Psychiatry might need some psychedelic therapy
Matthew W. Johnson
International Review of Psychiatry, Institute of Psychiatry and Johns Hopkins University, 2018, 30, 4, 285-290.
Psychiatry might need some psychedelic therapy In historical and modern-day studies, psychedelic drugs
have shown promise in managing a variety of psychiatric disorders, but their medical use has often raised controversies. The controversies have related to social, political, and legal challenges.
Although anthropological evidence suggests that classic psychedelic drugs (hereafter, ‘psychedelics’) have been used by various indigenous peoples as sacraments and healing agents before recorded history, in the mid-twentieth century they came to occupy a place at the cutting edge of psychiatric research (Johnson, Richards, & Griffiths, 2008). Although some psychiatrists and researchers might be under the impression that this interest was a fad, this is far from the case. Over 1000 papers were published describing the treatment of over 40,000 patients with psychedelics (Grinspoon, 1981). The discovery of lysergic acid diethyamide (LSD), with its extremely powerful subjective effects caused by infinitesimal
doses, and with its structural similarity to the newly-discovered neurotransmitter serotonin, was a
strong contributor to the emerging neuroscientific model that took hold in the 1950s and 1960s. In large part this new biobehavioural understanding of brain function came to replace psychodynamic models as the predominant paradigm in psychiatry.
In addition to the role of psychedelics as tools for investigating the biological substrates of the mind and
behaviour (considered two sides of the same coin by the present author), promising therapeutic applications were investigated, with particularly promising findings in the treatment of both addiction and cancer-related psychiatric existential distress (Johnson & Griffiths, 2017). However, despite initial excitement, research on these drugs became increasingly marginalized due to their growing use outside of clinical research settings, and their resulting association with the counter-culture movement in the late 1960s and early 1970s. These compounds are powerful tools. Like all powerful tools, use by the incautious and unwise can (and did) lead to demonstrable harms (Carbonaro et al., 2016; Johnson
et al., 2008).
Although a few investigators who abandoned a scientific approach became ‘poster children’ for why these
tools could not be trusted to scientists for human research, psychiatric pioneers such as Humphry Osmond, Abram Hoffer, Walter Pahnke, and Sidney Cohen, who are scientific heroes to the present author, were more representative of the many scientists who conducted ethical and responsible human research with psychedelics, and who knew that addressing the very real risks of these compounds was essential to making scientific and therapeutic progress. Unfortunately for investigators like these, and for patients who might have benefitted from the fruits of cautious human psychedelic research decades ago, the early promising scientific threads of psychedelic research remained dangling for decades (Tupper, Wood, Yensen, & Johnson, 2015).
In the 1990s a small number of investigators in Europe and the US re-initiated human studies with psychedelics. Non-human research in the intervening decades had identified agonist activity at the 5-HT2a receptor as a key mechanism underlying the effects of psychedelics (e.g. Glennon, Titeler, & McKenney, 1984), which include LSD as well as psilocybin (present in many species of mushrooms), mescaline (present in peyote and other cacti), and dimethyltryptamine (DMT; present in a wide variety of plants). Studies by researchers in the modern era have followed established safety guidelines
for administering psychedelics (Johnson et al., 2008). Like the best of the original era of research, these guidelines involve careful screening and preparation before drug administration sessions, intense monitoring during sessions, and follow-up care involving both clinically supportive discussion of session experiences and assessment for any adverse effects resulting from the session. Moreover, modern investigators have often approached this research using methods and technologies that were non-existent or not fully established in the earlier era of research, including psychometrically validated scales, double-blind and even more complex designs, and brain imaging. These early studies led to more studies at a growing number of prominent universities as the safety and potential efficacy of clinical psychedelic research was demonstrated. Therapeutic studies using psychedelics have been reported for depression and anxiety related to cancer and other life-threatening illness (Gasser et al., 2014; Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016), treatment-resistant depression (Carhart-Harris et al., 2016; Palhano-Fontes et al., 2018), tobacco addiction (Johnson, Garcia-Romeu, Cosimano, & Griffiths, 2014; Johnson, Garcia-Romeu, & Griffiths, 2017), and alcohol addiction (Bogenschutz et al., 2015). Some studies have been randomized trials, while others have been initial open-label pilot trials designed to establish
safety in new populations and test the waters for future randomized trials. Remarkably, some of these
studies have reported rapid efficacy persisting for at least 6 months after one or a few administrations. In comparison, ketamine, which is under investigation for depression treatment and has greater addiction potential than psychedelics (Johnson, Griffiths, Hendricks, & Henningfield, 2018; Kolar, 2018), has been considered rightly a potential breakthrough for showing immediate antidepressant effects that persist for about a week after administration (Molero et al., 2018). Therefore, psychedelics might be considered to have even greater breakthrough potential.
Consistent with these laboratory studies, a growing number of epidemiological studies have found suggestive associations between naturalistic use of psychedelics and positive outcomes using regression models controlling for other variables including use of other drugs. For example, one study, based on a nationally representative survey of over 190,000 individuals, found that lifetime classic psychedelic use (Hendricks, Thorne, Clark, Coombs, & Johnson, 2015), including psilocybin use (Hendricks, Johnson, & Griffiths, 2015), was associated with reduced psychological distress and suicidality in the US adult population. Potentially suggestive of anti-addiction effects, another study, based on over 25,000 individuals, suggested that psychedelic use (broadly defined) was associated with reduced recidivism from drugrelated and other criminal activity among drug-involved criminal offenders undergoing community supervision (Hendricks, Clark, Johnson, Fontaine, & Cropsey, 2014).