Jun 5, 2021 11:40 PM
(This post was last modified: Jun 5, 2021 11:41 PM by C C.)
https://www.wired.co.uk/article/psychede...t-the-high
EXCERPTS: David Olson is taking the high out of psychedelics. A chemical biologist at the University of California, Davis, Olson wants to tweak psychedelic drugs so they no longer produce a trip. His aim? To find out whether it’s possible to remove the hallucinogenic components of drugs while leaving behind the bits that could potentially treat mental illnesses.
Olson first became interested in psychedelics when he was a researcher at Massachusetts Institute of Technology in the early 2010s. At the time there was a lot of buzz around ketamine’s potential as a fast-acting antidepressant. Since then, studies involving nearly 200 people have found that a low dose of ketamine can quickly alleviate the symptoms of depression. In March 2019, the FDA approved a variant of ketamine for treatment-resistant depression, the first new way of medicating depression in decades.
Depression changes the structure of our brains. A neuron has branches like a tree, called dendrites, which reach out and connect with neighbouring neurons. Depression causes neurons in this brain region to atrophy, and their branches to wither and shrivel up, and connections between neurons detach. Ketamine is thought to encourage these shrunken neurons to regrow, and realign the circuits that have become disjointed, which could explain its antidepressant effects.
But using ketamine to treat depression has major drawbacks. For one, the drug’s potential for abuse. In 2015, Olson started a lab at UC Davis to figure out a way around this problem. He turned to psychedelics such as LSD, DMT and psilocybin, which are not considered to be addictive. Olson wanted to find out whether these drugs had the same effect on the brain as ketamine. In 2018, his lab published a study in rats and mice showing that these psychedelics also promoted the brain’s capacity to remould itself, a phenomenon known as neuroplasticity.
Olson’s group coined the term ‘psychoplastogen’ to describe this class of compounds. “The idea is that if you can regrow those atrophied neurons, re-establish the synaptic connectivity in the prefrontal cortex, you can kind of exert this top-down control on a lot of behaviours, and improve mood,” Olson says. He and his team thought they had found a whole new way of treating depression, but soon they realised the biggest limitation with using these drugs: the high.
[...] Take the high out of psychedelics, and the whole process could become a lot more simple. Olson doesn't think that getting high is the reason why psychedelics can treat conditions like depression, anxiety or PTSD. Take ketamine, for instance. There have been three studies where patients under anaesthesia were administered ketamine, a drug that falls into Olson’s class of psychoplastogens. The patients woke up with no recollection of the dissociative experience but still reported feeling less depressed.
[...] In December 2020, Olson and his lab published a study on their first compound, a tweaked version of the psychedelic ibogaine, which they named tabernanthalog, or TBG. The compound, they found, did not elicit a hallucinogenic trip in rodents but did retain its antidepressant effects. Then in April 2021, they published another study with similar results with another of their compounds, called AAZ-A-154. Both of these compounds have been licensed for clinical development by the company that Olson co-founded in 2019, Delix Therapeutics.
“My goal is not to try to convince someone who has undergone a psychedelic experience that the hallucinogenic effects that they experienced were not important to them,” he says. “And I'm not saying that a certain patient population might not benefit from the hallucinogenic effects.” But they just won’t work for everyone.
A tripping rat, however, is not the same as a tripping human. Olson’s ambition has been met with a healthy amount of scepticism from the other researchers in the psychedelic science space, he says. “Of course, they want to see this done in humans, because, you know, humans are not mice.” Delix is continuing to test both TBG and AAZ-A-154 before they can be tested in humans, and Olson expects they will be putting them through phase one trials in 2022... (MORE - missing details)
EXCERPTS: David Olson is taking the high out of psychedelics. A chemical biologist at the University of California, Davis, Olson wants to tweak psychedelic drugs so they no longer produce a trip. His aim? To find out whether it’s possible to remove the hallucinogenic components of drugs while leaving behind the bits that could potentially treat mental illnesses.
Olson first became interested in psychedelics when he was a researcher at Massachusetts Institute of Technology in the early 2010s. At the time there was a lot of buzz around ketamine’s potential as a fast-acting antidepressant. Since then, studies involving nearly 200 people have found that a low dose of ketamine can quickly alleviate the symptoms of depression. In March 2019, the FDA approved a variant of ketamine for treatment-resistant depression, the first new way of medicating depression in decades.
Depression changes the structure of our brains. A neuron has branches like a tree, called dendrites, which reach out and connect with neighbouring neurons. Depression causes neurons in this brain region to atrophy, and their branches to wither and shrivel up, and connections between neurons detach. Ketamine is thought to encourage these shrunken neurons to regrow, and realign the circuits that have become disjointed, which could explain its antidepressant effects.
But using ketamine to treat depression has major drawbacks. For one, the drug’s potential for abuse. In 2015, Olson started a lab at UC Davis to figure out a way around this problem. He turned to psychedelics such as LSD, DMT and psilocybin, which are not considered to be addictive. Olson wanted to find out whether these drugs had the same effect on the brain as ketamine. In 2018, his lab published a study in rats and mice showing that these psychedelics also promoted the brain’s capacity to remould itself, a phenomenon known as neuroplasticity.
Olson’s group coined the term ‘psychoplastogen’ to describe this class of compounds. “The idea is that if you can regrow those atrophied neurons, re-establish the synaptic connectivity in the prefrontal cortex, you can kind of exert this top-down control on a lot of behaviours, and improve mood,” Olson says. He and his team thought they had found a whole new way of treating depression, but soon they realised the biggest limitation with using these drugs: the high.
[...] Take the high out of psychedelics, and the whole process could become a lot more simple. Olson doesn't think that getting high is the reason why psychedelics can treat conditions like depression, anxiety or PTSD. Take ketamine, for instance. There have been three studies where patients under anaesthesia were administered ketamine, a drug that falls into Olson’s class of psychoplastogens. The patients woke up with no recollection of the dissociative experience but still reported feeling less depressed.
[...] In December 2020, Olson and his lab published a study on their first compound, a tweaked version of the psychedelic ibogaine, which they named tabernanthalog, or TBG. The compound, they found, did not elicit a hallucinogenic trip in rodents but did retain its antidepressant effects. Then in April 2021, they published another study with similar results with another of their compounds, called AAZ-A-154. Both of these compounds have been licensed for clinical development by the company that Olson co-founded in 2019, Delix Therapeutics.
“My goal is not to try to convince someone who has undergone a psychedelic experience that the hallucinogenic effects that they experienced were not important to them,” he says. “And I'm not saying that a certain patient population might not benefit from the hallucinogenic effects.” But they just won’t work for everyone.
A tripping rat, however, is not the same as a tripping human. Olson’s ambition has been met with a healthy amount of scepticism from the other researchers in the psychedelic science space, he says. “Of course, they want to see this done in humans, because, you know, humans are not mice.” Delix is continuing to test both TBG and AAZ-A-154 before they can be tested in humans, and Olson expects they will be putting them through phase one trials in 2022... (MORE - missing details)
