This review (2024) examines the recent approval by the Australian Therapeutic Goods Administration (TGA) of psilocybin for treatment-resistant depression (TRD) and MDMA for PTSD, effective 1 July 2023. It highlights the campaign led by Mind Medicine Australia and supported by leading researchers and institutions, as well as implications for future approvals and psychedelic drug development pathways.
The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administration (TGA) approved the use of psilocybin for treatment-resistant depression and MDMA for PTSD to take effect from 1 July 2023. The campaign for TGA approval was led by a coalition comprising the Australian charity Mind Medicine Australia with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from large numbers of clinical, academic and patient groups. Under the rescheduling, current prescribing rights are limited to psychiatrists who have become authorised prescribers under the TGA's Authorised Prescriber Scheme, and psilocybin can only be used for treatment resistant depression and MDMA can only be used for PTSD. This paper reviews the background for this decision, its implications for approvals in other jurisdictions, as well as for the development pathways for other psychedelic drugs.
Nutt and colleagues place recent clinical progress with classical psychedelics and MDMA in the context of a large, unmet burden of mental illness and limited effectiveness of existing treatments. They note rapid advances in clinical trials over the past decade (with many agents reaching Phase II and some moving into Phase III), and describe basic pharmacology relevant to clinical action: psilocybin and related 5-HT2A agonists act on cortical layer 5 pyramidal neurons in a way that can disrupt ruminative activity in depression, while MDMA primarily releases serotonin and through 5-HT1A-related mechanisms attenuates fear responses relevant to PTSD. The paper also flags important regulatory milestones, in particular the Australian Therapeutic Goods Administration’s (TGA) decision to approve psilocybin for treatment-resistant depression and MDMA for PTSD to take effect on 1 July 2023, and notes that the article was written before the US FDA’s later rejection of MDMA in June 2024. This paper sets out to explain the background to the TGA decision, to describe how the Australian authorisation framework will work in practice, and to consider implications for other jurisdictions and for the development pathways of other psychedelic drugs. Rather than presenting new trial data, the authors undertake a narrative review and policy analysis of the regulatory process, stakeholder submissions, trial evidence cited by proponents and opponents, and practical delivery models that have been proposed for bringing these medicines into clinical use in Australia.
Papers cited by this study that are also in Blossom
Goodwin, G. M., Aaronson, S. T., Alvarez, O. et al. · New England Journal of Medicine (2022)
Holze, F., Gasser, P., Müller, F. et al. · Biological Psychiatry (2023)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Mitchell, J., Ot’alora G, M., van der Kolk, B. et al. · Nature Medicine (2023)
The extracted text does not present a discrete Methods section describing a systematic search or formal meta-analytic procedure; instead the paper is a narrative review and policy analysis drawing on regulatory documents, stakeholder submissions, public consultation data, and published clinical trial evidence. Key information sources cited or described include the rescheduling applications lodged by the charity Mind Medicine Australia (MMA), the Delegate’s published rationale for initial rejection, subsequent written submissions and public responses to the TGA consultation, and major clinical trials and development programmes referenced by the authors (for example MAPS trials for MDMA and Imperial College trials for psilocybin). Where relevant, the authors incorporate quantitative figures reported in submissions and surveys (for example the number of public submissions and proportions in favour), regulatory timelines (initial applications, interim decisions, resubmissions), and descriptions of proposed clinical protocols. The paper therefore synthesises regulatory and policy material together with selected clinical trial findings rather than applying explicit systematic-review methods; the extracted text does not report search strategies, inclusion criteria, or formal risk-of-bias assessment.
