What is a cannabinoid from a biochemical point of view?
A cannabinoid is a lipophilic molecule capable of interacting with the endocannabinoid system (ECS). Chemically, it is generally a compound derived from a terpene-phenolic ring.
Cannabinoids can be:
Phytocannabinoids (derived from the hemp plant)
Endocannabinoids (naturally produced by the body, such as anandamide or 2-AG)
Synthetic cannabinoids or neo-cannabinoids (produced through controlled laboratory processes)
Their activity depends on their molecular structure, their affinity for biological receptors, and their bioavailability.
How do CB1 and CB2 receivers work?
CB1 and CB2 receptors are part of the G protein-coupled receptors (GPCR).
CB1 receptors are primarily located in the central nervous system. They are involved in the modulation of neurotransmission.
CB2 receptors are primarily expressed in the immune system and peripheral tissues.
The activation or modulation of these receptors influences various physiological mechanisms: inflammation, pain, mood, stress response, cellular homeostasis.
Not all cannabinoids act on these receptors in the same way. Some are direct agonists, others act as allosteric or indirect modulators.
What is the pharmacological difference between CBD and THC?
THC is a partial agonist of CB1 receptors, which explains its psychoactive effect.
CBD, on the other hand:
Has a low direct affinity for CB1 and CB2
Acts as an indirect modulator of the endocannabinoid system
Interacts with other biological targets (5-HT1A receptors, TRPV1, etc.)
This difference in mechanism explains why CBD does not induce a euphoric effect comparable to THC.
What is a neo-cannabinoid from a chemical standpoint?
A neo-cannabinoid is generally a molecule derived from a natural cannabinoid, whose structure has been modified by isomerization, hydrogenation, or other controlled chemical processes.
These changes may:
Modify the affinity for CB1/CB2 receptors
Change the duration of action
Change the perceived intensity
As these molecules are recent, long-term clinical data are often limited.
Are cannabinoids metabolized by the liver?
Yes. The majority of cannabinoids are metabolized by the liver via the cytochrome P450 enzyme system.
This means they can:
To be transformed into active or inactive metabolites
Interact with other substances metabolized by the same enzymes
Show variations in concentration according to the individual enzyme profile
This metabolism explains the importance of caution when using concomitant medication.
What is the bioavailability of cannabinoids?
Bioavailability corresponds to the proportion of active substance reaching systemic circulation.
It varies depending on the method of consumption:
Inhalation: rapid absorption, moderate to high bioavailability
Sublingual route: intermediate absorption
Oral route: lower bioavailability due to first-pass hepatic metabolism
This parameter influences the intensity and duration of the effects.
Can cannabinoids be detected in a saliva or blood test?
Screening tests primarily look for THC and its metabolites.
Even if a product complies with the legal THC limit, traces may be detectable depending on:
Cannabinoids other than THC are generally not targeted by standard tests, except in specific cases.
Is there any scientific data on neo-cannabinoids?
Scientific data on emerging molecules remain limited compared to CBD.
Some preclinical or pharmacological studies exist, but:
Large-scale clinical trials are rare
The long-term effects are still insufficiently documented
Toxicological profiles may vary
This justifies a gradual and cautious approach.
What criteria can be used to evaluate the quality of a cannabinoid product?
A reliable product should have:
An independent laboratory analysis
A precise indication of the concentration
Compliance with the legal THC threshold
Batch traceability
The absence of residual solvents or contaminants
Manufacturer transparency is a key indicator of reliability.
Do cannabinoids have the potential to cause addiction?
CBD does not have any identified addictive potential according to current data.
For some newer molecules, the data are still insufficient to establish a complete profile.
The potential for addiction depends on:
Moderate and supervised consumption limits the risks.
How to adopt a responsible approach?
Responsible consumption is based on:
A low-dose start
A gradual increase if necessary
The absence of driving after use
A medical consultation in case of illness or treatment
Regular regulatory monitoring
The world of cannabinoids is evolving rapidly, both scientifically and legally. Up-to-date information and constant vigilance are essential.
Scientific references
Endocannabinoid system
Di Marzo, V., & Piscitelli, F. (2015). The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics, 12 (4), 692–698.
https://doi.org/10.1007/s13311-015-0374-6
Lu, H.C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological Psychiatry, 79 (7), 516–525.
https://doi.org/10.1016/j.biopsych.2015.07.028
Pertwee, R.G. (2008). The diverse CB1 and CB2 receptor pharmacology of cannabinoids. British Journal of Pharmacology, 153 (2), 199–215.
https://doi.org/10.1038/sj.bjp.0707442
Pharmacology and safety of cannabidiol (CBD)
World Health Organization (WHO). (2018). Cannabidiol (CBD) Critical Review Report . Expert Committee on Drug Dependence, 40th Meeting.
Iffland, K., & Grotenhermen, F. (2017). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research, 2 (1), 139–154.
https://doi.org/10.1089/can.2016.0034
Campos, AC, Moreira, FA, Gomes, FV, Del Bel, EA, & Guimarães, FS (2012). Multiple mechanisms involved in the broad-spectrum therapeutic potential of cannabidiol. Philosophical Transactions of the Royal Society B, 367 (1607), 3364–3378.
https://doi.org/10.1098/rstb.2011.0389
Liver metabolism and drug interactions
Zendulka, O., Dovrtělová, G., Nosková, K., Turjap, M., Šulcová, A., Hanuš, L., & Juřica, J. (2016). Cannabinoids and Cytochrome P450 Interactions. Current Drug Metabolism, 17 (3), 206–226.
https://doi.org/10.2174/1389200217666151210142051
Stout, S.M., & Cimino, N.M. (2014). Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: A systematic review. Drug Metabolism Reviews, 46 (1), 86–95.
https://doi.org/10.3109/03602532.2013.849268
THC and neurobiological effects
Volkow, ND, Baler, RD, Compton, WM, & Weiss, SRB (2014). Adverse health effects of marijuana use. New England Journal of Medicine, 370 (23), 2219–2227.
https://doi.org/10.1056/NEJMra1402309
National Institute on Drug Abuse (NIDA). (2020). Marijuana Research Report . US Department of Health and Human Services.
Emerging cannabinoids and synthetic derivatives
Banister, S.D., & Connor, M. (2018). The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonists. Handbook of Experimental Pharmacology, 252 , 191–226.
https://doi.org/10.1007/164_2018_144
European Monitoring Center for Drugs and Drug Addiction (EMCDDA). (2022). Synthetic cannabinoids in Europe — A review . Publications Office of the European Union.
Methodological note
Scientific data relating to cannabinoids, particularly emerging molecules, is evolving rapidly. The publications cited above are major references for understanding:
Recent neo-cannabinoids still have limited scientific data, particularly regarding long-term effects.