Is cannabis consumption good or bad for you? It is a question that is at the heart of the discussion around cannabis legalization. When New York legalized cannabis for recreational adult use earlier this year, there was a wide celebration on the internet, but also much trepidation from people concerned about two problems: Fear of people operating vehicles in traffic under the influence of marijuana and diminished ability to restrict access of marijuana to children. Should we expect more DUIs in New York now? And what about the children? What about the risks of acute vs. chronic cannabis use on childhood development? The answer to those questions may prove to be more complicated than one would think! Cannabis and the cannabinoids within can have opposing effects on the human body. What the outcome is depends on the age of the person consuming it and the dosage and ratio of the cannabinoids in the plant.
How can cannabis be both good and bad?
Numerous examples of beneficial medicinal properties largely trailblaze the legalization of cannabis. Notably, cannabis can have analgesic, anti-convulsive and anti-emetic properties. So, it can be used to fight pain, seizures and nausea respectively. However, when you survey the medical literature on cannabis, you’ll run into conflicting pieces of information that are sure to lead to some confusion in the general media. The effect of phytocannabinoids on the human body has proven to be biphasic.
Depending on the dosage, delta-9 THC acts in a bi-phasic manner on the body
That means that phytocannabinoids like THC can have one effect at high-dosage and the opposite effect at low-dosage. For example, studies in animal models have shown THC to be both a depressant at high-dose while acting as a stimulant at low-dose; anxiogenic (anxiety promoting) at high-dose and anxiolytic (anxiety diminishing) at low-dose. The same appears to be the case for the body’s endocannabinoids like anandamide. In high doses, anandamide can act as an immunosuppressant and inhibit the phagocytic action of white blood cells while promoting it at low-dose. This duality of action is called “Hormesis.” Hormesis adds complexity to the scientific efforts required to map out the underlying mechanisms that dictate how cannabis and endocannabinoids regulate cells.
To complicate things even further, there is an apparent age dependence on the effects of cannabis and phytocannabinoids. Prof. Andreas Zimmer’s research group published a collection of very compelling data in Nature Medicine (2017). Their work suggests that chronic, low-dose treatment with THC or cannabis extracts could be a potential strategy to slow down or even reverse cognitive decline in the elderly. The research used animal models, so it is important to remember that it isn’t necessarily directly translatable to humans. However, the ability to increase learning capacity and reduce memory deficits in old mice is intriguing and surely warrants further investigation.
Similarly, a more recent study supports those findings. Sarne et al. saw a reversal of age-related cognitive impairments in old female mice after a single ultra-low THC injection. While promising for the elderly, Bilkei-Gorzo et al. (Zimmer’s group) also observed a mild but significant cognitive impairment in young mice under the same conditions. Young, THC-treated mice show similar expression patterns to old untreated control mice. This evidence suggests that disrupting the physiological endocannabinoid signaling might accelerate the aging process. Of course, the tetrahydrocannabinol (THC), used in these studies, is not the only phytocannabinoid in the actual cannabis plant. There are hundreds more and how exactly the whole plant affects people is a much more complicated question to answer. For example, co-administration of cannabidiol (CBD), the second most prominent phytocannabinoid, can mitigate some of the adverse cognitive effects caused by THC, making mixed CBD+THC plants more palatable for medical use but much harder to dose control than defined synthetic THC.
The age dilemma
This data adds to a growing body of work highlighting that there are lasting adverse effects cannabis has on the developing physiology of children and young adults. Even sporadic usage of cannabis can alter the developing brain’s architecture permanently. This is particularly troubling when you consider that a recent survey conducted by the University of Michigan (NIH/NIDA) shows that about 35-40% of 12th graders will have at least one encounter with cannabis, and about 6% use it daily. Overall, statistics tell us that the majority of recreational cannabis users are below the age of 30. If you are below the age of 25 or, in the case of ADHD, below the age of 28, then your brain is not yet fully developed. For the most part, and based on the current scientific knowledge, consuming cannabis while your brain is still developing has consequences that need to be weighed against the benefits of consumption. That being said, in some cases, the therapeutic properties of cannabis may outweigh the potential adverse risks to the developing brain. For instance, in severe drug-refractory childhood epilepsy, if therapy with common anticonvulsant drugs has failed, and surgery isn’t an option, then consuming cannabis will have overall more favorable outcomes. Even so, it is understandable that parents are worried about cannabis becoming more widely available and that their kids might have more contact with it. However, I’d argue that even with it being illegal, contact is still plentiful at schools. And with added legalization, we can enjoy the added benefits of better medical scrutiny, better researcher access to the plant, and more bureaucratic oversight. That means FDA regulations and guidelines will have to be met. However, it does mean that the responsibility to educate their children on the risks of cannabis consumption will land on the parents. Just as with alcohol, parents will need to moderate their children.
