In recent years there has been a resurgent scientific interest in the psychological effects of psychedelic drugs.
Consider the example of recent trials in which psilocybin was administered to people diagnosed with treatment-resistant depression. Those involved reported significantly positive responses even six months later.
Such studies point with increasing confidence to the therapeutic potential of psychedelics for treating depression, addiction, anxiety and post-traumatic stress disorder (PTSD), and enhancing palliative care.
Amidst this “psychedelic renaissance”, there is one recent study in particular that has grabbed my attention.
This study, published in a reputable, peer-reviewed international journal, makes even bolder claims about the potential of psychedelics – not only for improving mental health, but also, remarkably, as a key to overcoming inaction in the face of the climate crisis.
On what grounds? The authors justify their claim by zooming in on one explanation for their apparently positive effect on well-being, established in previous research.
As well as “resetting” key brain circuitry and enhancing emotional responsiveness, psychedelics commonly increase people’s positive feelings of connectedness – to one’s self and others, and to the natural world.
“Nature-connectedness” is now considered a research topic in its own right in the field of psychology, an individual quality that can be measured.
It refers not just to the extent of an individual’s contact with natural settings, but the extent to which they report feeling connected to and part of the natural world.
Using established measures of nature connectedness with more than 600 participants before and after one or more psychedelic experiences, the researchers found that psychedelic drug use enhanced participants’ sense of being connected to nature, an effect that deepened when that experience took place in natural settings. Perhaps this isn’t that surprising. It is what they argue on the basis of these results that is especially interesting.
Psychedelics for planetary health
They cite evidence suggesting direct experiences of nature and a sense of nature connectedness underpin enhanced environmental awareness and a desire to care for nature, therefore reducing people’s “environmentally destructive behaviour”.
This is nothing new. What is new is their claim that if psychedelic interventions significantly deepen a sense of connection, they might also have a role in contributing to both mental and planetary health.
Could this be true?
What is happening, psychologically speaking, during psychedelic experiences of connectedness?
Accounts point to feelings of self-transcendence, whereby the boundaries between one’s self and others, or the self and the natural world, are temporarily dissolved.
This is not so much an experience of one being connecting to another, as a temporary collapse of the very distinction between the self and nature.
On taking psychedelics, one can be momentarily absorbed in a state of “oneness” or “oceanic boundlessness”. This reminds me of a participant’s response in another study, published in 2017, exploring psychedelic treatments for depression:
“Before I enjoyed nature, now I feel part of it. Before I was looking at it as a thing, like TV or a painting. [But] you’re part of it, there’s no separation or distinction, you are it.”
The authors claim that such experiences, in which the self seems to have extended into nature, deeply impress an affiliation with nature that motivates us to care and protect.
They argue that this cannot but engender an increased sense of environmental responsibility. As a result, they suggest that administering controlled amounts of psychedelic drugs to people while they are immersed in natural environments could hold potential for fostering greater environmental awareness and the motivation to act in more environmentally responsible ways.
Caution: psychedelics ahead
You may or not be convinced by their argument, and the potential of psychedelics for provoking environmental awareness, behaviour change and activism is still to be seen. There is certainly no magic pill that can mobilise environmental responsibility on a mass scale, psychedelic or otherwise.
With or without psychedelics, we certainly need to strengthen our connection to nature.
And as a critical psychologist engaging with the climate crisis, I can see the danger here in focusing on individual behaviour change, when part of the problem is that our energies are not directed at structural change and those wielding the greatest power, which the authors of this study acknowledge. Workable solutions to the climate crisis require more than shifts in individual perspective, however radical or profound.
Nonetheless, for me at least, seriously considering the physical, psychological, social and even environmental value of psychedelic drugs is in itself a welcome challenge to the deeply held, and often hypocritical, cultural assumptions we have about drugs and their prohibition.
To be clear, I am not advocating an unregulated psychedelic free for all. The trials mentioned here consist of carefully controlled doses, with participants supported by professional therapists.
But there is value in considering how profound experiences, not necessarily unchallenging ones, might have transformative power. For a start, psychedelic experiences of connectedness might help get beyond feelings of futility and isolation in the face of the climate crisis, when we think of ourselves only as helpless individuals, helping us to forge connections and see wider patterns.
Powerful experiences of nature might be especially significant today too. We increasingly live in an age of extinction. Nature is in retreat, urbanism and everyday alienation from nature is establishing itself as the norm, and we are confronting loss on a scale we find difficult to acknowledge and process.
In such unprecedented times, we can find ourselves trapped in dissociative psychological states, knowing about environmental crisis while doing all we can to stop that knowledge affecting us. This is true at an individual level but also in familiar social settings of shared silence and discomfort.
