REGULATORS are under increasing pressure to expand access to psychedelic drugs for the treatment of mental illness. Experts say that while the science is promising, the hype is useless.
In December 2021, the Therapeutic Goods Administration (TGA) denied a request to downgrade psilocybin and MDMA (3,4-methylenedioxymethamphetamine) from Schedule 9 (banned substance) to Schedule 8 (controlled substance). This decision would have allowed patients to access drugs through channels such as the Special Access Program.
In its decision, the TGA cited expert advice that while psychedelics have shown promise in highly selected populations as a psychotherapeutic treatment, this was only in the context of closely clinically supervised environments, with intensive professional support. Further high-quality research using larger-scale studies was needed to determine the safety and effectiveness of the drugs, the TGA said.
In January 2022, then-federal health minister Greg Hunt announced that more trials were coming – $14.8 million in government funding was awarded to seven studies of innovative therapies for the disease mental. These include studies using MDMA-assisted psychotherapy for treatment-resistant social anxiety in young adults with autism spectrum disorders, psilocybin-assisted psychotherapy for anorexia nervosa and treatment-resistant depression. treatment, and MDMA-assisted exposure therapy for comorbid and post-traumatic alcohol use disorder. stress disorder (PTSD).
Leading psychiatrists have praised the government for investing in science while resisting pressure to make drugs more widely available.
Professor Ian Hickie, co-director of health and policy at the Center for Brain and Mind at the University of Sydney, is a researcher in the MDMA study involving young people with autism. “This is important research and there is an opportunity here; these drugs are different from what was available and there are a lot of people in need who are not responding to conventional therapies,” Prof Hickie said. Preview+.
“We need the science to answer the questions of which patients might benefit, at what dose, over what period and under what circumstances, and what the long-term effects are.”
Associate Professor Vinay Lakra, President of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) said Preview+ science has provided grounds for optimism.
However, he added: “Interest in and advocacy of psychedelics is way ahead of the science – good science keeps the enthusiasm and the rhetoric out.”
Psychotherapy assisted by MDMA and psylocibin
Melbourne psychiatrist Dr Nigel Strauss has been at the forefront of efforts to bring psychedelic medical research to Australia. He personally helps fund a trial at Monash University using MDMA-assisted psychotherapy for treatment-resistant PTSD.
He is also involved in a trial at St Vincent’s Hospital in Melbourne using psilocybin-assisted psychotherapy for end-of-life anxiety, and another at Swinburne University of Technology on psilocybin-assisted psychotherapy for treatment-resistant depression.
Dr. Strauss said he was optimistic that recent federal funding would help legitimize research in the area, which has been stigmatized due to a history of recreational psychedelic drug use.
“There’s probably enough hard evidence from the first era of psychedelics in the 1970s to suggest that these drugs are going to be effective,” he said. Preview+.
“They will not be a panacea; although I hear some organizations exaggerating their potential to solve the mental health crisis, careful patient selection is crucial.
Dr Strauss said psychedelic-assisted therapy typically involves a patient being administered the substance in a treatment session that can last up to 8 hours. The patient wears an eye mask and listens to soft music under the supervision of two therapists. Depending on the condition, psychotherapy can be done during the dosing session or afterwards, in what is described as integration work.
“It works by enabling neuroplasticity,” Dr. Strauss said. “People see things in a different way, and that helps in psychiatric conditions characterized by rigidity of thought.”
Regarding the treatment of PTSD with MDMA-assisted therapy, Dr. Strauss said that psychiatric and psychological treatments in the past have not always been effective.
“MDMA allows patients to look back on these frightening experiences and reprocess these events,” he said.
Dr. Strauss said MDMA-assisted psychotherapy for PTSD was the precursor to becoming the world’s first approved application of psychedelic medicine.
The U.S. Food and Drug Administration could approve the indication as early as 2024-2025, he said, based on a successful Phase 3 trial, and a second Phase 3 trial will be finished soon.
