Prevalence and epidemiological associates of novel psychedelic use in the United States adult population

James D. Sexton, Michael S. Crawford, Noah W. Sweat, Allyson Varley , Emma E. Green and Peter S. Hendricks

Journal of Psychopharmacology, 1-10

DOI : 10.1177/0269881119827796
journals.sagepub.com/home/jopract

Abstract

Background : 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.

Keywords : Novel psychedelic, phenethylamines, psychedelic, mental health, hallucinogen

Introduction

Classic psychedelic use has been prevalent for millennia in human history, typically within the context of religious sacrament (Guerra Doce, 2015; Schultes, 1969). From the 1950s through the 1970s and again in recent times, research on these substances (i.e. dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), mescaline, and psilocybin) has shown them to be safe and potentially therapeutic when administered in controlled settings. Indeed, a variety of neuroprotective effects have been attributed to the serotonin 2A receptor (5-HT2AR) activity of classic psychedelics (Carhart-Harris et al., 2014; Vollenweider and Kometer, 2010). To that extent, classic psychedelics have been and continue to be studied as treatments for mental health conditions including end-of-life anxiety, nicotine dependence, alcohol dependence, and treatment-resistant depression (Carhart-Harris et al., 2016; clinicaltrials.gov, 2014a, 2014b, Gasser et al., 2014, 2015; Johnson et al., 2014; Krebs and Johansen, 2012; Palhano- Fontes et al., 2018). Prior research has determined that lifetime classic psychedelic use has a prevalence of 13.6% in the US adult population, and is associated with reduced likelihood of past month psychological distress, past year suicidality, and criminal behavior (Hendricks et al., 2015, 2017). Although these substances are not without risk, they are well studied.

Conversely, there exists a group of novel psychoactive substances that is similar in pharmacodynamics and pharmacokinetics to classic psychedelics, new to human use, and not well studied. In this report, these substances are labeled “novel psychedelics”. It is known that these substances are primarily 5-HT2AR agonists, although they have had little to no clinical or epidemiological evaluation (Baumeister et al., 2014; Canal et al., 2010; De Boer and Bosman, 2004; Gasser et al., 2015). Indeed, unlike DMT, LSD, mescaline, and psilocybin, the prevalence of novel psychedelic use is unknown, and the associations of novel psychedelic use with mental health outcomes are undetermined. Many of these substances have only been synthesized within the last sixty years, a stark contrast to classic psychedelics such as psilocybin, which has naturally occurred and been used by humans since long before recorded history (Nichols, 1999, 2001). Although there are exceptions, the first generation of novel psychedelic substances were most notably reported by the chemist Alexander Shulgin and his wife Anne in the books PiHKAL and TiHKAL (Shulgin and Shulgin, 1991, 1997). Since these initial reports, there has been some semi-licit (i.e. online “grey market” and dark web markets) and illicit distribution and subsequent use of novel psychedelics. Online information regarding the procurement and ingestion of novel psychedelics has become increasingly available (Global Drug Survey, 2018; Halpern and Pope, 2001; Walsh, 2011). Use of novel psychedelics may be increasing in prevalence, as evidenced by small yet increasing numbers of emergency department mentions over recent years (Drug Abuse Warning Network, 2011). Alarmingly, little research has been done to determine the toxicity of novel psychedelics, though clinical reports have noted possible overdose deaths related to the ingestion of some of these substances (Curtis et al., 2003; Dean et al., 2013; Topeff et al., 2011).

Replicating prior analyses on classic psychedelics (Hendricks et al., 2015), the purpose of the present study was to evaluate the prevalence of self-reported, write-in lifetime novel psychedelic use (i.e. novel psychedelic use volunteered by survey respondents as opposed to specifically queried by predetermined survey items) and its associated psychosocial characteristics among adults in the USA, and to test the associations of lifetime novel psychedelic use with psychological distress and suicidality. These data are relevant for developing more efficient epidemiological surveys and screening protocols for clinical settings. Moreover, clinicians can use these data to characterize patient behavior as normative and consequently be better prepared to mitigate the risk of mortality when presented with potential overdose (Taylor et al., 1970; Vilke et al., 2012). Finally, these data can serve as one line of evidence to determine whether novel psychedelics might ultimately have clinical utility, and how to better direct public health efforts with regard to non-clinical use.

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