It’s starting again: the focus on the downsides of psychedelics.
Recently, I read this Vice article and this piece in the Australian & New Zealand Journal of Psychiatry, both outlining the downsides of and challenges ahead for psychedelic medicine. In this newsletter, I push back on some of the issues raised in these, and other, recent publications.
Let’s get into them.
It’s possible to have a bad trip or adverse outcome. I mean, duh? First of all, psychedelics are non-addictive and one of the safest central nervous system drugs, with no overdose deaths occurring from typical doses (of LSD, mescaline, and psilocybin)(1). Also, any therapeutic can have harmful effects. In fact, anything in life can have harmful effects. When we take prescription medications, we accept the (typically many) side effects that come with that medication. Is it possible to have a negative outcome, either physically or mentally, from a psychedelic substance? Of course, it is. But, it’s also possible to have a negative outcome every time you have a psychotherapy session. Healing is painful and difficult, and pursuing it is an arduous journey. Western scientific and medical culture has removed this narrative from psychological healing to some extent, catering to the desire of having quick and easy fixes to everything. But healing is more like a sinusoidal than a linear graph, and it would be beneficial to understand this trajectory to manage expectations. (I will write about bad trips and healing perspectives in a future newsletter issue.) Yes, the potential treatment harms of psychedelics should be systematically captured and categorized, including interactions with other substances, unforeseen physical or mental adverse events, etc. But, it’s not like we have no idea what the potential downsides of psychedelics are – they have been in the culture for decades, after all (and resources exist for harm reduction and support such as this and this and this). This brings me to my next point…
Why do we make it sound like there is no evidence of healing with psychedelics? The language used in reporting on the clinical trial evidence of psychedelics usually goes something like this: Clinical trials with psychedelic-assisted psychotherapy are beginning to show promising results for treatment-resistant disorders. I have used similar language myself. Yes, traditional clinical trials are lacking, or just beginning to be built up, because of the legal and societal roadblocks that have barred entry into the psychedelic space for the past few decades. However, there have been over fifty years of experience in this therapeutic field (not to mention the thousands of years of indigenous use). There exists tons of therapeutic data — data straight from the practices of behavioral health practitioners providing psychedelic therapy — from the 1950s to the 1970s (see some refs here). Additionally, from the 1970s to the current day, underground psychedelic treatment has continued operation, so therapeutic data has been continuously accumulating. The therapeutic use of psychedelics over all these years simply hasn’t been standardized and rigorously tested by clinical trials, but that doesn’t mean it’s not available and not valuable. The Vice article reported there is “zero clinical research on how to support people after difficult psychedelic experiences.” The use of this type of language might lead one to believe that no one has ever thought about how to support people after difficult psychedelic experiences, but of course, that is simply not true. Clinical trials are the gold standard, but they’re not the only kind of empirical evidence.
Are double-blind, randomized controlled trials (DB-RCTs) the only way forward? The paper in the Australian & New Zealand Journal of Psychiatry raises a common criticism of some of the recent psychedelic research trials: it’s difficult to “blind” patients because they can usually figure out whether they have been given a psychedelic substance or not. If you’re only trying to parse out the mechanism and controlling for the placebo effect, then yeah, this is a problem – but one that can be addressed with creativity. However, using tightly controlled experimental setups (i.e. DB-RCTs) has its downsides, such as reducing an intervention’s efficacy when it is moved to the real world (because the real world’s conditions are radically different and messier than DB-RCTs). So, some psychedelic researchers argue (and I agree) that research should use pragmatic randomized controlled trials (i.e. those mimicking usual clinical practice) in conjunction with DB-RCTs (2,3).
But, I’m also going to say something sacrilegious and unscientific: maybe the trials are a nice to have. Or in broader terms: is our society too risk-averse? Let me explain. We already know that psychedelics bring invaluable healing from decades of therapeutic use by behavioral health practitioners and indigenous use. We aren’t starting from scratch. There exists tons of experiential data. Obviously, we need the trials for knowledge — especially to parse which disorders benefit most from which kinds of therapies — but, this will take an inordinate amount of time to accomplish given the long time frames for clinical research that investigates variable by variable. In the meantime, people don’t get treatment because of the potential risk. Do we cause more harm being so risk-averse? What if there were a way to use (and give credit to) the massive amount of work and invaluable knowledge already accomplished and acquired on our path to officially “validating” psychedelics?
