The other week I interviewed for what is pretty much my dream job. The role was to support the running of two clinical trials looking at the effectiveness of talk therapy assisted by two drugs; psilocybin, a classic psychedelic, and MDMA, a psychedelic-amphetamine, or more accurately, an entactogen. During the interview, I was asked about why I’m interested in psychedelics. For a long time, I’ve thought that psychedelics hold great potential for mental health and are of significant interest to neuroscience, yet in the interview strong reasons came slowly. So, having had the chance to reflect, here are some of the reasons why I’m interested in psychedelics.
1. Their efficacy in treating mental health conditions demands our attention
Firstly, these drugs are interesting for their success rates in treating mental health conditions. Clinical studies have found promising benefits of psychedelic substances (when taken in a supportive context, following considerable preparation and followed by ‘integration’ psychotherapy sessions) for people with a wide range of treatment-resistant mental illnesses, including depression, PTSD, depressive and anxious symptoms related to terminal illness, OCD and substance use disorders.
Some examples: A recent randomised, placebo-controlled trial of psilocybin for people with a diagnosis of Major Depressive Disorder (MDD) found that 71% of participants experienced a clinically significant improvement after two sessions of psilocybin and 11 hours of supportive counseling before and after the sessions (Davis et al., 2020). This is over twice as effective as our current standard treatments (Kolovos et al., 2017). Similarly, in a small open-label study of psilocybin for people quitting smoking (Johnson, Garcia-Romeu, & Griffiths, 2017), two-thirds had quit smoking 12 months after treatment. Again this is twice as effective as our current standard treatments. MDMA-assisted therapy has been designated as a ‘breakthrough therapy’ by the FDA (MAPS, 2017), the US drug regulator, following studies that found that MDMA for PTSD resulted in a clinically significant reduction in symptoms for some 80% of participants (Mithoefer et al., 2019).
These results, while promising are preliminary. More studies are needed to better understand effectiveness of psychedelics, especially beyond the most studied condition-drug combinations (MDMA for PTSD, psilocybin for depression and psilocybin for anxiety associated with terminal illness). And there are good reasons to think that the effects won’t be as promising as initial trials have found (e.g., a likely greater placebo component due to the novelty of the agent, difficulties in blinding, heightened participant expectations, and increases in suggestibility linked to psychedelics [Payne, Chambers, & Liknaitzky, 2021]). But if the effects of future studies are in the ballpark of the trials to date, then psychedelic-assisted therapies have an amazingly favourable benefit-risk ratio when taken in the manner researched. While “bad trips” (characterised by overwhelming fear, panic and anxiety), intrusive flashbacks (or HPPD) and the risk of inducing psychosis are prominent in the discourse against psychedelics, clinical trials to date have suggested that the risks are favourable when used responsibly (Johnson, Richards & Griffiths, 2008). It’s also worth highlighting that they aren’t addictive (Johnson, Griffiths, Hendricks, & Henningfield, 2018). On balance, it seems that psychedelics will have an important place among mental-health treatments in the future.
Addendum: A recent randomised controlled trial highlights the point above about the probability that future results of psychedelic-assisted therapies are likely to be less outstanding than early results. Two treatments were compared; two large doses (25 mg) of psilocybin plus 6 weeks of daily placebo vs. two negligible doses (1 mg) of psilocybin plus 6 weeks of daily oral escitalopram (an SSRI). While secondary outcomes generally favored psilocybin over escitalopram, the primary outcome measure (of depression symptoms) did not show a significant difference between groups. As effective as the current gold standard isn’t bad, but it isn’t the revolution that some people are hoping for (unless the people it works for isn’t tightly overlapping with people who respond well to SSRI anti-depressants).
2. They reliably induce profound ‘spiritual’ experiences
At the right dosage, with the right preparation and in the right setting, psychedelics can induce powerful, meaningful experiences that seem to be genuine examples of the ‘mystical experiences’ that feature in the accounts of prophets and saints from religious and spiritual traditions that span the globe. These experiences are often described (e.g. Stace, 1960; Schrader 2008) as an intense and direct encounter with God and are characterised by; sacredness: a sense that what is encountered sacred; dissolution of the sense of self and sense of unity: a sense that all things are one, or an experience of a ‘void’ or ‘pure consciousness’; a noetic quality: a sense of encountering a reality or truth that is more real or true than usual everyday reality; deeply felt peace/joy/awe; ineffability: the experience is difficult to put into words; paradoxicality: to explain the experience, one seems to have to use illogical or contradictory statements and altered sense of time and space.
Remarkably, psychedelics can induce such experiences reliably. In a double-blind study Griffiths et al. from 2006, 33% of participants rated the psilocybin experience as being the single most spiritually significant experience of their life, with an additional 38% rating it to be among the top five most spiritually significant experiences. This is remarkable as it suggests that psychedelics provide a unique means to experimentally study a prototypical spiritual experience (not to mention a number of interesting aspects of how brains and subjective experience are related).
3. They have been used in important mainstream cultural rites, rituals and healing practices for people all around the world.
Historically, humans employed a wide variety of psychoactive substances from botanical and animal sources, as well as non-drug methods to alter consciousness in religious contexts. Carl Ruck describes the resulting non-ordinary states as “central to the historical record of humankind’s spiritual quest”. Indeed, humans around the world and throughout time had non-ordinary states as central to their sacred rituals and rites of passage. And in some of the most notable examples of such practices, psychedelics were the means of inducing these non-ordinary states.
