COMMENTARY

Misplaced Ecstasy? Questioning the Role of Psychedelics as Therapy

Jeffrey A. Lieberman, MD

Disclosures

October 26, 2017

Hello. This is Dr Jeffrey Lieberman of Columbia University in New York City speaking to you for Medscape. The general theme of my comments today is, "repurposing recreational drugs." Let me put in context what I mean by that.

If you followed any of my prior video blogs on Medscape, you'll know that I referred to myself as becoming somewhat of a curmudgeon. This is because I've taken umbrage with the lack of developments in the government's stewarding of our healthcare policies, as well as its financing of both care and biomedical research. It also comes from my not understanding why the government could not appreciate the logic of needing to address these things for our country, its citizens, the healthcare profession, and the biomedical research community.

Larger Trends at Work

In this case, I think the better term or epithet to describe my state of mind could be "wet blanket," as I'm offering a cautionary voice on emergent trends in the therapeutics for mental disorders. My last video blog was on the expanding use of ketamine for the treatment of, first and foremost, refractory depression but also other disorders. I viewed this in a way as practice leaping too far ahead of research and evidence and also succumbing to not just overzealous but reckless and profit-driven motives.

In this post, I'd like to talk about another trend that is occurring in parallel: revisiting the use of a class of substances, previously considered to be recreational in the 1960s and '70s, that are now being restudied for use as treatments for mental disorders. What prompts my comments today are reports from an April 2017 edition of Nature News[1] on the use of ecstasy, or MDMA, to treat posttraumatic stress disorder (PTSD).

We see reflected in this, in my opinion, two trends. One is a national trend, the leading edge of which is the popularization, decriminalization, and legalization of cannabis use for various indications or just for enjoyment. That's driven by the desire of a large portion of the population to have access and be able to use ad lib cannabis products, for whatever their stated purpose is, without being subject to potential criminal prosecution or limitations.

The other trend is this parallel movement to reintroduce or re-evaluate the potential use of psychedelic drugs, MDMA included. That is, to gain access to substances that offer individual users some ostensible benefit, which, in my opinion in this case, is still quite sketchy and unsubstantiated.

At the same time, while ecstasy is being revisited for this purpose, there's also been a smattering of work done with other recreational drugs of the '60s counterculture era, more genuinely designated as psychedelic drugs. This includes substances such as psilocybin or LSD, which have been used for various things including palliative care in terminal cancer patients or the treatment of refractory types of mental disorders or addictions. Here we have to be careful not to paint all of these substances with the same brush. Let me confine my comments mainly to MDMA.

MDMA for PTSD

Clearly, PTSD is a genuine disorder that is highly prevalent in the population and currently most visibly affecting individuals in the military. Truth be told, although we do try to provide care in the form of various types of treatments, exposures, psychotherapy, neurofeedback, or pharmacologics, these interventions are minimally-to-moderately effective at best. Therefore, we have huge unmet clinical needs here. Throwing MDMA at it I don't think is going to ultimately prove to be a winning effort.

The reason I would cite is that we have to make a distinction between agents that make you feel good, feel better, and agents that are genuinely therapeutic. You can take somebody who is suffering from pain and give them an opiate, and they'll feel better. It's not alleviating the source of their pain. It doesn't mean that opiates and other analgesics shouldn't be used, but the reality needs to be understood and accepted.

Ecstasy's pharmacology is similar to that of a stimulant, an indirect-acting catecholamine agonist, and also an indoleamine agonist. It's more likely to produce either euphoria or other types of analgesic-type activity than a genuine therapeutic effect at whatever the underlying pathophysiology of the illness is.

Ultimately, the proof will be in the pudding of the research. Over the long term, the treatments will prove effective, or they'll be shown to lose their efficacy, and patients will develop tolerance, producing chronic complicating effects like an increase in doses needed, addiction, dependence, or—even worse—if there is any potential for toxicity with long-term administration.

The source of recent reports about the renewed interest in ecstasy is an organization called the Multidisciplinary Association for Psychedelic Studies (MAPS). I'm not impugning their integrity or motives, but I'm a little bit skeptical just by their name that they're seeking to find a way to rehabilitate this class of substances that, due to their excessive use and the political overreaction of the government in the 1960s and '70s, was unfortunately outlawed. Let's just say that they may be biased in terms of their motivation.

Of course, the sine qua non of research is being able to replicate findings, particularly in laboratories that are dispassionate and objective in their attitude towards this particular class of agents. My comment isn't that we should throw this aside and not pursue it any further but rather that we have to be aware of the fact that we are dealing with a controversial area, treading on shaky ground, and caution is really needed. More specifically, rigorous research needs to be done.

In particular, we are talking about a condition that is most prominently reflected in the veterans who undergo enough in the way of potential harm that we don't want to add to it by our misguided therapeutic attempts. MDMA may be useful, but we have to make sure before we begin to tout it as the long-awaited breakthrough treatment for PTSD.

Healing Hallucinogens?

At the same time, there has been, albeit to a lesser degree, a resurgence of interest in other psychedelic substances: psilocybin, mescaline, and LSD. These could be potentially useful in a variety of conditions for which currently there are not effective treatments, including addiction, palliative care, and personality disorders.

Here I think there is less concern about potential harm being done but also still the need for caution and rigor in the research that's being done. The main reason is that these drugs, even though they were taken excessively for recreational purposes, have less abuse potential in the sense of having self-reinforcing and euphoric types of effects. They produce what are essentially mind-altering effects that change the perspective or mindset of somebody, but they don't necessarily induce an intensely hedonic effect like with stimulants and ecstasy. In my opinion, there is less reason for concern regarding their potential for abuse or harm given their particular pharmacology.

However, it's still very much of a black box phenomenon in that we don't know why they would necessarily work other than the fact that they are powerful in a way that is truly unique. We don't have treatments for these other conditions, and there was preliminary evidence generated in the '70s before these substances were politically outlawed that suggested their potential utility.

In this context, each compound or class of compounds needs to be taken individually. We need to be able to pursue them to the extent that it's warranted to, but we also need to try to limit the influence of what I perceive as a national popular trend to find ways to legitimize the use of feel-good substances. If the nation wants to legalize the recreational or personal use of any drugs, whatever the risks, that's fine, but we shouldn't deceive ourselves that these drugs are being liberalized in availability because they're truly therapeutic in a specific way, when they're really not.

Conclusion

To sum up, I would say that ecstasy, even though it's gotten the most attention recently, needs to be looked at in a very careful and rigorously controlled way to accrue evidence showing what it can do and what its potential liability is. At the same time, we need to think about and initiate the pursuit of research on other recreational drugs that have psychedelic properties that might be useful and could really advance our pharmacopeia in treating brain disorders that affect mental function and behavior.

The key here is to do it in a rigorous, controlled research setting and not allow other more ideologically driven or unsubstantiated motivations to influence, much less co-opt, the process. All in all, I think that this offers an opportunity and reasons for hope, but it also brings with it the need to pursue these opportunities responsibly and exercise caution.

I hope I haven't been too much of a wet blanket or a curmudgeon. I'm just trying to put things in the proper context to avoid creating further problems for ourselves, which, as I've said before, the field of psychiatry and mental health care can't afford to go through and shouldn't.

Thank you for listening. This is Dr Jeffrey Lieberman of Columbia University speaking to you for Medscape.

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