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Notice of interim decisions on proposed amendments to the Poisons Standard - ACMS, ACCS and Joint ACMS-ACCS meetings, November 2020
Scheduling of chemicals and poisons
2.5 N, α-Dimethyl-3,4-(methylenedioxy)phenylethylamine (MDMA)
We have changed the way to make submissions.
Submissions should now be provided through our consultation hub. Submissions will be considered by the Delegate in making the final decision.
2. Interim decisions on proposed amendments referred to the Advisory Committee on Medicines Scheduling (ACMS #32, November 2020)
2.5. Interim decision in relation to N, α-Dimethyl-3,4-(methylenedioxy)phenylethylamine (MDMA)
Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendment, made an interim decision not to amend the current Poisons Standard in relation to MDMA.
In making this interim decision, the Delegate considered the following material:
- The application to amend the current Poisons Standard with respect to MDMA;
- The 478 public submissions, including 254 written submissions, received in response to the pre-meeting consultation under regulation 42ZCZK of the Regulations;
- The advice received from the Meeting of the Advisory Committee on Medicines Scheduling (ACMS #32);
- Subsection 52E(1) of the Therapeutic Goods Act 1989, in particular (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters considered necessary to protect public health;
- The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018);
- The Scheduling handbook: Guidance for amending the Poisons Standard;
- The ClinicalTrials.gov database, provided by the U.S. National Library of Medicine;
- A review by Illingworth et al., A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis;
- A review by Bahji et al., Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis; and
- A clinical memorandum by the Royal Australian and New Zealand College of Psychiatrists, Therapeutic use of psychedelic substances (2020).
Summary of ACMS advice to the Delegate
The Committee recommended that the current scheduling of MDMA remains appropriate.
Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters considered necessary to protect public health.
The reasons for the advice included:
- the risks and benefits of the use of a substance
- There is limited but emerging evidence that MDMA-assisted psychotherapy may have therapeutic benefits in the treatment of PTSD. These benefits are currently under investigation in clinical trials.
- Acute effects include high blood pressure and pulse rate, faintness and panic attacks. In severe cases, MDMA can cause loss of consciousness and seizures.
- Secondary effects include involuntary jaw clenching, lack of appetite, depersonalisation, illogical or disorganised thoughts, restless legs, nausea, hot flashes or chills, headache, sweating and muscle/joint stiffness.
- Long-term use can result in sleep disturbances, difficulties with concentration, depression, heart disease, impulsivity and decreased cognitive function.
- MDMA can reduce the ability to perceive and predict motion and can therefore result in accidents.
- the purposes for which a substance is to be used and the extent of use of a substance
- MDMA is taken in combination with psychotherapy for the treatment of PTSD.
- MDMA-assisted psychotherapy sessions typically last 6 - 8 hours, relying on two trained specialists. The regime consists of 1 - 3 psychedelic-assisted therapy sessions, usually supplemented with 'integrative' therapy sessions where MDMA is not used.
- the toxicity of a substance
- The lethal dose is 10 - 20 mg/kg.
- The potential adverse effects are unknown in the context of psychotherapy.
- the dosage, formulation, labelling, packaging and presentation of a substance
- Optimal dosages have not been established, especially outside of PTSD treatment.
- A typical dose in the context of psychotherapy is 1-2 mg. This is often followed by an optional half-dose 1.5 to 2.5 hours into the session.
- the potential for abuse of a substance
- It is not clear whether MDMA causes dependence. However, it affects many of the same neurotransmitter systems in the brain that are targeted by drugs with an abuse and dependence liability, and some studies report symptoms of dependence in users.
- There is a high risk of diversion for misuse, even in conjunction with Schedule 8 controls.
- any other matters that the Secretary considers necessary to protect public health
- There are significant benefits to waiting for the results of clinical trials. MDMA-assisted psychotherapy may prove to be safe and efficacious, but the evidence does not yet suggest this - especially for conditions outside of PTSD.
- It will take time to develop a curriculum and accredited training process for psychiatrists. To protect public health and prevent inappropriate use, MDMA should not be down-scheduled until all necessary safeguards have been established and implemented.