The successful 2021 Phase 3 study included 90 patients with severe PTSD and found that manual therapy with MDMA was associated with “significant and robust” improvement in PTSD symptoms compared to manual therapy plus placebo. No major safety issues were reported in the MDMA arm of the study.
Addressing the limitations of blinding, the authors said it was reassuring that anecdotally at least 10% of participants incorrectly guessed their treatment arm.
The study was sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) and its protocol and statistical analysis plan were developed in conjunction with the FDA. In 2017, MDMA-assisted therapy for PTSD received “Breakthrough Therapy” designation from the FDA, a process designed to expedite the development and review of certain drugs.
Still, Prof Hickie said most research into MDMA and psilocybin-assisted therapies was “in their very early stages”.
“Most of the respectable centers are looking at who can benefit in what ways and trying to do comparisons with existing treatments and look at not just short-term but long-term effects,” he said.
“Establishing the efficacy of these compounds is really difficult because of the theater that surrounds the situation – the setting, the expectations, the psychological therapy, being accompanied throughout the journey,” he said. “That’s why functional [magnetic resonance imaging (MRI)] studies looking for independent brain markers are so important that we can evaluate the treatment more objectively and compare it with other treatments.
Prof Hickie said another important issue to consider with psychedelic therapies was the “very vulnerable state” patients find themselves in when under the influence.
“They are open to exploitation,” he said.
A recent ABC Four corners episode included an interview with a patient who had accessed MDMA-assisted psychotherapy in Canada as part of a MAPS trial. The patient claimed that her therapist sexually assaulted her after the therapy session ended. The trials are under review by Health Canada.
“These drugs make people very suggestible, and that’s why we have to be very careful about who provides the treatment and under what conditions,” Dr Strauss said.
Dr. Strauss urged the RANZCP to create a psychedelic medicine interest group and training programs for psychiatrists now to ensure they were prepared for the upcoming arrival of psychedelic-assisted psychotherapies.
Ketamine: a different drug
The anesthetic ketamine – and its components esketamine and arketamine – is sometimes referred to as a psychedelic, although it tends to induce a dissociative state rather than hallucinations.
There are several ongoing studies of ketamine infusions for major depression in Australia. Last year, the TGA also registered the first ketamine product for mental illness: esketamine hydrochloride nasal spray (Spravato, Janssen-Cilag). The product is approved as an adjunct therapy for treatment-resistant depression – the first new class of drug to be approved as an antidepressant in Australia for 30 years.
Professor Hickie, who is involved in the Australian trials of Spravato, estimated that around 300 Australians are now accessing the product for treatment-resistant depression. The spray is given twice a week in combination with a newly initiated oral antidepressant.
“One of the most promising features of esketamine is its rapid onset,” Professor Hickie said. “It is fast acting, unlike existing antidepressants, causing its reported effect in reducing suicidal behavior.”
However, the effect usually lasts less than a week after a single dose, and at hundreds of dollars per dose, the cost is prohibitive for patients not enrolled in clinical trials.
Prof Hickie pointed out that unlike MDMA and psilocybin, ketamine was not used to guide psychotherapy.
“The patient sits quietly and goes through the dream experience and 90 minutes later reports how he feels,” he said. “People who take it seem noticeably less depressed, but they don’t report that their whole life has changed in outlook – nothing like the hype that surrounds psychedelics like MDMA and psilocybin.”
The drug’s precise mechanism of action is not fully understood, although it has effects on the glutamatergic system as well as the monoamine, cholinergic, opiate, and cytokine systems.
An observational study published in 2022 found that of 537 patients with depression who received a series of ketamine infusions in US clinics between 2016 and 2020, about half had at least a 50% reduction in their depression symptoms.
Among patients with suicidal thoughts, 73% had a reduction in these symptoms. However, a subset (8.4%) of patients experienced an increase in depressive symptoms after induction, while 6% of patients reported an increase in suicidal ideation, according to the study.
Prof Hickie said more studies on the long-term effects of ketamine were needed, including an investigation into whether it is addictive.
The RANZCP has prepared detailed clinical notes on the therapeutic use of psychedelics and the use of ketamine in clinical practice (here and here).
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