There are two different ways to produce cannabis compounds – either through the traditional grow method which yields phytocannabinoids or from the lab which yields synthetic cannabinoids. The exception to the former is of course the recent production of cannabinoids from microorganisms like yeast; here, we will consider these biosynthetic cannabinoids.
Synthetic compounds created for medicinal purposes are nothing new to the cannabis industry. In fact, the FDA approved dronabinol (Marinol) and nabilone (Cesamet) for chemotherapy-induced nausea and vomiting in 1985 and added an indicated for dronabinol in 1992 for HIV-associated anorexia. Outside the US, Sativex has been approved for multiple sclerosis-related symptoms.1
Despite interest in synthetic methods for cannabinoids production, the traditional cultivation method is still greatly preferred by consumers. Therefore, it is important to understand how each method differs across cost, efficacy and safety, and other factors that will ultimately influence the final product.
Specificity of Action
Cannabis has been used for thousands of years across different cultures for various purposes, largely in whole-plant form. The modern industry however is creating extracts from the plant to isolate cannabinoids and create tailored products, a popular example being cannabidiol (CBD) oil. But, just like other hundreds of compounds in the plant, CBD has a “promiscuous” mechanism of action. In addition to impacting the cannabinoid 1 and 2 receptors, it also affects serotonin, TRPV1 (which modulates pain), and many other receptors.2 These physiological effects can be both viewed as beneficial, should one be using cannabinoids to treat a number of ailments, or disadvantageous if one wished to use a cannabinoid for a very specific purpose.
In general, lab-made compounds allow scientists to modify the structure of molecules with the goal of targeting one pathway in the body to address one condition. This method follows the traditional pharmaceutical pathway and is the way regulatory bodies like the FDA expect compounds to be tested for approval.3 One major exception to this rule is of course the most recently approved cannabidiol-based therapy for pediatric epileptic conditions, Epidiolex, which was evaluated in clinical trials but is not a synthetic compound.1
Potential Benefits and Harms
For patients and physicians, the most important aspect of medical cannabinoids is their effectiveness for a particular ailment. While there is not a plethora of available data on the subject, some studies have indicated that phytocannabinoids may confer an efficacy advantage over synthetics for some conditions.4
In addition, while cannabinoids certainly carry some risks, mostly due to drug-drug interactions (which are similar to most FDA-approved drugs on the market) and potential effects on mental health conditions like schizophrenia, it’s relatively safe.5,6 To this day, no one has ever died from cannabis consumption. On the other hand, people have had serious adverse reactions from compounds that affect the cannabinoid system.
A well-known case involves a synthetic compound called BIA 10-2474 tested in clinical trials in France for pain relief. The clinical trial was terminated after 1 person died and 4 were injured.7 This case was a bit complicated due to the protocol used and mishandling of events, but it does demonstrate the potential safety issues that can result from modifying cannabinoids in the lab. A similar safety incident resulted in a compound called rimonabant (approved outside of the US), meant to help people lose weight, being taken off the market due to increased risk of mental disorders and suicide.1
Cost Implications
While it may seem as though synthetic compound production is far more cost effective than traditional grow methods, it’s actually just the opposite. Traditional medicinal chemistry takes years to identify suitable compounds. Once a favorable compound is developed, it must still undergo years of pre-clinical testing.8 There are also considerable costs associated with securing IP rights.9 Let’s be perfectly blunt – big pharma prefers synthetics for IP and monetary reasons apart from any client considerations.
On the traditional grow side, producers can either opt for outdoor or indoor production. While these are not cheap endeavors, these methods allow for, in most cases, a standard growth and harvest cycle, followed by extraction and testing.
Environmental Impact
Labs produce significant hazardous waste, which accumulates with every failed experiment. While there are safety protocols put in place, manufacturing facilities will inevitably leak contaminants into the environment, which is particularly damaging for the water supply.10
Traditional growing also can take its toll. However, both hemp and cannabis are known bioaccumulators, removing heavy metals from the soil (a good reminder of the importance of thoroughly testing your products). Outdoor growing also requires large amounts of water and indoor grows demand a lot of electricity.
Consumer Preference
Many consumers who have been using cannabinoids for decades often view synthetic cannabinoids negatively. Some are wary of the motivation of pharmaceutical companies and others may feel that there’s no reason why phytocannabinoids need to be optimized at all.11
All medicines essentially come from nature in some form. Botanical-based products line pharmacy shelves and medicine cabinets across the world. Aspirin, for example, a very commonly used pain-relieving drug, is derived from willow bark. However, to optimize physiological aspects and scale up production, a synthetic compound based on the bark extract was developed that we now know as aspirin.12
Takeaway
The cannabis industry is still in its infancy but the production techniques we have at our disposal are quite numerous. So, whatever approach you decide to take, weigh the pros and cons, and make sure you are meeting your consumers’ needs.
References
- Papaseit E, Pérez-Mañá C, Pérez-Acevedo AP, et al. Cannabinoids: from pot to lab. Int J Med Sci. 2018;15(12):1286-1295.
- De Gregorio D, McLaughlin RJ, Posa L, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160(1):136-150.
- Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162(6):1239-1249.
- Myers AM, Siegele PB, Foss JD, Tuma RF, Ward SJ. Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. Br J Pharmacol. 2019;176(10):1552-1567.
- Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ. 2020;192(9):E206.
- Patel S, Khan S, M S, Hamid P. The association between cannabis use and schizophrenia: causative or curative? A systematic review. Cureus. 2020;12(7):e9309.
- Enserink M. “French company bungled clinical trial that led to a death and illness, report says.” Science Insider. Available at: https://www.science.org/content/article/french-company-bungled-clinical-trial-led-death-and-illness-report-says
- Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009-2018. JAMA. 2020;323(9):844-853.
- Saha CN, Bhattacharya S. Intellectual property rights: An overview and implications in pharmaceutical industry. J Adv Pharm Technol Res. 2011;2(2):88-93.
- Nawrat “Pharma and the environment: pollution continues despite public pressure.” Pharmaceutical Technology. Available at: https://www.pharmaceutical-technology.com/features/pharma-and-the-environment-pollution-trend/
- Zheng Z, Fiddes K, Yang L. A narrative review on environmental impacts of cannabis cultivation. J Cannabis Res. 2021:3:35.
- Desborough MJR, Keeling DM. The aspirin story – from willow to wonder drug. Br J Haematol. 2017;177(5):674-683.