When we lack direct experiences of nature, are we missing a vital component of what is needed to really care for and take action on behalf of the environment of which we are an integral part?
Maybe, just maybe, the profound experiential connectedness arising from psychedelic experiences in nature is analogous to the application of a defibrillator following cardiac arrest. Perhaps psychedelics could give us the shock that is needed to restart the beating heart of ecological awareness before it is too late.
Disorders of consciousness (DoC) are the most devastating form of impairment that may follow acquired brain injury. In contrast to comatose patients, those in the vegetative state (VS) and minimally conscious state (MCS) exhibit signs of wakefulness (eye opening).
VS patients show no overt signs of awareness, whereas MCS patients show minimal but clearly discernible behavioural evidence of awareness.
A range of therapies have been proposed for patients with DoC, including pharmacological (e.g. zolpidem, amantadine) (Gosseries et al. 2014), invasive- [e.g. deep brain stimulation (DBS) (Vanhoecke and Hariz 2017), vagal nerve stimulation (VNS) (Corazzol et al. 2017)] and non-invasive electrical stimulation [e.g. transcranial direct current stimulation (Thibaut et al. 2014)], and transcranial magnetic stimulation (TMS) (Pistoia et al. 2013).
Classic psychedelics are currently undergoing significant investigation for the treatment of a range of psychiatric disorders (Carhart-Harris and Goodwin 2017).
Here, we propose that the classic psychedelic, psilocybin, be explored as a treatment to increase conscious awareness in patients with DoC. A scientific rationale is proposed based on findings from research into the neurobiology of DoC and the effects of psychedelics.
Developments in these hitherto separate fields of inquiry now suggest a potential therapeutic avenue, based on the twin discoveries that measures of brain complexity reliably index conscious level, and that brain complexity can be increased by psychedelics (Fig. 1).
Brain Complexity and Consciousness
Complexity is a multifaceted concept that pervades many branches of the physical and life sciences. In the neurosciences, many theoretical accounts of consciousness have related the complexity of dynamics in a neural system to the manifestation of conscious experiences (Tononi et al. 1994; Edelman 2009; Ruffini 2017; Carhart-Harris 2018).
One influential formulation has been that of neural complexity, proposed by Tononi and Edelman in 1994 (Tononi et al. 1994).
This concept accounts for two fundamental features of consciousness, namely differentiation, the property that any particular experience is composed of many different components and is distinguishable from any other experience, and also integration, the property that any given conscious experience involves the integration of components into a unified whole.
Importantly, neural complexity could, in principle, be calculated empirically, as the average mutual information—a measure of information sharing—between each subset and the rest of a system. Tononi and Edelman posited that during conscious awareness, ‘heterogeneous patterns of short-term correlations within the corticothalamic system will result in [high neural complexity]’ (Tononi et al. 1994).
Several theories of consciousness have since been advanced that emphasize a link between different formulations of complexity within brain activity and conscious level. Alongside these theoretical developments has been the introduction of a wide range of measures of dynamical complexity.
These various measures reflect the diversity of definitions of complexity in use [for review, see Arsiwalla and Verschure (2018), Seth et al. (2006); see also Bassett and Gazzaniga (2011), Cocchi et al. (2017) for broader reviews in complex systems theory] and differ in the extent to which they directly capture the properties of differentiation versus integration, as well as temporal versus spatial complexity, and in their computational feasibility for large datasets.
Despite heterogenous definitions of complexity, a prediction shared by many theories of consciousness is that complexity should be high in the normal awake state and low whenever consciousness is lost, be it through anaesthesia, non-rapid eye movement (REM) sleep, or acquired brain injury.
In the past two decades, a raft of empirical support for these predictions has emerged. Massimini and colleagues have provided striking evidence in favour of the principle via use of the so-called perturbational-complexity index (PCI). PCI quantifies the complexity of electroencephalogram (EEG) responses to pulses of TMS (Fig. 1A) (Casali et al. 2013).
This perturbational approach has been likened to hitting a bell and measuring the complexity of the reverberations that follow. The PCI has been shown to robustly index conscious level across a range of states, including wakefulness (where the PCI is highest), sedation, non-REM sleep and anaesthesia. In patients with DoC, the PCI is lowest in VS patients, followed by patients in the MCS, then those emerged from MCS (denoted EMCS).
In contrast, patients with locked-in syndrome, who have intact conscious awareness but cannot respond motorically, show PCI levels as high as healthy awake subjects (Casali et al. 2013).