The paper recounts how a coalition led by Mind Medicine Australia and supported by clinicians, researchers and patient groups campaigned for rescheduling of psilocybin and MDMA. The coalition argued that existing treatments often fail: current data cited in the paper suggest about one third of people with depression and roughly 50% of people with PTSD derive no real benefit from pharmacotherapies, with remission rates quoted at about 35% for depression and as low as 10% for PTSD. The authors also emphasise high suicide rates in certain Australian groups (reported for first responders and defence veterans) as part of the rationale for seeking new treatment options. Regulatory and stakeholder dynamics are described in detail. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) opposed rescheduling and its clinical memorandum was criticised by the coalition for lacking transparency, peer review and consultation with international experts; the RANZCP’s position contrasted with its more positive stance on ketamine. MMA lodged an initial set of rescheduling applications that were rejected at interim stages, then refiled in March 2022 with additional data and public support. Public submissions increased markedly between the first and second applications, rising to over 13,000 written submissions with over 98% support for psilocybin and over 95% support for MDMA; among researchers and clinicians only very small absolute numbers were recorded as opposing (for psilocybin 2 out of 92 clinical researchers and no health professionals; for MDMA 1 out of 89 researchers and 2 health professionals, as reported). The paper outlines the Australian clinical model approved under the TGA’s Authorised Prescriber Scheme and the procedural requirements for clinicians. To become an authorised prescriber, a psychiatrist must obtain approval from a Human Research Ethics Committee and from the TGA and must demonstrate appropriate training and protocols. Required protocol elements include (as listed in the extracted text): - the stages of the therapeutic process (diagnosis, contraindications, tapering, informed consent, preparatory, dosing and integration sessions, final review and follow-up); - details of the clinical environment and safety measures for dosing sessions; - the identity, qualifications and training of therapists involved; - medicine details including manufacturer, quality and purity. A practical delivery model (Box 1) is presented: initial medicine supply would be arranged under contract with an overseas GMP manufacturer with distribution handled by an Australian pharmacist; patient selection would be limited to treatment-resistant depression or PTSD (treatment resistance defined as failure of at least two prior treatments, one being an adequate course of a registered medicine); treatment procedures mirror established trial protocols (preparatory session, dosing day, integration session the following day), with psilocybin repeatable once and MDMA up to two additional times at intervals of not less than one month; and a data-collection registry and regular public reporting were envisaged. On safety and harms the authors report that modern clinical and volunteer data involving hundreds of participants show very few reports of significant adverse effects in controlled settings. They also cite four independent studies using multi-criteria decision conferencing that ranked psilocybin and MDMA as low-harm substances compared with many other psychoactive drugs; the authors argue harms are expected to be even lower in medical settings given the small number of therapeutic administrations required. The paper notes logistical considerations — for example that several GMP producers of psilocybin and MDMA exist in Canada and elsewhere — and discusses the potential for non-commercial supply models to increase access in lower-resource settings. Opponents’ concerns, including the risk of self-medication, translation risks for moving a drug into wider medical use, and legal arguments about international conventions, are presented and the coalition’s counter-arguments are summarised.
The authors interpret the TGA decision as being driven by large unmet clinical need, accumulating positive clinical evidence, and strong public and professional support marshalled by the coalition. They contend that the available efficacy and safety data for psilocybin and MDMA are at least comparable to that for ketamine (a medicine already used off-licence in psychiatry), and that rescheduling under the Authorised Prescriber Scheme provides a regulated pathway to deliver treatments while collecting real-world evidence to inform ongoing practice. In positioning these findings relative to earlier research and practice, the paper argues that many negative perceptions of psychedelics are overstated when contemporary clinical data and historical medical use are taken into account. The authors emphasise that the risks can be mitigated through mandated training, clinical protocols and governance, and that supply challenges are solvable via existing GMP manufacturers and distribution arrangements. They also highlight broader implications: other jurisdictions may follow the Australian model or adapt it, and countries with limited resources might rely on non-commercial provision if market-priced products prove unaffordable. Key limitations and uncertainties acknowledged in the extracted text include ongoing debate among professional bodies (for example the RANZCP’s concerns regarding transparency and consultation), potential translation risks in scaling up use beyond trial settings, and the possibility that new chemical entities without historical clinical experience would not be able to follow the same regulatory route. The authors note the need for continued real-world monitoring and data publication from registries. Finally, they flag that the regulatory and commercial landscape remains dynamic — in particular they note this paper was prepared before the FDA’s subsequent decision on MDMA — and that future approvals, company strategies and further trial results will shape how these medicines are adopted internationally.
