A single dose of a fast-acting psychedelic nose spray containing toad venom could be the key to treating stubborn depression, scientists say.

For nearly one in three people with depression, antidepressants do little to dull their symptoms.

That is why scientists are looking into treatment avenues such as magic mushrooms or LSD, with studies showing psychedelics can provide relief for people with hard-to-treat depression.

But though they may alleviate feelings of low mood, hopelessness and lack of motivation, these experimental drugs are often strong and the psychedelic effects can be long lasting.

Patients may need to remain under medical supervision in a clinic for four to 12 hours after being given a dose, which presents a logistical hurdle to widespread use, said researchers from King's College London and Monash University.

Instead, scientists put a synthetic formulation of 5-MeO-DMT to the test.

It is a psychedelic compound naturally secreted by the Colorado River toad to deter predators.

5-MeO-DMT can have a very intense effect, such as hallucinations that come on within minutes, but they tend to fade over the course of 30 minutes.

It means patients will not have to remain in clinics for hours after administration.

Scientists trialled administering the compound in the form of a nasal spray.

What are the symptoms of depression?

The psychological symptoms of depression include:

  • continuous low mood or sadness
  • feeling hopeless and helpless
  • having low self-esteem
  • feeling tearful
  • feeling guilt-ridden
  • feeling irritable and intolerant of others
  • having no motivation or interest in things
  • finding it difficult to make decisions
  • not getting any enjoyment out of life
  • feeling anxious or worried
  • having suicidal thoughts or thoughts of harming yourself

The physical symptoms of depression include:

  • moving or speaking more slowly than usual
  • changes in appetite or weight, usually decreased, but sometimes increased
  • constipation
  • unexplained aches and pains
  • lack of energy
  • low sex drive, loss of libido
  • disturbed sleep, for example, finding it difficult to fall asleep at night or waking up very early in the morning

Source: The NHS

Researchers said their drug has potential as an effective, well-tolerated treatment for depression, as it is administered in a clinical setting with psychological support.

Almost 200 people between the ages of 18 and 75 were involved in the phase 2 trial.

All of them had treatment-resistant depression, having already tried between two and five antidepressant treatments without success.

Some were given a single dose of the drug, 8 mg or 12 mg, into one nostril, while the rest were given an inactive, dummy dose.

Neither participants, clinic staff nor the researchers knew which dose each person received.

Regardless of the dose, the spray's psychedelic effects wore off quickly, with 85 per cent of participants able to leave the clinic within two hours of being given the nasal spray.

Both the 8 mg and 12 mg dose of 5-MeO-DMT produced rapid and lasting improvements for patients with treatment-resistant depression.

Around a month after treatment, between 18 and 26 per cent of those using toad venom had reached remission, compared with eight per cent on the dummy drug, according to the findings, published in the journal JAMA.

Patients who received toad venom scored better in depression questionnaires, with roughly one-third of participants seeing symptom scores fall by at least half.

Some patients experienced side effects from 5-MeO-DMT such as nausea, anxiety, and panic attacks.

But the researchers said these were mild and usually occurred on the day of dosing.

The researchers concluded: "A single administration of intranasal mebufotenin benzoate, 8 mg or 12 mg, in adults with treatment-resistant depression was generally safe and well tolerated and produced a robust antidepressant effect that emerged one day after dosing and was largely maintained to eight weeks."

"These findings suggest that a prolonged psychedelic effect is not required for durable antidepressant efficacy."

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