2.4 Psilocybin

2. Interim decisions on proposed amendments referred to the Advisory Committee on Medicines Scheduling (ACMS #32, November 2020)

2.4 Interim decision in relation to psilocybin

Interim decision

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 psilocybin.

Materials considered

In making this interim decision, the Delegate considered the following material:

• The application to amend the current Poisons Standard with respect to psilocybin;
• The 575 public submissions, including 357 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 Reiff et al., Psychedelics and Psychedelic-Assisted Psychotherapy (2020);
• A review by Gill et al., The emerging role of psilocybin and MDMA in the treatment of mental illness (2020);
• A review by Vargas et al., Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases—A Systematic Review and Meta-Analysis of Clinical Trials (2020);
• A review by Goldberg et al., The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis (2020); 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 psilocybin 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:

1. the risks and benefits of the use of a substance
   • Benefits:
     • There is limited but emerging evidence that psychedelic therapies may have therapeutic benefits in the treatment of a range of mental illnesses. These benefits are currently under investigation in clinical trials.
   • Risks:
     • There remain many unknown factors and side effects, especially in the long term. The risks of developing psychosis, especially in vulnerable populations, must be established in a clinical trial setting.
     • Can cause tachycardia and transient increases in blood pressure.
     • Psilocybin, when misused, can caused psychosis.
   • the purposes for which a substance is to be used and the extent of use of a substance
     • Psilocybin is taken in combination with psychotherapy for the treatment of depression, PTSD, anxiety, or end of life distress.
     • Psilocybin-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 psilocybin is not used.
2. the toxicity of a substance
   • The lethal dose is thought to be 6 g, although evidence around toxicity may be premature.
   • The potential adverse effects, particularly relating to multi-drug toxicity, are unknown.
3. the dosage, formulation, labelling, packaging and presentation of a substance
   • A typical dose in the context of psychotherapy is 25 - 35 mg, depending on subject weight. An optimal therapeutic dosage has not been established.
4. the potential for abuse of a substance
   • There is a high risk of diversion for misuse, even in conjunction with Schedule 8 controls.
5. any other matters that the Secretary considers necessary to protect public health
   • There are significant benefits to waiting for the results of clinical trials. Psilocybin-assisted psychotherapy may eventually prove to be safe and efficacious, but the evidence does not yet suggest this.
   • It will take years to develop a curriculum and accredited training process for psychiatrists. To protect public health and prevent misuse, psilocybin 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 psilocybin 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, psilocybin fits these scheduling factors, and is not currently appropriate for listing as a Schedule 8 substance.

I note that psilocybin is an illicit drug with a high potential for misuse and an unknown safety profile. The medium and long-term effects of psilocybin-assisted psychotherapy are unknown, particularly in vulnerable populations, and the risk of developing psychosis may be high. Clinical trials will be essential to evaluating risks, but only three phase II trials have been completed. According to the ClinicalTrials.gov database, 11 phase II trials are currently either recruiting or underway, and no phase III trials have been registered. I note that St Vincent's Hospital Melbourne is currently undertaking Australia's first psychedelic clinical trial for terminally ill patients who are experiencing depression or anxiety. Given the emerging evidence base regarding safety and efficacy, I believe that down-scheduling is premature.

In forming this view, I have considered the findings of a recent review in the American Journal of Psychiatry, which concluded that, although research is promising, the overall database is insufficient for regulatory approval for clinical use. Several other reviews and meta-analyses published this year also draw similar conclusions, which describe promising results for early trials but advise that the current sample size is small (Gill et al., 2020; Vargas et al., 2020; Goldberg et al., 2020). After reviewing these papers, I affirm my conclusion that further research is required, with larger treatment populations and stringent placebo controls.

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 psilocybin 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 psilocybin should be limited to carefully monitored research trials.

In making my decision, I have taken into account the two 'Breakthrough Therapy Designations' that have been granted by the U.S. Food and Drug Administration. I note that, while these designations indicate that the therapy shows promise, they do not equate to FDA approval. Currently, no comparable country has down-scheduled psilocybin to a category equivalent to Schedule 8, and at present, there is no international framework for how to handle psychedelic-assisted therapies.

I have taken into account all 575 responses that were received during the pre-meeting consultation, noting that 553 were supportive of the proposed amendment, 11 partially supportive and 11 opposed. While the submissions indicate significant public support for rescheduling, few submissions addressed the factors relevant to scheduling. 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, to ensure safe and ethical use, any decision to downschedule should include an extensive three-year implementation plan. In addition, psilocybin-assisted psychotherapy has not yet commenced phase 3 trials, and will require several years of further research to establish efficacy.

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 psilocybin. I note that my decision does not affect current access to psilocybin for use in a clinical trial setting. Pending the outcome of current clinical research, the scheduling of psilocybin could be reconsidered in future applications. It is also important to note that the supply of psilocybin outside approved clinical trial settings is a criminal offence.

I agree with the Committee's advice that the current spelling of the Schedule 9 entry remains appropriate, noting that the spelling "psilocybine" is consistent with the International Nonproprietary Name and British Approved Name of the substance.