New research has found that THC in blood and saliva are poor measures of cannabis impairment, potentially having major implications for global drug-driving laws.

Researchers at the University of Sydney’s Lambert Initiative analysed all available studies on the relationship between driving performance and concentrations in blood and saliva of tetrahydrocannabinol (THC), the intoxicating component of cannabis.

The results indicate that blood and oral fluid THC concentrations are relatively poor or inconsistent indicators of cannabis-induced impairment.

This contrasts with the much stronger relationship between blood alcohol concentrations and driving impairment.

Lead author Dr Danielle McCartney, from the Lambert Initiative for Cannabinoid Therapeutics, said: “Higher blood THC concentrations were only weakly associated with increased impairment in occasional cannabis users while no significant relationship was detected in regular cannabis users.

“This suggest that blood and oral fluid THC concentrations are relatively poor indicators of cannabis-THC-induced impairment.”

For the study, researchers analysed data from 28 publications involving consumption of either ingested or inhaled forms of cannabis. They then characterised the relationships between blood and oral fluid THC concentrations and driving performance (or driving-related skills such as reaction time or divided attention).

For infrequent, or occasional cannabis users, some significant correlations between blood and oral fluid THC concentrations and impairment were observed. However, the researchers note that most of these relationships were “weak” in strength. 

No significant relationship between blood THC concentration and driving performance was observed for ‘regular’ (weekly or more often) cannabis users.

The research raises questions about the validity of the methods used to assess cannabis-related impairment. 

This includes the widespread random mobile drug testing for THC in saliva in Australia and the testing for specific concentrations of blood THC that is used to detect impaired drivers in some US states and in Europe.

Dr McCartney said: “Our results indicate that unimpaired individuals could mistakenly be identified as cannabis-intoxicated when THC limits are imposed by the law. Likewise, drivers who are impaired immediately following cannabis use may not register as such.”

The researchers also found that subjective intoxication – how “stoned” individuals reported that they felt – was also only weakly associated with actual impairment.

This means that drivers should not necessarily rely on perception of their own impairment in deciding whether they are fit to drive.

Co-author Dr Thomas Arkell from the Lambert Initiative said: “Individuals are better to wait a minimum length of time, between three and 10 hours, depending on the dose and route of administration, following cannabis use before performing safety-sensitive tasks. Smartphone apps that may help people assess their impairment before driving are currently under development and may also prove useful.”

Academic director of the Lambert Initiative, Professor Iain McGregor, said: “THC concentrations in the body clearly have a very complex relationship with intoxication. The strong and direct relationship between blood-alcohol concentrations and impaired driving encourages people to think that such relationships apply to all drugs, but this is certainly not the case with cannabis.

“A cannabis-inexperienced person can ingest a large oral dose of THC and be completely unfit to drive yet register extremely low blood and oral fluid THC concentrations. On the other hand, an experienced cannabis user might smoke a joint, show very high THC concentrations, but show little if any impairment.  

“We clearly need more reliable ways of identifying cannabis-impairment on the roads and the workplace. This is a particularly pressing problem for the rapidly increasing number of patients in Australia who are using legal medicinal cannabis yet are prohibited from driving.

“The increase in legal recreational use of cannabis across multiple jurisdictions worldwide is also making the need for reform of cannabis-driving laws more urgent.”

The UK campaign for law reform

Earlier this year the Seed Our Future campaign in the UK, called for urgent reforms to legislation around cannabis and driving, as its latest report revealed the extent of patients risking criminalisation

Although patients who hold a legal prescription have a right to a medical defence, this is not always taken into account and those who are unable to afford one risk being criminalised and having their licences removed without any evidence of driving impairment.

The group, which lobbies for the decriminalisation of cannabis, is calling for the removal of THC from Section 5 and reverted to Section 4 of the Road Traffic Act 1988 (RTA), where evidence of impairment would be required to convict.

The Australian study was published in Neuroscience & Biobehavioral Reviews.

