Psychedelics are an increasingly fashionable medical treatment, but are they anything other than a powerful form of snake oil, or a recreational experience? Do they have any objective health benefits? Can we be confident they are safe? These questions need answering urgently as the number of people being enticed or persuaded to have these drugs is increasing. Here I draw attention to some of the issues raised by the current popularity of these drugs.

The original psychedelics include psilocybin, the active ingredient of ‘magic mushrooms’ and lysergic acid diethylamide, popularly known as LSD. The recreational drugs MDMA (ecstasy) and ketamine have some psychedelic-like effects, in that there is a ‘trip-like’ quality to the altered state they produce. 

Psychedelics are now being recommended to treat an ever-lengthening list of problems, including depression, anxiety, addiction, PTSD, chronic pain and distress associated with having a terminal illness. Books about them have become best-sellers (1), and various foundations are promoting and funding research into psychedelics, presumably in the hope that they will soon be licensed for medical use (2). Ketamine, usually delivered intravenously, is already on offer through numerous private clinics in the US, and several have opened in the UK, including at least one provided by the NHS (although the treatment has to be paid for privately) (3). This is possible because ketamine is licensed as an anaesthetic and can therefore be re-purposed ‘off-licence’ for other medical uses. Esketamine, an isomer of ketamine taken as a nasal spray, has been licensed for the treatment of treatment resistant depression in the US, UK and Europe.

The rationale behind this trend is confusing and contradictory. On the one hand, psychedelics are promoted as assisting the process of psychotherapy through the insights that the ‘trip’ or drug-induced experience can generate – on the other they are claimed to represent a targeted medical treatment for various disorders, through correcting underlying brain deficiencies. In an interview published in Nature, psychopharmacologist and psychedelic researcher, David Nutt, suggests that psychedelics ‘turn off parts of the brain that relate to depression’ and ‘reset the brain’s thinking processes’ via their actions on cortical 5-HT_2A receptors (4). Others assert they enhance brain ‘connectivity’ (5). John Hopkins University website alleges they offer the promise of ‘precision medicine treatments tailored to the specific needs of individual patients’ (6). All these claims are pure speculation.

Some promoters refer to psychedelics as ‘antibiotics of the mind,’ arguing that psychedelic treatment is ‘curative’, requiring only one or two ‘dosed sessions’, compared to the long-term treatment needed with antidepressants or psychotherapy (7). This is an important sales pitch for what is an expensive therapy. In reality, psychedelics do not produce the miracle cures people are led to expect, as experience with ketamine confirms. Some people may feel a little better after a treatment, and then the effect wears off and they come for another one and another one, and get established on long-term treatment just as people do on antidepressants (8).

Esketamine, the ketamine isomer delivered in a nasal spray, has been launched by Janssen and is clearly intended as a long-term treatment, with randomised trials testing and proclaiming its ‘relapse prevention’ effects (9) (for a critique of this and other research on esketamine, see a previous blog).  The concept of microdosing with LSD or other psychedelics follows the same principle, promoting the idea that small doses of the drugs, taken on a daily basis, enhance people’s mood, creativity and productivity (10). This practice appears to be increasingly common, with one recent survey finding that 17% of respondents, with an average age of 33, had engaged in it on a regular basis at some point (11). It seems once unleashed, drugs tend towards a pattern of long-term use, with all the physical and psychological complications that that entails.

So are the effects of psychedelics likely to be beneficial? The psychedelic-induced experience or ‘trip’ has long been advocated as a means of expanding one’s consciousness, of seeing the world in a different way that can lead to new insights and inspiration. MDMA produces intense feelings of warmth and connectedness and ketamine leads to a trance like state. All these drugs can make people ‘high’ or euphoric, but, despite this, not everyone likes the feelings they induce, and some of them, particularly those with the most intense psychedelic effects, can produce experiences that are frightening and distressing- the ‘bad trip’.

Some people might learn important things about themselves through experiencing the effects of psychedelic drugs. Author and psychotherapist, Gary Greenberg, describes taking ecstasy in his book, Manufacturing Depression, and how the emotion he felt while under the influence of the drug made him realise the depth of his feelings for his girlfriend, which he had not been aware of before (12). Personal development through drugs does not have to be limited to psychedelics, however. One patient I knew commented that the effects of alcohol had shown him how to overcome his shyness or social anxiety, such that he then learnt to socialise without it (of course, sometimes, alcohol used in this way can become a problem in its own right). Another patient described how her experience of taking stimulant-type drugs for Parkinson’s disease (which she subsequently had to stop) taught her to loosen up and do things for herself instead of focusing solely on her family’s needs. 

But these benefits are not medical or health effects. They are akin to the personal development that people achieve through other sorts of activities and life experiences like singing, dancing, being in nature, sports and many more things. And although the concept of drug-assisted psychotherapy acknowledges that it is the way the psychoactive effects of the drugs are used to promote a process of personal learning that is relevant, why not employ other, safer and cheaper methods? Why not nature-assisted psychotherapy (a walk in the park), for example? Moreover, as described above, increasingly the use of these drugs is portrayed in other ways, as if they work by targeting underling dysfunctional brain processes. When, and if, psychedelics get a medical license, the psychotherapy is likely to be dropped or minimised. As with ketamine, the tendency of all psychedelic treatment will be towards the provision of the drug in the cheapest possible way, which means the minimum of supervision and therapy (8).   

As usual, official research over-plays the actual beneficial effects of the drugs. In a small, randomised trial comparing psilocybin assisted psychotherapy to a regular antidepressant and psychotherapy, there was no difference on the primary outcome. The trial was still published in the prestigious New England Journal of Medicine. Secondary outcomes that found small differences were highlighted with no consideration of the ‘placebo’ effects of having a recognisable drug-induced experience, and the participants recruited were not typical of those with depression, consisting mainly of well-educated men, almost a third of whom had tried psychedelics before (which means they certainly knew whether they received the active psilocybin or the placebo, and were likely disappointed if they received the placebo) (13).

