Cannabis and psychosis, genes or sex?

Do you feel a bit of academic insanity reading that, in 2023, a new study found unidirectional causation between cannabis use and psychotic disorders? Consider that the new research focusing on sex and age, published by Cambridge’s Psychological Medicine, omits genes that correlate cannabis use and psychosis, but no verifiable causative links. Thankfully, The Lancet’s Psychiatry journal recently published a study that dives deep into the genetic correlation.

The person who taught me how to use a bong, before they had their psychotic break, years later told me in his now typical daze that he still enjoys THC’s effect. It gave him the giggles — but he claimed it also worsened his psychosis. While this was far from a case study, it was in line with research suggesting that cannabis increases, at least, positive psychosis symptoms. (1)

Causation or cannabis-seeking?

Imagine if a pre-requisite behind most psychotic disorders, before onset, includes a penchant for cannabis’s intoxicating effects. Essentially, cannabinoids mesh with a person’s altered brain chemistry, regardless of the benefit or risk. Published in Psychological Medicine and conducted by Danish and American authors, the new study looking at sex and age factors disagrees with genomic reasoning. (2, 3)

Genetic confounding factors would be unlikely to explain the steeper increases in the [population attributable risk factors] of [cannabis use disorder] on schizophrenia that we identified for males than females, as changes in the genetic risk-profile of an entire population would have to occur over generations. — Hjorthøj et al.

Contrary to their statement, estrogen breaks down COMT, a gene involved in both cannabis-seeking and schizophrenia. (3, 4, 5) And females experience greater memory impairment from cannabis than males. While the expression of the genes may not be genetically distinct, their metabolic interactions in the body depend on gender-specific hormones. Research must, therefore, assess genetic factors to better understand the sex differences involved in cannabis use and psychosis. Unfortunately, based on their confidence that age and genes are not closely related in this context, the Danish study omitted genetic confounding factors previously characterized in greater detail by Johnson et al. (2)

Sex and psychosis

The damning study published by Cambridge assumes that genetics are not involved in the risk factors between cannabis use and schizophrenia, openly rejecting conclusions made by previous research. Yet, males lack the adequate machinery to break down one of two known likewise, but separate factors responsible for both cannabis use and schizophrenia. And females are less likely to experience schizophrenia from cannabis use, according to Psychological Medicine’s new study.

As per the recent Psychiatry study, though, it’s evident that similar genetic factors separately increase cannabis use and cause schizophrenia. Psychotic disorders and cannabinoid-seeking share a cumulative total of 57 similar gene locations. Unfortunately, though, genome banks currently lack adequate data to conclude that cannabis use does or does not cause chronic psychotic symptoms. Bipolar disorder and schizophrenia do, however, correlate uniquely to cannabis use, with the latter sharing 27 gene locations and the bipolar disorder only sharing 3 loci. Furthermore, genetic correlations only existed between cannabis use and bipolar disorder with the occurrence of psychosis-like symptoms.

It’s a chicken or egg question in the sense that psychotic symptoms might cause cannabis seeking, according to one theory. On the still unproven side of the relationship, however, cannabis leads to psychotic symptoms. And while correlation exists through shared genetic code, the authors of the new Psychiatry study discerned,

We caution readers on concluding that psychotic disorders cause cannabis use, and that cannabis use does not cause psychotic disorders.

Let us know in the comments if someone you know consumes cannabis and independently experiences psychotic symptoms.

Sources

1. Cheng W, Parker N, Karadag N, et al. The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study. The Lancet Psychiatry. 2023;10(6):441-451

2. Johnson, E. C., Hatoum, A. S., Deak, J. D., Polimanti, R., Murray, R. M., Edenberg, H. J., Gelernter, J., Di Forti, M., & Agrawal, A. (2021). The relationship between cannabis and schizophrenia: a genetically informed perspective. Addiction (Abingdon, England), 116(11), 3227–3234.

3. Hjorthøj C, Compton W, Starzer M, Nordholm D, Einstein E, Erlangsen A, Nordentoft M, Volkow ND, Han B (2023). Association between cannabis use disorder and schizophrenia stronger in young males than in females. Psychological Medicine 1–7.

4. Zammit, S., Owen, M., Evans, J., Heron, J., & Lewis, G. (2011). Cannabis, COMT and psychotic experiences. The British Journal of Psychiatry, 199(5), 380-385. doi:10.1192/bjp.bp.111.091421

5. White, T. P., Loth, E., Rubia, K., Krabbendam, L., Whelan, R., Banaschewski, T., Barker, G. J., Bokde, A. L., Büchel, C., Conrod, P., Fauth-Bühler, M., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Lawrence, C., Mann, K., … IMAGEN Consortium (2014). Sex differences in COMT polymorphism effects on prefrontal inhibitory control in adolescence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39(11), 2560–2569.