EXPERT REACTION: TGA approves the use of psychedelics for mental health treatment

Psychae Institute, a non-profit medicinal psychedelics research institute (which works in partnership with eminent Australian and international universities), welcomes the Australian TGA's decision to reschedule psilocybin and MDMA for limited medical use, which we believe will help to reduce the stigma around these substances and advance mental health care.

This decision and the proposed approach enabling psychiatrists to prescribe MDMA and psilocybin via the Authorised Prescriber scheme strikes a pragmatic balance between potential benefits and risks by enabling limited access for patients with PTSD and depression who have exhausted all other treatment options, while still providing strong oversight via both TGA and human research ethics committee approval.

As the evidence of efficacy and optimal therapeutic treatment models progresses, we expect this level of regulatory oversight will not be required. However, we note that while currently evidence is encouraging, with few signals for adverse effects, long-term outcomes data and improved understanding how to optimise accompanying psychotherapeutic support remain critical.

We also note that contrary to some media reporting, Australia is not the first country in the world to enable limited patient access. This has been occurring successfully in Switzerland since 2014 where treating physicians can request a permit from the Federal Office of Public Health (FOPH) for the clinical use of MDMA, LSD, and psilocybin, and unlike Australia this does not require ethics committee approval - 101 patient licenses issued by the FOPH in the first 6-months of 2022.

We welcome the TGA Delegate’s Final Decision to reschedule MDMA and psilocybin specifically for prescription by authorised psychiatrists in conjunction with psychotherapy for the treatment of PTSD and depression, respectively.
However, we caution that the overall efficacy of these treatments has not yet been established to a sufficient level for broad-scale implementation, and that significant further research is required to establish the conditions under which these treatments should be administered in order to optimise therapeutic outcomes and minimise risks.
Active research is underway, in Australia and globally, to address these important questions. Meanwhile, we believe that the following should be kept in mind as the rescheduling of MDMA and psilocybin takes place on 1 July, 2023:
• Expectations of patients, practitioners and the general public should be managed very carefully, to avoid excessive optimism and mitigate risk of negative consequences should the treatments not be fully effective, for any of a large number of reasons.
• Prescriber and therapist training is of utmost importance, but to date, there is a very small cohort of appropriately qualified and experienced therapists and practitioners of psychedelic-assisted psychotherapy. This situation will take some considerable time to be addressed.
• Clinical research is conducted in accordance with strict procedural and ethical guidelines, and the results of academic research are generally accessible to the broader research community and ultimately to the public. Although the Delegate’s Final Decision stipulates the involvement of an ethics committee in the prescription and administration of MDMA- and psilocybin-assisted psychotherapy under this scheme, there is no explicit requirement for clinical outcomes achieved through the Special Access Scheme to be collated and used to inform future clinical practice, or regulatory decisions.
In summary, we regard the Delegate’s Final Decision as a significant step, both within Australia and in the global context, toward the eventual acceptance of psychedelic therapies by the medical and broader communities alike. We can only hope that the consequences of this decision will match the hopes and aspirations of those who have supported it so strongly.

The TGA have just released a statement that from 1st July this year authorised psychiatrists will be able to prescribe substances containing psilocybin and MDMA for treatment-resistant depression and PTSD respectively.  Their decision is the result of expert panel reviewing the outcomes of 14 studies and showed treatment positive outcomes for the defined groups. Side effects were minimal for both agents and well tolerated by patients. Both Treatment-resistant depression and PTSD are traditionally challenging to treat, and it is promising that alternative and efficacious pharmacotherapeutic options are now available.  As with all mental health outcomes, a combination of pharmacotherapy and psychotherapy may be in the patient’s best interest and it was promising that all studies used a combined approach to mental health management.

However, it is also important to note that a specific risk-benefit analysis at a patient level should be considered when selecting these drugs as treatment options. We are yet to know the long-term risks associated with the use of these psychedelic agents and further data on this should be collected over time.

