Cannabinoids and Biosynthesis

Any time a living organism synthesises a chemical compound on its own, we term that activity ‘biosynthesis’ (or anabolism). These chemical reactions are different than ones we do in test tubes (in vitro) because biological systems have a host of mechanisms in place to drive energetically unfavourable reactions to completion, including enzyme catalysers (substances capable of initiating or speeding up a chemical reaction) and energy currency in the form of adenosine triphosphate or ATP (adenosine molecule bonded to three phosphate groups, present in all living tissue). Chemists mimic these processes by imbuing the system with heat, mechanical agitation, metal catalysers and more, but these are mere shadows on the wall compared to the vast beauty and efficiency of a biological synthetic pathway.

Image result for cannabis leaf macro images

Biosynthesis of cannabinoids generally takes place in the plant cells of leaves, which makes sense. Building up these complex molecules involves a large amount of energy expenditure and leaves are the main powerhouse of the plant. Cannabinoids are also big and bulky; Tetrahydrocannabinol (THC) alone requires 21 carbon atoms. All this carbon matter has to come from somewhere and in the case of plants, this matter comes right from the air, from carbon dioxide (CO2). Plants take up CO2 in their leaves, some of it becoming photosynthesised into molecular oxygen (O2) and some being catabolised (degradative metabolism) into simple organic compounds for use throughout the plant.

Figure 1. Isopentyl diphosphate (1) and dimethylallyl diphosphate (2) are the precursor molecules of all terpenoids. They are shunted into the cannabinoid pathway by enzymatically catalysing their addition into geranyl diphosphate (3).

Interestingly, cannabinoid biosynthesis is a branch of terpenoid biosynthesis, sharing the same precursor molecules and pathways (Figure 1). There is more than one pathway to create these precursors. Once these precursors are made, they are shunted into the cannabinoid pathway by a series of enzymatic reactions which produce the penultimate cannabinoid precursor Cannabigerolic acid, or CBGa (Figure 2).

Figure 2. Geranyl diphosphate (3) and olivetolic acid (4) are combined to form CBGa (5).

From there, the cannabinoids that we have discovered seem to differentiate mostly via non-catalysed modifications to the skeletal structure. This explains the similar structure shared by all cannabinoids. These modifications include decarboxylation (loss of CO2 moiety [part of a molecule]), isomerisation (structural rearrangement without change in chemical composition) and oxidation (loss of electrons). There are also three enzymes that specifically modify CBGa into more specific cannabinoid moieties, including the all-important Tetrahydrocannabinolic acid (THCa) and Cannabidiolic acid (CBDa) (Figure 3).

Figure 3. CBGa is modified by three particular enzymes, producing Cannabichromenic acid (CBCa) (6), THCa (7), or CBDa (8). The numbers surrounding the structures of 6 and 7 help identify carbon atoms, facilitating understanding and communication.

Adapted from Biosynthesis of Cannabinoids 

Full Spectrum CBD is Superior to Single Isolate CBD

cannabis, recreational cannabis, medical cannabis, cannabinoids, CBD, THC, endocannabinoid system, research, legalization, scientific studies

There has been a lot of debate regarding the superiority of whole plant medicine versus extracts and the converse. For a long time it was believed tetrahydrocannabinol (THC) was the most beneficial part of the Cannabis plant (at least when it came to medicinal value) and that all of the other bits didn’t really matter. Now we know many parts of the plant, including the cannabinoids, flavonoids and terpenes have tremendous value in healing. Not only that, these parts work together, within full spectrum medicine, to amplify the pharmacological activity of the whole via the Entourage Effect. The Cannabis plant has over 140 different cannabinoids with medicinal value as they interact with the body’s Endocannabinoid System. This is a signalling system of receptors found on the surface of certain cells, critical for the control of many bodily functions, such as digestion, nervous control, pain, immune functioning and homoeostasis (balance). The most abundant cannabinoid is THC, followed by cannabidiol (CBD). Other significant cannabinoids include cannabichromene (CBC), cannabigerol (CBG) and cannabinol (CBN).

cannabis, cannabinoids, CBD, THC, CBG, endocannabinoid system, research, medical cannabis, recreational cannabis, health benefits

It takes a lot of effort to isolate CBD or THC from the Cannabis plant. Even though you are processing the plant, the isolate that comes out the other end is not synthetic; this is a common misconception. The plant is refined to a pure form of CBD, typically a white powder. It used to be an isolate was the gold standard of ‘cannabis medicine’. But, as further research was conducted on how CBD interacts with the human body, something strange was observed – patients that took high CBD strains tended to have faster healing and less pain than those that merely took the CBD isolate. For example, a study looking at the anxiety of public speakers noted that with the isolate, CBD followed a bell-shaped curve for therapeutic effectiveness. This means when the amount of CBD ingested exceeded a certain point, its therapeutic impact declined dramatically. Therapeutic effect was only observed when CBD was given within a very limited dose range, whereas no beneficial effect was achieved at either lower or higher doses. Following this interesting finding, further studies were conducted to determine how to overcome the bell-shaped dose response curve effect. 

cannabis, CBD, THC, CBG, anandamide, research, scientific studies, cannabinoids, endocannabinoid system, CBD isolate, bell-shape dose response

One notable Israeli study was Published in the journal Pharmacology & Pharmacy (February 2015) and was entitled “Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol”. It is important to note that one of the co-authors, Lumir Hanus, was instrumental in the discovery of the endogenous cannabinoid, anandamide. The Israeli team obtained a CBD-rich strain called “Avidekel” which has only trace amounts of THC and studied it against a CBD extract referred to as “clone 202”. Both forms of CBD were administered to lab rats and the therapeutic effects were clinically observed and charted. The pure CBD isolate, once again, revealed that single-molecule CBD administration produced a bell-shaped dose-response curve with a small therapeutic window. However, rather than showing a bell-shaped curve, the whole plant CBD-rich extract caused a direct, dose-dependent inhibition of pain. Moreover, the Israeli researchers discovered that a smaller amount of CBD was needed for significant pain relief compared to the much larger amount of CBD isolate required to achieve similar analgesic effect. RxLeaf

When the CBD isolate was delivered in excess of therapeutic dose, there was a decline in efficacy, but an excess of whole plant CBD-rich extract did not undermine its therapeutic potency. What happened when the full spectrum extract was given in excess is that the therapeutic effect reached a medicinal plateau phase and levelled off, rather than declined. These results have revolutionised how Cannabis’ therapeutic effects are understood. So much so we can confidently call this a landmark study in the Cannabis space. Subsequent studies have further proved this finding. The effect mentioned above is now referred to as the Entourage Effect, achieved when Cannabis is consumed as a whole plant, whether that be flower, oil, or tincture. Full spectrum CBD oil contains terpenes, cannabinoids and flavonoids. These compounds work synergistically to produce a more potent and longer-lasting effect than a single compound can achieve on its own.


Adapted from Full Spectrum CBD is Superior to CBD Isolate Because It Works For A Range of Doses

Bees and Cannabis

Image result for honey bees and cannabis

Very little research appears in the literature about how honey bees (Apis mellifera) interact with Cannabis plants which contain levels of tetrahydrocannabinol (THC) and cannabidiol (CBD) appropriate for recreational or medical use (only one scholarly article about the interaction between Cannabis plants and bees can be found). So what are the biologic and physiological relationships between Cannabis and Apis mellifera? In 2016, Sharon Schmidt, who holds a doctoral degree in Clinical Psychology, is a Psychiatric Nurse Practitioner, beekeeper and a volunteer Director for the Oregon (US) Honey Festival, located some bee hives on a property that had beautiful land resources; organic plants and flowers in the summer and a clean, continuously flowing stream in the vicinity of the hives. Facing south-east with a big thicket of tall, mature plants on the north side of the hives to protect against winter winds, there were pigs in a neighbouring field that would stir up and loll in puddles of muck and sometimes the bees seemed attracted to the puddles. Community gardens, visible from the property, interested the bees greatly. The setting was idyllic and the bees proved to be good pollinators. 


