Ketamine normalizes hyperactivity in key brain region of depressed patients

There is no shortage of psychological and pharmacological therapies to combat the world’s most widespread mental health issue, major depressive disorder (MDD). However, a significant portion of the affected population fail to respond to many of these traditional therapies. For this reason, new drugs must be tested and validated. One promising candidate is ketamine –famously but somewhat improperly known as a horse tranquilizer.

However, the manner by which ketamine acts is not well known, meaning that clinicians are still circumspect regarding its use in treating MDD. Recently, researchers in New York look at how ketamine affects the subgenual anterior cingulate cortex (sgACC), a region of the brain whose hyperactivity has proven ties to MDD. The recent study, which appeared in Neuropsychopharmacology, helps bridge this gap in the literature.

Full Article: https://www.psypost.org/2021/04/ketamine-normalizes-hyperactivity-in-key-brain-region-of-depressed-patients-60295

Researchers believe the drug might help loosen the brain's fixed pathways, which can then be "reset" with talking therapy afterwards.

A powerful hallucinogenic drug known for its part in shamanic rituals is being trialled as a potential cure for depression for the first time.

Participants will be given the drug DMT, followed by talking therapy.

It is hoped this could offer an alternative for the significant number of people who don't respond to conventional pills for depression.

Psychedelic-assisted therapy might offer longer-term relief from symptoms, some researchers believe.

A growing body of evidence indicates other psychedelic drugs, particularly alongside talking therapy, are safe and can be effective for treating a range of mental illnesses.

This will be the first time DMT is given to people with moderate to severe depression in a clinical trial.

Dr Carol Routledge, the chief scientific officer of Small Pharma, the company running the trial said: "We believe the impact will be almost immediate, and longer lasting than conventional antidepressants."

'Spirit molecule'

The drug is known as the "spirit molecule" because of the way it alters the human consciousness and produces hallucinations that have been likened to a near-death experience.

It is also the active ingredient in ayahuasca, a traditional Amazonian plant medicine used to bring spiritual enlightenment.

Researchers believe the drug might help loosen the brain's fixed pathways, which can then be "reset" with talking therapy afterwards.

Dr Routledge likened the drug to "shaking a snow globe" - throwing entrenched negative thought patterns up in the air which the therapy allows to be resettled into a more functional form.

But this hypothesis still needs to be proven.

The team is consulting Imperial College London, which runs the pioneering Centre for Psychedelic Research.

As part of the study, they hope to investigate whether the drug can be administered as a one-off or as part of a course.

Subjects will be followed up for at least six months to see how long the effects of the treatment last.

Ketamine clinic

Meanwhile, a ketamine-assisted therapy clinic is set to open in Bristol next week.

First ketamine-assisted psychotherapy clinic opens

While the drug is already used for depression in clinics like the ketamine treatment service in Oxford, it is not accompanied by psychotherapy.

Rather, it is used to provide temporary relief from symptoms for people who have very serious, treatment-resistant depression.

So-far unpublished researched presented at a conference by professor of psychopharmacology at the University of Exeter, Celia Morgan, suggests ketamine accompanied by therapy has much longer-lasting effects.

Prof Morgan said there was mounting evidence that drugs, including psilocybin, LSD, ketamine and MDMA (Ecstasy), were safe and could play a role in the treatment of mental health disorders.

And there was some early evidence they could have longer-term effects than the medicines conventionally prescribed as antidepressants, known as SSRIs, but more research was needed.

They also worked using a completely different mechanism, Prof Morgan explained.

'Long-lasting change'

While conventional drugs may numb negative feelings, "these drugs seem to allow you to approach difficult experiences in your life, sit with that distress and process them," she said.

"It might be getting at something more fundamental" that was the root cause of the problem, Prof Morgan said.

"Through that we think you can get much more long-lasting change."

Prof Michael Bloomfield, a consultant psychiatrist at University College London, said although it was a "really exciting" area of research, caution was needed in overpromising the drugs' potential.

It was also a field of therapy that could be open to abuse and misuse, he said.

Prof Morgan also stressed the importance the drugs being used within the context of therapy as there were concerns that "people might think they can give it a go with some recreational drugs".

"But it's really not how it works" she said.

‘The ketamine blew my mind’: can psychedelics cure addiction and depression?

Psychedelic drug DMT to be trialled in UK to treat depression

UK regulators have given the go-ahead for the first clinical trial of the use of the psychedelic drug dimethyltriptamine (DMT) to treat depression.

The trial will initially give the drug – known as the “spirit molecule” for the powerful hallucinogenic trips it induces – to healthy individuals, but it is expected to be followed by a second trial in patients with depression, where DMT will be given alongside psychotherapy.

Taking the drug before therapy is akin to shaking up a snow globe and letting the flakes settle, said Carol Routledge, chief scientific and medical officer at Small Pharma, the company running the trial in collaboration with Imperial College London.

“The psychedelic drug breaks up all of the ruminative thought processes in your brain – it literally undoes what has been done by either the stress you’ve been through or the depressive thoughts you have – and hugely increases the making of new connections.

“Then the [psychotherapy] session afterwards is the letting-things-settle piece of things – it helps you to make sense of those thoughts and puts you back on the right track. We think this could be a treatment for a number of depressive disorders besides major depression, including PTSD, treatment-resistant depression, obsessive-compulsive disorder, and possibly some types of substance abuse.”

DMT is found in several plants and is one of the active ingredients in ayahuasca, a bitter drink consumed during shamanistic rituals in South America and elsewhere. DMT is also available as a street drug in the UK, where it classified as a class A substance, carrying a maximum penalty of seven years in jail for possession and life imprisonment for supply.

The Medicines and Healthcare products Regulatory Agency (MHRA) approved the trial on Monday, and Small Pharma is currently involved in discussions with the Home Office, which must also give permission because DMT is a controlled substance.

The hope is that the initial trial, which aims to establish the lowest dose of DMT that elicits a psychedelic experience, could begin in January. It will involve 32 healthy volunteers, who have never previously taken a psychedelic drug, including ecstasy or ketamine. This will be followed by trial in 36 patients with clinical depression.

The treatment will be modelled on studies of psilocybin – the psychedelic ingredient in magic mushrooms – in depression. Here patients are brought into a clinic, where they undergo a “setting” session, during which the clinician primes them to open their mind to the drug, and ensures that they are comfortable and relaxed. Next, they are administered the drug, and once the psychedelic experience ends, the patient immediately undergo a session of psychotherapy.

https://www.theguardian.com/science/2020/dec/09/psychedelic-drug-dmt-to-be-trialled-in-uk-to-treat-depression