Experts have highlighted the need for Government-funded studies, if the UK is to catch up with countries leading the way in medical cannabis research.

Experts in the field have said it is “short-sighted” that the UK Government is not investing in medical cannabis research, while independent bodies step in to fill the gap.

Dr Anne Katrin Schlag, head of research and Rayyan Zafar, honorary research assistant at Drug Science, joined Dr Simon Erridge, head of research and access at Sapphire Medical Clinics for a broad discussion for Medical Cannabis Awareness Week on Wednesday 3 November.

The panellists are all playing their part in building the UK evidence-base for the safety and efficacy of medical cannabis, through Drug Science’s Project Twenty21 and Sapphire Clinics, UK Medical Cannabis Registry. 

What does the evidence say?

Project Twenty21 (T21) now has more than 1,000 patients enrolled, aged between 18 and 85, for a range of indications including chronic pain, anxiety, ADHD and Tourette’s syndrome.

The first findings from T21, published in May, show cannabis improves quality of life in patients by more than 50 per cent. A  meta-analysis also found it to be more beneficial for improving quality of life in patients with chronic neuropathic pain, when compared to 12 of the most commonly prescribed pharmaceuticals. 

In a separate study, a bayesian analysis of the tendency for medical cannabis to reduce seizures in 21 patients with childhood epilepsy, found it has a 96 per cent likelihood of significantly reducing them.

Dr Erridge has also published two studies with Sapphire, looking specifically at chronic pain, which found reported benefits in terms of pain interference and effect on a patient’s quality of life, anxiety and sleep.

It is hoped this data will help influence policy makers and regulators and can be used to inform randomised controlled trials (RCTs).

But the panelists also highlighted the lack of Government-funded research in the UK, which is holding the country back compared to elsewhere such as Israel, Canada and Australia, which is thought to have around 20 ongoing RCTs.

Many countries, including France and Germany, also benefit from Government-funded patient data registries, the findings of which will be used to help shape future policy around medical cannabis prescribing.

“Bridging the gap”

Dr Erridge said access schemes are having to “bridge the gap” when it comes to UK evidence, despite the NHS being an “optimum environment” for data collection.

“In the NHS we have an optimum environment in terms of the collection of data. At Sapphire and T21 we’re doing our best to bridge that gap, but there is a lot more that could be done with facilitation within a national healthcare system… if medical cannabis was being prescribed in the NHS,” he said.

“It comes back to having the institutions and the funding to go alongside that, in order to be able to produce high quality research.

“A lot of the universities in Canada, Israel and Australia have been fortunate benefactors of large endowments in terms of helping them to support large medical cannabis research groups, and to be able to support RCTs.

Dr Erridge added: “I don’t think that we should be completely reliant upon small subsections of rich individuals who are able to fund this. It needs to come from a centralised source.”

Despite the NIHR stating that it would make medical cannabis research a priority, following the law change in 2018, few grants have been issued, according to Zafar, who described the pledge as “lip service”.

“The NIHR have said that they want to specifically fund cannabis-based research… but having worked within cannabis research, I’m not aware of many grants being awarded to researchers in the UK from that,” he said.

“This is perhaps an example of policy on one side saying ‘we support medical cannabis’… but actually maybe [this is] just lip service right now.”

Dr Erridge believes that the NIHR was too quick to prioritise cannabis research after the UK law change.

“Their priority setting around medical cannabis came very quickly after the November 2018 legislation change and the UK wasn’t in a place where it could facilitate the research at that time,” he explained.

“By the time of the next funding round that prioritisation had gone away and now their main priority has been Covid-related research.”

Lack of policy

While the Covid-19 pandemic has been the focus of the medical sector for the last two years, it isn’t solely to blame for the lack of Government investment.

“Policy is partially driven by ideology, and that is always going to be an issue when it comes to science in the space of medicinal cannabis, but I think it’s short sighted that there isn’t enough research,” said Dr Erridge.

