The hidden potential of MDMA and psilocybin

Earlier this week I went to a talk by Professor David Nutt entitled ‘Time to Grow Up?’ where he spoke about the damage caused by the UK government’s approach towards drugs. David Nutt has become quite well known in the UK after he was fired in 2009 by the Home Secretary as the chairman of the Advisory Council on the Misuse of Drugs for clashing with government policy. Most notably, he published an editorial in the Journal of Psychopharmacology in which he said that the dangers from ecstasy were comparable to that of horse-riding.

I was already well aware of his views on the relative risks of drugs (alcohol causes far more damage overall than anything else) and his views on the government’s approach to banning new drugs (such as mephedrone, which potentially saved more lives than it took). He laid out the evidence very clearly and presented it in a very engaging manner – I would recommend checking out his blog if you’re interested.

When adding together harm to self and harm to others, alcohol tops the list of most harmful drugs. Image credit: The Economist

When adding together harm to self and harm to others, alcohol tops the list of most harmful drugs. Image credit: The Economist

However, one aspect really caught my attention – the study of illegal drugs as therapeutics or medicine. The case for cannabis is well-known: its potency as a pain reliever has led to it now being prescribed by doctors in some countries. But what about MDMA (ecstasy) used to treat post-traumatic stress disorder, or psilocybin (the hallucinogen found in magic mushrooms) used to treat depression or obsessive-compulsive disorder? These drugs have been suggested as potential treatments but there are so few studies conducted that we can’t be sure.

Science on drugs

Cannabis, MDMA and psilocybin are all considered have no therapeutic value by the UK government and so are listed as Schedule 1 drugs. This means that not only are researchers required to get a licence from the Home Office, but they also have to find a supplier who also has the correct licence. These licences cost thousands of pounds, take about a year to be approved and then result in police inspections on a regular basis. Not only that, many research funding bodies are reluctant to sponsor studies on illegal drugs or refuse to fund it altogether.

It is easy to see why there hasn’t been much research done.

Nonetheless, David Nutt made a big splash two months ago when he televised a study on the neurological effects of MDMA. In Drugs Live: The Ecstasy Trial, 25 volunteers were studied by fMRI after taking either the drug or a placebo in a double-blind trial – making it the largest ever brain-imaging study of MDMA conducted. In time, the full results will be published in peer-reviewed journals and they are actually expecting to publish 5-6 papers from this single study.

The researchers used pure MDMA, avoiding the contaminants usually found in ecstasy

The researchers used pure MDMA, avoiding the contaminants usually found in ecstasy pills

This research was not just to look at the effects of taking an illegal drug – understanding the neurological mechanism of MDMA could potentially help millions. Back in 2010, a US study of patients with post-traumatic stress disorder showed that MDMA, combined with psychotherapy, cured 10 out of the 12 people given the drug in a randomized-control trial. These were people who had not responded to government-approved drugs or psychotherapy alone, and two months after the study they were free of symptoms. MDMA appears to dampen negative emotions, which allows a patient to revisit their traumatic memories without the associated emotional pain. This can be the starting point for the patient to come to terms with their trauma and deal it with through therapy. These results, although from a very small sample size, are near miraculous and yet it took over ten years for the researchers to get approval.

The magic of mushrooms

David Nutt has also previously studied the effects of psilocybin on the brain and the results were surprising. Psilocybin is a hallucinogen, causing colours, sounds and memories to appear much more vivid than usual. With this kind of effect it was expected that psilocybin would activate certain areas of brain, which would be seen as bright patches on an fMRI scan. However, they actually saw dark blue patches of decreased brain activity, but only in a specific area of the brain that acts as a central hub for connections.

Psilocybin is the hallucinogen in magic mushrooms. Like MDMA is a class A drug in the UK

Psilocybin is the hallucinogen in magic mushrooms. Like MDMA, it is a class A drug in the UK but could it used to treat depression?