There was no warning the bees would eventually be in the middle of a Cannabis grow. However, on the day Oregon law changed to allow citizens to grow Cannabis, an odour some described as ‘heavenly’ and others referred to as ‘skunk-like’ emanated from the fields. When told the bees had access to Cannabis, people would ask whether the bees were ‘buzzed’ and whether their honey would make people ‘high’ (euphoric). This was a fascinating question! Would the bees (quite unintentionally) produce neuro-active honey? This began a line of inquiry by Sharon to determine whether bees are interested in Cannabis, what they might glean from it nutritionally and the effects of Cannabis on bees and bee products. Her observation of the bees revealed there was apparently no interaction in spite of the abundance of Cannabis plants in close proximity to the hives. Why not? One hypothesis was that the bees were not attracted to the aroma of Cannabis plants.  

Bees have an exquisite olfactory sense that they use to detect pheromones of other bees and to find nectar. They are also attracted to colours and these two appeals to the senses are like neon billboards for finding food and mating opportunities. Cannabis does not have these attributes. It does not produce a smell that would attract bees, nor is it colourful and finally, and most importantly, it is unable to provide a reward in the form of floral nectar.  As those familiar with Apis mellifera know, it is nectar and not pollen that is required by bees to make honey. There are other reasons bees would not find Cannabis attractive. However, an apparently contradictory piece of video footage turned up on social media in 2015. The video showed seemingly excited honey bees buzzing around and alighting upon a Cannabis plant from which they appeared to be feeding. Many viewers seeing that footage probably believe the bees derived some chemical excitement from their contact with the plant. However this is very unlikely because bees have no neuro-receptors that would allow them to apprehend the neuro-active elements present in Cannabis. Image result for Nicholas Trainerbee

In a 2001 article, Cannabinoid receptors are absent in insects, the authors revealed insects do not produce arachidonic acid (polyunsaturated Omega 6 fatty acid) which is a precursor of necessary ligands (molecules that bind to other, usually larger molecules). It is thought that the cannabinoid (CB) receptor was lost in insects over the course of evolution. The authors also noted the CB receptor appears to be the only known neuro-receptor present in mammals and absent in insects. Because of its documented absence, bees are unable to experience Cannabis the same way humans do. Apparently the story circulating behind the bee video footage was that middle-aged French bee-keeper ‘Nicolas Trainerbees’ (a pseudonym), freely admitted to spraying ‘sugar water’ on female Cannabis flowers to entice the bees. He was trying to ‘train’ them to harvest the resin of the Cannabis plant to make propolis, a special gum which the bees use everywhere in the hive. As to his purported ‘Canna Honey’, the female Cannabis flowers produce tiny, resinous, crystal like structures called trichomes. These sticky structures help pollen to stick to the flower for pollination and within these trichomes are the cannabinoids.


However, trichomes are oil-soluble, not water-soluble and honey is water-based. The next often asked question is whether honey made by bees having access to Cannabis plants contains THC and whether it exerts a neuro-active effect on those consuming it. The Cannabis plant is dioecious, meaning male and female flowers are produced by different individuals, male and female plants. The Cannabis plant is also anemophilious, wind pollinated (mostly), and therefore has not evolved to attract bees, except perhaps in extreme dearth situations. Male flowers, which produce pollen, do not contain any cannabinoids, however, so lack the active ingredients which are what give the desired ‘effects’. The existing scholarly article, Cannabis sativa – an important subsistence pollen source for apis mellifera, on the topic notes that Cannabis pollen seems to be a food of last resort for bees. The author notes that bees (in India) turned to Cannabis plants as a source of protein but only visited male plants during times of dehiscence (spontaneous bursting open) when the male plant’s reproductive organs released pollen and that bees were only interested in that pollen during a pollen dearth. 

Bees and male marijuana

The Abstract of Cannabis sativa – an important subsistence pollen source for apis mellifera, states:

Cannabis sativa is an important source of pollen for Apis mellifera during the period of floral scarcity (May and June) when major flora is absent. Foraging of bees on the herb under experiment took place during morning and evening hours, while during rest of the day activity remained totally ceased. All the foraging bees were pollen gatherers as the plant provides pollen only. Maximum foraging took place during  morning, however pollen was also collected thoroughly by specific sweeping activity and scrabbling behaviour during evening hours. Foraging frequency of bees was more during morning as compared to that at evening. Average pollen load observed was 4 mg / bee. Abundance, Foraging behaviour and pollen loads indicated that this annual herb is a good source of pollen during dearth period in summer”.

So how do we account for reports of persons who say they have seen bees congregating and apparently foraging on female plants or of images available on social media? Sharon approached Norman Carreck (Science and Senior Director of the Journal of the Apiculture Research) who suggested the possible source of the female plant’s attractiveness to bees could be ‘extra floral nectaries’ documented as an attribute of the Cannabis plant by John Free (1970) in his book, Insect Pollination of Crops. Extra floral nectaries include glands residing outside the calyx producing both water and sugars. There are no formal reports of extra floral nectaries in Cannabis plants other than the one referenced by Mr Free. However, if Cannabis plants are shown to have these, they could serve a defensive purpose by attracting ants which protect the plant from herbivores, or they might serve to attract bees. However, Cannabis is known to have glandular trichomes (plant hairs that secrete fluid), which could also be a plant feature interesting to bees suggested Dr Marjorie Weber, Postdoctoral Fellow, Centre for Population Biology, University of California Davis, in January 2016.

Image result for capitate-stalked trichomes

In Cannabis plants, bulbous type trichomes are the smallest at 15-30 microns and barely visible. Capitate-sessile trichomes measure from 25-100 microns across and capitate-stalked trichomes measure from 150-500 microns and are the most abundant. The latter contain the majority of the neuro-active cannabinoids (THC, THCV, CBN) and the effects of use are at least partly mediated by how much degradation is allowed prior to harvest. It appears that trichomes may have evolved for the purpose of making a plant less tasty to animals and insects, making the idea that bees are feeding from trichomes less plausible and more likely that they might be collecting resin from them. In a discussion with noted entomologist, Dr Dewey Caron, more ideas were advanced. First, that another naturally occurring source of interest for bees called ‘honeydew’ is often the object of their interest. Honeydew is simply the waste product of scale or other sucking insects which Cannabis is likely to host. These tiny insects probably concentrate their feeding (and excretion) at the tender surfaces of new plant growth and produce tasty waste products that bees might feed on.

Honey bees and cannabis

Second is the possibility that bees might be collecting resins for purposes of making propolis (a sticky bee product used to sanitise, reinforce and weatherproof the hive) and third, that bees demonstrating activity on Cannabis plants might even be seeking moisture from irrigation, as suggested by Dr Caron. Presently, it seems that some aspects of the relationship between bees and Cannabis are not yet verified. Judging from statements occurring in public discourse, misinformation about bees, Cannabis and honey based upon legend and lore exists among some of the public. Much may yet be discovered, but some hypotheses are more likely true than others: First, it appears that bees cannot experience altered neuro-physiology as a result of exposure to Cannabis given they have no neuro-receptors for the chemical it contains. Second, the literature suggests they do not prefer Cannabis pollen but will resort to visiting male plants and collecting pollen from them mostly during a floral dearth. Third, if bees congregate and appear to be feeding upon female plants it is not to collect floral nectar because Cannabis does not produce flowers containing nectar; there is no known reason for the plant to produce nectar to attract pollinators due to the fact that it has evolved as a wind pollinated plant. 

