Guest Editorial: The Association of Cannabis Potency with Adverse Psychiatric Effects of Cannabis

Dept. of Psychiatry, University of Maryland School of Medicine
Editor-in-Chief, Journal of Cannabis Research

  Cannabis potency, the content of ∆9-tetrahydrocannabinol (THC), usually expressed as the percentage of dry weight, has increased substantially worldwide over the past four decades [1]. This higher potency poses a risk of increased harms because of evidence of a positive association between cannabis potency and adverse psychiatric effects from long-term cannabis use. This article reviews the evidence for this association. 

Increasing Cannabis Potency

Cannabis potency has increased two- to three-fold in both illicit markets and US state-legalized markets over the past four decades. A recent systematic review evaluated changes in potency in more than 66,000 cannabis samples seized by law enforcement between 1970 and 2017 [1]. These samples were seized in the U.S., Western Europe, and New Zealand. Mean THC concentration of herbal cannabis increased from about 4% during the 1980’s to 6-12% during the 21st century. The potency of cannabis resin increased from about 10% during the 1980’s to about 30% during the 21st century. In a separate study of over 18,000 illicit cannabis samples seized by the US Drug Enforcement Administration found that the mean potency of cannabis flower products increased from 6% in 2008 to 13.6% in 2017 [2]. The mean potency of hashish (a concentrated form of cannabis flower) increased from 23% in 2008 to 46% in 2017, with wide variability in THC concentrations. Some samples had THC concentrations as high 42% in 2008 and 72% in 2017. 
      Cannabis potency is also high in products sold in legal cannabis dispensaries in the US.A  2019 survey of the online advertised THC content of 8,505 cannabis flower products sold by 655 licensed dispensaries in 9 US states found a mean cannabis potency of 20% THC, but some products had potencies up to 50% THC [3].There was no significant difference in mean potency between products advertised by medical dispensaries (19.2% THC) and products advertised by recreational dispensaries (21.5% THC). The legalization of cannabis and resulting commercialization of the industry has driven development and marketing of products with higher and higher potency; these include concentrates and extracts [4]. Such products now have potencies as high as 60-90% THC.  

Cannabis Potency and Adverse Effects

The acute psychological and psychomotor effects of THC in laboratory studies are largely dose-dependent [5] [6], i.e., higher doses usually produce stronger and longer lasting effects. Thus, it is plausible to hypothesize that long-term use of high-potency cannabis would be associated with increased risk of adverse effects. The association between cannabis potency and risk for each of four major psychological harms from cannabis use: psychosis, cannabis use disorder, anxiety, and depression — has been investigated in multiple studies [7]. These studies all used observational study designs — case-control, cross-sectional, or prospective cohort. No study used an interventional study design, which would provide conclusive evidence of causality. 

Use of higher potency cannabis, compared with use of lower potency cannabis or no cannabis use, significantly increases (at least two-fold) the probability of developing first-episode psychosis and of relapse after remission, increases the intensity of positive symptoms, and shortens the latency for developing psychosis (up to four years shorter).  

Studies of cannabis use disorder yield less consistent results. Four of six studies found a significant association between use of higher potency cannabis and likelihood of developing cannabis use disorder. Two studies did not find a significant association. There were no obvious differences in quality among the studies (five of the six studies were rated as poor quality).  

Studies of the association between cannabis potency and anxiety or depression yield inconsistent results. Some studies show a significant positive association, while others show no significant association. The majority of studies were rated of poor quality. 

Interpreting the Data

The observed associations between cannabis potency and adverse psychiatric effects should be interpreted cautiously. Most studies are rated as of poor quality because of major methodical limitations. Common limitations include small or unrepresentative samples and failure to statistically control for relevant confounding variables such as duration of cannabis use and use of other psychoactive compounds. Cannabis potency is almost always based on self-report, rather than actual analysis of THC content; definitions of high-potency vary across studies. Most importantly, even the most rigorously designed associational study cannot prove causality. It is always possible that confounding factors, either known or unknown, actually account for the observed association. For example, some antecedent factor could account for both a tendency to use high-potency cannabis and the likelihood of adverse effects from cannabis use.  

A set of nine criteria can help judge whether an observed association reflects a causal relationship. These criteria were developed almost 60 years ago by the British epidemiologist Austin Bradford Hill [8], commonly termed the Bradford Hill criteria (see Box).  Judged against these criteria, only the association with psychosis is likely to be causative, based on current evidence. All eight studies showed consistent results of at least a two-fold increase in psychosis risk, with cannabis use preceding onset of psychosis. There is a clear dose-response gradient across no cannabis use, low-potency use, and high-potency use. Associations with cannabis use disorder, anxiety, and depression are less likely to be causative, as many of the studies do not show a significant association. Studies involving users of medical cannabis are especially problematic because it is often unclear whether anxiety or depression symptoms preceded or followed the cannabis use. 

Conclusions

     The potency (THC content) of cannabis, both illicit and legal, has increased substantially over the past four decades, which may result in increased likelihood of developing adverse psychiatric effects. However, the evidence for the association between cannabis potency and adverse psychiatric effects is strong only for psychosis. The evidence for an association with cannabis use disorder, anxiety, or depression is inconsistent; most studies are of poor quality. Given the potential clinical and public health harms from the higher-potency cannabis now available, high-quality research studies are urgently needed. 

References 

1. Freeman TP, Craft S, Wilson J, et al. Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta-analysis. Addiction. 2021;116(5):1000-1010.

2. Chandra S, Radwan MM, Majumdar CG, et al. New trends in cannabis potency in USA and Europe during the last decade (2008-2017). Eur Arch Psychiatry Clin Neurosci. 2019;269(1):5-15.

3. Cash MC, Kunnane K, Fan C, et al. Mapping cannabis potency in medical and recreational programs in the United States. PLoS ONE. 2020;15(3): e0230167

4. Hinckley JD, Hopfer C.  Marijuana Legalization in Colorado: Increasing Potency, Changing Risk Perceptions, and Emerging Public Health Concerns for Youth. Adolesc Psychiatry. 2021;11(2): 95–116.

5. Hindley G, Beck K, Borgan F, et al. Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis. Lancet Psychiatry 2020;7: 344–53

6. Boggs DL, Cortes-Briones JA, Surti T, et al. The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans. J Psychopharmacology 2018;32(12):1308–1318.

7. Petrilli K, Ofori S, Hines L, Taylor G, Adams S, Freeman TP. Association of cannabis potency with mental ill health and addiction: a systematic review. Lancet Psychiatry. 2022;9(9):736-750.

8. Fedak KM, Bernal A, Capshaw ZA, et al. Applying the Bradford Hill criteria in the21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol. 2015;12:14.