Reasons for the interim decision (including findings on material questions of fact)
I have made an interim decision to retain the scheduling of MDMA in the current Poisons Standard.
I agree with the Committee's findings that the relevant provisions of section 52E of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.
The Scheduling Policy Framework (SPF 2018) provides that substances included in Schedule I to the United Nations Convention on Psychotropic Substances 1971, and without an established therapeutic value, should be classified in Schedule 9. In my view, MDMA fits these scheduling factors, and is not currently appropriate for listing as a Schedule 8 substance.
I note that MDMA is an illicit drug with a high potential for misuse in the Australian community, resulting in significant harms including seizures and deaths. MDMA shows some evidence of causing dependence, and may additionally lead to cognitive dysfunction in the medium or long term. Clinical trials will be essential to evaluating these risks. While several phase II trials have been completed, these lack appropriate sample sizes and control groups, and require rigorous follow-up in phase III. According to the ClinicalTrials.gov database, a single phase III trial has been registered, and completed, though its results are not yet publically available. Given the emerging evidence base regarding safety and efficacy, I believe that down-scheduling is premature.
In forming this view, I have also considered the findings of a recent systematic review and meta-analysis in the Journal of Psychopharmacology, which concluded that MDMA-assisted psychotherapy requires data from larger scale studies before approval for clinical use. The same sentiment was echoed in an earlier review, published in Progress in Neuro-Psychopharmacology and Biological Psychiatry, which concluded that larger sample sizes and longer durations of treatment and follow-up were warranted. After reviewing these papers, I affirm my conclusion that further research is required.
I also note the findings of a recent clinical memorandum on psychedelic therapies, published by the Royal Australian and New Zealand College of Psychiatrists (RANZCP), which found that evidence of safety and efficacy is limited but emerging. The memorandum highlights a number of potential risks, particularly the possibility that MDMA can induce prolonged psychotic disorders in patients with a family history of psychosis. To minimise these risks, the RANZCP concluded that further research is required - much of which is already underway. I believe that these findings support my conclusion that current use of MDMA should be limited to carefully monitored research trials.
In making my decision, I have taken into account the 'Breakthrough Therapy Designation' that has been granted by U.S. Food and Drug Administration. I note that, while this designation indicates that the therapy shows promise, it does not equate to FDA approval. Currently, no comparable country has down-scheduled MDMA to an equivalent category to Schedule 8, and there is no international framework for how to handle psychedelic-assisted therapies.
I have taken into account all 478 responses that were received during the pre-meeting consultation, noting that 453 were supportive of the proposed amendment, 14 partially supportive and 11 opposed. While the submissions indicate significant public support for rescheduling, a significant fraction included no written justification, or directly paraphrased the sponsor, and few submissions were from practicing psychiatrists. I have read and considered all responses in making my interim decision.
I find that the points raised in public submissions from several peak bodies were highly pertinent, noting the following concerns and recommendations:
- The RANZCP advised that further research is required to assess the efficacy, safety, and effectiveness of psychedelic therapies, emphasising that appropriate treatment methodologies and training protocols do not yet exist.
- The Australian Medical Association advised that more high-quality research, using larger-scale studies, is required to establish the safety and efficacy of psychedelic therapies. The risk of psychosis and persistent hallucinations, especially in susceptible subpopulations, is likely to be high.
- Psychedelic Research in Science and Medicine advised that any decision to down-schedule should include an extensive two-year implementation plan. Only a limited number of Australian medical professionals are currently trained to provide MDMA-assisted psychotherapy, and premature down-scheduling may put patients at increased risk of harm.
Having considered the risks to consumers, the lack of training for physicians, and the current state of research, I am of the view that Schedule 9 remains appropriate for MDMA. I note that my decision does not affect current access to MDMA for use in a clinical trial setting. I would also like to note that the supply of MDMA outside of its use in approved clinical trials remains a criminal offence.
Pending the outcome of current clinical research, the scheduling of MDMA could be reconsidered in future applications.