Pharmacy’s link with the natural world

I write this post on the day that The Lancet has published its 2022 report ‘Countdown on health and climate change: health at the mercy of fossil fuels’, which highlights how — at 1.1°C of heating — climate change is “increasingly undermining every pillar of good health and compounding the health impacts of the current COVID-19 pandemic and geopolitical conflicts”. 

It warns of the various consequences of climate change; damaging the natural and social systems on which health depends. 

The report leads me to ponder another impact on humanity, one based on pharmacy’s unique link with the natural world and our longstanding exploration of medicinal plants for the prevention and treatment of disease. I am not the first to ask this question — if the papers in this month’s RPS journals are anything to go by, products of natural origin remain of high interest to a wide community of people. 

One paper, published in Journal of Pharmacy and Pharmacology (JPP), examines boropinol-B for sleep. Boropinol-B is a phenylpropanoid compound originally isolated from Boronia pinnata Sm, a shrub belonging to the Rutaceae family native to New South Wales, Australia. 

The paper examines the sedative–hypnotic effects of Boropinol-B in rodents, based on its structural similarity to another natural compound with sedative effects known as α-asarone. 

A quick background check on α-asarone reveals both therapeutic promise and potentially carcinogenic effects, and it acts as a reminder of two important concepts. First is that products of natural origin should be treated with caution and fully investigated before use; second, that structure–activity relationships — the idea that the biological activity of a compound is linked with its chemical structure — maintain their importance in pharmacy and can be exploited in research. The JPP paper illustrates the sedative-hypnotic potential for boropinol-B via several neat experiments. 

Using pentobarbital sodium to promote sleep in mice, the researchers found that Boropinol-B, given at the higher dose of 80mg/kg, tested against a control and a benzodiazepine comparator (estazolam) given at 2mg/kg), showed a synergistic effect on promoting sleep. This was measured by the number of mice that fell asleep, how long it took to get to sleep and the duration of sleep. Additionally, using caffeine to increase locomotor activity in mice, measured by distance moved and frequency of standing up, they found that Boropinol-B illustrated the ability to confer resistance to increased locomotor activity similar to the estazolam comparator. 

The paper details other experiments to illustrate boropinol-B’s potential in sleep; for example, there was no residual effect on locomotor activity in caffeine-treated mice six hours after administration suggesting rapid elimination; pharmacokinetic studies in rats showed a rapid onset of action (T_max = 0.12h) and a short elimination half-life (t_1/2β = 0.87 h); and homogenised brains of mice who were caffeine-treated, then sacrificed, showed higher γ-aminobutyric acid (GABA) levels with both boropinol-B (80mg/kg) and estazolam, suggesting modulation of the GABAergic pathway to induce sleep.  

Of course, in vitro and in vivo animal experiments are just the starting point in the long journey of drug discovery and development, and scientists will need to repeat these experiments and build on them to further illustrate the usefulness and safety of this herb-derived compound in humans.

This need to examine the safety of products of natural origin is highlighted in a paper in the International Journal of Pharmacy Practice. The retrospective, observational cohort study uses data collected as part of a ‘Cannabis access clinics observational study’ to explore the incidence of adverse events reported by patients initiating medicinal cannabis for chronic non-cancer pain. 

The cannabis plant has two main species, Cannabis indica Lam and Cannabis sativa L, containing more than 60 cannabinoid compounds, of which the two most researched are delta-9-tetrahydrocannabinol (d-9-THC) and cannabidiol (CBD). 

In this study, prescribers selected any pharmaceutical grade, plant-derived, cannabinoid-containing oral product, which might have included CBD, d-9-THC, a combination of CBD/9-d-THC and other cannabinoids. These details were recorded, as were patients’ concomitant medications, and their experience of adverse events. From a total of 275 patients, each had a median of six concomitant medicines, with opioids (n=179; 65%) the most common. A main finding was that those (n=123) taking products with both CBD and THC were 1.5 times more likely (p=0.004; relative risk (RR) = 1.47, confidence interval (CI): 1.13–1.91) to report adverse events than those (n=152) given a CBD-only product. Those also taking the CNS-active substances, gabapentinoids and tricyclic antidepressants, appeared particularly prone to dizziness, fatigue and somnolence. 

Real-life studies such as this have their limitations, but they are also vital to developing our understanding of everyday practice, in this case showing differences in adverse events according to the constituent phytocannabinoids and concomitant medication use. 

The third paper of my pick this month is published in the Journal of Pharmaceutical Health Services Research and looks at women’s use of complementary and alternative medicines (CAMs) for gynaecological disorders in Jordan. A self-administered questionnaire reveals 232 (69%) of participants have used CAMs, with 135 having used a herbal medicine.

Qualitative interviews revealed perceived safety and ease of access as main reasons for using CAMs. Those using a herb had obtained these mainly from herbalists or planted them at home; only a quarter discussed their herb use with their doctor and just over a tenth with their pharmacist. The most commonly used herbs were cinnamon (used by 44 people) and marjoram (used by 25). Of course, there are currently no robust studies confirming the efficacy of these herbs in the treatment of gynaecological disorders and using them could delay much-needed medical input. 

Yet, the study highlighted people’s continued trust and reliance on products of natural origin at times of need. We must remain mindful of this both as healthcare professionals and citizens of the world as we ponder the demise of our fragile earth. 

Parastou Donyai is chief scientist at the Royal Pharmaceutical Society