At the heart of the PCI approach is quantification of the complexity of TMS-evoked EEG responses using an implementation of the Lempel-Ziv algorithm, a measure of compressibility which counts the number of unique patterns in a sequence, hence its everyday use in compressing large computer files (‘zipping’).
Importantly, the Lempel-Ziv complexity (LZC) measure can also be applied to EEG recordings of spontaneous brain activity, i.e. without TMS perturbation. Whilst there are substantial differences between the spontaneous and perturbational approach, particularly that PCI evaluates only the complexity of deterministic responses of the cortex to TMS (Casali et al. 2013), the LZC of spontaneous EEG also effectively differentiates between conscious and unconscious states [including anaesthesia (Bai et al. 2015; Schartner et al. 2015) and sleep (Schartner et al. 2017b)].
In DoC, LZC-based values of spontaneous EEG reliably discriminate VS from MCS patients (Wu et al. 2011; Sitt et al. 2014) and values increase monotonically with patients’ conscious level (Sitt et al. 2014).
Our interpretation of these spontaneous EEG results is that LZC principally captures the variability or diversity of brain activity (i.e. differentiation rather than integration), and so behaves similarly to other measures of information entropy (i.e. capturing signal diversity over time).
Please see Schartner et al.(2015) and Mediano et al. (2019) for further discussion of these topics, and note that, for the sake of disambiguation, from here on, when we refer to ‘complexity’ we are referring to the ‘differentiation’ component in the original conception of ‘brain complexity’, i.e. the component that is measurable via LZC or a related entropy-based metric.
Psychedelics Increase Brain Complexity
Until recently, it was generally assumed that, in terms of states of consciousness, brain complexity would be maximal during normal wakefulness, since all other tested states of reduced consciousness (e.g. non-REM sleep, anaesthesia, DoC) feature correspondingly lower complexity values.
It was therefore remarkable to discover that brain complexity values recorded during the psychedelic state exceed those found in normal waking consciousness (Fig. 1B). Specifically, in human subjects, increases in brain complexity (LZC) in excess of those seen in normal wakefulness were observed with psilocybin, lysergic acid diethylamide (LSD) and ketamine (at ‘psychedelic-like’ doses) (Schartner et al. 2017a).
This finding has been replicated using a variety of complexity measures and measurement tools, including EEG, magnetoencephalography and functional MRI [see Carhart-Harris (2018) for review]. Furthermore, the magnitude of complexity increases correlated with the subjective intensity of the psychedelic experience (Schartner et al. 2017).
Increase Complexity, Increase Conscious Awareness?
Given that impairments in conscious awareness appear to closely relate to reductions in measures of brain complexity and psychedelics robustly increase brain complexity, could psychedelics elevate conscious awareness in patients with DoC?
Note that this hypothesis does not require that brain complexity be the cause of conscious awareness. Brain complexity per se may rather, in the terminology of Seth and Edelman (2009), be an explanatory correlate of the neural processes intimately related to conscious awareness.
With this qualification in mind, a key question for our proposal is whether it is possible to increase measures of brain complexity without increasing conscious awareness.
If it were possible, then this would negate our hypothesis and call into doubt the relationship between consciousness and brain complexity, at least as we define it here.
The classic psychedelic, psilocybin, is currently undergoing substantial clinical investment (Carhart-Harris and Goodwin 2017). Psilocybin is a prodrug of psilocin (4-hydroxy-dimethyltryptamine), whose principal psychoactive effects appear to be mediated by serotonin 2A (5-HT2A) receptor agonism.
Psilocybin elevates measures of brain complexity in healthy humans (Schartner et al. 2017a; Carhart-Harris 2018) and many other lines of evidence support the idea that psilocybin could elevate conscious awareness in patients with DoC. The 5-HT2Areceptors have their densest expression in the high-level cortical areas belonging to the default-mode network, which has been strongly implicated in conscious processing as well as the psychedelic state (Guldenmund et al. 2012; Beliveau et al. 2017; Carhart-Harris 2018). Most 5-HT2A receptors are expressed post-synaptically on layer 5 pyramidal neurons (Berthoux et al. 2018).