Increasingly clinical research has provided promising evidence that MDMA and psilocybin may have therapeutic benefits in the treatment of a range of mental illnesses including treatment-resistant depression (representing about 30% of people with depression) and post-traumatic stress disorder (PTSD). Now the Therapeutic Good Administration (TGA) has approved of a Special Access Scheme that would allow qualified psychiatrists to use psychotherapy in combination with MDMA for the treatment of PTSD and with psilocybin for treatment-resistant depression. This is an important development because these disorders represent a significant health burden on society and are chronic and debilitating. The SAS instructs that the presence of psychological support is an essential component of the psychedelic treatment model, as recommended by the Royal Australian and New Zealand College of Psychiatrists’ (RANZCP) Clinical Memorandum the Clinical Use of Psychedelic Substances.

This will be no ordinary prescription. The patient will be required to have tried and repeated failed to respond adequately to conventional treatments and drugs. The prescription must be made by a psychiatrist who is authorized under the Authorized Prescriber Scheme. Specific training will be needed for prescribers, and two independent psychiatrists will need to review each patient’s diagnosis and proposed treatment plan. The treatment must be conducted in medically controlled environments. Approval must be granted by both a Human Research Ethics Committee (HREC) that is registered with the National Health and Medical Research Council (NHMRC), as well as a senior medical officer of the TGA.

The cost of the treatment is not yet determined but is likely to be expensive. Like medicinal cannabis products, which are also available for prescription under the SAS, psilocybin and MDMA are likely to be more expensive than conventional psychiatric drug prescriptions. Unlike medicinal cannabis products, the therapeutic use of psilocybin and MDMA will involve being dosed in a medical setting with the psychiatrist and other support staff on hand for up to 8 hours. The TGA announcement noted the publication of Goodwin et al, (New England Journal of Medicine 2022; 387:1637-1648) where the treatment protocol for treatment-resistant depression was very involved. The therapist-training program was extensive. The patients, who were not on other antidepressants, met with a therapist at least three times to build trust, receive psychoeducation, and prepare for the psychedelic experience. The treatment session lasted 6 to 8 hours, with the lead therapist who had prepared the participant for the intervention and an assisting therapist in attendance. Treatment rooms were designed to provide a nonclinical, calming atmosphere. During the session, participants listened to a specially designed music playlist while wearing eyeshades to help direct attention internally. Importantly, this study indicated that a single dose of 25 mg psilocybin reduced depression scores significantly more than a 1 mg dose over a period of 3 weeks. While this study is very encouraging, to deliver a system of treatment of similar intensiveness in Australia, as contemplated by the TGA, will be costly over the price of the psilocybin itself. Psychedelics are not yet on the Australian Register of Therapeutic Goods (ARTG) or the Pharmaceutical Benefits Scheme (PBS), so they attract no cost support from federal funds.

Despite the authority hurdles and the likely high costs of treatment, I think that specialty centres are likely to emerge in Australia that will offer this kind of treatment with psilocybin for treatment-resistant depression and MDMA for PTSD. These conditions cause tremendous suffering and are themselves expensive in terms of lost productivity and chronic treatment costs. So it is possible that as psychiatrists become more familiar with the promise of these psychedelic drugs and how best to deliver them, that they may provide an attractive value proposition.

 However, we should note that these psychedelics are not breakthrough wonder drugs. They are poised to become an additional weapon in the fight to relieve these disorders. Many patients are still likely to have incomplete or no remission, and more research is needed to understand what is the optimal dose schedule (e.g. once off, or in multiple sessions). But I think these drugs, delivered appropriately, could be an asset and I welcome their cautious and well-regulated introduction into the Australian psychiatric toolbox.

The TGA’s announcement is really promising news for patients living with difficult-to-treat conditions like PTSD and treatment-resistant depression, and their treating psychiatrists. 

Psychedelics such as methylenedioxymethamphetamine (MDMA) or psilocybin (derived from certain species of mushrooms) are currently being tested by researchers in Australia and internationally in strictly controlled clinical settings to see if they could be an effective treatment alongside psychotherapy for mental health related illnesses. The TGA’s decision now allows these drugs to be prescribed by specially authorised psychiatrists in controlled medical settings.

