Risks of psychosis and cognitive impairment
Although pro-legalization advocates tend to tout the safety of cannabis, it is well established that there are at least 2 potentially serious adverse effects from the regular use of cannabis (THC) to the developing brain: increased incidence and earlier onset of psychosis in individuals already at risk and cognitive impairments that can be irreversible. Ideally, as with alcohol and cigarettes, cannabis should not be used until the brain is fully developed, somewhere between the ages of 21 and 25. Moreover, based on multiple, large epidemiological studies, we have learned that 10% of THC users will become addicted, with a well-defined withdrawal syndrome upon acute discontinuation.
With our current understanding of the neurobiology of the endocannabinoid system, it is not surprising that constant agonism at the CB1R during brain development affects brain function in significant ways. The brain structures that are rich in CB1R, and the impact of CB1R agonism on neurotransmitters are essential for optimal neuronal circuitry function.
THC appears to accelerate the onset of a first psychotic episode by 2 to 3 years in individuals who are at risk. In addition, an exposure dependent effect has also been demonstrated—frequent cannabis use and more potent THC levels increase the risk of psychosis. Finally, ongoing cannabis usage after a first psychotic episode is correlated with an increased risk of relapse, as well as a higher severity of positive symptoms and a greater decline in overall functioning; abstinence reduces the relapse risk.5
A recent study by McGuire and colleagues6 demonstrated that individuals with schizophrenia who were maintained on their baseline antipsychotic medication while augmenting with 1000-mg CBD daily experienced improvements. After 6 weeks of augmentation, the CBD group demonstrated significant improvement over the placebo group on measures of positive psychotic symptoms, the clinicians’ impressions of improvement and illness severity, as well as a non-statistically significant improvement in cognitive and overall functioning.
There is a solid body of prospective studies that report a significant irreversible decline in cognitive functioning in adolescents who regularly use cannabis. In his editorial, Harvey7 nicely summarizes our current understanding of the effect of cannabis on cognition. He references a seminal paper by Meier and colleagues8 who followed 1037 individuals in Dunedin, New Zealand born in 1972 or 1973. This cohort was evaluated every 2 years from birth up to age 38, with 95% retention. Cannabis use was monitored, and IQ testing was performed at ages 8, 11, 13, and 38. Individuals with persistent cannabis use that began during the adolescent years lost an average of 8 IQ points. In contrast, individuals who began using cannabis as adults had no decline in their IQ score. These data support the likelihood of a neurotoxic effect with the regular use of cannabis in the developing brain, resulting in an enduring decline in cognitive function.
So, the debate goes on about whether to legalize cannabis nationally. Both sides of the debate can present arguments to support their position. As a father, psychiatrist, and scientist, in my opinion it is time to re-schedule cannabis as a legal, but controlled substance. This would create increased safety and predictability in the production, distribution, and individual use of cannabis. And, the legal status of cannabis would be nationally cohesive. Research on the basic science of cannabinoids, as well as novel clinical applications would increase, and funding would be more available for public education about the evidence-based facts of the risks and benefits of cannabis use.
1. National Academies on Sciences, Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 2017. http://www.nap.edu/24625. Accessed March 13, 2019.
2. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States. Biol Psychiatry. 2016;79:613-619.
3. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2:241-254.
4. Maccarrone M, Guzmán M, Mackie K, et al. Programming of neural cells by (endo) cannabinoids: from physiological rules to emerging therapies. Nature Rev. 2014;12:786-801.
5. Andrade C. Cannabis and neuropsychiatry, 2: the longitudinal risk of psychosis as an adverse outcome. J Clin Psychiatry. 2016;77:e739-e742.
6. McGuire P, Robson P, Cubala WJ, et al: Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175:225-231.
7. Harvey PD. Smoking cannabis and acquired impairments in cognition: starting early seems like a really bad idea. Am J Psychiatry. 2019;176:90-91.
8. Meier MH, Caspi A, Ambler A, et al: Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci USA. 2012;109:E2657-E2664.