Decreasing brain activity doesn’t sound like a good thing, but one of these connector hubs, known as the posterior cingulate cortex, is over-active in people with depression. This area is responsible for several roles but can cause anxiety, particularly when it is over-active. When David Nutt and his colleagues asked people on psilocybin to think of a happy memory, they found that the volunteers could remember happy memories more vividly – almost as if they were reliving them. These test subjects were also much happier after recalling positive memories. Dampening the activity in the connector hubs and getting a boost from recalling happier times could be enough to get people out of the vicious circle of depression. Fortunately, the Medical Research Council has since funded David Nutt to conduct further studies into the use of psilocybin as a treatment for depression.

Post-traumatic stress disorder and depression are two of the biggest mental health issues that we face and current treatments are plainly inadequate. It seems ridiculous that the government’s policies on drugs prevent scientific studies aiming to reap benefits from them. These treatments show good potential and yet little is being done to take advantage of them. This situation is nothing new – after being fêted as a treatment for alcoholism in the 1960s, LSD has largely been ignored ever since it was declared illegal. Even though, according to David Nutt, it is probably as good at treating alcoholism as anything we’ve got now, researchers are limited to reanalysing studies completed 50 years ago.

What treatments are out there, undiscovered because of governments’ heavy-handed approaches towards recreational drugs? I’m just glad that there are researchers like David Nutt who are willing to make the effort, and take the flak, in order to find out.



Red Alert: How red hair can cause skin cancer without sun exposure

I’m not usually that interested in research completely based on mouse studies, but any paper that starts with ‘People with pale skin, red hair, freckles and an inability to tan…‘ is always going to get my attention.

People like me, with the ‘red hair/fair skin’ phenotype, are pretty bad at dealing with the sun. Not only do we get sunburnt much more easily, but we have the highest risk of developing melanoma, the deadliest form of skin cancer. It is (hopefully) very well known that exposure to UV light increases the risk of melanoma. However, unlike other other skin cancers, melanoma also appears to develop independently of UV light, although this has been poorly studied to date.

The sun can be your worst enemy when you’re ginger. (Photo credit: coltera)

In a letter published in Nature this week, researchers wanted to see if hair-colour pigments affect this UV-independent pathway for melanoma. To do this, they engineered mice to mimic human complexions by mutating a gene known as MC1R. This is responsible for producing the pigment eumelanin which is dark coloured and results in dark hair. Most people with red hair have an inactive form of MC1R, which instead leads to the red-coloured pheomelanin being produced.

The researchers compared mice with black hair (active MC1R), red hair (inactivated MC1R) and albinism (produces neither pigment). In addition, all the mice had a specific mutation that causes benign moles, but leaves them predisposed to developing melanoma. The mice were kept away from sources of UV light and their health was charted over time.

The differences are startling. In under a year 50% of the red-haired mice had died compared to only 20% of the black-haired or albino mice. This, and further tests, seem to suggest that producing pheomelanin is actually harmful, increasing the rate of melanoma when there is no UV light.

Pheomelanin is responsible for the colour of red hair, but could also cause cancer

It was also apparent that the DNA of the red-haired mice had suffered twice as much oxidative damage as the albino mice. It is known that UV light causes oxidative DNA damage and that this increases the chances of mutations occurring. In previous studies looking at UV radiation, it was thought that eumelanin protects against this damage. However, the mice in this study show that pheomelanin is actually harmful and eumelanin has little effect under these conditions. It’s still not clear how this damage was created in the absence of UV light or why production of pheomelanin made it worse.

The authors of the paper make it very clear that UV radiation is still an important factor in the development of skin cancer, but suggest that this UV-independent pathway should be considered in the future for strategies to prevent melanoma, especially for gingers.

Redheads have long understood that we lack the natural sun protection that others enjoy, but it is still quite a shock to think that our distinctive colouring is actively causing us damage. However, this study was done under very artificial conditions, and the rates that the researchers saw are far higher than we can plainly observe. After all, we don’t see half of redheads dying every year. But whatever your hair colour, melanoma is still very deadly – one American dies from melanoma every hour. So make sure you don’t forget your sunscreen.