Image result for Cannabis bees propolis

However the plant may produce water and sugars if extra floral nectaries are proved to be present, which could account for observations and anecdotes about bees congregating. Fourth, it is possible that an extra floral plant exudate might be used by bees to make honey and one can speculate about the presence of the precursors of neuro-active chemicals. It seems unlikely though unless the bees are actually foraging on trichomes. Trichomes have evolved to protect the plant from the predatory interests of animals and insects so the idea of bees foraging from them seems unlikely. The common use of the term ‘sugar’ to describe the frosty looking trichomes which have become opaque may further cloud the issue, bringing some to equate trichomes with sweetness. In fact, people who advocate juicing Cannabis reference the need to mix it with other vegetable juice to cut the bitter taste. Generally bees do not seem to seek out bitter fluids. Fifth, even if the resulting honey did contain such alkaloids, bee products would not be neuro-active without heat being applied for the purpose of converting alkaloids from an inactive to an active state (decarboxylation). 

Image result for cannabis honeyThus persons reporting euphoria after eating raw honey made by bees with access to Cannabis are much more likely to be reporting a psychological phenomenon rather than a physiological one. Bees also have an affinity for honeydew (waste products of scale and other insects that inhabit and forage in Cannabis plants) therefore any interest bees demonstrate toward this plant could be based on the presence of honeydew, or even due to bees’ interest in collecting moisture or resin. A final possibility is that bees might be ‘trained’ to collect whatever substances are available from the plant as a result of experiencing a conditioning paradigm. Under such circumstances they might learn to associate the plant odour with a reward (sugar water) which could account for the enthusiasm they appear to be showing in the above-referenced video. Future observation will likely yield more information about Cannabis and how bees interact with this plant. Not known is the composition of contents of the guts of bees appearing to forage on Cannabis or even the composition of their propolis. No micro observation of their interaction with the plant is readily available either. Given the expansion of legal Cannabis growing in some American states it seems likely there will be more interest and opportunity for systematic observation and research allowing anecdotal reports and scientific data to be accurately reconciled. 

The Benefits Of Cannabis-Infused Honey

Elizabeth Vernon, known as “Queen Bee” in her home state of New Jersey in the US, is an apiarist and certified massage therapist with a degree in Eastern Medicine. She combines her two passions, healing and beekeeping, by infusing botanicals like Cannabis into honey with her Magical Butter machine. Adding Cannabis to honey creates a powerful and healthy natural remedy, since both are known to have healing anti-bacterial and anti-inflammatory properties. Cannabis-infused honey can be used topically or ingested, depending on the desired effects. Infusing honey has been practiced for over 3,000 years. Honey is an extremely versatile base with a large number of healing properties. Adding different herbs and blends of herbs can create a powerful combination that can prevent and fight illness and disease. There are many different methods and the best practice with crafting anything is to find your own balance, do research and figure out what works best for you.

Image result for bees on cannabis flowers

There are so many different variables to consider; Working with fresh ingredients or dry? Planning a cold infusion or warm infusion? What season is it? Honey is always best to work with when the temperature is warmer and using a Magical Butter machine (or similar) saves time and energy. As honey can’t bind to Cannabis, and honey can’t be made into Cannabis-infused honey by bees themselves, the best way is to make a tincture and to add it to the honey. But without any fat, the herb has nothing to bind to, so adding infused coconut oil with the tincture works amazingly well, as without binding the THC to a fat molecule in the likes of coconut oil, most of the effect will be lost. Coconut oil is a saturated fat, allowing maximum absorption of cannabinoids and is much more healthful for you than saturated animal fat; definitely the best option for vegans and those concerned about health. Tinctures are, without a doubt, the oldest mass-market way of extracting and consuming cannabinoids and terpenes found in the trichomes of the Cannabis plant. During the majority of the 19th century, physicians from North America, the United Kingdom and Europe dispensed, recommended and prescribed Cannabis tinctures for a wide variety of common ailments. 


Adapted from Bees and Cannabis with The Benefits Of Cannabis-Infused Honey


Therapeutic and Medicinal Uses of Six Cannabinoids

Cannabinoids are a diverse class of chemical compounds produced in plants like Cannabis, endogenously in many animals and, synthetically. Those produced in plants are known as phytocannabinoids, the most well-known source of which is the Cannabis plant. They are able to illicit physiological effects chiefly via their ability to act on receptors in the human Endocannabinoid System (ECS), primarily by their interactions with the CB1 and CB2 receptors. To date, 113 cannabinoids have been  isolated from the Cannabis plant, many of which have been linked to potential medicinal benefits, from killing cancer cells to reducing pain and anxiety. Cannabis contains a treasure trove of compounds with potential medical uses. Highlighted here are the medicinal uses of six of the more studied cannabinoids, offering a glimpse into the incredible potential of the Cannabis plant.

THC – Tetrahydrocannabinol


  • The FDA has approved THC for the treatment of: anorexia in AIDS patients, nausea and vomiting in cancer chemotherapy patients, muscular spasticity in multiple sclerosis (when combined with cannabidiol)
  • Clinical evidence supports the potential use of THC for the treatment of: muscular spasticity following spinal injury, fibromyalgia, peripheral neuropathic pain, glaucoma, post-traumatic stress disorder (PTSD)
  • Preclinical evidence supports the potential use of THC for the treatment of: multiple cancers, sleep disorders, opiate addiction, depression

CBD – Cannabidiol


  • Clinical evidence supports the potential use of CBD for the treatment of: Epilepsy, Parkinson’s disease, pain, anxiety, inflammatory bowel disease (IBD), Crohn’s disease, schizophrenia, muscular spasticity in multiple sclerosis, glioblastoma (when combined with THC)
  • Preclinical evidence supports the potential use of CBD for the treatment of: Alzheimer’s disease, Huntington’s disease, hypoxic-ischemic injury, depression, multiple cancers, nausea, inflammatory diseases, rheumatoid arthritis, antibiotic-resistant bacterial  infection, cardiovascular disease, diabetes-related complications

THCV – Tetrahydrocannabivarin


  • Preclinical evidence supports the potential use of THCV for the treatment of: Obesity, Type 2 diabetes, Alzheimer’s disease, osteoporosis, Parkinson’s disease, epilepsy, anxiety, PTSD

CBN – Cannabinol


  • Clinical evidence supports the potential use of CBN for the treatment of: Sleep disorders
  • Preclinical evidence supports the potential use of CBN for the treatment of: Antibiotic-resistant bacterial infection, pain, allergic airway diseases, Crohn’s disease, rheumatoid arthritis, appetite loss, seizures

CBG – Cannabigerol


  • Clinical evidence supports the potential use of CBG for the treatment of: Psoriasis, eczema
  • Preclinical evidence supports the potential use of CBG for the treatment of: Glaucoma, neuropathic pain, antibiotic-resistant bacterial
  • infection, IBD, ulcerative colitis, Crohn’s disease, multiple sclerosis, multiple cancers, autoimmune encephalomyelitis, appetite loss

CBC – Cannabichromene


  • Preclinical evidence supports the potential use of CBC for the treatment of: Multiple cancers, osteoarthritis, inflammation (when combined with THC), acne, depression (when combined with THC and CBD)