Most psychedelic research pays no attention to the way the immediate psychoactive effects of the drugs inevitably impact on people’s feelings and behaviour, in a way that will influence mood symptom ratings and may produce the impression of improvement. In its report on ketamine treatment, the American Psychiatric Association (APA) state that there is ‘compelling evidence’ that ‘the antidepressant effects of ketamine infusion are rapid and robust’ (14). Despite admitting they are also ‘transient’, the APA do not explain how these so-called ‘antidepressant effects’ can be distinguished from the euphoria and other mental alterations associated with acute ketamine intoxication. If ketamine’s effects are ‘antidepressant’ then so are the effects of all the other drugs that produce short-term euphoria including alcohol, cocaine, heroin, amphetamines etc

Along with pharmacologically-induced alterations, any powerful mind-altering drug is likely to have ‘placebo’ effects; in other words, the drug-induced experience will lead people to expect that they will improve, and this expectancy may, in turn, cause them to improve, or at least to think they have improved. To determine whether psychedelic effects are specifically associated with insights that help people recover from depression or other conditions requires a comparison between psychedelics and other psychoactive drugs such as amphetamines, benzodiazepines or opiates, for example. Similar effects might also be obtained by other methods for inducing trance-like states such as meditation or strenuous exercise.  

Research on psychedelics also neglects the profound placebo effect that is likely to be produced by the hours of medical supervision and professional attention associated with psychedelic treatment, whether this constitutes formal psychotherapy or not. Some of the esketamine trials, for example, found that people taking the placebo spray had a huge reduction in their depression rating scale scores (15). In these trials, participants, who had ‘treatment resistant depression’, had twice weekly administration of the drug or placebo spray followed by up to 4 hours of medical observation on each occasion – that’s 8 hours of professional attention every week (16)! We know that clinical contact improves people’s outcomes in depression (17), and it seems this high level of contact in the esketamine trials exerted a powerful effect even in people with severe and persistent symptoms. 

The current craze for psychedelics also means the adverse effects are being minimised or overlooked. The ‘bad trip’ is a well-recognised phenomenon, and may not be that uncommon. Psychiatrist, Rick Strassman, author of DMT: the Spirit Molecule, described how half of the 60 volunteers he injected with the powerful hallucinogen, DMT (N,N-dimethyltryptamine), experienced terrifying hallucinations and anxiety, and he discontinued his research, in part because of these effects (18). Science journalist, John Horgan, describes months of depression and flashbacks following a ‘bad trip’, and also reminds us that Albert Hofman, who first synthesised LSD, also had doubts about it, calling his 1981 memoir LSD: My problem child (18).

Advocates point out that context helps determine the nature of the drug-induced experience, so  providing staff to support people while they are under the influence of the drug, and to process their thoughts and feelings afterwards, should prevent bad trips. On the other hand, a clinical situation might be a highly alienating experience and might even induce a bad trip for some people. In any case, psychedelic experiences are by their nature unpredictable. 

There is something fascinating about psychedelics drugs – the fact that certain chemicals can distort sensory perception and produce vivid hallucinations calls into question our normal experience of the everyday world. Some people find their effects enlightening, some do not. This depends as much on how the drug-induced experience is interpreted. ‘How we imagine these substances as “plant medicines,” “drugs,” or as “a doorway to the divine” is just as important as their neurochemical effects,’ as Shariq Khan points out (19). Nevertheless, they can be frightening or unsettling at times, and evidence that they produce consistent benefits for people’s wellbeing or mental health is lacking. While one or two doses of most drugs is unlikely to do much harm, the tendency is for long-term use, and repeated use of psychedelics as of other drugs is unlikely to be completely harmless. As with so many other medical treatments, they have become popular through the potent mixture of financial interests and desperation. If the occasional benefit of psychedelics is to promote personal development through an unusual experience, then there are many safer routes to this goal.  

Notes and references

1. Pollan, M. (2018) How to Change Your Mind: The New Science of Psychedelics. Allen Lane
2. https://mindmedicineaustralia.org.au/
3. https://www.oxfordhealth.nhs.uk/ketamine-service/
4. https://www.nature.com/articles/d41573-021-00087-7
5. https://www.dazeddigital.com/science-tech/article/52274/1/inside-the-uks-first-ketamine-therapy-clinic-psychedelic-psychotherapy
6. https://hopkinspsychedelic.org/
7. https://d3n8a8pro7vhmx.cloudfront.net/catefaehrmann/pages/455/attachments/original/1599540132/MindMedicineAustralia_Presentation.pdf?1599540132
8. https://www.scientificamerican.com/article/is-the-ketamine-boom-getting-out-of-hand/
9. https://pubmed.ncbi.nlm.nih.gov/31166571/
10. https://longevitylive.com/anti-aging/psilocybin-mushrooms-are-making-a-comeback/
11. https://www.tandfonline.com/doi/full/10.1080/02791072.2020.1718250
12. https://www.amazon.co.uk/Manufacturing-Depression-Secret-History-Disease/dp/1408800977
13. https://www.nejm.org/doi/full/10.1056/NEJMoa2032994
14. https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15040465 (P 958)
15. https://www.fda.gov/media/121376/download
16. https://pubmed.ncbi.nlm.nih.gov/32087801/
17. https://pubmed.ncbi.nlm.nih.gov/17401033/
18. https://blogs.scientificamerican.com/cross-check/as-psychedelics-revival-rolls-on-don-t-downplay-bad-trips/
19. https://www.madinamerica.com/2020/02/psychiatry-capitalism-recuperation-psychedelics/