Depending on the age of the consumer, cannabis can have opposite effects
For the older generation, the cannabis industry has a much more positive outlook. Cannabis has apparent therapeutic potential for several ailments that plague humanity. It shows promise in pain, nausea, and seizure relief, along with potential therapies for neurodegenerative and some inflammatory conditions. It is still too early to say whether scientists will successfully translate this to a clinical setting, but at the very least, it will be worthwhile to explore the underlying mechanisms more.
The older we get, the smaller our “physiological reserve” becomes and the harder it is for the body to maintain homeostasis. That is one of the core ideas that Prof. Andreas Zimmer put forth in his Nature Medicine paper from 2017. The figure above is taken from one of his lectures and should illustrate the concept.—In other words, as we age, our body progressively loses the ability to return cells from an activated state back to the default steady state. When specific immune cells fail to maintain homeostasis, it can be particularly harmful, as uncontrolled chronic immune activity can damage our tissues. Ongoing inflammation is the potential root cause for many chronic age-related diseases. Cannabis can potentially be used to boost the “physiological reserve” and artificially induce homeostasis. So, in the end, is cannabis good or bad?—Well, we can say one thing for sure: It depends on dosage and age.
- Calabrese EJ, Rubio-Casillas A. Biphasic effects of THC in memory and cognition. Eur J Clin Invest. 2018 May;48(5):e12920. doi: 10.1111/eci.12920. Epub 2018 Apr 2. PMID: 29574698. https://pubmed.ncbi.nlm.nih.gov/29574698/
- Rey AA, Purrio M, Viveros MP, Lutz B. Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission. Neuropsychopharmacology. 2012 Nov;37(12):2624-34. doi: 10.1038/npp.2012.123. Epub 2012 Aug 1. PMID: 22850737; PMCID: PMC3473327. https://pubmed.ncbi.nlm.nih.gov/22850737/
- McPartland JM, Duncan M, Di Marzo V, Pertwee RG. Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol. 2015 Feb;172(3):737-53. doi: 10.1111/bph.12944. PMID: 25257544; PMCID: PMC4301686. https://pubmed.ncbi.nlm.nih.gov/25257544/
- Steffens S, Veillard NR, Arnaud C, Pelli G, Burger F, Staub C, Karsak M, Zimmer A, Frossard JL, Mach F. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature. 2005 Apr 7;434(7034):782-6. doi: 10.1038/nature03389. Erratum in: Nature. 2005 May 26;435(7041):528. Karsak, Meliha [added]. PMID: 15815632. https://pubmed.ncbi.nlm.nih.gov/15815632/
- Bilkei-Gorzo A, Albayram O, Draffehn A, Michel K, Piyanova A, Oppenheimer H, Dvir-Ginzberg M, Rácz I, Ulas T, Imbeault S, Bab I, Schultze JL, Zimmer A. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 2017 Jun;23(6):782-787. doi: 10.1038/nm.4311. Epub 2017 May 8. PMID: 28481360. https://pubmed.ncbi.nlm.nih.gov/28481360/
- Ozaita A, Aso E. The cannabis paradox: when age matters. Nat Med. 2017 Jun 6;23(6):661-662. doi: 10.1038/nm.4348. PMID: 28586333. https://pubmed.ncbi.nlm.nih.gov/28586333/
- Zeiger JS, Silvers WS, Fleegler EM, Zeiger RS. Age related differences in cannabis use and subjective effects in a large population-based survey of adult athletes. J Cannabis Res. 2019 Jul 29;1(1):7. doi: 10.1186/s42238-019-0006-9. PMID: 33526101; PMCID: PMC7819305. https://pubmed.ncbi.nlm.nih.gov/33526101/
- Sarne Y, Asaf F, Fishbein M, Gafni M, Keren O. The dual neuroprotective-neurotoxic profile of cannabinoid drugs. Br J Pharmacol. 2011 Aug;163(7):1391-401. doi: 10.1111/j.1476-5381.2011.01280.x. PMID: 21323910; PMCID: PMC3165949. https://pubmed.ncbi.nlm.nih.gov/21323910/
- Calabrese EJ. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations. Pharmacol Res. 2016 Aug;110:242-264. doi: 10.1016/j.phrs.2015.12.021. Epub 2016 Jan 3. PMID: 26757428. https://pubmed.ncbi.nlm.nih.gov/26757428/
- Calabrese EJ. Preconditioning is hormesis part II: How the conditioning dose mediates protection: Dose optimization within temporal and mechanistic frameworks. Pharmacol Res. 2016 Aug;110:265-275. doi: 10.1016/j.phrs.2015.12.020. Epub 2015 Dec 31. PMID: 26748033. https://pubmed.ncbi.nlm.nih.gov/26748033/
- Johnston, L. D., Miech, R. A., O’Malley, P. M.,Bachman, J. G., Schulenberg, J. E., & Patrick, M.E. Monitoring the Future national survey
results on drug use 1975-2021: Overview, keyfindings on adolescent drug use. Ann Arbor:Institute for Social Research, University of Michigan. (2022). http://monitoringthefuture.org/pubs/monographs/mtf-overview2021.pdf