Psychosis relapse, medication non-adherence, and cannabis
Authors: John A Engh, Jørgen G Bramness
Journal: The Lancet Psychiatry (2017)

In The Lancet Psychiatry, Schoeler and colleagues present a study1Schoeler T Petros N Di Forti M et al.Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first episode psychosis: a prospective analysis.Lancet Psychiatry. 2017; 4: 627-633Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar describing the mediating effect of medication adherence on the association between continued cannabis use and relapse risk in patients with first-episode psychosis. They have previously reported a relapse rate of 36% in this patient group over a 2-year period.2Schoeler T Petros N Di Forti M et al.Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study.Lancet Psychiatry. 2016; (published online July 10.)http://dx.doi.org/10.1016/S2215-0366(17)30233-XGoogle Scholar Acknowledging the potential risk of psychosis relapse related to the high proportion of patients continuing cannabis use after the onset of psychosis, the current study1Schoeler T Petros N Di Forti M et al.Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first episode psychosis: a prospective analysis.Lancet Psychiatry. 2017; 4: 627-633Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar investigates the same patient group consisting of 245 patients, obtaining retrospective data on active cannabis use and medication adherence shortly after illness onset, as well as risk of relapse at 2-year follow-up. The authors find that relapse of psychosis associated with continued cannabis use is partly mediated through non-adherence to prescribed antipsychotic medication. It is well established that cannabis use increases the risk of schizophrenia, not only from the early Swedish conscript studies3Andreasson S Engstrom A Allebeck P et al.Cannabis and schizophrenia: a longitudinal study of Swedish conscripts.Lancet. 1987; 330: 1483-1486Summary Scopus (884) Google Scholar but also from studies on people who use sinsemilla in London, UK, showing that high potency cannabis increases the risk of schizophrenia.4Di Forti M Morgan C Dazzan P et al.High-potency cannabis and the risk of psychosis.Br J Psychiatry. 2009; 195: 488-491Crossref PubMed Scopus (395) Google Scholar Twin studies from Norway have shown that cannabis increases the risk of psychosis, even when controlling for genetic factors.5Nesvåg R Reichborn-Kjennerud T Gillespie NA et al.Genetic and environmental contributions to the association between cannabis use and psychotic-like experiences in young adult twins.Schizophr Bull. 2017; 43: 644-653PubMed Google Scholar There has been discussion on the direction of the association, as none of these studies can rule out reverse causality, but it seems reasonable to conclude that cannabis is one of many stressors that can precipitate schizophrenia, at least in susceptible individuals. The association between cannabis use and psychosis continues to interest clinicians and researchers. Cannabis does not precipitate psychosis in most users.3Andreasson S Engstrom A Allebeck P et al.Cannabis and schizophrenia: a longitudinal study of Swedish conscripts.Lancet. 1987; 330: 1483-1486Summary Scopus (884) Google Scholar What are the risk factors in the pathway from cannabis use to psychosis? The use of cannabis in patients with psychosis can be divided into three groups: those not using cannabis, those using cannabis with few negative consequences, and those in whom cannabis use is followed by relapse and worsening of the disease. Too little effort has been put into studying people with psychosis who can use cannabis without many negative consequences. Further research should also be put into different variants of cannabis. Strains cultured to produce high content of D-9 tetrahydrocannabinol (THC) are probably associated with higher risk for psychosis than those strains with less THC.4Di Forti M Morgan C Dazzan P et al.High-potency cannabis and the risk of psychosis.Br J Psychiatry. 2009; 195: 488-491Crossref PubMed Scopus (395) Google Scholar In healthy participants, cannabidiol has been shown to inhibit THC-elicited paranoid symptoms and hippocampal-dependent memory impairment.6Englund A Morrison PD Nottage J et al.Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment.J Psychopharmacol. 2013; 27: 19-27Crossref PubMed Scopus (302) Google Scholar The use of more balanced forms of cannabis could possibly be less detrimental to mental health. Genetic predisposition is one factor that is related to the development of psychosis after the use of cannabis.5Nesvåg R Reichborn-Kjennerud T Gillespie NA et al.Genetic and environmental contributions to the association between cannabis use and psychotic-like experiences in young adult twins.Schizophr Bull. 2017; 43: 644-653PubMed Google Scholar However, there is still a long way to go in clarifying the interplay between genes and environmental factors in the cannabis–psychosis association. Therefore, we support the request for doing more studies to investigate the possible interaction between polygenic risk score for schizophrenia and cannabis use in causing psychosis.7Murray RM Quigley H Quattrone D et al.Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis.World Psychiatr. 2016; 15: 195-204Crossref PubMed Scopus (146) Google Scholar Furthermore, there is a need to examine the use of antipsychotic medication and investigate if some medications are particularly useful for patients with psychotic disorders who intend to continue to use cannabis. In a randomised trial comparing the effects of different antipsychotics,8Brunette MF Dawson R O'Keefe CD et al.A randomized trial of clozapine vs. other antipsychotics for cannabis use disorder in patients with schizophrenia.J Dual Diagn. 2011; 7: 50-63Crossref PubMed Scopus (41) Google Scholar clozapine seemed to stand out in reducing craving for cannabis, a finding that is in need of replication. Previous research has shown that stopping cannabis use after a first episode of psychosis has beneficial outcomes compared with continued use.9González-Pinto A Alberich S Barbeito S et al.Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use.Schizophr Bull. 2011; 37: 631-639Crossref PubMed Scopus (93) Google Scholar A meta-analysis of observational studies published in 201710Foglia E Schoeler T Klamerus E et al.Cannabis use and adherence to antipsychotic medication: a systematic review and meta-analysis.Psychol Med. 2017; (published online Feb 09.)https://doi.org/10.1017/S0033291717000046Crossref PubMed Scopus (38) Google Scholar compared adherence to antipsychotic medication between cannabis users and non-users, and found that cannabis use increases the risk of non-adherence to anti-psychotic medication and quitting cannabis may help adherence to antipsychotics. In the current study by Schoeler and colleagues,1Schoeler T Petros N Di Forti M et al.Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first episode psychosis: a prospective analysis.Lancet Psychiatry. 2017; 4: 627-633Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar the authors found that adherence to medication was a possible mediator in the association between cannabis use and risk of psychosis relapse when taking potential confounders into account. They found that medication adherence partly mediated the effect of continued cannabis use on outcome, including risk of relapse (proportion mediated=26%, pindirect effects=0·040, 95% CI 0·004–0·16), number of relapses (36%, pindirect effects=0·040, 0·003–0·14), time to relapse (28%, pindirect effects=0·051, −0·53 to 0·001), and care intensity (20%, pindirect effects=0·035, 0·004–0·11), but not length of relapse (6%, pindirect effects=0·35, −0·030 to 0·09). Acknowledging the complexity of psychosis relapse prevention, the current findings point to reduction in cannabis use as an intervention target to improve medication adherence, thereby preventing psychosis relapse. The understanding of a triangular association of ongoing cannabis use with medication adherence and psychosis relapse may be a step forward in counteracting further psychotic episodes in some patients. We declare no competing interests Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first-episode psychosis: a prospective analysisBetween 20% and 36% of the adverse effects of continued cannabis use on outcome in psychosis might be mediated through the effects of cannabis use on medication adherence. Interventions directed at medication adherence could partly help mitigate the harm from cannabis use in psychosis. Full-Text PDF Open Access