1. DEA. Pharmaceutical products already exist; they are called Marinol & Cesamet.
2. GW Pharmaceuticals. Sativex (delta-9-tetrahydrocannabinol and cannabidiol). 
3. Maurer, M., Henn, V., Dittrich, A., & Hofmann, A. (1990). Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. European archives of psychiatry and clinical neuroscience, 240(1), 1-4.
4. Fiz, J., Durán, M., Capellà, D., Carbonell, J., & Farré, M. (2011). Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS One, 6(4), e18440.
5. Serpell, M., Ratcliffe, S., Hovorka, J., Schofield, M., Taylor, L., Lauder, H., & Ehler, E. (2014). A double‐blind, random- ized, placebo‐controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. European journal of pain, 18(7), 999-1012.
6. Flach, A. J. (2002). Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Transactions of the American Ophthalmological Society, 100, 215.
7. Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012). Mitigation of post‐traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug testing and analysis, 4(7-8), 649-659.
8. Dinic, J., Podolski-Renic, A., Stankovic, T., Bankovic, J., & Pesic, M. (2015). New approaches with natural product drugs for overcoming multidrug resistance in cancer. Current pharmaceutical design, 21(38), 5589-5604.
9. Babson, K. A., Sottile, J., & Morabito, D. (2017). Cannabis, cannabinoids, and sleep: a review of the literature. Current psychiatry reports, 19(4), 23.
10. Manwell, L. A., & Mallet, P. E. (2015). Comparative effects of pulmonary and parenteral 9-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats. Psychopharmacology, 232(9), 1655-1665.
11. Cannabidiol (CBD) Pre-Review Report Agenda Item 5.2. 
12. GW Pharmaceuticals. GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of Concept Study in Glioma.
13. Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V., & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends in pharmacological sciences, 30(10), 515-527.
14. Wargent, E. T., Zaibi, M. S., Silvestri, C., Hislop, D. C., Stocker, C. J., Stott, C. G., … & Cawthorne, M. A. (2013). The cannabinoid 9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & diabetes, 3(5), e68.
15. Fernández-Ruiz, J., Romero, J., & Ramos, J. A. (2015). Endocannabinoids and neurodegenerative disorders: Parkinson’s disease, Huntington’s chorea, Alzheimer’s disease, and others. In Endocannabinoids (pp. 233-259). Springer, Cham.
16. Idris, A. I., & Ralston, S. H. (2010). Cannabinoids and bone: friend or foe?. Calcified tissue international, 87(4), 285-297.
17. Hill, A. J., Weston, S. E., Jones, N. A., Smith, I., Bevan, S. A., Williamson, E. M., … & Whalley, B. J. (2010). 9‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia, 51(8), 1522-1532.
18. Steep Hill. Cannabinol (CBN): A Sleeping Synergy. 
19. Appendino, G., Gibbons, S., Giana, A., Pagani, A., Grassi, G., Stavri, M., … & Rahman, M. M. (2008). Antibacterial cannabinoids from Cannabis sativa: a structure− activity study. Journal of natural products, 71(8), 1427-1430.
20. Zygmunt, P. M., Andersson, D. A., & Högestätt, E. D. (2002). 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism. Journal of Neuroscience, 22(11), 4720-4727.
21. Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L., & Nagarkatti, M. (2009). Cannabinoids as novel anti-inflammatory drugs. Future medicinal chemistry, 1(7), 1333-1349.
22. Croxford, J. L., & Yamamura, T. (2005). Cannabinoids and the immune system: potential for the treatment of inflamma- tory diseases?. Journal of neuroimmunology, 166(1), 3-18.
23. Farrimond, J. A., Whalley, B. J., & Williams, C. M. (2012). Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology, 223(1), 117-129.
24. YOSHIDA, H., UsAMi, N., OHISHI, Y., WATANABE, K., YAMAMOTO, I., & YOSHIMURA, H. (1995). Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives. Chemical and pharmaceutical bulletin, 43(2), 335-337.
25. AXIM Biotech. AXIM Biotech Begins Human Clinical Trials with Cannabigerol (CBG) for Psoriasis and Eczema in Patients. Available at 
26. Nadolska, K., & Go , R. (2008). Possibilities of applying cannabinoids’ in the treatment of glaucoma. Klinika oczna, 110(7-9), 314-317.
27. Russo, E. B. (2008). Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management, 4(1), 245.
28. Appendino, G., Gibbons, S., Giana, A., Pagani, A., Grassi, G., Stavri, M., … & Rahman, M. M. (2008). Antibacterial cannabinoids from Cannabis sativa: a structure− activity study. Journal of natural products, 71(8), 1427-1430.
29. Borrelli, F., Fasolino, I., Romano, B., Capasso, R., Maiello, F., Coppola, D., … & Izzo, A. A. (2013). Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochemical pharmacology, 85(9), 1306-1316.
30. Granja, A. G., Carrillo-Salinas, F., Pagani, A., Gómez-Cañas, M., Negri, R., Navarrete, C., … & Calzado, M. A. (2012). A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. Journal of Neuroimmune Pharmacology, 7(4), 1002-1016.
31. Borrelli, F., Pagano, E., Romano, B., Panzera, S., Maiello, F., Coppola, D., … & Izzo, A. A. (2014). Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis, 35(12), 2787-2797.
32. Carrillo-Salinas, F. J., Navarrete, C., Mecha, M., Feliú, A., Collado, J. A., Cantarero, I., … & Guaza, C. (2014). A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis. PloS one, 9(4), e94733.
33. Brierley, D. I., Samuels, J., Duncan, M., Whalley, B. J., & Williams, C. M. (2016). Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology, 233(19-20), 3603-3613.
34. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L., … & Di Marzo, V. (2006). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Journal of Pharmacology and Experimental Therapeutics, 318(3), 1375-1387.
35. Maione, S., Piscitelli, F., Gatta, L., Vita, D., De Petrocellis, L., Palazzo, E., … & Di Marzo, V. (2011). Non‐psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. British journal of pharmacology, 162(3), 584-596.
36. DeLong, G. T., Wolf, C. E., Poklis, A., & Lichtman, A. H. (2010). Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by 9-tetrahydrocannabinol. Drug & Alcohol Dependence, 112(1), 126-133.
37. Oláh, A., Markovics, A., Szabó‐Papp, J., Szabó, P. T., Stott, C., Zouboulis, C. C., & Bíró, T. (2016). Differential effectiveness of selected non‐psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment. Experimental dermatology, 25(9), 701-707.
38. El-Alfy, A. T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., … & Ross, S. (2010). Antidepressant-like effect of 9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology Biochemistry and Behavior, 95(4), 434-442.

How Cannabis Works to Control Pain and Anxiety

Image result for the limbic system

The Limbic System

Cannabis is well known as a herbal painkiller, but is also increasingly being used in other conditions involving the limbic system, sometimes referred to as the mid or so-called reptilian brain. So, just how does Cannabis cause these effects? Cannabis contains over 500 compounds, 80 of which are cannabinoids. Many of these compounds have medicinal value and research continues to provide more knowledge about how they work. The medicinal effects of Cannabis are mediated by the Endocannabinoid System (ECS). The system includes two neurotransmitters (anandamide and 2AG) two receptors (CB1 and CB2) and two enzymes (MAGL and FAAH). The ECS is responsible for modulating neurotransmission and cannabinoids regulate the ECS. There are two types of cannabinoids, those produced by the human body, endogenous cannabinoids, and those sourced from the Cannabis plant, the phytocannabinoids. An increase in cannabinoids, either endogenous or phyto, increases the amount of the neurotransmitter dopamine to the brain.


Cannabinoids work differently to any other neurotransmitter. Instead of stimulating the next neuron on the pathway up the central nervous system, endocannabinoids actually double back to the presynaptic neuron from the post synaptic neuron they just stimulated and de-polarise the pre-synaptic neuron. This is referred to as retrograde inhibition. This depolarisation of the pre-synaptic neuron occurs by causing release of dopamine, which reverses the concentration of sodium and potassium inside and outside the cell. This depolarisation makes it harder for the pre-synaptic neuron to be stimulated by the next neural impulse being transmitted by the nervous system. The effect of this is a slowing down of neurotransmission which is ideal in pain management and control.

