Industry leaders have given a cautious welcome to the interim ruling to down schedule low-dose CBD, but significant doubts persist over how meaningful the decision will be for patients and manufacturers.
Concern will inevitably focus on the strength of efficacy data required by health authorities for a product to be registered on the Australian Register of Therapeutic Goods (ARTG) and therefore available for sale through pharmacies.
According to the Therapeutic Goods Administration (TGA), products must be “individually evaluated for quality, safety and effectiveness prior to inclusion on the ARTG”.
The eight-page interim ruling published yesterday also spelt out the need for solid data, emphasising that “only products that have been approved for a specific indication appropriate under a schedule 3 listing will be available without a prescription”.
With a paucity of clinical data for low-dose CBD, major questions remain whether over-the-counter product will really appear in Australian pharmacies.
Advisory committee “not persuaded”
Given the application to reschedule CBD had been initiated by the Department of Health, the TGA’s favourable interim decision had been widely expected.
But it was a determination that appeared to go against the views of the Advisory Committee on Medicines and Chemicals Scheduling, the majority of whom were “not persuaded… that cannabidiol meets the scheduling factors for schedule 3”.
Nevertheless, the TGA concluded that 98% pure CBD products could be made available for sale behind the counter from early next year, with a limit of 60mg per day and a maximum supply for 30 days.
Available products will be limited to oral ingestibles – topical creams or vapes will not be permitted – only sold to over 18s and supplied in child-proof containers.
Advertising will also be banned, while the TGA has proposed restricting pharmacists from compounding schedule 3 CBD which could have bypassed difficulties around proving efficacy.
A fresh round of consultations on the interim decision will now begin ahead of a final ruling on November 25.
More questions than answers
Despite the positive verdict, it raised more questions than answers in terms of making medicinal cannabis more accessible to patients. The major concern is that companies will struggle to prove the worth of CBD at such a low dose.
The Medicinal Cannabis Industry Australia (MCIA) described the decision as a “good start” and welcomed the TGA’s pledge to seek more information before a final decision.
But speaking to Cannabiz, MCIA chairman Peter Crock reiterated concerns that companies face two years of data gathering just to lodge an ARTG application.
In its current form, the down scheduling may simply be “politically expedient”, he said.
“The big risk is that they have selected this 60mg limit per day on the basis that the literature says it’s largely safe, but the literature also shows it’s largely not efficacious at that level,” Crock said. “It could be politically expedient for the TGA and politicians to say ‘we’ve done our part, we’ve got the process through and we’ve down scheduled, now it’s up to the industry’. That’s a concern.”
Crock said a project is underway to assess exactly what level of data will be required by the TGA. The MCIA will make a further submission to “refine the argument”, he added.
In its submission to the advisory committee, the MCIA described the capping of a daily dose as “unusual” and “far lower than doses… from which the safety profile is drawn”.
“Further, it is unclear to us how patient access will be enabled under the proposed changes given that CBD is not on the Permissible Ingredients List and product registration would be improbable given the lack of demonstrated clinical utility at the levels stated,” the submission read.
“We would envisage little likelihood that it would be feasible for companies to bring such products to market through this pathway.”
A “lame duck”
Meanwhile, the Australian Medicinal Cannabis Association (AMCA) said restricting pharmacists from compounding CBD as a schedule 3 medicine would negate the benefits down-scheduling was intended to achieve.
It said: “Pharmacists have professional obligations, which include an obligation to satisfy themselves that the supply of any medicine to a patient is clinically appropriate.
“The interim decision suggests pharmacists are not sufficiently equipped to make decisions about the supply of CBD as an over-the-counter medicine unless it is ARTG-registered. AMCA strongly disagrees with that proposition.”
AMCA added: “The interim decision to down schedule low-dose CBD will not lead to better access.”
It urged stakeholders to lobby the TGA “so that any further deliberations can refine the interim decision towards a final decision that actually does facilitate access”.
Speaking on a panel discussion with Health House pharmacist Paul Mavor, Leafcann chief executive Elisabetta Faenza also warned of impending “disappointment” as products remain absent from pharmacy shelves.
“There is ample evidence at the standard required by the TGA for both efficacy and safety at higher doses,” she argued. “What we don’t see at that 60mg dose is efficacy. While it’s great that it has been down scheduled it could turn out to be a bit of a lame duck.”
Faenza said it was unclear whether the TGA would waive some of the usual efficacy requirements.
But even if it did, the outcome for patients “may not be good”.
“What we want patients to receive is efficacious and safe medicines that will give them, at the recommended dose, therapeutic benefits,” she explained.
“While we’re not looking for doses that would be required for complex conditions where you definitely need participation and oversight of a doctor, what we should see is [patients] with less severe clinical presentations getting access to this product under the care of a pharmacist. But we don’t believe that benchmark is going to be reached at that low dose so we are struggling to see how efficacious product will be registered, and therefore reach the public and make a difference to public health.
“If companies manage to get through and jump all of the hoops for registration – and spend a fortune doing so – the products coming out the other end are likely to be a disappointment.”
Faenza added that by suggesting CBD could be more widely available, the TGA has inadvertently created awareness and an expectation among consumers that medicinal cannabis will be far more accessible.
She argued that the expectation of consumers must be tempered.