The announcement will also be great encouragement for a number of local Australian companies whose goal is to commercialise psychedelic therapies based on psilocybin or MDMA. CSIRO works with local medtech companies to improve existing psychedelic products and develop new ones.

By working with local industry to improve drug manufacture and effectiveness, and the patient experience, CSIRO can push Australia into a leadership position in the development of these potentially life-changing medications.

This is a huge step for the treatment of PTSD and treatment-resistant depression in Australia, providing access to alternative interventions for individuals who have exhausted all treatment options.

The TGA stated that by limiting the prescribing to authorised psychiatrists, and only for treatement resistant depression and PTSD means that the benefits to patients and public health will be greater than the risks.

However, safety and efficacy has been demonstrated in other indications such as nicotine/alcohol dependence, obsessive compulsive disorder, and end-of-life distress. Further, depression is often co-occurring with these psychiatric disorders. The TGA clearly acknowledges that it does have therapeutic value and states that these substances are relatively safe when administered in a medically controlled environment.

The re-classification of psilocybin to schedule 8 should at least be extended to these additional indications where clinical trials have demonstrated significant improvement in symptoms.
 
In Australia, there are clinical trials investigating psilocybin in substance abuse, generalised anxiety disorder, end-of life anxiety, anorexia nervosa as well as depression. Currently, researchers will have to go through the process of handling psilocybin as a schedule 9 drug and this approval does not change this. I hope that the TGA will consider re-scheduling psilocybin for all treatment-resistant psychiatric disorders so there is greater capacity for researchers to explore its therapeutic potential.

This is an important step for psychedelic-assisted therapies in Australia, although it should be taken with caution. With the potential for increased access to MDMA and psilocybin-assisted therapies, it is now critically important that high-quality therapist training be made available to promote safe therapeutic conditions when working with these medications.

Access to psilocybin and MDMA in Australia has been long-awaited for both research and treatment.  There are many people in the community experiencing PTSD and depression, particularly army veterans and people who have worked in emergency services, where standard psychiatric drugs have not worked and offer no relief.

The prescribing of these drugs has been prohibited for use by government drug agencies (TGA, FDA) even though early research over the last two decades has produced some promising results, the resistance to their use has remained. 

The reluctance to using these potential medications is associated with them being used as drugs of abuse where agencies often report on the harm they cause.  All psychiatric drugs have some level of side effects which can be harmful and these mind-altering drugs, often referred to and used as ‘party drugs’ are no different. 

They do however offer hope to thousands of people across Australia where traditional medications have not helped their condition.  With the advent of the threshold for these two drugs being reduced to ‘controlled drugs’ we can now start new research trials for their effectiveness in treatment.

The Australian Therapeutic Drugs Administration has permitted the use of two psychedelic substances, psilocybin and MDMA (3,4-methylenedioxy-methamphetamine) [3rd February 2023], which can now be prescribed by specifically authorised psychiatrists for the treatment of conditions that were resistant to treatment using traditionally available psychiatric drugs. 

The long-awaited availability of these drugs will allow for research and novel treatments for conditions like Post Traumatic Stress Disorder, depression, and other psychiatric disorders.  The change in status of these drugs has moved from a prohibited substance down to a controlled drug enabling a psychiatrist to use small doses of the drug, known as “microdosing”. 

These drugs alter the mind and reduce inhibitions whereby the person being treated may be able to cope with some of the difficult images, memories or thoughts which are accessed more readily and potentially with reduced associated feelings of anxiety. 

Important research has already begun around the world on both drugs where they are gaining mainstream acceptance. The physical effects can be observed using functional Magnetic Resonance Imaging (fMRI’s) showing the physical changes in the brain and even changes to the vascular system. 

The journal ‘Nature’ suggested that these drugs are “shaking up psychiatry” providing treatments for conditions which were previously seen as intractable.  There are risks however with any new drug and there is a potential that using a mind-altering drug can lead to psychosis, which has been seen with drugs like cannabis.