results in Phase 2 and are also moving to Phase 3. Clinical developments with the amfetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) are further advanced as the Multidisciplinary Association for Psychedelic Studies (MAPS) has already completed two Phase 3 studies in treatmentresistant Post traumatic stress disorder (PTSD)and submitted their dossier to the US Food and Drug Administration (FDA). (Please note: This article was written before the rejection of MDMA as a medicine by the FDA in June 2024). Given this progress in the traditional commercial pathway of medicines development, it is surprising to some that the Australian equivalent of the FDA-the Therapeutic Goods Administration (TGA)-has already with effect from 1 July 2023 approved the use of two of these agents: psilocybin for treatment-resistant depression and MDMA for PTSD. Psilocybin like most other commonly used psychedelics such as LSD and DMT is a 5-HT2A receptor agonist (RRID:AB_2264259). These receptors are highly expressed on the Layer 5 glutamatergic pyramidal neurons of the cortex that coordinate cross-cortical integration. The 5-HT2A receptor stimulant massively depolarises these neurons, and so disrupts ongoing cortical activity which breaks down ruminative thinking in depression. MDMA is a serotonin releasing agent that has lesser effects on both dopamine and noradrenaline release. It also blocks the reuptake of all three amines to enhance activity of all of them, but especially serotonin. This, acting through a 5-HT1A receptor (RRID: AB_2313875), attenuates fear responding in the amygdala so allowing PTSD patients to fully engage with their psychological treatments. This paper reviews the background for the TGA decision, its implications for approvals in other jurisdictions, as well for the development pathways for other psychedelic drugs.
The campaign for TGA approval was led by an Australian charity called Mind Medicine Australia (MMA) with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from a large numbers of clinical, academic and patient groups (hereafter together referred to as the Coalition). The Coalition came together because each participant had independently come to the conclusion that current treatments for mental illnesses are often ineffective with up to a half of patients getting inadequate responses, and because the effectiveness and safety of psychedelic therapies was showing positive results in clinical trials. Current data suggest that about one third of depression sufferers and about 50% of PTSD sufferers get no real benefit from current pharmacotherapeutic treatments with remission rates for depression being about 35% and for PTSD being as low as 10%. Moreover, the most widely used alternative treatment for treatment-resistant patients, Electroconvulsive therapy (ECT), has substantive side effects and low patient acceptability. A particularly powerful argument for new approaches was the suicide rate in Australia of first responders, that is, professionals dealing with vulnerable people in urgent need, such as paramedics (average of one every month) and Australian Defence Force (ADF) veterans (average of one every week)despite having guaranteed access to current best treatments in one of the world's leading health care systems. Most of these people will have had either depression or PTSD or both. In Australia, the control of medicinal drugs is mediated through RANZCP's position dominated the Delegate's decision. However, there were some concerns that the RANZCP statement was not fully representative. To begin with, the writers of the RANZCP's clinical memorandum were not publicly identified so it was unclear whether they had any expertise in this area or whether their views had been peer reviewed. Secondly, it was also apparent that the RANZCP had not consulted either their members or leading experts in the field of psychedelic medicine research from around the World. Thirdly, the RANZCP did not appear to have consulted with New Zealand experts who were in the process of doing a harm assessment study which included these agents. The RANZCP opposition to the rescheduling of psilocybin and MDMA contrasted with its much more positive analysis of the use of ketamine for depression, a medicine used off-licence in psychiatry. The Coalition argued that the evidence-base for efficacy and safety of psilocybin and MDMA was as least as strong as that for ketamine, yet the RANZCP had come to opposite conclusions. While the first rescheduling applications were rejected, the published reasoning of the Delegate gave MMA an ability to lodge new applications in March 2022. These specifically targeted the Delegate's reasoning with a comprehensive data set to show that it was either incorrect or the problems identified could be adequately managed within the Australian Health System. See Table. One argument raised against rescheduling from some opponents was to wait for the US FDA to approve these medicines after which the sponsoring companies could