From 2002 to 2021, the number of individuals aged 12 or older reporting last year cannabis use increased steadily from 26 million to 53 million (SAMHSA, 2022). Accompanying this increase in the number of individuals using cannabis is a decline in the percentage of individuals who believe that cannabis use is associated with a risk of harm, with the greatest percentage decline seen among high school aged adolescents (Johnson, et al., 2022). Despite this perception, the harms associated with cannabis use have been researched and well-documented, including those that occur during intoxication such as impairments in cognitive and motor functioning to those that occur with heavy and regular cannabis use such as lower educational attainment and lower life satisfaction (Volkow, et al., 2014; Thompson, et al., 2019). Another area of research about the harmful effects of cannabis has focused on the development of psychosis.
Individuals who use cannabis have a significantly increased risk of developing psychosis compared to those who do not use cannabis (Sideli, et al., 2020). While any use may be associated with an increased risk of developing psychosis, the frequency of cannabis use, as well as cannabis potency may be more relevant factors. For example, daily cannabis use has been associated with a three-fold increase in the odds of developing psychosis among individuals with first episode psychosis (FEP) (Marconi et al., 2016). Daily use of high-potency cannabis, defined as having a concentration of Δ-9 tetrahydrocannabinol or THC greater than 10%, conferred a five-time greater risk of developing psychosis among individuals with FEP (Di Fiorti, et al., 2015). The finding that regular use of high potency cannabis may be associated with developing psychosis is of particular concern because the THC concentration in cannabis has been rising over time. Indeed, the average THC concentration of illegally grown cannabis seized by the United States Drug Enforcement Agency (DEA) nearly doubled from approximately 9% in 2008 to 17% in 2017 (Chandra, et al., 2019). Lastly, initiation of cannabis use at an early age, frequently defined as age 15 or younger, is related to an increased risk of developing psychosis but confounding factors such as the use of other substances has not allowed for a clear association to be made (van der Steur, et al., 2020).
Other biological and environmental factors among those who use cannabis also may influence psychosis risk. Some studies have shown that genetic variations affecting dopamine metabolism increased the risk of developing psychosis during adolescence among those who smoked cannabis, but other studies have not found such an association (Wahbeh, et al., 2021). The combination of childhood trauma such as physical and emotional abuse combined with cannabis use increased the risk of developing psychosis in adolescents (Harley, et al., 2010) and exposure to high levels of childhood trauma and severe cannabis use (defined as more than once per week to daily use) was significantly associated with an increase in psychosis risk (Arranz, et al., 2018).
In addition to the influence cannabis can have on the development of psychosis, cannabis use negatively affects the course of individuals who have experienced a first psychotic episode. Poor adherence to psychosocial and pharmacological treatments (Schoeler, et al., 2017), significantly higher levels of psychotic symptoms (Clausen, et al., 2014), and an increased frequency of hospitalizations, an increased likelihood of involuntary hospitalization, as well as a greater number of days hospitalized (Patel, et al., 2014) have been associated with ongoing cannabis use by individuals with FEP. Conversely, cessation of cannabis use after a first psychotic episode was found to diminish negative symptoms significantly and improve overall functioning (Gonzalez-Pinto, et al., 2011). These findings highlight the importance of treatment interventions targeting reductions in cannabis use to improve clinical and functional outcomes among individuals with FEP.
Unfortunately, effective, evidence-based treatments for individuals with psychosis who use cannabis are lacking. Although there is good evidence that cognitive behavioral therapy (CBT), motivational enhancement therapy (MET), and contingency management (CM), alone or in combination, can be effective treatments for cannabis use disorder (CUD), their effectiveness in reducing cannabis use in individuals with psychosis has not been demonstrated (Lees, et al., 2021). However, integrated treatments* that simultaneously address psychosis and cannabis use may be more effective for this population than therapies that only target cannabis use. For example, a combination of Motivational Interviewing (MI) and interaction skills training that teaches problem solving skills for managing conflicts related to symptoms of psychosis to the parents of young adults with the recent onset of a psychotic disorder was found to be superior to routine family support in reducing cannabis use, suggesting that family involvement may be an important component of treatment for this population (Smeerdijk, et al., 2012). Additionally, cannabis users with FEP who received a specific CBT for cannabis cessation combined with treatment as usual (TAU) for FEP not only had reductions in cannabis use severity but also had reductions in psychotic symptoms and improvement in overall functioning (Gonzalez-Ortega, et al., 2022).
In terms of pharmacological treatments, a systematic review examining the effectiveness of antipsychotic medications among individuals with psychosis who use cannabis found no significant differences among clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone in reducing psychotic symptoms or cannabis use (Wilson, et al., 2016). One 12-month, randomized, controlled trial did find that both clozapine and ziprasidone were associated with significant reductions in cannabis use and psychotic symptoms, but the sample consisted of only 30 subjects, limiting the generalizability of the findings (Schnell, et al., 2014).
In summary, the frequent use of high potency cannabis by genetically and environmentally vulnerable populations is associated with the development of psychosis. While there is some promising preliminary evidence for integrated treatment and certain pharmacological interventions for psychosis and problematic cannabis use, more research is needed to determine what are the most effective treatments for individuals with psychosis who also use cannabis. Finally, part of the public health approach to psychosis must be preventing and limiting the harm that individuals who are vulnerable to developing psychosis and those living with psychosis may experience if they use cannabis. Prevention strategies such as delaying the initial use of cannabis until after adolescence and harm reduction strategies such as using low THC content cannabis may help decrease the co-occurrence of cannabis and psychosis in the future.
*A SAMHSA publication about creating programs that integrate treatment for mental health conditions and substance use, Integrated Treatment for Co-Occurring Disorders: Building Your Program, can be found at https://store.samhsa.gov/sites/default/files/d7/priv/ebp-kit-building-your-program-10112019.pdf
Grace Hennessy, MD, is Associate Chief Medical Officer for Addiction Psychiatry, NYS Office of Addiction Services and Supports (OASAS), and Clinical Assistant Professor of Psychiatry, New York University Grossman School of Medicine.
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