The ancient Greeks added a variety of psychedelic and other potent psychoactive substances to wine including serpent and salamander venoms, hemlock, jimsonweed, aconite, cannabis, wormwood, ergot, and probably N,N-Dimethyltryptamine (DMT) from acacia and similar plants. And a psychedelic brew likely featured at the climax of the once in a lifetime rite of passage known as the Eleusinian Mysteries, about which Cicero said “nothing is higher than these mysteries…they have not only shown us how to live joyfully but they have taught us how to die with a better hope”. Similarly, the ‘Soma’ that is much lauded in the texts of the Hindu religion (and some of the oldest extant texts in any Indo-European language), was likely a psychedelic or other potent psychoactive drink. Cannabis was also used among religious practices and pursuits in India. To this day, Ayahuasca, (a plant compound containing DMT, a psychedelic) is used in the healing ceremonies of people in the Amazon and the Indigenous people of North American use the Peyote cactus (containing mescaline, another psychedelic).
Some theorists have even proposed a pivotal role for psychedelics in the birth of human spirituality and religion and the recent evolution of the brain. Such claims are highly speculative. A more conservative and less controversial proposal is that psychedelics significantly influenced our metaphysical and spiritual beliefs. Regardless, I find it intriguing that non-ordinary states were likely pursued and installed in cultures – possibly because of the belief that they were spiritually profound, and/or due to their socially beneficial behavioural effects.
4. They seem to work in a very different way to current psychiatric medications.
Beyond their efficacy and impressive benefit-risk profile, psychedelics are notably different from other psychiatric medications in terms of how they work. We don’t talk about the spiritual import of other psychiatric medications! This is because, in contrast to other psychiatric medications, meaningful subjective experiences are an important factor in the effectiveness of psychedelics. The more powerful an experience someone has, the greater the likely benefit they will show from the treatment. More generally, the experience people have while taking psychedelics seems important for their therapeutic effect, while conventional medications are understood to work more mechanistically, and can be more effectively described on a primarily neurochemical level.
Pragmatically, psychedelics tend to have long lasting effects resulting from a very brief treatment protocol, for a significant proportion of the mental health burden. This stands in strong contrast to conventional psychiatric medications which treatment guidelines recommend for long-term use (American Psychiatric Association, 2010). And moreover, people often use these conventional medications inconsistently or stop taking them altogether due to common undesirable side-effects (Oslow et al., 2017).
In fact, mystical-type experiences (mentioned above) are an example of a powerful subjective experience that is strongly linked to therapeutic benefit. In study after study, whether looking at tobacco addiction, depression, or anxiety, the greater the degree to which someone has a mystical-type experience on psychedelics the greater the therapeutic change and benefit. These experiences seem to make possible extraordinary change, like non-psychedelic induced transformative experiences sometimes reported by people at a turning point in their addiction-recovery, for example. And with so much of the mental health burden seemingly related to an excess of rigidity (think depression, anxiety, OCD, addiction), the ability to reliably promote the possibility of change and flexibility could be an important therapeutic procedure.
Conclusion
I find psychedelics interesting for their efficacy, the fact that they work differently from other psychiatric medications, and their profound (both individually and culturally) subjective effects. Increased efficacy and/or different mechanisms of action to other psychiatric medications means that more people with mental health challenges will be helped, potentially including those who have not been helped by other means. The spiritual and cultural importance of the psychedelic experience is suggestive of its ability to not only reduce symptoms, but to promote growth and wellbeing. Better understanding how psychedelics work (and how they can be used) promises to be a fascinating enterprise for psychology and neuroscience, and one that will likely lead to a better understanding of mental health, wellbeing and consciousness.
Ps. I got the job!
References
American Psychiatric Association . Practice guideline for the treatment of patients with major depressive disorder. Washington, DC: American Psychiatric Association, 2010.
Davis, A. K., Barrett, F.S., May, D.G., et al. (2020) Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2020.3285
Johnson, M. W., Richards, W., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety. Journal of psychopharmacology (Oxford, England), 22(6), 603–620. https://doi.org/10.1177/0269881108093587
Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American journal of drug and alcohol abuse, 43(1), 55–60. https://doi.org/10.3109/00952990.2016.1170135
Johnson, M. W., Griffiths, R. R., Hendricks, P. S., & Henningfield, J. E. (2018). The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology, 142, 143–166. https://doi.org/10.1016/j.neuropharm.2018.05.012
Kolovos, S., van Tulder, M. W., Cuijpers, P., Prigent, A., Chevreul, K., Riper, H., & Bosmans, J. E. (2017). The effect of treatment as usual on major depressive disorder: A meta-analysis. Journal of affective disorders, 210, 72–81. https://doi.org/10.1016/j.jad.2016.12.013
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 236(9), 2735–2745. https://doi.org/10.1007/s00213-019-05249-5
Multidisciplinary Association for Psychedelic Studies (MAPS):FDA agrees to phase 3 trials of MDMA-assisted psychotherapy forPTSD. November 29, 2016. https://maps.org/research/mdma/ptsd/6480-fda-agrees-to-phase-3-trials-of-mdma-assisted-psychotherapy-for-ptsd
Ostrow, L., Jessell, L., Hurd, M., Darrow, S. M., & Cohen, D. (2017). Discontinuing Psychiatric Medications: A Survey of Long-Term Users. Psychiatric Services, 68(12), 1232–1238. https://doi.org/10.1176/appi.ps.201700070