Shrooms for therapy? This award-winning scientist thinks there might be potential

Q. You spoke in detail about the reported use of psychedelics in ancient civilisations across the world. What has caused scientists to become interested in them recently, especially in mental health therapy?

Well, major depression rates have gone up world over. So has generalised anxiety disorder. Given the substantial mental health burden that we are seeing across the world, one would want to provide effective and appropriate treatment.

More worryingly, the subset of individuals who don't respond to any available pharmacological therapy is something as close to 30 percent. That means one out of every three individuals who has major depression is treatment resistant. So clearly, there is an unmet need, and therefore, an interest in more effective, long-lasting therapy.

So the question is, why the interest in these molecules?

To a certain degree, that’s tied to the emergence of ketamine. Ketamine [colloquially known as special K] is a party drug in a sense. It’s actually an anaesthetic, and at low doses, it’s an important regulator of mood. So in the past decade, it has emerged in the clinic as a major potential add-on. It’s an add-on, not a replacement, but the interesting thing about ketamine is that it gives you rapid effects.

Otherwise, when someone in a state of severe suicidal ideation visits a psychiatrist, even if they administer a relatively effective medicine, it takes about three to six weeks to show effects. That’s a really long time to ask someone to comply with a drug when it isn’t necessarily making them feel better in the moment. So I think the opening window came with ketamine, and the fact that it can give you effects within hours. It caused a total shift.

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Q. What about other so-called party drugs? What evidence have we seen of their use in therapy?

So the really big breakthrough came when MDMA was used in 2017, in a trial for people who were diagnosed with terminal illnesses. They were allowed to use it because these were patients with end-of-life anxiety and end-of-life depression, and it was used as a last resort to at least help with the mood component of a terminal diagnosis.

And they found powerful effects—so much so that the FDA approved MDMA as a potential breakthrough drug for post-traumatic stress disorder (PTSD). And that opened the idea of low-dose Zoloft, or LSD being used for generalised anxiety, PTSD and major depression.

Q. What we understand so far of party drugs is that while they can be immediate mood lifters, the crash is often worse…

The big worry is, of course, unrestricted use. These are schedule 1 compounds, so they are currently listed as restricted drugs. They're banned for recreational and regular use, but they have been opened up in certain countries to being used under controlled conditions for psychiatric patients. It depends obviously on the disorder; but they would be under very tightly regulated usage.

I think the general view would be that there's much we still need to understand about how exactly they work and how effective they are, and how they interact with different people, depending on genetic factors. The point you made about a drop post-utilisation… there’s anecdotal evidence the other way as well, where a single use has caused effects to last for several months. We just don’t have enough accumulated evidence to say we understand everything; there’s still much to do.

Q. You mentioned in your lecture that this is an exciting time in this space, and the West is leading the way. Can you give us a sense of what’s going on in other countries and where India stands?

Australia, of course, has had clinical trials of its own, as has the US and certain European countries. In South America, psilocybin and Ayahuasca are allowed as part of indigenous ceremonies in any case, because they're considered traditional practices that are part of the cultural landscape. In India, ketamine is used, but as I understand it, psychedelics are not.

It would be great if Nimhans could lead a clinical trial study in this regard. It’s important to have a local Indian context on this. Each country has its own understanding of how it navigates mental health. Mental health has traditionally been a taboo in India, and while that’s changing, going to a psychiatrist is still hush-hush. Given all of this, our policies won’t be a cut-copy-paste of what’s happening in the US or Europe or Australia. We would need solid preclinical studies in the Indian context to understand the effects of these drugs better.

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Q. How would you say we can regulate and create that difference between recreational and therapeutic use?

I think understanding the difference between a strong legislation for recreational use and the flexibility to utilise specific interesting compounds and molecules for clinical trials is two separate bins, and that should actually be treated in some ways, as two separate considerations, because otherwise we'll end up paying a catch-up game eventually. That may sort of go with half or incomplete result, not well studied and not well done in the Indian context.

I think it's critical to at least allow for specific research that needs to be done, clinical research that needs to be opened up with experts in the country. Nimhans would be one such community.

We have the expertise in the country, but unless we bring it to the table for discussion and really can have that dialogue, it doesn't move the envelope forward. I think that the legislation of these molecules is extremely necessary. Within that legislation, there is a context in which there can be an opening to say, is there a possibility of flexibility for specific research, clinical trials, et cetera, to understand better controlled usage under very supervised circumstances for individuals who are treatment resistant, in major depression or suicidal ideation or PTSD, where you have the expertise, requisite expertise and controlled administration at low dose? That would be the sort of approach I would imagine.

Q. What would your recommendations be?

India needs a high-level committee that contains both practising psychiatrist clinicians as well as potentially some preclinical researchers to come up with a strategic plan that will allow for the emergence of preclinical and clinical research in the Indian context.

In the absence of that, we will be playing catch-up. We need our own approaches to how we will navigate the emerging space for psychiatric disorders over the next 10 to 15 years. If we are slow on that, then we are not doing full service to the mental health requirements and demands of our own population.

And so I would recommend that this needs to be treated independently and separately from the fact that most of these molecules are schedule 1. Through clinical trials that are supervised very closely, and preclinical research that is under strong ethical, biological human clearance with checks and balances laid down in place, there has to be some room and mobility for research in this area to grow within India.