Emulsification times are known to vary with the quantity of surfactant and the viscosity of the formulation. The SEDDS in this work could emulsify completely within 6.5 min. In agreement with previous work, increasing the surfactant quantity promoted faster emulsification. The Korsmeyer-Peppas model is commonly used to describe drug release from polymeric systems and was fitted to the drug release in this work based on the highest r 2 value. This model has previously been applied to drug release from microemulsions and film-forming polymeric solutions. There are three classes of non-Fickian diffusion that can be differentiated by the velocity of solvent diffusion. In this work, the release exponents of CBD and THC from SEDDS were 0.644 and 0.646, respectively. Drug dissolution with n values between 0.43 and 0.85, as in this work, is classified as anomalous transport, with the velocity of solvent diffusion and polymeric relaxation possessing similar magnitudes. The drug dissolution rate appeared constant over the first hour of the drug dissolution test. This is associated with a high drug concentration gradient and generally attributed to the release of the drug deposited on the oil droplet surface. The drug dissolution rate decreased between the first and second hours, with the diffusion rate of the drug within the oil droplet lower than that on the outer surface. As illustrated by Fick’s first law, a decreasing drug concentration gradient over time negatively affects drug dissolution. The poor water solubility of cannabis extract and cannabinoids results in their slow absorption via gastrointestinal mucosa and thus low bioavailability.Its use was reported to increase CBD plasma level, enhance bioavailability, and speed absorption as compared to hemp extract diluted with medium-chain triglycerides.
A nanoemulsion formulation of CBD composed of vitamin E acetate, ethanol, Tween® 20, and water was found to improve both the intestinal absorption of CBD and the stability and onset of activity. Cannabis extract has been prepared in olive oil–filled hard capsules, although its effect on bioavailability was not investigated. Based on the physicochemical properties of the formulations, it is unlikely that it would increase the bioavailability above that of nanoemulsions or SEDDS. Oil-based CBD formulations, such as CBD dissolved in corn oil, have been reported to decrease the time to peak plasma level and increase oral bioavailability four-fold compared to CBD powder. The work performed here successfully enhanced the dissolution of cannabis extract obtained via SFE, indicating the potential to improve the bioavailability of cannabis extract, although this will require confirmation in vivo. The last decade has seen a dramatic shift in global attitudes relating to the therapeutic use of cannabis-based medicines, with over 50 countries now having established legal access pathways allowing patients to utilise medicinal cannabis products across a wide range of medicalconditions . Reflecting this shift, the United Nations General Assembly voted in December 2020 to remove cannabis from Schedule IV of the Single Convention on Narcotic Drugs , the most restrictive of the schedules . However, this recasting of cannabis as a potentially legitimate medicine has created some tensions with other regulatory frameworks in which marijuana grow system remains positioned as a dangerous drug with no legitimate therapeutic application. A notable example of this is the so-called ‘zero tolerance’ drug driving legal frameworks that have been adopted in many countries, which criminalise the presence of a drug in a driver’s blood or oral fluid irrespective of impairment .
Here we undertake an analysis of this issue, with a focus on medical only access frameworks , based on a case study of the introduction of legal medicinal cannabis access pathways in Australia. The paper explores this policy issue by outlining the Australian medicinal cannabis access framework and considers the current regulatory approaches to reduce road safety risks associated with other potentially impairing prescription medicines and illicit drugs. It then reviews the evidence relating to cannabis and road safety risk, and unintended impacts of the ‘zerotolerance’ approach on patients taking or wanting to take medicinal cannabis. At the core of this issue is the need to optimise the regulatory framework to minimise potential harms relating to road safety risk, impediments to accessing a needed medication, and exclusion of a vulnerable patient group from motor vehicle access, while ensuring that medicinal cannabis patients are not discriminated against due to the historical status of the drug.The introduction of legal medicinal cannabis access in Australia was initiated in November 2016, via regulatory amendments implemented by the Commonwealth Government that enabled Australian patients to legally access medicinal cannabis when prescribed by their doctor with relevant Commonwealth and State/Territory Government approvals. In doing so, it brought an end to the blanket prohibition on cannabis, which had been classified as a Schedule 9 substance in the Australian Poisons Standard and was considered to have no recognised medical value. Unlike some other countries, the regulatory framework for medicinal cannabis in Australia is based on the provision of pharmaceutical grade medicines available only via prescription from a doctor after any required Commonwealth and State/Territory Government approvals have been obtained. These medicines are prescribed at precise doses and dispensed from a pharmacy. All other use of cannabis remains illegal.
