Can we take the high out of psychedelics?

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.

Psychedelics have major drawbacks. The hallucinogenic experience, gone wrong, can be traumatising, scarring. There’s also the portion of the population for whom these drugs may not be advisable, because of pre-existing psychiatric conditions or a family history of psychotic illnesses, like schizophrenia and bipolar disorder. If it turns out that psychedelic drugs are the best weapon in our arsenal to treat mental illness, then these people could be left behind.

Then there are the messy logistics of treating people with psychedelics. COMPASS Pathways, a mental health company in the UK, is running trials testing out psychedelic-assisted therapy. Patients involved in the trails first have to visit the clinic to be prepared for the experience. After receiving the drug they have to stay at the clinic for eight hours while being closely monitored. Then they must return to the clinic afterwards to talk through the experience with a therapist. The lengthy process means the cost of one therapy cycle would be unfeasible for many, and requires a lot of specially-trained providers with special settings. Synthesis, a company that offers psychedelic wellness retreats in the Netherlands, provides its programme for prices up to $9,000 (£6,350). For these reasons, Olson doesn’t think that traditional psychedelics will be scalable.
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.
Meanwhile, there is research hinting that non-hallucinogenic psychedelic drugs such as MDMA can be powerful therapeutics. Taking MDMA does not illicit the trip associated with some drugs, but new research suggests it may be an effective treatment for people with PTSD. Olson says you could view MDMA as a proof-of-concept that their theory that the hallucinogenic experience of psychedelics might not be necessary may indeed be right.

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