Image result for retrograde inhibition

Endocannabinoid Retrograde Inhibition

Migraines are caused by an overload of the electrical circuits in a certain part of the brain, so slowing down the speed of neurotransmission leads to fewer neural impulses. This in turn decreases the likelihood or severity of a migraine. That is not the only effect, CaImage result for reptilian brainnnabis is an anti-nauseant as well, but probably exerts that effect in some other manner. The same thing is true of people who have panic attacks, if the negative thoughts are moving to the brain at warp speed, the limbic system (emotional control centre of the brain), is overwhelmed and there is little or no time for the frontal cortex to override the more primitive mid or reptilian brain. This makes us more likely to act before we think. That is because the reptilian brain sees things in terms of black and white, life and death. This mechanism may have served our ancestors well in the time of sabre-toothed tigers, but in modern day it is more often not very helpful. Much in modern life is shades of grey and more nuanced than life and death.

Cannabis slows down the speed of neurotransmission, exposing the cerebral cortex to fewer slower moving neural stimuli. This allows the higher centres of the brain to more rationally assess relative danger or the negativity and put a more rational point of view on that sensory input, often taking the edge off anxiety or preventing a panic attack. In medical school, doctors are taught 70% of the brain exists to turn off the other 30%. Dopamine is one of the “off switches” that helps modulate sensory input. One suggestion is that Cannabis and cannabinoids increase the amount of free dopamine in the brain by preventing the dopamine from binding to another neurochemical dopamine transporter. The transporter and dopamine form an electrochemical bond that ties up the dopamine so that it is not free to act as an “off switch”. These cannabinoids replace the dopamine and the amount of free dopamine available to depolarise the presynaptic neuron also increases.


And that’s just pain and anxiety. There are a host of conditions that appear to be tied to an endocannabinoid deficiency syndrome that has been postulated by such scientists as pharmacologist Danielle Piomelli, PhD and neurologist, Ethan Russo, MD. The possible cause of an endocannabinoid deficiency syndrome is most likely genetic and due to the fact that most, if not all, human characteristics are distributed on a bell shaped curve – some of us have less of the constituents of the ECS and some have more. It is not clear that is the explanation or the only explanation for Clinical Endocannabinoid Deficiency  (CECD), however, if there is a lower amount of free dopamine present in the brain, neural impulses will likely move more rapidly.

Image result for endocannabinoid deficiency syndrome

This mechanism of slowing the speed of neurotransmission, retrograde inhibition, contributes to the treatment of many conditions that respond to cannabinoids and Cannabis. Cannabinoids compete with dopamine for the binding sites on the dopamine transporter, and in sufficient quantity they win, which frees up more dopamine to slow down the speed of neurotransmissions. This, according to many cannabinoid researchers, is responsible for much of the therapeutic value of Cannabis in such conditions as migraines, seizure disorder, ADD, ADHD, Crohn’s disease, Irritable Bowel Syndrome (IBS), Social Anxiety and Autism Spectrum Disorder, to name some of the more obvious.

Adapted from How Cannabis Works to Control Pain and Anxiety by Dr David Bearman, with Granny Storm Crow’s List and Hemp Edification


Neuroprotective Properties of Cannabinoids

Cannabis was considered medicine for thousands of years and only over the last eighty years has it been stigmatised as a ‘drug of abuse’. Thanks to countless scientists and their curiosity we now understand that the compounds in cannabis interact directly with a widespread and complex system named the Endocannabinoid System (ECS), which works to maintain homoeostasis (equilibrium) within our brains and bodies. Almost every physiologic process in the human body is affected by the ECS including our natural protective response to injury and inflammation.

11The ECS was discovered as a result of scientists searching for the mechanism of action of tetrahydrocannabinol (THC). Working as a ‘key and lock’ mechanism, cannabinoid receptors (the ‘locks’) that sit in the cell membrane are activated by ‘key’ chemical compounds. The keys include endocannabinoids, compounds that we make internally, phytocannabinoids, compounds made by the cannabis plant and laboratory-derived synthetic cannabinoids, used mostly in research. When the cannabinoid activates the receptor by binding to it, a chemical reaction takes place in the cell, telling the cell to change its message.  For instance, if a person suffering from pain uses cannabis medicine, pain is often minimised or eliminated.  This happens because the brain cell alters the perception of pain in response to the activation of the cannabinoid receptor by the cannabinoids, which in turn tells the cell to stop sending the message of pain. Knowing where cannabinoid receptors are located allows us to understand the conditions that cannabis medicine can affect. In the brain the receptors are located in areas that control pain, nausea, vomiting, learning, stress, memory, appetite, motor coordination and higher cognitive function. In the body, cannabinoid receptors are mostly located in the gut, immune system and liver and are largely involved in regulation of inflammation.

rsz-history-of-endocannabinoid-systemWhen there is a traumatic brain injury (TBI), damage from the initial insult occurs followed by a number of secondary damage mechanisms. Injured brain cells release a neurotransmitter called glutamate, which is toxic to cells when it accumulates. This over-abundance of glutamate leads to a cascade of chemical reactions that produce even more compounds that further damage the brain. Brain injury also causes the release of chemicals that cause blood vessels to constrict, decreasing blood flow that leads to cell energy loss and cell death. Brain inflammation is triggered within hours of injury and adds to the massive destruction of brain cells. These multiple mechanisms that harm brain cells are the reasons why TBI is so difficult to treat. We need treatment that will address all of the different mechanisms, glutamate accumulation, decreased blood flow and inflammation, taking place in the injured brain.

Image result for thc and cbd

Cannabis’ two major cannabinoids, THC (tetrahydrocannabinol) and CBD (cannabidiol) are responsible for the beneficial effects following TBI’s. Cannabinoids have been shown to act on the CB1 and CB2 receptors of the ECS, which in turn prevents release of pro-inflammatory cytokines after brain trauma. Activating the CB1 and CB2 receptors has been shown to stimulate the release of minocycline, which reduces brain swelling and neurological impairment and diffuses further injuries to the brain’s axons. Research shows that the ECS is activated immediately after injury. Endocannabinoids block the release of compounds that cause secondary damage to brain cells. 

Endocannabinoids have been found to decrease intensity and duration of toxicity to brain cells and enhance brain cell survival after injury. Endocannabinoids are anti-inflammatory and antioxidant, so simply put, your brain makes self-protective endocannabinoids in response to injury with the goal of minimising cell damage and death in a multitude of ways. As both synthetic and plant cannabinoids mimic our endocannabinoids, researchers have investigated them to see if they can provide neuroprotection for TBI with promising results. From the 2004 study, Cannabinoids as neuroprotective agents in traumatic brain injury;

“Cannabinoids of all classes have the ability to protect neurons from a variety of insults that are believed to underlie delayed neuronal death after traumatic brain injury (TBI), including excitotoxicity, calcium influx, free radical formation and neuro-inflammation. The pathways and experimental models supporting a neuroprotective role for the various classes of cannabinoids are critically reviewed vis a vis their potential to support the development of a clinically viable neuroprotective agent for human TBI”.

Brain Injury
This flow chart outlines the pathway of secondary damage from brain injury and the modulation of the resulting outcome via endocannabinoids. Negative signs correspond to a decrease in the respective effect, whereas positive signs correspond to an increase.

