The success of ibogaine, a somnogenic anti-depressant, in a mouse model of psychosomatic instability
Any study participants on antidepressants were required to wean themselves from those medications prior to the start of the trial. Psychedelic treatment doesn’t work on people who are actively taking antidepressants — the receptors where psychedelics attach in the brain are already flooded with serotonin from their current mood-altering drugs.
The success is just the latest involving tripless versions of psychedelic drugs. A previous attempt made a hallucination-free version of ibogaine, which is made from the root bark of a shrubby tree native to Central Africa.
The leader of the ibogaine project says it’s encouraging to see multiple groups approach the problem in different ways.
Someone asked what they wanted to look for during a meeting. I said if nothing else we’ll have the world’s greatest drugs.
The team chose the molecules that affect the brain’s dopamine system, which is involved in regulating mood. They still weren’t looking for an anti-depressant.
Brian Shoichet, an author of the study and a professor in the pharmaceutical chemistry department at the University of California, San Francisco, says there were interesting reports about people getting great results after just a few doses.
“They had the best properties,” Shoichet says. “They were the most potent, and when you gave them to a mouse, they got into the brain at the highest concentrations.”
There are studies that show that a depressed mouse gives up quickly when it is placed in an unpleasant situation. If the same mouse gets Prozac, it’s going to keep trying.
They didn’t show any signs of a crazy experience, where a mouse twitches its nose in a different way. “We were surprised to see that,” Roth says.
A study of the phenomenological effect of psilocybin in schizophrenia patients with treatment-resistant depression in November 2021
The team says it will need to work on the new molecule before it can be used in people. They appear to mimic the ability of lysergic acid diethylamide to increase heart rate and blood pressure.
The day after the treatment, the maximum effect was seen. This contrasts with standard antidepressants, which take several weeks to reach maximum effect,” said Dr. Anthony Cleare, a professor of psychopharmacology and affective disorders at King’s College London, in a statement. He was not a part of the study.
In November 2021, when the psychedelics company Compass Pathways released the top-line results of its trial looking at psilocybin in patients with treatment-resistant depression, the stock of the company plunged almost 30 percent. The dive was reportedly prompted by the somewhat-middling results of the research—but also because of the scattering of serious adverse events that occurred during the trial. Amid the psychedelic renaissance, bringing up their potential harms has been somewhat of a taboo. After being vilified for decades, the field has just recently reentered the mainstream. More negative outcomes are expected to emerge as the trials get bigger. The results of the trial could mean that we should open up the dialogue about the negative effects of the drug even if it means lightening the hype.
Results of the study, published Wednesday in The New England Journal of Medicine, found “an immediate, fast, rapid-acting, sustained response to 25 milligrams (of COMP360),” said study coauthor Dr. Guy Goodwin, a professor emeritus of psychiatry at the University of Oxford in the United Kingdom.
The drug can be made from magic mushrooms, but that is not how our compound is created. The study was conducted by the chief medical officer of the company that manufactures COMP360 and he said it was synthesised in a pure chemical process.
“We can see new connections in a single day with a single dose of psilocybin,” says Kwan. “And then they can last more than a month” is the equivalent of a long time in a human.
“If you were in the 25-milligram group, you were nearly three times as likely to respond than if you were in the 1-milligram group,” said Johnson, who coauthored safety guidelines for psychedelic research in 2008.
“The effects did start to wear off by three months, and we need to know how best to prevent the depression returning,” Cleare said, adding that not enough is yet known about potential side effects.
There are 233 study participants who had treatment-resistant depression and can only be diagnosed when someone fails to respond to two courses of antidepressants. Of the 9 million people in the US with medically treated depression, 3 million patients are resistant to treatment, studies have estimated. 100 million people worldwide have treatment-resistant depression.
“Participants were requested to remain off antidepressant treatment during the first 3 weeks after the trial-drug administration; however, these medications could be started at any time during the trial if deemed clinically necessary by a physician investigator,” the study said.
At week 12 there was a 20% response in the 25-mg group, 15% in the 10-MG group, and 10% in the 1-MG group, according to Dr. Madras. She did not participate in the study.
“This is not a spectacular response rate for a psychiatric treatment … and we would only expect this to worsen over a longer follow-up period,” said Dr. Ravi Das, an associate professor of educational psychology research methods and statistics at University College London via email. He who was not involved with the study.
This is expected in a trial like this. To some degree, yes,” says Natalie Gukasyan, assistant professor and medical director for the Johns Hopkins Center for Psychedelic & Consciousness Research. The high levels of suicidal thoughts that occur with a patient group as vulnerable as those with depression are expected. It is worth mentioning that there were higher rates of these events in the higher group, which raises the question if the drug played a role. One thing she thinks would have been helpful to include in the study was the lifetime history of previous suicide attempts in the participants, which is an important predictor of future suicidal behavior.
The researchers who did the study reported headaches, nausea, fatigue, and dizziness in almost 70% of the participants, and experts say that is a typical response on psilocybin administration.
A small number of people in all three dosage groups experienced suicidal thoughts or injured themselves over the 12-week follow-up period, the study found. Within the first three weeks alone, two people in the 25-milligram group thought about suicide and two intentionally injured themselves. Two people in the 10-milligram group were suicidal, one self-injured and one was hospitalized for severe depression, the study reported.
Those behaviors are “common in treatment-resistant depression studies — most cases occurred more than a week after the COMP360 psilocybin session,” the company said.
“Remember that this is in people who were assessed not to be at significant risk of suicide when they entered the trial. The numbers were small, but Kevin said that they will need to be taken into account in future trials.
The study results are promising, but many questions remain and it’s unknown if this drug would be successful for different types of depression, said McConway, who was not involved in the study.
The results were promising, if not painting the picture of a miracle cure. The group of patients who were randomized to 25mg had a higher number in remission after 3 weeks than the placebo group. The placebo group that was not statistically significant improved after 12 weeks when less than 20 percent of the high-dose patients were still responding.
Joost Breeksema, a PhD candidate that studies patient experiences of psychedelics at the University Medical Center in the Netherlands, says that the fact that Compass was upfront about the adverse events is a good thing. According to a review done in August, 2022, adverse events in psychedelics research have been under reported and may have been flagged. The trials that Breeksema looked at had no adverse effects. The Compass Pathways research “reported adverse effects more rigorously than many of the other trials in our systematic review,” he says.
A group of about 1,000 brain scientists squeezed into an auditorium at the San Diego convention center for a symposium.
They’d been to hear about drugs that can alter individual brain cells, as well as the new ways to treat disorders such as depression and chronic pain.
Dendrites form connections by attaching small objects to each other. And in mice that got psilocybin, the size and number of these spines increased by about 10%, which allowed cells to form new connections.
How psychedelics changed the lives of people: How much did you learn from the experiment and what did you need to learn from it?
It can be a lot of work to get people used to it. You need to be with them while they are in the experience, and you have to prepare them for that.
“When people have been through a psychedelic experience in my lab, they say, ‘Wow this was amazing, this was just a fantastic experience,'” she says. “Would you come back next week for another session?” They say, ‘Thank you, but no thanks’.
And in 2016, a pair of studies published by prominent researchers “really piqued everyone’s interest,” says Dr. Joshua Gordon, who directs the National Institute of Mental Health.
But the effects found in large studies of psychedelics have been much less dramatic than in some of the earlier, smaller studies, Gordon says. He says that some companies overstated their benefits.