Cannabidiol manufacturers could face a long and expensive battle to sell low-dose products through pharmacies even if health authorities – as expected – down schedule CBD and make it available without a prescription.

The Advisory Committee on Chemicals Scheduling (ACCS) and Advisory Committee on Medicines Scheduling (ACMS) met in June to discuss the prospect of reclassifying low-dose CBD as a schedule 3 pharmacy-only medicine.

It currently sits in schedule 4 of the Poisons Standard and is only available via prescription. A decision to down schedule will be made public on September 9 after which further consultations will take place ahead of a final ruling in November.

Submissions to the application remain confidential.

With a TGA review concluding that low-dose CBD – defined as a maximum daily dose of 60mg – had an “acceptable safety and tolerability profile”, and with the Department of Health behind the application to down schedule, a positive decision is expected.

But while the down scheduling would be welcomed by many, manufacturers have warned the public not to expect a glut of products any time soon.

Under tight TGA regulations, all schedule 3 medicines must be registered on the Australia Register of Therapeutic Goods (ARTG) and, critically, must be proven to work.

Yet according to the TGA safety review there is a “paucity of high-quality published trials”.

A TGA spokesperson said: “All S3 medicines require registration on the ARTG before they can be supplied in, imported into, or exported from Australia. Such products are individually evaluated by the TGA for quality, safety and effectiveness prior to inclusion on the ARTG.

“A registration application for a CBD-containing product must be accompanied by quality, safety and efficacy data to support the proposed formulation for its intended use and the direction for use of the product. The data submitted with an application would be assessed to determine whether or not the intended use, including the proposed indications for the product, are supported by the evidence provided.”  

Bod Australia chief executive Jo Patterson told Cannabiz that for the down scheduling to have meaning, low-dose CBD should be listed, rather than registered. According to the TGA, listed medicines do not require such rigorous testing.

“The TGA want it to be schedule 3 registered which means going through clinical trials and registering it for a specific indication,” Patterson said. “But one would argue at 60mg per day it’s not a high enough dose to actually secure a specific indication, or worth going through a clinical trial process. I struggle to see why you would go through that.

Pharmacy - Medical Cannabis - Cannabiz
Pharmacists will be able to access unapproved schedule 3 cannabidiol through the Special Access Scheme if the TGA down schedule low-dose CBD

“There might be something where you could do two arms of a study to make it worthwhile. You could do a 60 milligrams versus a higher dose trial, and look at a full plant extract versus an isolate. So you could probably design a clinical trial to make it worth your while but it still won’t achieve what I believe the TGA wants to achieve, which is world’s best practice and making low-dose CBD which is deemed to be safe to consumers and that is accessible and affordable.

“I think they’re quite motivated and they can see the benefits of having an offering to the consumer, so hopefully they’ll reassess that situation. If the TGA wants affordability and accessibility it [low-dose CBD] must be listed.”

Patterson added that where low dose levels do have benefits is around mild cases of anxiety and stress and sleep.

Should the ACCS and ACMS approve the change, February 1 has been mooted as the possible date when product will be available, albeit at the discretion of the pharmacist.

But Althea chief executive Josh Fegan said it will not be as straightforward as some believe.

“You need a robust submission to get a product registered and you have to claim that it does something,” he said. “So these food companies who operate with CBD products out of the US and Europe will have little to no chance of getting product registered.

“Anyone can put a label on anything. It’s how it’s produced, the quality, and how and where it’s manufactured. And you need evidence that it works.

“It’s going to be hard and will take a long time, so don’t expect to see products on the shelves in February.”

In its safety report, the TGA stated that no conclusion could be drawn on the efficacy of low-dose CBD as larger phase III and conclusive efficacy trials have not been carried out.

The majority of literature for analysis was deemed “lower quality explorative studies or case series with no placebo control”.

If the TGA expects a double blind RCT with 1,000 people to statistically prove a product is effective for treating a specific condition then no-one is going to do it. It’s not feasible

Freshleaf analytics principal consultant rhys cohen

However, the health regulator did suggest that cannabidiol in less than or equal to 1 mg/kg/day, or up to 60 mg/day – the proposed maximum dosage that will be permitted as a schedule 3 drug – has “possible utility in the management of chronic and generalised pain of broad aetiologies… and in anxiety and insomnia”.

Side effects also appeared minimal, the TGA said, with only minor signals of mild drowsiness and fatigue.

“This could be managed as for similar S3 medicines, such as requiring a label that indicates ‘should not use’ if driving or operating machinery as for other medicines that can cause potential drowsiness,” the report said.

“Schedule 3 requires that both Product Information and Consumer Medicine Information is available. These documents could include information about drug-drug interactions. In addition, a S3 medicine requires interaction with a pharmacist that would further reduce any unintended drug-drug interactions.”

Rhys Cohen, principal consultant with FreshLeaf Analytics, said the application could turn into a “red herring”, with companies facing “onerous” challenges to get product over the line, particularly at such a low dose.

“It’s difficult and expensive to get any S3 medicine registered,” he warned. “The additional challenge we are facing is, should the TGA decide to set a maximum dose of 60mg a day, companies will need to prove their product is effective in treating an indication at 60mg a day. At the moment no-one has demonstrated in a clinical trial that CBD at those doses is effective for treating anything.

“What people are concerned about is the evidence is still unknown with regards to CBD’s efficacy in general. It’s possible that 60mg per day might not be effective for any condition and therefore no-one will be able to demonstrate efficacy and get their drugs registered. So there is concern it might be a red herring.

“We are hoping the regulators are cognisant of that and will engage in good faith with the industry to make sure it’s possible that these drugs become available. That, after all, is the intention of the down scheduling.”

Cohen added: “If the TGA expects a double blind RCT with 1000 people, statistically proving a product is effective for treating a specific indication, then no-one is going to do it. It’s not feasible.”

AusCann chief executive Ido Kanyon said: “If the TGA is reviewing efficacy data and saying there is probably no clinical utility, how would we register a product?

“To demonstrate efficacy you need to run a trial which costs millions of dollars, plus they constrain your dose.

“It’s a bit of a paradox and a challenging one commercially, so I don’t know how this will unfold.

The Medicinal Cannabis Industry Australia (MCIA) told Cannabiz it gave the down scheduling “qualified support” in its submission.

Peter Crock - Cannabis News Australia - Cannabiz
MCIA chairman Peter Crock: qualified support for TGA proposal

But MCIA chairman Peter Crock conceded there was concern whether the low dose was efficacious.

“We want to make sure it’s not just an arbitrary limit that’s been put on for safety reasons which could have an impact on efficacy for patients,” he explained. “We are up for reviewing scheduling but want to make sure it’s done on the right basis and doesn’t confuse the issue around what’s going to be effective for patients.

“The worst case is that it becomes a very expensive placebo, so let’s not jump in and set an arbitrary low level that may not be servicing patients correctly.”         

Regardless of the safety profile set out in the TGA review, the Australian Medical Association (AMA) opposed the down scheduling.

While accepting there was a “slowly growing body of evidence”, it stressed the therapeutic use of cannabinoids is still “experimental, in some cases conflicting and far from decisive or reassuring”.

“The AMA is concerned that down scheduling CBD products sends out the wrong message to the public,” it said. “There is a risk of normalising the concept that cannabis is a good therapeutic product without established evidence to support it and potentially dissuades use of products with a genuine evidence base. Prescription-only CBD will ensure it is used only for evidence-based indications.”

The AMA also argued that the drug-drug interactions set out in the TGA report could see patients substitute their regular medications with low-dose CBD.  

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