“A lot patients will be surprised to know this doesn’t mean products under the Special Access and Authorised Prescriber schemes can suddenly become schedule 3,” she said.
Cannabis consultant and Cannabiz editor-at-large Rhys Cohen warned the current down scheduling proposals risked creating the “worst of both worlds”.
Holding companies to the highest standards of efficacy would effectively prevent product from getting to market, rendering the entire down scheduling process a “pointless exercise”.
Yet relaxing the usually high efficacy requirements risked undermining Australia’s medical regulations, he said.
“So the regulator abbreviates, or is reasonable about requiring a lower standard of evidence. But if the regulators want to approve products at a lower-than-usual standard of evidence, doesn’t that suggest it would be more appropriate to be schedule 2 or unscheduled entirely?”
The black market
Advocates of down scheduling have argued that easier over-the-counter access to CBD would reduce the need to source illicit products.
The Lambert Initiative said providing high-quality CBD products as a pharmacy-only medicine should “help transition many current medicinal cannabis users from illegal sources to a legal and well-regulated form of supply”.
“This would particularly be the case for patients with mild-to-moderate forms of anxiety, depression, insomnia and pain who may be currently self-medicating with illicit THC-dominant street cannabis of uncertain composition and origin,” the research body said.
FreshLeaf Analytics managing director Cassandra Hunt agreed that it could reduce reliance on illegal substances.
“This will be the biggest thing to happen in the industry since the legalisation of medicinal cannabis,” she said. “We expect it will result in more Australians benefiting from the healing properties of cannabis and will reduce the number of people seeking products through unregulated illicit channels.
“The next challenge will be getting products in the market as quickly and cost effectively as possible.”
Applied Cannabis Research Advisory Board member Dr Melissa Benson added: “This is a win for supporting further clinical research in the area of low-dose CBD medicines. It could also promote greater safety for patients if it leads to less use of illicit CBD products, which can expose patients to potential harms associated with unregulated products including contamination with heavy metals, pesticides and the like.”
Medlab CEO Sean Hall agreed the move was a positive one for patients. He said: “To sell products under schedule 3 will still require manufacturers to follow a drug approval process that is similar in rigour to schedule 4 or any other scheduled drug.
“We think ultimately that’s a good thing for patients, providing assurance that they are accessing products that have clinical validation of safety and efficacy.”
However, Cohen argued patients could be lured into the black market rather than drawn from it.
“The concern I have is that down scheduling sends a message to the community that it’s appropriate to access low-dose CBD from a pharmacy,” he said. “There is tacit government approval. And when people find they aren’t able to access products, it’s easier for them to justify buying an unregulated product online or on the black market.”
Former TGA official and regulatory expert Tony Whittaker, from Category 1 Pharma Consulting, said the decision created a “theoretical opportunity” for CBD to be available over the counter.
But he said it could be “challenging”, based on current evidence, to obtain TGA approval for low-dose CBD products.
“What we aren’t sure about it is how the TGA is going to approach this,” he told Cannabiz. “The TGA will need to weigh up the risks and benefits of the product as a whole.
“There were issues identified at the Senate hearing regarding the difficulty of accessing CBD products, with patients using the black market. So there are advantages of having it on the ARTG where the TGA has control.”
ASX-listed AusCann said in its submission to the committee that the low-dose nature of the down scheduling “constrains the clinical utility of CBD”.
“[It is] counter to the intent of making the drug available to the public without a prescription but still with the oversight of a health care provider (the pharmacist),” the company said.
The view was echoed by Cronos Australia which said the lack of evidence or justification of the therapeutic benefit meant product was unlikely to materialise.
“It will be almost impossible for manufacturers to demonstrate efficacy,” it said. “Thus while the proposal is a positive direction, it may not result in improved outcomes for patients or the industry.”
However, the Lambert Initiative struck a more optimistic tone. While acknowledging more robust efficacy has been demonstrated in higher doses, “it remains possible that lower doses do have efficacy”.
There are “sporadic signs” of positive outcomes emerging in the limited number of published studies to date, it said.
“Recent observational studies provide some support for the effectiveness of low-dose CBD formulations while pre-clinical studies broadly confirm anxiolytic, analgesic, sleep-enhancing, anti-inflammatory and antioxidant effects of CBD.”
The Lambert Initiative added that rescheduling CBD might have the added benefit of switching thousands of Australians away from wellness products, multivitamins, herbal and other complementary medicines “where there is even less evidence” than CBD in the treatment of anxiety, depression and insomnia.
Addiction specialist and CA Clinics medical advisory board member Dr Mark Hardy added: “This is a welcome move but it’s important to note that the effects of low-dose CBD may be negligible for many patients. Patients seeking treatment for chronic conditions that may benefit from medicinal cannabis may require higher dosages or other cannabinoids such as THC and should therefore consult their GP before taking these products, even in small amounts.”
There are currently 17 low-dose CBD products available via the SAS-B and Authorised Prescriber pathways in Australia, with CBD products currently making up about 40% of all medicinal cannabis prescriptions. FreshLeaf Analytics expects the over-the-counter CBD market to grow rapidly and exceed $200 million in revenue.
Some ASX-listed companies saw shares lift on the news.
The closing date for submissions addressing the interim decision is October 13.