then apply for marketing authorization in Australia. However, both the application as well as the potential timing of it by the owning pharmaceutical companies remained undercertain (as has been the case for MAPS in Europe; see later) which might in effect deny a proven medicine to Australian patients who were suffering. After lodging its second rescheduling applications in March 2022, MMA developed a public campaign to generate a higher number of submissions in support of the rescheduling from key stakeholder groups than had occurred with the first applications. MMA's second applications were again rejected by the Delegate at the interim stage in July 2022. However, MMA and the Coalition were able to specifically deal with each of the Delegate's arguments in their final submission in response (Mind Medicine Australia, 2022). At the same time, the written submissions lodged in response to the applications had increased 12-fold from the first applications to over 13,000 with over 98% in support for psilocybin and over 95% in support for MDMA (see Figure). For psilocybin, only 2 out of 92 clinical researchers and no health professionals opposed the rescheduling (Figure), and for MDMA, the figures were 1 out of 89 clinical researchers and 2 health professionals opposing. After the interim decision in 2021 against rescheduling, supporting survey reponses increased substantially (see Figure). While restrictive, there are an enormous number of patients in Australia suffering from these conditions.
To become an authorised prescriber of these medicines in Australia, a psychiatrist must apply for approval from both a Human Research Ethics Committee (i.e. the same type of committee that reviews a proposed clinical trial) and from the TGA. The application process requires psychiatrists to demonstrate that they have received appropriate training in the use of these medicines as part of therapy and that they will be using appropriate protocols. These protocols must cover, amongs other things: Breakdown of survey responses: MDMA. MDMA, 3,4-methylenedioxymethamphetamine. T A B L E 1 : Summary of arguments given by Mind Medicine Australia in its second applications responding to the delegate published rationale for rejecting its first applications. Rescheduling would allow the collection of much needed real-world evidence on efficacy of both of these medicines in the patient population most in need of treatment innovation. Also, positioning in the poisons standard is not based on whether a substance has been registered as a medicine but on relative risk. There are a number of Schedule 8 medicines that are not registered and are currently the subject of clinical trials.
Reliance on the views of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) and the Australian Psychological Society (APS) See discussion in text. The Australian Psychological Society (APS) simply adopted the RANZCP positioning on rescheduling and focused its comments on widespread application which is more relevant to registered medicine. 12. Rescheduling would be in breach of the UN Convention on Psychotropic Substances 1971 This is incorrect as the convention contains an explicit exemption for restricted medical use. (Continues) i. the stages of the therapeutic process that the psychiatrist and the therapist team must follow including diagnosis, contraindications, management of medicine tapering (if required), obtaining informed patient consent, preparatory, dosing and integration sessions and the final review session and follow-up; ii. where the dosing sessions will occur and a description of the clinical environment and available safety measures; iii. the identity, qualifications and training of the proposed therapists; and iv. medicine details including manufacturer, quality and purity. T A B L E 1 (Continued) The Delegate's argument for rejection Mind Medicine Australia's response 13. There is a translation risk associated with a new medicine being adopted by the medical system in Australia. There are always translation risks associated with the adoption of any new medicine but these are ameliorated through the use of appropriate training, protocols and procedures. The Australian medical system is used to managing translation risks. F I G U R E 3 Breakdown of survey responses: Psilocybine. In relation to safety in a clinical context, in the modern era with many hundreds of patients and similar numbers of healthy volunteers given these medicines, there are very few reports of significant adverse effects. While there may be concern with the therapeutic authorization that people might try to self-medicate Box 1 How the Australian model works. Step 1. Medicine supply Psilocybin and MDMA are being used as unregistered medicines in Australia. Mind Medicine Australia has entered into a major supply contract with an overseas Good Manufacturing Practice (GMP) manufacturer whereby Mind Medicine Australia will contract the supply, storage and distribution role to an Australian pharmacist