“Quite consistently we see MPs cite the financial and economic benefits of a thriving medical cannabis sector within the UK. I think they think that the route to that is that they say it in Parliament and it will happen, but what you need to do is put in very clear policy steps and that involves research and development. 

“It’s an ongoing discussion between patients, doctors, researchers and those policymakers to see what we can do to try and push them in the right direction.”

In the meantime private investors are stepping in, as Zafar explained: “There’s been a lot of investment in the cannabis space and academic collaborations can and have come off that, so it’s not as if the cannabis research space is empty at the academic or institutional level. There are a lot of corporate sponsored studies or philanthropic studies going on which are important to grow the evidence base.”

The UK now faces the question of whether the data collected by independent registries such as T21 and Sapphire will be accepted and acknowledged by policymakers.

Dr Schlag added: “We now need to ensure that the evidence generated is actually accepted and acknowledged and used in policy decision making. I think that is the next hurdle that we will be working towards.”

Watch the full webinar and catch up on all the events taking place during Medical Cannabis Awareness Week here

A new study on mice from the University of Sydney found that three acidic cannabinoids found in cannabis reduced seizures in Dravet syndrome, an intractable form of childhood epilepsy.

The three cannabinoids are cannabigerolic acid (CBGA), cannabidivarinic acid (CBDVA), cannabigerovarinic acid (CBGVA). All three but CBGA in particular “may contribute to the effects of cannabis-based products in childhood epilepsy” noted the researchers and were found to potentially have ‘anticonvulsant properties.”

The study marks the first time that three acidic cannabinoids were found to potentially help reduce seizures for Dravet syndrome.

Speaking with Cannabis Health News, the lead author of the study, Dr Lyndsey Anderson, said: “We found that CBGA exhibited both anticonvulsant and pro-convulsant effects. CBGA was more potent than CBD against febrile seizures in a mouse model of Dravet syndrome. We also found that a combination of CBGA and clobazam was more effective than either treatment alone. Additionally, we found that CBGA was anticonvulsant in the maximal electroshock acute seizure model, a model for generalized tonic-clonic seizures.”

She added: “CBGA did, however, present some proconvulsant effects. The frequency of spontaneous seizures in the mouse model of Dravet syndrome was increased with a high dose of CBGA. Also, CBGA was proconvulsant in the 6-Hz acute seizure model, a model of focal, psychomotor seizures.”

Although CBGA shows promise, Dr Anderson also stressed that it needs more research before it can replace CBD. She cautioned that Dravet syndrome patients may still need to proceed with caution.

“Artisanal cannabis-based products are believed to reduce seizures in Dravet syndrome patients,” she said. “As these oils contain rare cannabinoids like CBGA, it is possible CBGA then contributes to the anticonvulsant effects of these artisanal cannabis oils. However, there were proconvulsant effects observed with CBGA, suggesting that Dravet syndrome patients may need to proceed with caution. The proconvulsant liability of CBGA would need to be addressed before it replaced CBD as an anticonvulsant.”

What is CBGA?

Sometimes referred to as ‘the mother of all cannabinoids,’ CBGA is the precursor molecule to many different cannabinioids including CBD and THC. It is thought to help some diseases such as colon cancer, metabolic disease and cardiovascular disease. It is a non-intoxicating cannabinoid much like CBD.

Dr Anderson explains that more research is needed to explain how the three cannabinoids work together.

This isn’t the end of the research into CBGA for Dravet Syndrome. Dr Anderson said there is more to explore when it comes to creating more treatment options for Dravet syndrome.

She said: “Next on the horizon for this research is to explore whether the anticonvulsant properties of CBDVA and CBGVA translate to other seizure types including spontaneous seizures in the mouse model of Dravet syndrome. Additionally, we have extensively interrogated the anticonvulsant potential of individual cannabinoids and identified ten with anticonvulsant properties.”

“We are now interested in investigating what happens when we combine these anticonvulsant properties. It remains an open possibility that greater anticonvulsant effects are achieved when the cannabinoids are administered in combination.”