What is disruptive psychopharmacology and what does it have to do with MDMA and ketamine?

Can you use MDMA, psilocybin and ketamine to treat depression and mental illness?
 

By Dr Chandni Hindocha

A new era of medications for mental health dawns upon us! My first article for getthedose.com is about the area that I work in - Psychopharmacology.

 

We haven’t had new medications to treat mental health disorders in 50 years

The prevalence of mental health problems; depression, anxiety, PTSD, drug addictions, to name a few, is growing and we haven’t had any new medications to treat mental health disorders in over 50 years. The NHS spends £100m on private firms which help deal with the overspill of people with mental health problems needing hospital beds. The drugs we do have work on the same pathways, and there is a delayed response after one starts taking them.

Recreational drugs like MDMA, psilocybin and ketamine might be next in line for treatment of mental illness

Out of the ashes of persecution and prohibition soars the “new prescription psychiatric drugs for 2020: psilocybin, MDMA and (es)ketamine. These mind bending old chestnuts are on the rise again and may be the best we have”.

Recently, the US Food and Drug Administration approved the use of esketamine (basically ketamine) as a quick-acting antidepressant e.g. for people who are feeling very suicidal. They also gave MDMA and psilocybin “breakthrough therapy designation” so they think that these drugs have better outcomes than those currently available. These drugs could receive regulatory approval by 2021.

 

We would need a new mental health infrastructure to deal with such drugs

Assistant Professor Boris Heifets (@TheBorisLab and Professor Robert Malenka (@StanfordPSY) argue that we will require a new mental health infrastructure to deal with the these potentially highly effective, but also highly psychoactive (consciousness altering), substances. So just as the NHS is struggling to provide prescription cannabis, it also the case that if these drugs are approved, doctors would have to deal with safety, choosing the right patents, potential issues about substance misuse and emergency psychiatric and medical issues.

These drugs, of course aren’t taken on their own, they are taken alongside lots of psychotherapeutic support. Gold standard psychological therapies are hard enough to access at the moment, incorporating psychedelic therapies could be a good way of reducing these long waiting lists.

How do the drugs work anyway?

Ketamine, MDMA, psilocybin and cannabis all act on different pathways in the brain but they all have the ability to alter consciousness – which with an appropriate therapeutic context can lead to an effect  that’s lasts far longer than after the drug have left the body. Heifets and Malenka argue that it’s about psychological transformation, and about having mystical experience reminiscent of those drugs found in ancient religious ceremonies like ayahuasca, peyote, and ibogaine.

From a neuroscience perspective, the question is what areas of the brain are working together to produce this effect? And what brain chemicals are being released to produce these effects? For example with LSD, similar to psilocybin, it has been discovered that the psychedelic effects in humans can be blocked by a drug that blocks the 5HT2a receptor (i.e. serotonin, so in the same family of receptors that antidepressants work on, but a different type of the receptor).

 

With psychoactive drugs, setting is key

The specifics of how these drugs work can’t be underestimated. “Setting” can’t be underestimated – just like with the recreational use of these drugs – if you’re in a bad place, you’re going to have a bad time. The therapy sessions are vital, the relationship with the therapy provider is key, as is the dose of the drug, the timing of the therapy around the drug sessions (usually 6 or 12 therapy sessions and 2/3 psychedelic sessions).

It’s so exciting to think that when we find out in the next 10 years exactly how these drugs work, we will be able to develop newer and better drugs that target these systems – the development of a new generation of disruptive psychopharmacology

As Heifets puts it;

“It is telling that the current wave of therapeutic innovation is based not on insights gained from studying established drugs, but rather on a disruptive new therapeutic approach involving compounds that have been known for quite some time in other contexts”

How do you feel about psychoactive drugs to treat mental illness?