with the relevant licences and permits. In the future, the medicine could be provided directly by pharmaceutical companies or other distributers as volumes increase. The treating psychiatrist is required to send a prescription for the required medicine on a named patient basis to the pharmacist. Step 2. Patient selection Only patients with treatment-resistant depression or PTSD will be eligible after assessment by the treating psychiatrist who must be an authorised prescriber for these medicines under the TGA's Authorised Prescriber Scheme. Treatment resistance is defined by documented failure to respond to at least two previous treatments, one of which must be an adequate course of a registered medicine. Step 3. Treatment procedures The psychiatrist will take clinical responsibility for patient diagnosis, screening, writing the prescription, overseeing other therapists, drug administration and follow-up. Patients will be given the medicines according to standard procedures derived from the MAPS (MDMA) and Imperial College (psilocybin) trials which include a preparation session prior to the treatment day, dosing on the treatment day and a psychotherapeutic session on the following day to help the patient make sense of the medicine experience (often called an integration session). This treatment regime will be repeated up to once more for psilocybin and up to twice more for MDMA at no less than monthly intervals. Subsequent medical or psychology follow ups will be according to clinical need. Importantly the TGA has confirmed that the treating psychiatrist does not have to be present during the dosing and therapeutic sessions. Step 4. Data collection and analysis been used to demonstrate the power of psilocybin therapy. Step 5. Reporting of results Data from the registry will be published on a regular basis in the public domain, through a dedicated website and through peer reviewed papers. without the safeguards of a clinical environment, this apprehension only highlights the need for regulated patient access to reduce associated harms. Data collected over the past 60 years indicate that many of the harms of these two drugs have been exaggerated. In the past decade, four independent studies conducted by western academics using the state-of-the-art multi-criteria decision conferencing approach have concluded that, even when used recreationally, these two drugs score very low on harms compared with other legal and illegal psychoactive substances. These harms will be even lower in medical settings, especially given the low number of drug treatments required for clinical benefit. The challenge of provision of GMP products is already resolved as there are several producers of both psilocybin and MDMA in Canada, and sources in other countries are being developed. The acquisition and provision of these medicines could be done through charities such as MMA, pharmacy groups or governmental departments. Even if psilocybin and MDMA gain marketing authorizations in the United States and Europe, this noncommercial approach is likely to be necessary in countries with high trauma incidences such as Ukraine, Syria and Palestine that will not be able to afford the substantial costs of buying these treatments from western pharmaceutical companies. The fact that many psychedelics are found in nature may also offer a lower-cost approach to supply in less well-off countries. If Also, the current situation is not typical. Firstly, innovation in mental illness treatment is limited at present. Secondly, the demands for treatments, and especially for treatment-resistant disorders, are growing. Thirdly, psilocybin and MDMA are not New Chemical Entities (NCEs), rather they are existing drugs that were used as medicines before being banned largely for political, rather than scientific, reasons. Their clinical use prebanning, coupled with the vast numbers of people using them nonclinically, supports the modern-day trial evidence of efficacy and safety, with a low level of harm incurred from their use. shows that medical risks are often minimal and that many-albeit not all-of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a medical context. In. Another might be mescaline given its safety data from centuries of use for religious/social bonding purposes but modern clinical studies are only just beginning. It seems unlikely that new chemical entity variants of psychedelics or MDMA would be able to progress this route given they have no historic data, though a mixed model of Randomised controlled trial (RCT) plus Real-world evidence (RWE) studies might accelerate their reaching patients.
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Nichols, D. E. · Pharmacological Reviews (2016)
Nutt, D. J., Erritzoe, D., Carhart-Harris, R. L. · Cell (2020)
King, C., Nichols, D. E. · Nature Reviews Neuroscience (2013)
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Papers in Blossom that reference this study
Smith, K. A., Harcourt, E., Cipriani, A. · BJPsych Open (2026)