In a three-year retrospective reviewEffect of Marijuana* Use on Outcomes in Traumatic Brain Injury (2014), adult patients presenting with TBI to a trauma centre with a positive THC screen at the time of TBI had decreased risk of death; 2.4% versus 11.5% for those who tested negative for THC. The three-year retrospective review of 446 separate cases of similarly injured patients highlighted to researchers that TBI patients who had a history of cannabis consumption possessed increased survival rates compared to non-consumers (97.6% survived surgery, versus 88.5% of those who didn’t consume cannabis).

“Our data suggest an important link between the presence of a positive THC screen and improved survival after TBI”, the researchers concluded. “With continued research, more information will be uncovered regarding the therapeutic potential of THC and further therapeutic interventions may be established”.

Many studies highlight the incredible neuroprotective role of cannabinoids. While effective therapies to treat ongoing TBI symptoms have been difficult to come by, thanks to researchers like Professor Yosef Sarne of Tel Aviv University, we’ve discovered Cannabis may prevent long-term brain damage by administering THC before or shortly after injury. Sarne and his team published their results in 2013, demonstrating that administering just a fraction of the amount of THC that would be found in a typical cannabis joint anywhere from one to seven days prior to, or one to three days after an injury, induces the biochemical processes necessary to protect critical brain cells while preserving long-term cognitive function.

Clinicians in jurisdictions where cannabis medicine is recognised and appreciated, see many patients struggling to recover from TBI and can attest that cannabis medicine has profound positive effects. Patients report restorative sleep, emotional balance and an overall sense of well-being with cannabis. Many report discontinuation of ineffective pharmaceutical medications that cause a multitude of unwanted and sometimes dangerous side effects. That being said, clinical trials using plant cannabinoids during the acute phase of injury are warranted. TBI patients should not have to suffer for months or years after the injury to reap the neuroprotective, antioxidant and anti-inflammatory benefits of cannabis. Researchers and clinicians need to be free to study cannabis compounds and dosing in humans so that with early treatment, we can minimise and likely prevent the devastating consequences of TBI.

, is a physician who specialises in cannabis medicine in Los Angeles, California. She specialised in Paediatric Emergency medicine for years before witnessing the amazing benefits of this treatment in an ill loved one. Since then, she has successfully treated thousands of adult and paediatric patients with cannabis. She regularly speaks about cannabis medicine at conferences and patient groups around the world. She is the owner and medical director of CannaCenters and medical advisor to
*Cannabis sativa L., is the correct botanical term, marijuana is a North American colloquialism


RDT – Maximising Harm, Australia-wide

rdt2In January 2016, an eminent Australian barrister discussed issues raised when a person driving a motor vehicle is roadside tested and found positive for ingestion of cannabis. The opinion alluded to the extension of this legislation to future Australian medical patients who, having reasonably and lawfully ingested cannabis as part of their pharmacotherapy, will inevitably face the same legal standards as those who have ingested cannabis ‘recreationally’. Furthermore, the opinion claimed the underlying drug1-driving laws are grossly unfair and not based on data or scientific knowledge. This opinion called into question not only the fairness of the laws, but the very evidence supporting the roadside drug testing procedures, based on testing of saliva/oral fluid that underpin present laws.

Fundamental pharmacological principles propose a drug effect will be related in a graded response to dose, up to a maximum effect. After administration the dose eventually brings to equilibrium (not equalises) throughout body fluids and tissues. The degree of dilution in the body is reflected in drug blood concentrations. The pharmacological effects are reflected in the relevant drug (or metabolite) concentrations in the receptor-containing site of action, the ‘biophase’. After equilibration, sampled biofluid concentrations (blood, plasma or serum2) can act as a proxy for those in the biophase and thereby allow greater insight into responses than can be gained from dose alone.


The intrinsic variability in how the body handles a drug becomes magnified by unpredictability in the rate and extent of systemic absorption associated with the mode of administration. This is typically referred to as pharmacokinetic variability (what the body does to a drug in a quantitative sense). The relationship between dose and resultant time-course of biofluid (particularly blood) drug concentrations can be complex and such concentrations are the primary determinants of drug effects. Moreover, the same drug doses, or biofluid drug concentrations, do not necessarily produce the same levels of pharmacological effects. This is referred to as pharmacodynamic variability (what a drug does to the body in a quantitative sense) and is typically reflected by drug concentrations associated with the same effects differing between individuals and even within individuals.

tetrahydrocannabinolCannabis, being a natural plant product, consists of many hundreds of phytochemical substances, some with chemical structures recognisably similar to ∆9-tetrahydrocannabinol (THC). These are collectively referred to as cannabinoids and many are active, pharmacologically. Both the actual and relative amounts of these substances vary with many influences, including strain of the plant, parts harvested and methods of processing. THC is the most studied substance, being recognised as having a variety of salutary pharmacological effects and being the principal neuro-active substance in cannabis. Many other phytocannabinoids, such as the acid precursors of THC (THCa) and Cannabidiol (CBDa), Cannabigerol (CBG) and Cannabidivarin (CBDv) for example, are currently under investigation for possible pharmacotherapeutic uses. Cannabis also contains several hundred non-cannabinoid substances, with many contributing to the therapeutic and other pharmacological effects attributable to cannabis (terpenes, for example). 

rdtMany laboratory research studies of cannabis determine biofluid concentrations of THC after ingestion. These typically show marked variability of the biofluid (blood) THC concentration-time profiles despite apparently the same experimental conditions. Controlled laboratory research studies performed in healthy volunteer subjects who used cannabis for purported recreational purposes found a reasonably consistent ‘impairment relationship’. However, the same conclusions have not been well supported from opportunistic studies performed by the comparison of fatal and non-fatal road traffic crashes where;

“Equating impairment to blood cannabinoid concentrations is not straightforward: a clear dose-response relationship has not been established, unlike for alcohol. The pharmacology of cannabis makes it difficult to interpret cannabinoid concentrations, both in life and in post-mortem blood samples”.

rdt3It is argued the principle of using oral fluid for cannabis (THC) testing is problematic. Oral fluid is not a ‘body fluid pool’  such as blood that contains drug concentrations in equilibrium with those in the biophase. Whereas blood provides a reasonable proxy for the pharmacological effects of cannabis (particularly THC), oral fluid THC concentrations may be associative with, but are not causative of, the pharmacological effects attributed to THC. Oral fluid is useful for supposing the past ingestion of a drug, but has reliability limitations in predicting the acute pharmacological effects of a drug. However, its usefulness was found to be more limited than anticipated, mainly due to unpredictable inter- and intra-individual variability. Saliva sampling was largely abandoned in pharmacotherapy research only to become progressively re-introduced over the past decade by the forensic quest for a convenient, non-invasive sampling matrix to test for ‘drugs of abuse.

drugsinbloodWith some notable exceptions (anti-coagulants for example), drugs rarely act by being in the blood. The blood ‘pool’ acts as a conduit for drug delivery to, and removal from, the tissues, including the biophase. The important point is drugs typically distribute between blood, serum or plasma, blood cells and tissues, in a rational manner so sample-able blood drug concentration measurements may be used as a reasonable proxy for biophase concentrations and thus pharmacological effects. Oral fluid is not a body ‘pool’ with an anatomically defined distribution and the oral fluid concentrations of drugs need bear no rational relationship to the amount of that substance present in the body; moreover, unlike drug blood concentrations, they do not have an intrinsic role in driving the attributed pharmacological effect.

