By Lauren Wheeler
You may or may not be familiar with the term ‘psychedelics’, used to describe a group of psychoactive drugs that have the potential to induce non-ordinary states of consciousness, producing changes in a person’s perception, thoughts and feelings.
Two such drugs are psilocybin (which occurs naturally in ‘magic mushrooms’) and lysergic acid diethylamide (LSD) which were first synthesised in the 1950s by the chemist, Albert Hoffman. The potential therapeutic use of these compounds to treat patients with psychiatric conditions quickly became clear when scientists studying the drugs found them to be effective in the treatment of a range of disorders such depression, anxiety and addiction.
Unfortunately, despite their tremendous promise in the treatment of mental health conditions, by the end of the 1960s, the drugs had become associated with dangerous recreational practices and eventually with the anti-Vietnam war movement in the US. This ultimately led to them being banned globally, classed as schedule 1 (or Class A) drugs alongside the likes of heroin, cocaine and methamphetamine.
Recently, however, the drugs have been catapulted back into the neuropsychiatric spotlight, as new research into their effect on the brain has begun to emerge. This includes findings from the lab of Dr Rowland Griffiths who demonstrated, in an initial study (Griffiths et al., 2011) on healthy volunteers, that a single dose of psilocybin could alter brain function in a way that induced profound spiritual experiences and lasting anti-depressant effects.
In contrast to the transitory nature of most recreational drug ’trips’, Griffiths showed that psychedelics could induce ‘sustained positive changes in attitudes, mood, and behaviour’. Over one year later, 94% of participants still reported the experience as ‘among the 5 most spiritually significant experiences of their life’, with 39% rating it ‘the single most meaningful experience’.
Researchers at Imperial, working under Dr Robin Carhart-Harris, are also conducting trials investigating the use of the psilocybin to combat treatment-resistant depression. These involve patients with severe depression who have observed no improvement in their symptoms after a least two rounds of treatment with traditional antidepressants (Carhart, 2016). Initial results from these studies suggest that the drug is not only safe but also highly effective in relieving depressive symptoms. One week after taking a single dose of psilocybin, over two-thirds of patients were in remission (i.e. no longer classed as depressed according to the Hamilton Depression Rating Scale) and 58% remained in this state for at least three months after the initial experience. These results hint at the untapped potential of these drugs for improving outcomes in psychiatric care.
But how do psychedelics work? What are the mechanisms that result in the drugs having such profound and enduring positive effects in the brain?
Psychedelics, such as LSD, psilocybin and 5-DMT (found in ayahuasca – a psychoactive brew used by indigenous tribes in the Amazon), act on serotonin 2A (5-HT2AR) receptors in the brain, increasing the neuronal firing rate and ‘initiating a cascade of neurobiological changes’ (Carhart, 2019). This includes the alteration of the typical, rhythmical pattern of brain waves, which become increasingly disordered (see figure 1). The 5-HT2AR receptors are most commonly found in the cortex, ‘the thinking brain’, likely explaining their ability to trigger fundamental changes in higher-level consciousness (i.e. being conscious that you are conscious). The hypothesis that the existential experience described by subjects is initiated by the drugs, at the molecular level, through the stimulation of these receptors is further supported by the fact that when the receptor is blocked, no effect on brain function is observed.
The increased entropy, or disorder, which psychedelic drugs create in the brain enables the mind to ‘escape’ its usual rigid thought patterns and modes of operation (Nutt et al., 2020). There is a disintegration of established neural pathways accompanied by a rise in communication between distinct regions of the brain, referred to as an increase in global brain connectivity (depicted in figure 1).
Psychedelic-assisted psychotherapy takes advantage of this relaxation of higher-level beliefs, taking advantage of the brain’s increased plasticity to revise pathological thinking styles and maladaptive beliefs. For example, to target negative beliefs about an individual’s self-worth in depression, or to examine the consequences of failing to perform ritualistic behaviours in obsessive-compulsive disorder.
Figure 1: A diagram to illustrate psilocybin’s 3 primary mechanisms of action: an increase in global brain connectivity, entropic brain activity and pyramidal neuron excitability. The image was taken from Psychedelic Psychiatry’s Brave New World (Nutt et al., 2020)
It should be noted, however, that psychedelics are not suitable for everyone. Patients who suffer from, or who have a family history of, psychotic disorders such as schizophrenia or bipolar disorder are advised against taking the drugs. Whilst the increase in brain entropy caused by psychedelic drugs is useful for disrupting rigid thought patterns in mental health conditions categorised by fixed beliefs, this phenomenon can wreak havoc for psychosis suffers, whose brains are on the high-chaos end of the consciousness spectrum. It has therefore been proposed that the drugs may lead to a person with a predisposition to mania or psychosis to develop a full-blown disorder, or may worsen symptoms of patients with these conditions. As a result, recent trials have excluded this cohort from participation.
Despite this caveat, for the majority of people, especially the vast numbers of patients suffering from severe mental illness, psychedelics offer a perfectly safe and potentially life-changing opportunity to explore entrenched patterns of thoughts and behaviour. Furthermore, the combination of the drugs with psychotherapeutic intervention presents scope for replacing these established ways of being with favourable belief systems and practices.
Griffiths, R.R., Johnson, M.W., Richards, W.A., Richards, B.D., et al. (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology. [Online] 218 (4), 649–665. Available from: doi:10.1007/s00213-011-2358-5.
Carhart-Harris, R.L., Bolstridge, M., Rucker, J., Day, C.M.J., et al. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry. [Online] 3 (7), 619–627. Available from: doi:10.1016/S2215-0366(16)30065-7.
Carhart-Harris, R.L. (2019) How do psychedelics work? Current Opinion in Psychiatry. [Online] 32 (1), 16–21. Available from: doi:10.1097/YCO.0000000000000467.
Nutt, D., Erritzoe, D. & Carhart-Harris, R. (2020) Psychedelic Psychiatry’s Brave New World. Cell. [Online] 181 (1), 24–28. Available from: doi:10.1016/j.cell.2020.03.020.