Speaking of double-blinding, and as an aside, I still find it odd and question why we isolate and ignore the placebo effect instead of putting resources into figuring out the mechanism behind the phenomenon to amplify it, given that it’s free and natural healing. I frequently hear people say things like, “Oh, it was just the placebo effect. It didn’t work.” Maybe the substance didn’t work, but something did and it wasn’t “just nothing.” The placebo effect hovers around 30-40% in clinical trials (4), but has been increasing over the years, causing problems for pharmaceutical company drug development (5). In case you’re wondering, nope, neuroscience doesn’t have any models for how this could work. We isolate it with control groups, then ignore it. I know this is dramatic, but our dedication to – hmm, what exactly? Mechanistic explanations? Pharmacological intervention? – is harming us.
Proper scientific review. Another criticism raised is that up to now, all recent psychedelic research has been funded by grants from philanthropic organizations and that these “often do not undergo the same type of rigorous peer review and scientific assessment that grants sent to a research council would” (6). Okay, listen, if we need all research to go through research councils, we are doomed. All research will be bottlenecked. While this is an obvious, easy criticism to throw around (for any field of research), it’s a completely impractical one to implement at a large scale. It also brings focus to one of my grievances about science funding in the U.S.: the majority comes from the U.S. federal government and is driven by government interests. This is not a unique problem to psychedelics, and not a fair one to throw out. I would argue that the criticism should rather be aimed at why more funding sources for scientific research (outside of federal money) don’t exist.
Roadblocks lie ahead; temper your excitement, please. Others have highlighted the bureaucratic hurdles that lie ahead of integrating psychedelic therapy into existing healthcare systems and the possible risks of self-medication. “With all the excitement around the potential of psychedelic medicine, it is important to remain objective and realistic about the difficult path that lies ahead given the pandemic it aims to treat” (6). Why can’t we be excited? Because we might be disappointed if it doesn’t work out as grandly as we imagine? So what? Did you know that pharma companies have opted out of developing psychiatric drugs because it is too difficult and costly? Have we forgotten the massive mental health crisis we find ourselves in and the lack of solutions and therapies? Being aware of these issues while examining the long, established history of psychedelic therapeutic use and the results of recent clinical trials on psychedelic treatment — 60-80% no longer meet diagnostic criteria for PTSD (7,8), 60-80% depression symptom improvement (9), 80% tobacco abstinent (10), 70-80% reporting the experience as the most spiritually significant or personally meaningful experience of their lives (11) — we should be excited! Psychedelic therapies provide hope and that’s something worth striving for. In fact, hope is something humans need to survive.
So, given the state of the world, just let us be excited about this one thing, please.
1. Nichols DE. Psychedelics. Pharmacol Rev 2016; 68: 264–355.
2. Carhart-Harris RL, Wagner AC, Agrawal M, et al. Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine? J Psychopharmacol. Epub ahead of print 22 April 2021. DOI: 10.1177/02698811211008567.
3. Christian JB, Brouwer ES, Girman CJ, et al. Masking in Pragmatic Trials: Who, What, and When to Blind. Ther Innov Regul Sci 2020; 54: 431–436.
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7. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 2021 276 2021; 27: 1025–1033.
8. Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl) 2020; 237: 2485–2497.
9. Romeo B, Karila L, Martelli C, et al. Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis. J Psychopharmacol 2020; 34: 1079–1085.
10. Johnson MW, Garcia-Romeu A, Cosimano MP, et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014; 28: 983–992.
11. Barrett FS, Griffiths RR. Classic hallucinogens and mystical experiences: Phenomenology and neural correlates. In: Current Topics in Behavioral Neurosciences. Springer Verlag, 2018, pp. 393–430..