Image result for transpulmonary vaporization of cannabisRoadside testing for cannabis (THC) ought to be capable of providing a useful predictor of diminished performance, rather than evidence of ingestion alone. Although blood concentrations of a drug can be useful proxies for the relevant biophase concentrations, with modes of rapid systemic delivery (transpulmonary, i.e., inhaled into lungs), there is often a marked and highly variable mismatch (hysteresis) between the times-courses of drug effects and the blood concentrations until equilibration occurs. Hysteresis depends on many factors, including how and when blood sampling is performed, as well as the properties of a drug. Hysteresis complicates the interpretation of effects from measured drug biofluid concentrations alone, mainly in the first several hours after drug ingestion. Thereafter, the time course of drug, blood and effect occur essentially in parallel (pseudo-equilibrium). The maximum measured biofluid drug concentration (Cmax) is the most obviously affected metric, often occurring at a time well different to the maximum drug effect (Emax). Various pharmacokinetic-pharmacodynamic models have been proposed to account for this observation and some have been proposed for THC, but it seems none have been developed specifically for THC and driving impairment.


All Australian states and territories have instituted roadside (and certain workplace) oral fluid testing for methamphetamine, methylenedioxy-methamphetamine (MDMA) and THC, based upon Australian Standard (AS) 4760-2006, ‘Procedures for specimen collection and the detection and quantitation of drugs in oral fluid’. However, the National Association of Testing Authorities (NATA) Australia (established to ensure compliance with international and Australian standards) dismissed the flawed 2006 oral fluid standard for on-site testing. Regardless of NATA raising the alarm at a FACTA Symposium in 2010 and a five-year rule review due in 2011, Standards Australia have done absolutely nothing to fix their faulty standard, still being sold as if in perfect working order by the likes of SAI Global (risk management, standards compliance and information business). A dubious practice from a standard-setting body, a damning demonstration of neglect and failure to deliver ethical and credible standards and a far cry from Standards Australias official Code of Conduct. In July 2013, accreditation of on-site drug testing of oral fluid (AS 4760, Section 3) was suspended by NATA due to significant technical issues with the standard.

drager-drugtest5000-640x640Though the portable drug testing device – the Dräger DrugTest® 5000 – is capable of testing for all sorts of drugs, including cocaine, prescription painkillers and benzodiazepines, current operating procedure is to only test for cannabis, methamphetamine and MDMA. “Someone can be pulled over on a roadside drug test, be literally drugged up to their eyeballs on cocaine and benzo’s, administer the test and be given the all clear to drive”, said New South Wales (NSW) Greens MP, David Shoebridge, in April 2016. “The police will literally wave you through. How is that a rational road safety campaign? These classes of drugs can already be picked up by the existing Dräger 5000 equipment, they just choose not to”, he said. The NSW Minister for Roads, Maritime and Freight claimed the current mobile drug testing cannot detect cocaine. “The technology does not allow for it”, he said in Parliament, in February 2016. He also said police can however require anyone suspected of a cocaine or benzo impairment to undergo a blood and urine test, and they do. “Let me be very clear that these drivers on cocaine or other drugs will not go undetected or unpunished regardless of where they are from”, he said. However, the Dräger Australia & New Zealand website quite clearly states that the system detects a variety of substances such as;

  • Amphetamines
  • Benzodiazepines
  • ∆9-tetrahydrocannabinol (THC)
  • Cocaine
  • Methamphetamines
  • Opiates
  • Methadone
  • Ketamine

Image result for benzodiazepinesDuring the 2013 Australasian Road Safety Research, Policing and Education Conference it was noted that approximately 30% of road deaths are associated with drivers having an illegal blood alcohol concentration (BAC), with evidence over the past decade this proportion has increased. Alcohol contributes to the three major causes of teen death: injury, homicide and suicide. Data from the Coroners Court of Victoria listed the main drugs that contributed to drug-related deaths in 2009–15. Analysis of the data revealed pharmaceuticals contributed to 80% of overdose deaths; benzodiazepines and opioids were the main drug groups involved. Drug overdose deaths rose for a fifth consecutive year in 2016, led by addictive medications such as benzodiazepines, linked to more drug deaths than illegal drugs. In 2015 in Australia, almost twice as many overdose deaths were linked to legal prescription medication, compared to illegal drugs.

The United Kingdom (UK) implemented new drug driving legislation based on a 2013 report by Professor Kim Wolff (Addiction Science, King’s College, London) and a panel of experts, Driving Under the Influence of Drugs, which states;

“Contamination of the buccal (oral) cavity is an issue for the detection of cannabis use since the drug is often used by oral, intra‐nasal or smoking routes of administration (insufflations). ‘Shallow depots’ of cannabis may, following recent use, accumulate in the buccal cavity and produce elevated concentrations in oral fluid for several hours after ingestion. Unfortunately, the cannabinoids do not pass readily from blood into saliva and the detection of … THC in oral fluid is largely reported to be due to contamination of the oral cavity following smoking”.


Professor Wolff blogged that they know a great deal about patterns of use concerning cocaine. Its acute effects and “come down” are well described in relation to the deleterious effects on driving behaviour. With regard to drivers consuming benzodiazepines, research has shown that use leads to increased risk of motor vehicle accidents. Specific scientific evidence has been published citing road traffic effects for a raft of different benzodiazepines. The risk of RTA following benzodiazepine use has been demonstrated in several studies in both older and young population groups, estimated to increase the risk of having an accident by 62% compared with non‐use.  Analysis of benzodiazepines by half‐life revealed that those with a long half‐life were associated with an increased risk of RTA; anxiolytics and hypnotics for example, suggesting a greater need for attention to driver‐safety for long acting anxiolytics (temazepam and nitrazepam).


Critics claim Shoebridge and his ilk are making mountains out of molehills, and that anyone who agrees must be living comfortably in the pocket of the “pro-drugs” lobby. But even the most casual, illicit-drug takers have cause to be concerned if they are unable to measure their own ‘body purity’ before getting behind the wheel – the potential for having their lives ruined despite representing no enhanced threat to road safety is very real. The only current option to ensure you’re safe from mobile drug testing is don’t take any illegal drugs or don’t drive, which is not necessarily the most realistic approach to drug safety on the roads. 

r0_56_1080_663_w1200_h678_fmaxShoebridge described NSW state roadside drug testing operations as a highly politicised “zero tolerance extension on the war on drugs dressed up as road safetyIt’s a class war”. Shoebridge maintains cocaine, benzo’s and prescription painkillers are “middle to upper class drugs” which police and politicians are reticent to prosecute on. “There are people driving on our roads with enormously high levels of these drugs in their system and nobody is checking” he said. The Australian Institute of Health and Welfare’s 2013 National Drug Strategy Household Survey reported use of such as cannabis, ecstasy and methamphetamine have been on the decline since 2004 while the proportion of people using cocaine has been increasing since the same year, particularly those aged between 20 to 39 years. “Cocaine use in Australia is currently at the highest levels yet seen”, the report said.

Image result for pharmaceutical benefits schemeAround 80% of all prescription drugs dispensed in Australia are subsidised by the taxpayer funded Pharmaceutical Benefits Scheme (PBS, in existence since 1948). Close to seven million prescriptions for benzodiazepines are dispensed in Australia each year under this scheme and their main indications for use are short-term treatment of anxiety and insomnia. However, such high rates of ongoing benzodiazepine prescribing indicate it is used for long-term problems. This is of concern given evidence of its association with addiction, overdose and other harms such as falls in the elderly and motor vehicle accidents. Benzodiazepines were reported to be the second most commonly misused class of medications, after analgesics, in the 2013 Australian Institute of Health and Welfare, National Drug Strategy Household Survey report. Diazepam, the most commonly prescribed benzodiazepine, is also the most common benzodiazepine found at post-mortem.

