A hallucinogenic drug is being trialled as a potential treatment for depression.
So-called n, n-dimethyltryptamine (DMT) – known for its use in shamanic rituals – is being offered to a group of people with a moderate to severe case of the mental illness.
The patients are being given the psychedelic compound, followed by talking therapy, with research suggesting this treatment regimen is both safe and effective.
Existing antidepressants are thought to lead to an improvement in 50% to 65% of individuals, with the effect usually being felt after one to two weeks.
Executives at the pharmaceutical company behind the DMT trial believe intravenously administering the compound alongside talking therapy will offer "almost immediate" benefits, which are expected to be "longer lasting than conventional antidepressants".
Although unclear, DMT may "loosen" brain pathways that become fixed towards depression. These can then be "reset" via counselling.
DMT is known as the "spirit molecule", with users reporting hallucinations likened to a near-death experience.
It is also the active ingredient in ayahuasca, a traditional Amazonian plant used to bring spiritual enlightenment.
Carol Routledge from Small Pharma – the firm behind the trial – likened DMT to "shaking a snow globe", loosening negative thought patterns that can then be reset.
The trial is recruiting 68 participants. DMT's safety and tolerability will be investigated in healthy volunteers up to three months after a single dose. Its efficacy will also be assessed as up to two doses two weeks apart in people with moderate to severe depression.
The trial is expected to complete in February 2023.
Antidepressants are known to become less effective over time in certain individuals.
According to Small Pharma, "tolerance does not develop to the psychological effects of DMT".
"We believe the impact will be almost immediate and longer lasting than conventional antidepressants," said Routledge, as reported by the BBC.
The psychedelic effects, however, are said to last just 20 minutes, compared to up to eight hours with psilocybin – the hallucinogenic compound in magic mushrooms, which has also shown promise as a depression treatment.
DMT is also thought to be safe, based on the fact the compound is "endogenously produced in the brain".
Watch: Depression supplement warning
It is unknown exactly how DMT and existing antidepressants work.
Antidepressant pills available on prescription are thought to increase certain chemical levels in the brain linked to a person's emotions and mood.
"These drugs [containing DMT] seem to allow you to approach difficult experiences in your life, sit with that distress and process them," said Routledge.
This may enable a patient to get to the root cause of their depression, she suggested.
"Through that we think you can get much more long-lasting change," said Routledge.
Read more: Father reveals how he copes with depression
Imperial College London, which runs the Centre for Psychedelic Research, is consulting on the research.
Professor Michael Bloomfield from University College London has called the study "really exciting", but stressed DMT's potential is unclear and could be open to abuse.
This comes as a ketamine-assisted therapy clinic is set to open in Bristol.
Already administered by an Oxford service, the drug is known to provide temporary relief from very serious, treatment-resistant depression.
Accompanying ketamine with therapy is thought to have longer-lasting benefits.
Watch: Exercise eases depression in children