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  • Writer's pictureAlexander Lebedev

The Use of Psychoactive Substances and the Risk of Developing Psychosis

Updated: Sep 17, 2023


A captivating vector art piece of a female face and cannabis leafs.

Let me begin by saying: the relationship between the consumption of psychoactive substances and the risk of developing psychotic disorders is a complex topic. To date, no study has been able to establish a clear cause-and-effect relationship between the use of a particular substance and the onset of disorders (except for, perhaps, amphetamine psychosis). Yet, as I observe heated debates among both professionals and laypeople, I increasingly feel the urge to inject a dose of objectivity.

For various reasons (one of which seems to be the recent decriminalization of marijuana in several developed countries), discussions about the risks associated with cannabinoids (the primary active compounds derived from cannabis) are particularly intense.

To date, several comprehensive meta-analyses have been conducted. They unanimously agree that there is a statistically significant association. Consumption of THC-containing products (like marijuana and hashish) is linked to an approximately threefold increased risk of developing schizophrenia and other disorders of this spectrum.

There's compelling evidence suggesting that individuals with certain genetic and personality predispositions can indeed experience states reminiscent of acute schizophrenic spectrum psychoses when consuming tetrahydrocannabinol (THC). For instance, in Freeman's experiment, a sample of 271 individuals prone to paranoid thoughts was randomly administered either THC or a placebo. The intensity of their paranoia was assessed using virtual reality technology, simulating tense social situations (like behavior on public transport). The study convincingly showed that THC could induce paranoid experiences in predisposed individuals. The intensity of these experiences was more closely related to the emotionally negative perception of the altered state of consciousness than to working memory impairments, as some authors previously assumed. However, this doesn't necessarily mean that individuals who have such experiences are more likely to develop schizophrenia.

Indeed, despite active research in this area, there's still no concrete evidence supporting the direct influence of THC on the development of chronic psychoses, including schizophrenia.

So, what's the crux of the matter? Why don't population studies suffice to confirm this cause-and-effect relationship? The real challenge lies in discerning the true cause of the frequent history of long-term or short-term substance use among patients with relevant diagnoses. The "cannabis-psychosis" link could be interpreted in reverse. There's even a hypothesis that individuals at higher risk of developing schizophrenia might consciously or unconsciously use cannabinoids as a form of "self-medication." Some cannabinoids, like cannabidiol, have been shown to have neuroprotective effects on the central nervous system and psyche (Campos et al., 2016). However, a large portion of the scientific community remains skeptical about this "self-medication" hypothesis, and the results from Freeman's experiment certainly contradict it.

A more plausible hypothesis might be "comorbidity." It's well-known that a general predisposition to addictions is linked to increased risks for a broad spectrum of mental disorders, and psychoses are no exception. In a study by Callaghan et al. (2012), several groups of people regularly using three different classes of psychoactive substances - methamphetamine, cannabis, and cocaine - were analyzed. Each of these groups had significantly increased risks of developing schizophrenia.

Take a moment to study this graph closely. How often have you heard that one of the most widely consumed drugs, alcohol, also has a statistically significant link with schizophrenia? Yes, its association is half as potent as that of methamphetamine, but it's comparable to the data on THC-containing substances.


Now, let's delve into the vast reservoir of data from the most comprehensive meta-analyses and population studies, which typically offer the most reliable statistical insights. Notice how the strength of the effects of some substances previously mentioned shifts when we analyze the general population, as opposed to just patients with addictions:

I'd also like to draw your attention to a new "contender" in our comparison, one that's hot on the heels of the leader. How often do we hear that tobacco consumption also has a link with psychotic spectrum disorders, a link that's quite equivalent to the much-scrutinized cannabis? How many studies are conducted in this direction? It's worth noting that we're talking about a completely legal psychoactive substance that any adult can freely purchase at a store.

These facts are hard to ignore. However, some staunch proponents of the theory linking THC intake directly to psychosis have met these findings with skepticism. They suggest that since cannabis and tobacco are often used in tandem, the elevated risks associated with nicotine-containing substances might actually reflect those of THC. This seems unlikely from a common-sense perspective, given that the percentages and volumes of tobacco and cannabis consumption are not comparable in most countries.

Lastly, two recent population studies dispelled the aforementioned skepticism. They demonstrated, with samples of 5,300 and 34,653 individuals, that tobacco consumption is a significant factor that independently doubles the risks of developing psychotic spectrum disorders and psychosis-like states (Jones et al., 2018; Mallet et al., 2018).

*******

In penning this article, I certainly didn't aim to exonerate any psychoactive substance. Everything we do in life comes with its own price and very real risks. Armed with reliable information, every adult has the autonomy to decide which risks they deem acceptable. This applies to all psychoactive substances without exception.


Someday, we'll realize that our imposed distinction between alcohol and tobacco from other drugs, followed by the criminalization of the latter, is one of the gravest injustices against humanity. I sincerely hope this realization dawns before it's too late.

© Alexander Lebedev



REFERENCES:

  1. D. Freeman, G. Dunn, R.M. Murray, N. Evans, R. Lister, A. Antley, M. Slater, B. Godlewska, R. Cornish, J. Williams, M. Di Simplicio, A. Igoumenou, R. Brenneisen, E.M. Tunbridge, P.J. Harrison, C.J. Harmer, P. Cowen, P.D. Morrison, How cannabis causes paranoia: using the intravenous administration of 9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia, Schizophrenia bulletin, 41 (2015) 391-399.

  2. A.C. Campos, M.V. Fogaca, A.B. Sonego, F.S. Guimaraes, Cannabidiol, neuroprotection and neuropsychiatric disorders, Pharmacol Res, 112 (2016) 119-127.

  3. R.C. Callaghan, J.K. Cunningham, P. Allebeck, T. Arenovich, G. Sajeev, G. Remington, I. Boileau, S.J. Kish, Methamphetamine use and schizophrenia: a population-based cohort study in California, Am J Psychiatry, 169 (2012) 389-396.

  4. P. Gurillo, S. Jauhar, R.M. Murray, J.H. MacCabe, Does tobacco use cause psychosis? Systematic review and meta-analysis, Lancet Psychiatry, 2 (2015) 718-725.

  5. A. Marconi, M. Di Forti, C.M. Lewis, R.M. Murray, E. Vassos, Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis, Schizophrenia bulletin, 42 (2016) 1262-1269.

  6. T.S. Krebs, P.O. Johansen, Psychedelics and mental health: a population study, PLoS One, 8 (2013) e63972.

  7. J. Ma, X.D. Li, T.Y. Wang, S.X. Li, S.Q. Meng, F.C. Blow, M. Ilgen, L. Degenhardt, J. Lappin, P. Wu, J. Shi, Y.P. Bao, L. Lu, Relationship between the duration of methamphetamine use and psychotic symptoms: A two-year prospective cohort study, Drug Alcohol Depend, 187 (2018) 363-369.

  8. H.J. Jones, S.H. Gage, J. Heron, M. Hickman, G. Lewis, M.R. Munafo, S. Zammit, Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With Psychotic Experiences, JAMA psychiatry, 75 (2018) 240-246.

  9. J. Mallet, N. Mazer, C. Dubertret, Y. Le Strat, Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample, J Clin Psychiatry, 79 (2018).



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