Effects of Cannabis Use on Psychotic and Mood Symptoms: A Systematic Review

Abstract

Background: The association between cannabis use and psychiatric disorders has been extensively investigated, but the effect of cannabis use on the induction and persistence of psychiatric symptoms in healthy individuals is less clear. We determines whether cannabis contributes to the induction and persistence of psychotic, depressive, or (hypo)manic symptoms in healthy individuals. We identified populations that are most susceptible to these effects, in addition to cannabis use behaviors that increase the risk of developing cannabis-related psychiatric symptoms. Method: A systematic review was performed using the PubMed, Medline, and PsychInfo databases. We conducted our search using the following terms: (“cannabis” OR “tetrahydrocannabinol” OR “cannabidiol” OR “marijuana” OR “cannabinoid” OR “nabilone” OR “dronabinol” OR “nabiximols”) AND (“psycho∗” OR “mood disorder” OR “depress∗” OR “mania” OR “manic” OR “hypomania”). Experimental and observational studies published from January, 1987 to March, 2021 were considered in our analysis. Results: We assessed evidence from 47 studies, including 6 experimental studies, 28 cohort studies, and 13 cross-sectional studies. Adverse effects of cannabis or cannabinoids were found in 30/32 (93.8%) of studies reporting psychotic symptoms, 13/18 studies (72.2%) reporting depressive symptoms, and 4/4 studies (100%) reporting (hypo)manic symptoms. Cannabis use robustly increased the risk of developing psychotic and (hypo)manic symptoms, but the effects of cannabis use on depression were mixed. Risk of developing symptoms was influenced by the age of onset, tetrahydrocannabinol potency, and frequency of cannabis use. Conclusions: Cannabis use increases the risk of developing and maintaining psychotic and (hypo)manic symptoms, with mixed effects for depressive symptoms, in healthy individuals. These effects occur in a dose-dependent manner and are dependent upon THC potency. More research is necessary to understand the effects of cannabis, particularly on the induction and persistence of depressive and (hypo)manic symptoms. Contexte: L’association entre la consommation de cannabis et les troubles psychiatriques a été largement étudiée, mais l’effet de la consommation de cannabis sur l’induction et la persistance des symptômes psychiatriques chez les individus en bonne santé est moins clair. Nous avons déterminé si le cannabis contribue à l’induction et à la persistance de symptômes psychotiques, dépressifs ou (hypo)maniaques chez des individus en bonne santé. Nous avons identifié les populations les plus sensibles à ces effets, en plus des comportements de consommation de cannabis qui augmentent le risque de développer des symptômes psychiatriques liés au cannabis. Méthode: Un examen systématique a été réalisé à l’aide des bases de données PubMed, Medline et PsychInfo. Nous avons effectué notre recherche en utilisant les termes suivants: (“cannabis” OU “tétrahydrocannabinol” OU “cannabidiol” OU “marijuana” OU “cannabinoïde” OU “nabilone” OU “dronabinol” OU “nabiximols”) ET (“psycho∗” OU “trouble de l’humeur » OU « déprimé∗ » OU « manie » OU « maniaque » OU « hypomanie »).” Les études expérimentales et observationnelles publiées de janvier 1987 à mars 2021 ont été prises en compte dans notre analyse. Résultats: Nous avons évalué les résultats de 47 études, dont 6 études expérimentales, 28 études de cohorte et 13 études transversales. Des effets indésirables du cannabis ou des cannabinoïdes ont été trouvés dans 30/32 (93,8%) des études rapportant des symptômes psychotiques, 13/18 études (72,2%) rapportant des symptômes dépressifs et 4/4 études (100%) rapportant des symptômes (hypo)maniaques. La consommation de cannabis augmentait fortement le risque de développer des symptômes psychotiques et (hypo)maniaques, mais les effets de la consommation de cannabis sur la dépression étaient mitigés. Le risque de développer des symptômes était influencé par l’âge d’apparition, la puissance du tétrahydrocannabinol (THC) et la fréquence de consommation de cannabis. Conclusions: La consommation de cannabis augmente le risque de développer et de maintenir des symptômes psychotiques et (hypo)maniaques, avec des effets mitigés pour les symptômes dépressifs, chez les individus en bonne santé. Ces effets se produisent de manière proportionnelle à la dose et dépendent de la puissance du THC. Des recherches supplémentaires sont nécessaires pour comprendre ces effets du cannabis, en particulier sur l’induction et la persistance des symptômes dépressifs et (hypo)maniaques.

Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis

“…This systematic review and meta-analysis found a dose–response relationship between the frequency of cannabis use and the development of psychosis, as shown by previous reviews (Hasan et al, 2020 ; Kiburi et al, 2021 ; Marconi et al, 2016 ; Moore et al, 2007 ; Polkosnik et al, 2021 ; van der Steur et al, 2020 ). Prior meta-analyses specifically documented a higher risk among daily users, mostly as compared to no or lower frequency use, with ORs ranging from 2.09 to 3.90 (Kiburi et al, 2021 ; Marconi et al, 2016 ; Moore et al, 2007 ).…”

“…Recent research has confirmed the importance of genetic influences, specifically polymorphisms on specific genes (e.g. COMT, AKT1) that make affected individuals more vulnerable to the psychogenetic effects of cannabis (Misiak et al, 2018 ; Polkosnik et al, 2021 ; van der Steur et al, 2020 ). The present review further compounds the evidence that specific (frequent) cannabis exposure patterns appear to significantly contribute to the multifactorial interplay toward psychosis outcomes.…”

“…Recent reviews have confirmed a moderately significant association between cannabis use and psychosis (Kiburi, Molebatsi, Ntlantsana, & Lynskey, 2021;Polkosnik, Sorkhou, & George, 2021;van der Steur, Batalla, & Bossong, 2020). The association between cannabis use and mental health problems, most notably psychosis, receives prominent attention in policy debates, even though other adverse outcomes (e.g.…”

“…While evidence for cannabis use as a causal contributor to psychosis development exist (Polkosnik et al, 2021 ; Wright et al, 2020 ), additional cannabis use-specific characteristics that function as moderating factors for this relationship have been identified. These factors include the age-of-use onset, high potency cannabis use, and the frequency of use (Matheson & Le Foll, 2020 ; Sideli, Quigley, La Cascia, & Murray, 2020 ; van der Steur et al, 2020 ).…”

“…Elsewhere, a two-fold increase (AOR = 2.09, 95% CI 1.54–2.84) in the odds of psychosis had been found in a comparison of frequent to no cannabis use (Moore et al, 2007 ). Other reviews, however, have been limited in their level of detail about the relationship between cannabis use frequency and psychosis risk where, for example, frequent use is commonly compared to only infrequent or non-use (Campeny et al, 2020 ; Hasan et al, 2020 ; Kiburi et al, 2021 ; Marconi et al, 2016 ; Polkosnik et al, 2021 ; van der Steur et al, 2020 ). Binary categorizations between frequent use v. no use cannot distinguish possibly different risk-by frequency of use levels (e.g.…”