How do our genes influence our response to cannabis?
By Dr Chandni Hindocha
Why do people react differently to cannabis, and why do some people get addicted while others don’t?
People experience cannabis differently when they smoke it. Understanding how our genes are involved with the cannabis response is essential since cannabis currently stands poised to join alcohol and tobacco as a legal drug across the globe, meaning rates of cannabis addiction may also rise.
1 in 10 people become addicted to cannabis
Cannabis is the most commonly used illicit drug worldwide with 191 million users. It is also a medical product that provides relief for many people worldwide for disorders of pain, spasticity and epilepsy, to name a few. Alongside these medical benefits comes some mental health risks. The main risk from chronic cannabis use, is cannabis addiction. Roughly 10 % will become addicted to cannabis – and we currently have no pharmacological treatments for it. Lots of people say you can’t get addicted to cannabis, that’s a myth – you certainly can.
Why do people experience cannabis differently?
The system in the brain that controls the effects of cannabis is called the Endocannabinoid System. This system controls many fundamental processes in the body, which may explain why cannabis is associated with such different effects in different people. Genetic variation in this system, particularly the main receptor (cannabinoid receptor 1; CB1), and the main enzyme that breaks down anandamide (called FAAH), may contribute to the addictive effects of cannabis. Thus, potentially explaining why about ~10% of people become addicted (1,2).
What are the origins of addiction?
Addiction is complicated. The root of addiction is likely to be biological, psychological and social in origin. If we just think about the biology, we can study “intermediates of addiction” which may be closer to the biological basis of the disease in comparison to just a diagnosis, because there are so many problems with diagnostics. By just looking at the biology, this study is limited, but it’s a start!
Studying cannabis addiction
In this study (3), 48 people who had used cannabis before came into the lab four times – once they were given the main psychoactive ingredient of cannabis, THC, on another occasion, they were given the main non-intoxicating ingredient in cannabis, CBD, on a third occasion they were given a combination of these two (THC+CBD). Finally they were given a placebo. These were all administered with a Volcano Medic Vaporizer. The order was random with the experimenters and participants not knowing what they would get on each occasion. We tested intermediates related to addiction e.g. craving after the high, how one's attention is drawn to cannabis cues in the environment (e.g. a bit like the one in the photo) and how much one wants to smoke cannabis after acute intoxication with the drug. We took a spit sample to get their DNA, to see how genetic variation is related to these intermediates.
The results were exciting and confusing
We found that genetic variation in the endocannabinoid system predicts how much you want to smoke cannabis, after having taken THC as well as how people's attention is drawn towards cannabis in their environment. Interestingly, we didn't find that any of these genes predicted craving for cannabis. This is interesting because these intermediates should correlate with each other.
One of the main findings was that FAAH rs324420 A carriers (rare people, only about 5% of the population) were having their attention still drawn to cannabis cues after having THC, in comparison with CC carriers, suggesting that A carriers may be more susceptible to addiction.
The results could help clinicians who prescribe cannabis
These results further helps us understand the role of the endocannabinoid system in individual differences in risk and resilience for cannabis addiction. These results have implications for both the recreational and medical use of cannabis, and will help us predict who is more vulnerable to the negative effects of cannabis.
We hope that our findings could lead to the development of a test that could inform clinicians who are considering prescribing a cannabis-derived medication, as we learn more about which genes affect how people react to cannabis.
Do you know anyone who has been addicted to cannabis?
Lopez-Quintero, C., Perez de los Cobos, J., Hasin, D. S., Okuda, M., et al., Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend, 2011. 115(1-2): p. 120-30. PMC3069146.
Florez-Salamanca, L., Secades-Villa, R., Hasin, D. S., Cottler, L., et al., Probability and predictors of transition from abuse to dependence on alcohol, cannabis, and cocaine: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Am J Drug Alcohol Abuse, 2013. 39(3): p. 168-79. PMC3755735.
Hindocha, C., Freeman, T. P., Schafer, G., Gardner, C., Bloomfield, M. A., Bramon, E., ... & Curran, H. V. (2019). Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. Addiction biology, e12762. https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12762