The past three decades have witnessed a gradual return to
research on classic psychedelics. Though limited in number,
these studies indicate that classic psychedelics may warrant the
attention they received five decades ago, not least in part because
they appear to target a number of factors that modulate suicide
risk. For instance, affective disturbance is one of the most promi-
nent contributors to suicidality (Hawton and van Heeringen,
2009). Under carefully controlled conditions, a single adminis-
tration of psilocybin can occasion profoundly meaningful experi-
ences that bring about persisting elevations in mood among
healthy, hallucinogen-naïve volunteers (Griffiths et al., 2006,
2008, 2011). In a pilot trial among individuals with advanced-
stage cancer a single dose of psilocybin was associated with
long-term reductions in anxiety and depression (Grob et al.,
2011), and in a pilot trial among individuals with life-threatening
diseases two administrations of LSD produced lasting reductions
in anxiety (Gasser et al., 2014; in press). Substance misuse also is
robustly related to suicide risk (Borges et al., 2000; Britton and
Conner, 2010; Center for Substance Abuse Treatment, 2008;
Hawton and van Heeringen, 2009; Wilcox et al., 2004), and sev-
eral lines of research suggest that classic psychedelics have anti-
addictive effects (Bogenschutz and Pommy, 2012). For example,
a recent meta-analysis of six randomized clinical trials of treat-
ment for alcoholism conducted between 1966–1970 found that a
single dose of LSD reduced the probability of alcohol misuse
almost two-fold relative to comparison conditions (Krebs and
Johansen, 2012). Furthermore, a single-arm trial of smoking ces-
sation involving up to three administrations of psilocybin yielded
abstinence rates of 80% at long-term follow-up, more than dou-
bling abstinence rates typical of approved contemporary tobacco
dependence interventions (Johnson et al., 2014). Moreover, natu-
ralistic hallucinogen use predicted a reduced likelihood of recidi-
vism among more than 25,000 individuals under community
corrections supervision with a history of substance involvement
(Hendricks et al., 2014). Additional prominent suicide risk fac-
tors include impulsive-aggressive personality characteristics and
early traumatic life events (Hawton and van Heeringen, 2009).
Psilocybin may occasion enduring improvements in inner peace,
patience, good-natured humor/playfulness, interpersonal regard,
anger, and compassion (Griffiths et al., 2006, 2011), and may
facilitate processing of prior trauma by enhancing recall of auto-
biographical memories (Carhart-Harris et al., 2012a). Finally,
classic psychedelics may boost spirituality (Bogenschutz and
Pommy, 2012; Griffiths et al., 2011), which has been shown to
protect against suicidality (Rasic et al., 2009, 2011; Weber and
Pargament, 2014). Although sample sizes in recent medical
administration studies have been limited, no serious adverse
events were reported, consistent with historical data indicating
that these substances can be administered safely in medical con-
texts by using appropriate safeguards (Johnson et al., 2008).
Neurobiological experiments echo clinical findings, adding
further evidence to suggest that classic psychedelics may modify
processes implicated in suicidality. Increased 5-HT 2A receptor
density in the prefrontal cortex is associated with suicide risk fac-
tors (e.g. major depression) and suicidal behavior, and may
reflect compensatory up-regulation of 5-HT 2A receptors stem-
ming from dysfunctional serotonergic transmission (Bhagwagar
et al., 2006; Carballo et al., 2008; Meyer et al., 2003; Shelton
et al., 2008). Classic psychedelic use down-regulates 5-HT 2A
receptors in the prefrontal cortex which may, in turn, normalize
limbic hyperactivity associated with affective disturbance
(Baumeister et al., 2014, Kraehenmann et al., in press;
Vollenweider and Kometer, 2010). Reduced neuroplasticity (i.e.
expression of brain-derived neurotrophic factor) is also associ-
ated with affective disturbance and suicide, and classic psyche-
delic use may elicit neuroplastic adaptation via glutamatergic
transmission (Baumeister et al., 2014; Bogenschutz and Pommy,
2012; Dwivedi, 2010; Dwivedi et al., 2003; Vollenweider and
Kometer, 2010). Furthermore, the default mode network (DMN)
is hyperactive and hyperconnected among those with affective
disorders, a state that may underpin negative rumination and
rigid pessimism characteristic of these conditions (Carhart-Harris
et al., 2014; Whitfield-Gabrieli and Ford, 2012). Classic psyche-
delics may normalize the DMN, thereby reducing this cognitive
fixedness (Carhart-Harris et al., 2012b; Carhart-Harris et al.,
2014; Muthukumaraswamy et al., 2013; Roseman et al., 2014;
Tagliazucchi et al., 2014). In support of this view, a single dose of
psilocybin increased personality openness 14 months post-
administration (MacLean et al., 2011). Some studies show that
openness may protect against suicide in older adults, though find-
ings are mixed (Segal et al., 2012). Finally, emerging evidence
suggests that classic psychedelics might reduce markers of cen-
tral nervous system inflammation that are implicated in a host of
mental health conditions and suicidal behavior (Black and Miller,
in press; Szabo et al., 2014). |
