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Psychedelic medicines are expanding into the public consciousness

Magic mushrooms are just the start

By Natasha Loder: Health-policy editor, The Economist

THE COMING YEAR will see a number of milestones in the emerging era of psychedelic medicines. The recreational drug MDMA will complete a second phase-3 trial for the treatment of post-traumatic stress disorder (PTSD). If this trial confirms the findings of the first, from 2021, then in 2023 MDMA will be considered by America’s Food and Drug Administration for approval. MAPS, a public-benefit corporation, has so far shown that three doses of MDMA, along with a course of therapy over 18 weeks, can deliver a significant reduction in the symptoms of PTSD.

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It is not known how long the FDA will take to consider the drug, or whether it will approve it. But a decision will be expedited because the current treatments available for PTSD are so limited. An approval for PTSD treatment would also prompt MAPS to expand research to support the use of the drug for other indications, says Berra Yazar-Klosinski, its chief scientific officer. These might include eating and anxiety disorders.

MDMA is not a psychedelic drug in the classic sense of the word, but it is a psychoactive one. It produces a sense of emotional openness and empathy. MDMA, ketamine and conventional psychedelic drugs, such as psilocybin and lsd, all have one thing in common: they cause rapidly acting changes in brain function. They trigger receptors such as those for serotonin, and thereafter a cascade of signals important for the growth of neurons. It is probably not necessary to cause hallucinations to create the sort of neuronal plasticity that is increasingly thought to be important in the treatment of brain disorders. One theory is that many psychiatric and neurodegenerative conditions are a result of “cortical atrophy”, the loss of connectivity between the connections of neurons in the pre-frontal cortex. Psychedelics seem to allow these connections to be strengthened and reconnected.

In recent years the number of clinics around the world offering ketamine, as an intravenous infusion, largely for treatment-resistant depression, has grown. That will continue. There are more than 100 clinics across America, and others in Europe, that administer it, and they are in an ideal position to deliver MDMA, if approved, to PTSD patients. Other psychedelics are also being tested against conditions such as addiction and eating disorders. The drugs are believed to leave patients’ brains more flexible and thus receptive to psychotherapy, which is usually given before and after treatment with psychedelics.

On January 1st the therapeutic use of psilocybin becomes legal in Oregon

Also in the pipeline is psilocybin for treatment-resistant depression (TRD). Results of a trial suggest that 12 weeks after treatment, one patient in five was in remission. But the small number of durable responses, and some adverse events, highlight the challenging road ahead for those trying to get approvals from medical regulators. And the difficulty of running placebo-controlled trials with psychedelic medicines means there are concerns about whether positive results found in tightly controlled trials will be replicated in practice.

Either way, these drugs are coming in 2023. On January 1st the therapeutic use of psilocybin becomes legal under licence in Oregon. From January the Canadian province of Alberta will also allow the regulated use of psychedelic drugs for therapy. This will cover psilocybin, MDMA, LSD, mescaline, DMT and ketamine.

Efforts by states to facilitate the use of psychedelics are moving faster than trials and drug regulators. Early availability will help many, but is also likely to bring risks. Trials of psilocybin for TRD led to an increase in suicidal behaviour in some patients. A closer examination of those patients revealed that they were the ones who had not responded to therapy. Rupert McShane, a professor of psychiatry at the University of Oxford, treats TRD patients with ketamine but emphasises the importance of setting expectations. Having failed to respond to treatment, sometimes for decades, patients can put “so much hope in it that when it doesn’t work they feel more desperate,” he says.

Other causes for concern are the potential for adverse events such as bad trips, and worries about cardiotoxicity with some psychedelics. Drug trials are not just meant to winnow out the drugs that do not work. They also increase the understanding of risks. The coming year will be an exciting one, but it will highlight the need to move cautiously, too.

Natasha Loder: Health-policy editor, The Economist

This article appeared in the Science and technology section of the print edition of The World Ahead 2023 under the headline “The magic of mushrooms”

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