There are now an estimated 190 medicinal cannabis products available in Australia, which vary in composition of the two primary cannabinoids, delta-9-tetrahydrocannabinol , and cannabidiol . Most contain at least some level of THC and many are described as ’full spectrum’, containing a wide range of other chemical constituents present in the cannabis plant . Unlike illicit cannabis , all legal medicinal products available in Australia are standardised pharmaceutical grade medicines . A wide range of product formulations are available, however recent analysis by the Commonwealth Department of Health found that the vast majority of approvals are for oral solutions , while around 10% involve preparations including wafers, transdermal gels and dried plant intended for vaporisation. As of 31 March 2021, over 100,000 approvals for medicinal cannabis products had been granted by the Australian Therapeutic Goods Administration. However, the interaction of legal medicinal cannabis and driving continues to be contentious, with most road safety agencies around Australia remaining committed to a drug driving regulatory framework that treats patients taking legally prescribed medicinal cannabis containing THC in the same manner as users of some illicit drugs, by criminalising the presence of the drug regardless of impairment. Some advocacy groups and politicians have asserted the need for change due to perceived inequitable treatment of medicinal cannabis patients . A 2015 report by the Victorian Law Reform Commission noted the right of patients ‘not to be discriminated against because of their treatment’ when managing risks such as driving. In one of the first legal tests in January 2020, a South Australian magistrate found a medicinal cannabis patient guilty of driving with a prescribed drug in his system but then exercised her legal discretion to dismiss the charge on the basis of a lack of evidence of impairment.
The magistrate did note that a conviction would be upheld if the patient was charged again .It is well-known that a range of prescription medications cause impairment that may pose a risk to the safe operation of a motor vehicle. This issue is managed in Australia via a regulatory framework including the Commonwealth Poisons Standard and corresponding state-based legislation. The Poisons Standard uses a scheduling system reflecting the differing levels of potential harms and therapeutic benefit of various substances. Drugs with a recognised medicinal value are identified as Schedule 2, 3, 4 or 8 depending on the level of regulatory control restricting their availability, while those with no recognised medicinal value and the potential for harm, abuse/misuse are listed as Schedule 9 prohibited substances. Recognised medicinal drugs may still have risks associated with their use, including causing impairment that can affect the ability of patients to drive. A significant number of medicines prescribed in Australia are known to have such effects, including anticonvulsants, opiates, antihistamines, antipsychotics, benzodiazepines, muscle relaxants, hypnotics, and antidepressants . Experimental studies have found these medicines to have negative effects on psychomotor, cognitive, and driving skills, with an increased crash risk reported in epidemiological studies . Table 1 provides a summary of such effects reported in systematic and meta-analytic reviews. However, it is important to note that there are methodological difficulties in achieving accurate estimates of impairment and crash risk, cannabis vertical farming particularly in patients. Experimental studies are almost always undertaken on healthy controls, for whom it is impossible to incorporate potential health benefits of the medication that may lead to a net reduction in impairment and improved driving ability. For epidemiological studies, which are typically observational, it is very difficult to adequately control for all potential confounding variables such as simultaneous use of other drugs , polypharmacy, time delays between crashes and drug testing, plus un-observed confounding factors.
In addition, risks associated with some medications appear to diminish after a tolerance to the impairing effects has developed .It is well-known that a range of prescription medications cause impairment that may pose a risk to the safe operation of a motor vehicle. This issue is managed in Australia via a regulatory framework including the Commonwealth Poisons Standard and corresponding state-based legislation. The Poisons Standard uses a scheduling system reflecting the differing levels of potential harms and therapeutic benefit of various substances. Drugs with a recognised medicinal value are identified as Schedule 2, 3, 4 or 8 depending on the level of regulatory control restricting their availability, while those with no recognised medicinal value and the potential for harm, abuse/misuse are listed as Schedule 9 prohibited substances. Recognised medicinal drugs may still have risks associated with their use, including causing impairment that can affect the ability of patients to drive. A significant number of medicines prescribed in Australia are known to have such effects, including anticonvulsants, opiates, antihistamines, antipsychotics, benzodiazepines, muscle relaxants, hypnotics, and antidepressants . Experimental studies have found these medicines to have negative effects on psychomotor, cognitive, and driving skills, with an increased crash risk reported in epidemiological studies . Table 1 provides a summary of such effects reported in systematic and meta-analytic reviews. However, it is important to note that there are methodological difficulties in achieving accurate estimates of impairment and crash risk, particularly in patients. Experimental studies are almost always undertaken on healthy controls, for whom it is impossible to incorporate potential health benefits of the medication that may lead to a net reduction in impairment and improved driving ability. For epidemiological studies, which are typically observational, it is very difficult to adequately control for all potential confounding variables such as simultaneous use of other drugs , polypharmacy, time delays between crashes and drug testing, plus un-observed confounding factors. In addition, risks associated with some medications appear to diminish after a tolerance to the impairing effects has developed .Impairing medications such as those described above are prescribed in very high volumes in Australia for the treatment of various medical conditions. In 2016-17, for example, there were 15.4 million prescriptions dispensed for opioids and in 2014-15 4.9 million benzodiazepine prescriptions were dispensed . To reduce road safety risks associated with the use of such medications, their use is regulated via mandatory labels and warnings, road safety legislation outlawing driving when impaired, and fitness to drive assessments.To reduce risks associated with the use of prescription drugs such as those in the table above, a product labelling and warning system has been established via several legislative instruments, including the Poisons Standard, Therapeutic Goods Orders 91 and 69 , the Medicines Advisory Statements Specification, and the Required Advisory Statements for Medicine Labels . This system includes warnings about possible sedating effects/drowsiness, recommendations not to drive or operate machinery if experiencing such effects, and to avoid alcohol or be aware that the medication may increase its effects. The label required on sedating medications, including medicinal cannabis products that contain THC, is shown in Fig. 1. Prescribing doctors and dispensing pharmacists are also required to provide patients using these medications with warnings to monitor drug effects and refrain from driving if impaired.