differential effects of ecstasy/polydrug use on executive components: Shifting, inhibition, updating and access to semantic memory. Psychopharmacology182: 262–276.
40.
NicholsDE (1999) Improvements to the synthesis of psilocybin and a facile method for preparing the O-acetyl prodrug of psilocin. Synthesis1999: 935–938.
41.
NicholsDE (2001) LSD and its lysergamide cousins. Heffter Rev Psychedelic Res2: 80–87.
42.
NicholsDEFrescasSMarona-LewickaD, et al. (2002) Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD). J Med Chem45: 4344–4349.
43.
NicholsDEFrescasSPChemelBR, et al. (2008) High specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A high affinity 5-HT(2A) receptor-selective agonist radioligand. Bioorg Med Chem16: 6116–6123.
44.
Palhano-FontesFBarretoDOniasH, et al. (2018) Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomized placebo-controlled trial. Psychol Med 15: 1–9.
45.
ParkerMAMarona-LewickaDLucaitesVL, et al. (1998) A novel (Benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor. J Med Chem41: 5148–5149.
46.
RayTS (2010) Psychedelics and the human receptorome. PLoS One5: e9019.
47.
RepkeDBGrotjahnDBShulginAT (1985) Psychotomimetic N-methyl-N-isopropyltryptamines. Effects of variation of aromatic oxygen substituents. J Med Chem28: 892–896.
48.
RickliAMoningODHoenerMC, et al. (2016) Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Euro Neuropsychopharmacol26: 1327–1337.
SandersBLankenauSEBloomJJ, et al. (2008) “Research chemicals”: Tryptamine and phenethylamine use among high-risk youth bill. Subst Use Misuse 43: 389–402.
51.
SardHKumaranGMorencyC, et al. (2005) SAR of psilocybin analogs: Discovery of a selective 5-HT2C agonist. Bioorganic Med Chem Lett15: 4555–4559.
52.
SchultesRE (1969) Hallucinogens of plant origin. Science163: 245–254.
53.
ShulginATShulginA (1991) PiHKAL: Phenethylamine I Have Known and Loved. Berkeley, CA: Transform Press.
54.
ShulginATShulginA (1997) TiHKAL: Tryptamines I Have Known and Loved. Berkeley, CA: Transform Press.
55.
StollerADolderPCBodmerM, et al. (2017) Mistaking 2C-P for 2C-B: What a difference a letter makes. J Anal Toxicol41: 77–79.
56.
TaylorRLMaurerJITinklenbergJR (1970) Management of “bad trips” in an evolving drug scene. J Am Med Assoc213: 422–425.
57.
TeterCJFaloneAECranfordJA, et al. (2010) Nonmedical use of prescription stimulants and depressed mood among college students: Frequency and routes of administration. J Subst Abuse Treat38: 292–298.
58.
TopeffJEllsworthHWillhiteL, et al. (2011) A case series of symptomatic patients, including one fatality, following 2C-E exposure. Clin Toxicol49: 526.
59.
VilkeGMBozemanWPDawesDM, et al. (2012) Excited delirium syndrome (ExDS): Treatment options and considerations. J Forensic Leg Med19: 117–121.
60.
VillalobosCABullPSáezP, et al. (2004) 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT 2A receptor antagonists in Xenopus laevis oocytes. Br J Pharmacol141: 1167–1174.
61.
VollenweiderFXKometerM (2010) The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders. Nat Rev Neurosci11: 642–651.
62.
WalshC (2011) Drugs, the Internet and change. J Psychoactive Drugs43: 55–63.
