The current psychedelic renaissance began in 1994 but no one could have predicted the cultural explosion of interest in the past 5 years and how desperate we are for new mental health treatments. However, some say we’re now preparing for the bursting of the psychedelic hype bubble and that may turn out be a good thing for the future of psychedelics. What began as a welcome glimmer of hope for new ways to treat mental illness has perhaps morphed into actual misinformation. Such claims such as psychedelics can “cure” mental illness, solve massive social problems, and create a “psychedelic utopia” are at the very least unsubstantiated. Clearly, things need to even out and that doesn’t necessarily mean the opposite extreme of disenchantment and doubt. However, there does need to be a mature, realistic sense of what psychedelics can do and will do. In this next article, I will discuss the more challenging issues facing psychedelics and what needs to happen to keep their potential promise on track.
The good news is that the most recent studies on psilocybin for Major Depression, Treatment Resistant Depression, and Alcohol Use Disorder continue to show promising signals even among skeptical researchers. It’s very clear that a single dose of psilocybin at 25 mg works for depression in an appropriate clinical context; most people will have a positive response but it may turn out that a couple of doses may work better—we don’t know that yet. The benefit does last for some length of time and there is a suggestion that in non-Treatment Resistant Depression the effect may be more durable but we don’t know about studies over a year; those studies will be done and so we will know eventually how often people need to be dosed. Psilocybin is just about to start Phase 3 trials that will be larger, more rigorous, and FDA (Federal Drug Agency) regulated which will probably take several years to complete before it can be FDA approved. As positive studies accumulate, key questions on how to optimize psilocybin treatment will start to be answered.
One of the challenges in performing quality studies on psychedelics like psilocybin is that with high public interest, there is a certain expectancy in subjects that effects the clinical outcome. The approval of any medication by the FDA hinges on how the medication compares to placebo. Unfortunately, blinding success has generally been poor because it’s pretty obvious to a subject and a clinician what the subject received if there is a psychedelic experience or not during the session. Hence, subjects are good at guessing what they received and that has been shown to be problematic: if the person received the psychedelic, and had the psychedelic experience but they don’t feel better (i.e. non-responder), that person can be at risk for self-harm because they believed the hype that the medication would fix them and now all hope is gone. Conversely, if a person guesses correctly about receiving a placebo, there may be negative expectations that cause the placebo to have a more negative effect than it otherwise would have (i.e. nocebo effect). The treatments need to be explained correctly: psychedelics are not perfect or miracle cures and there are risks and non-responders. In a recent trial, 40% of subjects who received 25 mg of psilocybin for Treatment Resistant Depression still requested to go back on their usual anti-depressants during the trial. In order to have a more realistic view of these substances, there needs to more time and space for the boring but necessary rigorous research with less public and corporate interest.
Another challenge is how psychedelics will be paid for. In order for treatment to be covered by insurance, psychedelics will likely have to outperform existing treatments (like generic SSRIs) and also prove to be cost effective to what’s already available. Currently, that may not be an easy task. Another psychedelic, MDMA, which is still on track to be approved for Post Traumatic Stress Therapy as early as mid-2024, may cost $13,500 for just the 3 doses of medication. Then, there’s the cost of 2 therapists for the 42 hours of therapy which could run about $15,000. The FDA is not budging on the requirement for having 2 therapists present so the grand total is close to 30K.
Psilocybin is a bit cheaper and may ultimately be available in at least 2 parallel systems: the medicalized system where insurance could apply and the “quasi-clinical” setting being set up by certain states like Oregon and Colorado. However, right now the Oregon Model will still cost a person $3500 due to the requirement of a preparation session, the actual treatment session, and then an integration session; perhaps even the Oregon Model is too expensive and impractical.
Another unanswered question is what type of psychotherapy is really essential. What is the minimal effective amount of therapy necessary for a good outcome? Could there be less supervision in more straightforward cases (i.e. only 1 therapist required)? None of these have been well-studied. Will people end up voting with their feet and wallets about how they want to go about getting treatment? Perhaps there will be some other system that is more economical such as doing the treatment in larger groups. Interestingly, the FDA does not regulate psychotherapy so if they don’t dictate this perhaps the drug manufacturer will decide.
There are two underlying assumptions among researchers and clinicians when it comes to psychotherapy and psychedelics: The first is that the psychedelics work better with therapy but there still hasn’t been a head-to-head study that compares a psychedelic with therapy versus a psychedelic without therapy for treating depression. Furthermore, it’s still unclear what type of psychotherapy works best and right now there are at least 13 types of psychotherapy models being introduced into psychedelic treatment sessions. The second assumption being made is that the entire psychotherapy/psychedelic model for using psychedelics (i.e. preparation, treatment, integration) which was primarily based on research done pre-prohibition (1943-1970) works best but there has never been any real examination of the components of this model and whether there are other ways to go about it. It turns out there has already been a model in place for centuries among indigenous cultures; they may not be considered formal therapists but they are shamans who have acted as guides with plant medicines like psilocybin and I would at least consider them to be valid practitioners in their own right. I wonder if we need to seek more guidance from the shamans who have worked with these powerful plant medicines in ceremony for centuries to have a better understanding of how to have a humble and respectful relationship with these plants in contrast to the Western attitude of just extracting the active ingredient of the plant, developing our own system of how to use it, and making the plant do what we want.
A final concern is due to the scars of prohibition (1970 to the current date), psychedelic communities have tended to downplay negative effects of these substances but that needs to change. I don’t believe prohibition can really be the solution again but we can’t sweep mistakes under the rug. A hot topic in research is trying to understand when people have challenging and emotionally disturbing experiences. There’s some evidence that a minority of people (4-5%) may struggle on a longer-term basis after receiving psychedelic treatment that we don’t understand and so there are longer psychological and spiritual risks and we still need to figure out how to mitigate these risks. Five percent may not seem like a big number but if a million people are treated with a psychedelic, that’s 50,000 people that are affected in a negative way.
The take home message from this article is that psychedelic research, for all its promise, is still at the embryonic stage and we still need to do the studies. They will take time but we will get the answers. We need to find out if it works. We need to suspend pre-existing beliefs and follow the evidence even if it’s uncomfortable. We also need to be patient with this process. In recent years, I’ve recommended several patients to receive ketamine treatment for Treatment Resistant Depression but that doesn’t work for everyone. Then, I’ve had a handful of patients who decided on their own volition to either start self-administering their own psilocybin or get an “underground” MDMA session; unfortunately, most of these well-intentioned efforts did not achieve the desired outcome. My hope is that we can still do this in a good way but there could be more to working with psychedelics than meets the eye and what the early studies are revealing. Time will tell with all these issues but I believe it’s wise to go slow in the right direction, then go fast in the wrong direction.