The recent approval for MDMA-assisted therapy for PTSD is a promising and exciting development, based on positive results in initial clinical trials. Developing novel treatments for PTSD is sorely needed, particularly for PTSD patients for whom our gold-standard treatments have failed. However, further rigorous research is required to understand the mechanisms underpinning MDMA-assisted therapy, so we can address the critical question of what therapy works for each individual with PTSD. No one PTSD treatment is a panacea that will treat everyone with PTSD effectively, and MDMA is not an exception. Additional research on this topic would allow us to streamline our health resources, direct people to the most effective treatment for them and improve the accessibility of treatments for people living with PTSD.

There is initial evidence that MDMA can be beneficial in treating PTSD but there is much we do not know. We currently have strong evidence-based treatments for PTSD, and to date, we do not know how MDMA compares relative to these proven treatments which are much cheaper and simpler to administer. The science is at a point where we can say it is too early to be prescribing MDMA for PTSD patients. Instead, we should be investing in research to understand how MDMA can be used in relation to proven treatments.

This decision by the TGA makes Australia the first country in the world to officially recognise MDMA and psilocybin as medicines.

Recognising that illegal drugs like MDMA and psilocybin have medical utility is an important step in drug policy reform; however, the safe provision of these treatments requires extensive training which is why they have been limited to clinical research in Australia to date.

To ensure that people accessing these treatments are not harmed, it will be important that the TGA provides a clear expectation regarding the minimum training standards required for psychiatrists who the TGA approves to prescribe these drugs.

Further, given people are already accessing the treatments illegally in Australia, this announcement has the potential to create further awareness among the public resulting in more people accessing these treatments illegally through desperation. It will be important that resources are provided by the government to minimise these unintended effects of the legislation change.

The approval of MDMA and psilocybin represents an inevitable outcome for a process that in different political circumstances, might have occurred at least 5 years ago. The data that supports this move has been in play for some time, and it is perhaps a reflection of a change in the policy ecosystem that has seen changes being introduced at this late stage, rather than when the evidence to support the move originally became available.

MDMA was being used as medication in 1985, when it was banned by executive order of the President of the USA, and against the advice of medical professionals and administrative agencies. In the last decade, with advances in functional neuroimaging, it has become abundantly clear that a controlled supply of known doses of both MDMA and psilocybin can have dramatic effects on conditions often considered refractory to contemporary treatment.

Perhaps most excitingly, many of the treatments that are emerging with these previously banned products require only a brief exposure to facilitate therapy, and not the life-long prescription of drugs that do little more than dull the edge of psychological trauma. One of the key groups that stand to benefit in Australia are returned service men and women from the ADF. Their parlous situation is currently the subject of a Royal Commission into Defence and Veteran Suicide.  

The safe ‘re-medicalisation’ of certain historically illicit drugs is a very welcome step away from what has been decades of demonization. In addition to a clear and evolving therapeutic benefit, it also offers the chance to catch up on the decades of lost opportunity in delving into the inner workings of the human mind, abandoned for so long as part of an ill-conceived, ideological ‘war on drugs’.

I lead one of only a few sites in Australia that is already delivering psychedelic-assisted therapies to clinical patients - we have witnessed up-close the potential of our treatment to change people's lives for the better; yet the safety and effectiveness of psychedelic therapies depends on a unique set of professional competencies and considerations that are in scarce supply within mental healthcare.

For clinical psychedelic services to be sensible, safe, and useful, considerable professional and public education will be needed, and questions of affordability, eligibility, oversight, and standards of care should be addressed. With this schedule change coming in a matter of months, Australia has very little time to get across this.

I have a significant degree of caution about this decision because these treatments are not well established at all for a sufficient level of broad-scale implementation. Substantial further research needs to be done.

First, to confirm efficacy to international standards for all psychotropic medications and to understand which conditions are best treated and which formulations will best serve the patients and minimise risks. We've got no data on long-term outcomes at all,  so that worries me a lot, which is one of the reasons why I'm doing my very large study.