These large, deep layer neurons are known to be key integration units in the cortex, and are the only cell type with dendrites spanning all cortical layers (Shai et al. 2015). In addition, presynaptic 5-HT2A receptors located at thalamo-cortical synapses have been shown to play an important role in the control of thalamo-frontal connectivity, also known to be important for consciousness (Giacino et al. 2014; Barre et al. 2016). 5-HT2Areceptor agonism in animals is associated with enhanced cognitive flexibility as well as cortical neural plasticity (Frankel and Cunningham 2002; Boulougouris et al. 2008; Furr et al. 2012; Zhang and Stackman 2015; Ly et al. 2018; Olson 2018) whereas 5-HT2A receptor antagonism is associated with reduced cognitive flexibility and increased slow-wave sleep (Carhart-Harris and Nutt 2017). We recognize that one should be cautious when extrapolating from findings in animals to humans. However, there is some tentative evidence that cognitive flexibility is also enhanced in humans under psychedelics (Kuypers et al. 2016), although we would be hesitant to infer from this that psychedelics can enhance cognitive performance [see also Bayne and Carter (2018) and Carhart-Harris and Nutt (2017)].
Complexity, Conscious Content and Arousal
The standard conception of consciousness is that it encompasses two inter-related dimensions (Laureys et al. 2009; Boly et al.2013): (i) the ‘content’ of consciousness, thought to be primarily related to cortical mechanisms, and (ii) wakefulness, or arousal, which subserves (i) and is controlled by the ascending activation systems of the brainstem and basal forebrain (i.e. the reticular activating system) (Boly et al. 2013). A key question is: how do these dimensions relate to measures of brain complexity like LZC?
Studies of impaired consciousness suggest that LZC and related measures of complexity chiefly index conscious content rather than arousal, e.g. as shown by the reductions in LZC that differentiate VS from MCS patients (Casali et al. 2013; Sitt et al. 2014) and non-REM from REM sleep (Abásolo et al. 2015).
To our knowledge, there is no evidence that stimulant drugs, such as D-amphetamine or methylphenidate, which primarily increase arousal, increase brain complexity measures. In the case of psychedelics, our own experience is that arousal provides minimal explanatory value for describing the quality of the psychedelic experience.
Moreover, we have argued that the evidence overwhelmingly suggests that psychedelic-related elevations in LZC or information entropy (to which LZC is closely and formally related) reflect an increased richness of conscious experience (Carhart-Harris 2018). Together, these observations suggest that targeting increases in conscious content, rather than (or perhaps in addition to) arousal, may be key to increasing conscious awareness in DoC patients.
Experiments comparing psychedelics with stimulant medications may help address the question of whether drugs presupposed (here) to increase conscious content (e.g. psilocybin) have more significant effects on brain complexity, and conscious content, than drugs that primarily promote arousal.
Neurotransmitter systems implicated in the regulation and maintenance of arousal include noradrenaline, dopamine, acetylcholine, orexin, adenosine, histamine and 5-HT (Boutrel and Koob 2004; Ciurleo et al. 2013; Mura et al. 2014).
Most classic stimulants act on catecholamines, and drugs such as D-amphetamine (Zhang et al. 2009), levodopa (Krimchansky et al. 2004) and modafinil (Dhamapurkar et al.2017) have been used in DoC patients, with evidence of modest and variable clinical effects [see Ciurleo et al. (2013) and Mura et al.(2014) for review]. Our working hypothesis is that psilocybin is able to enhance conscious awareness to a greater extent than these stimulant-based alternatives.
The Relevance of a Multidimensional Conception of Consciousness
The current classification of DoC uses a taxonomy of states of consciousness ordered along a single scale, i.e. with EMCS patients having a higher level of consciousness than MCS patients who, in turn, have a higher level of consciousness than VS patients. However, recent challenges to this standard unidimensional construct of ‘levels of consciousness’ have been proposed (Bayne et al. 2016, 2017; Bayne and Carter 2018).
These commentaries argue that the full range of consciousness-related capacities would be better classified using a graded, multidimensional space that captures, e.g. cognitive, sensory, affective and behavioural characteristics (Bayne et al. 2017).
The same criticism has been levelled to applying the ‘levels of consciousness’ construct to all global states of consciousness—e.g. alert wakefulness, REM sleep, general anaesthesia, absence seizures and the psychedelic state—in that it fails to do justice to the evidently multifaceted nature of these states (Bayne et al. 2016; Bayne and Carter 2018).
We are sympathetic to this view but also mindful of the pragmatic value of simple guiding principles in science. Thus, it remains to be seen how such a multidimensional framework, the details of which remain somewhat underspecified (Bayne et al. 2016), will align with the unidimensional complexity measures such as PCI and LZC that dominate empirical studies of states of consciousness and indeed current theories of consciousness (Baars 2005;Tononi et al.2016; Carhart-Harris 2018).
As we acknowledged earlier, we see our proposal (to explore psychedelics as a treatment in DoC) as a challenge to the unidimensional conception of conscious level as indexed by brain complexity, in that to find a dissociation between complexity increases and conscious awareness would suggest important limitations to this simplistic framework.