“When people are getting false and misleading information from authoritative government sources and rely upon that in their decision making, they fail the test, land up in front of a magistrate, then what more can you do to argue against a genuine mistake of fact?” Shoebridge said. “It’s an enormous problem for police”. There have already been court-cases where these issues were raised, with adjourned cases and judgements NSW police are looking to challenge. The drug testing operation (in NSW) was a $6 million government tender over four years to 2018, just for the devices. On top are costs for drug testing vehicles, police man hours roadside and in court, the magistrate, a police prosecutor and court costs. The cost to tax-payers ranges into even more millions of dollars. “What would be really useful is if NSW police lifted their eyes above their navel and get the international evidence on this growing body of research”, Shoebridge said.

Image result for NSW police lifted their eyes above their navel and get the international evidence on this growing body of research

It’s now generally well-known the devices used by police don’t test for levels that have been proven to cause driver impairment, as breathalysers do for alcohol. Rather, drug testing devices detect tiny trace elements of just three illicit substances, one of which is THC. The Northern Rivers region has been the epicentre of the NSW police blitz on roadside drug testing over the past year (in Queensland, testing has also tripled in both urban and regional areas). Local courthouses, in particular the Lismore Courthouse, have been overwhelmed hearing cases of this type. Michael Balderstone, President of the Nimbin HEMP Embassy has been campaigning for the legalisation of the plant for the last 30 years. Michael is also President of the Australian HEMP Party. He ran as the Western Australian candidate for the party in the 2016 federal election with the aim to “re-legalise and regulate personal, medical and industrial use” of cannabis.

HEMP Party

In an interview in December 2016, Michael was asked about the blitz on roadside drug testing in the Northern Rivers region, what’s happening in the local area and the effect on the community. He replied that it has had a huge effect on the whole of the Northern Rivers community now, for at least a year. “People are regularly getting bust[ed] … it seems that the first test is really unreliable. So there’s no guarantees how efficient it is. And once you’ve registered positive on the first test you’re stuffed … the second test … they send to a lab – 98% … have come back positive. It picks up a tiny trace of pot. You might have smoked a joint two weeks before, or a month before. Or been in a room with your old man smoking. Once you go down on the first test, you’re history”. He went on to say, “We’ve got more car accidents than ever up here. The road tolls up. I can’t say it’s contributed. But it certainly isn’t helping. I know a lot of people who don’t smoke now during the day and they’re much more anxious. They’re worse drivers. If you do smoke, you’re terrified if you see a cop. So I actually think it’s contributed to more anxiety”.

Image result for National Road Safety Strategy australia

The National Road Safety Strategy, established to reduce road deaths and injuries by 30% over ten years, was running around four years behind in some states, the Australian Automobile Association’s last report, released September 2016, stated. The ‘Benchmarking the Performance of the National Road Safety Strategy’ report showed there were 1,273 fatalities on Australian roads in the year to September 2016, an increase from 1,187 a year earlier. It also showed some states are years behind in achieving the targeted lower numbers of road deaths. “The NRSS, signed by all Australian governments, aims to reduce the number of road deaths and serious injuries by at least 30% between 2011 and 2020” AAA Chief Executive Michael Bradley said. “Despite progress in the first few years, we are again seeing increased fatalities on our roads”. Bradley estimated around 626 Australians are seriously injured each week, but without proper national data, it is impossible to know for sure. 

Image result for oral fluid drug concentration measure

An oral fluid drug concentration measure is not causative of any pharmacological effect; it may correlate with some pharmacological effect, but then again it may not. A blood, plasma or serum measure would present a more reasonable case, if calibrated to exclude the lower portions of the dose-response relationship where uncertainty is greatest. Moreover, various reports indicate that even among seasoned ‘recreational’ users, most have insight as to their degree of mental impairment and would judge their ability to drive accordingly. Medical patients reportedly achieve the desired effects to live a normal life and to meet their social obligations.

Public safety is often cited as the reason behind drug driving laws – but many have expressed the view that if that were the case, minimum concentration levels would be prescribed – like the low, mid and high range prescribed concentrations for drink driving charges – rather than charging people for minute quantities which cannot affect driving ability. Such a regime, it is argued, would represent a fairer system – punishing those with very high concentrations – rather than putting everyone on the same boat. But rather than adopt an ‘evidence based’ approach, the NSW Minister for Roads, Maritime and Freight indicated in the first quarter of 2016 that NSW would be targetting all so-called drug drivers;

“The simple message every driver needs to hear from this campaign is that if you take drugs and drive, the boys in blue are going to catch you … We’re throwing millions at enforcement, dedicated drug testing vehicles and campaigns from our Community Road Safety Fund to eradicate and anti-socialise drug driving”.

While it is claimed that illicit drug use is a major factor in road accidents, current legislation does not differentiate between drivers with a level of drugs in their system capable of affecting driving ability, and those who are found with miniscule amounts long after the effects have worn off. It is hoped that the government will ultimately see sense and formulate a fairer approach which prescribes minimum levels, like in the UK and other countries, thereby promoting road safety rather than unfairly sending large numbers of guiltless people to court.

Expanded from Griffith Journal of Law & Human Dignity – The Issue Of Driving While A Relevant Drug, Δ9-Tetrahydrocannabinol, Was Present In Saliva: Evidence About The Evidence, with Drug Policy Implications of Inhaled Cannabis: Driving Skills and Psychoactive Effects, Vaporized Pharmacokinetic Disposition, and Interactions with AlcoholSmoked Cannabis’ Psychomotor and Neurocognitive Effects in Occasional and Frequent SmokersPopulation Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short-and Long-Term PharmacokineticsDrug Testing Today – Australian SubStandards, Current Therapeutic Cannabis Controversies and Clinical Trial Design IssuesAustralia is Falling Years Behind on Reducing the Road Death TollAustralian guidelines to reduce health risks from drinking alcoholNational Drug Strategy Household Survey detailed report 2013Legalise It: An interview with Australian Hemp Party President Michael BalderstoneADF Quick Statistics – CocaineADF Quick Statistics – Benzodiazepines, An analysis of single-vehicle fatality crashes in Australia at various Blood Alcohol Concentrations, Prescription drugs led by Valium linked to more deaths than heroin and alcohol, Prescription drug abuse – A timely update, and Magistrate Slams Police for Misadvising About Drug Driving

  1. A drug is designed to produce a specific reaction inside the body as opposed to a medicine, which is a substance designed to prevent or treat diseases. While there is considerable overlap between the two types of substances, these differences are quite important. Most of the medicines that are also drugs are considered “controlled substances”. This means laws govern their use and using them in ways contrary to those laws can lead to criminal charges. Antidepressants are drugs, in that they are designed to help alleviate the physical symptoms of depression. However, they are also used in the treatment of the chemical imbalance that purportedly leads to depression, so also a medicine. Cocaine, on the other hand, is a drug designed to create a specific mental reaction that leads to a “high” for the user. However, the medical establishment does not recognise any medical benefits for cocaine at this time. Over-the-counter anti-inflammatory medicines are designed to treat pain, but they do not have a strong enough effect to fit into a controlled substance classification, unlike stronger pain relievers. This means these are medicines rather than drugs. Understanding the similarities and differences between drugs and medicines is an important part of medical and pharmaceutical training. The very reasons Cannabis is NOT a drug, it is a herb, nor is it a toxin, narcotic nor hallucinogen.
  2. Plasma and serum are cell-free portions of blood. Measured ‘drug’ concentrations within a defined blood specimen may differ quite markedly depending upon the extent of distribution into the blood cells and its affinity for the various proteins dissolved in the cell-free phase. In the case of THC, the blood concentration is nearly one half the corresponding plasma or serum concentration due to minimal uptake of THC into the blood cells. Serum is similar to blood but with clotting-factors removed. This pharmacological minutia affects many quantitative aspects of pharmacology. The various measures are used in particular contexts, unless required for such context, the general term ‘blood’ is used.

back to top