Cannabis and psychosis: understanding the smoke signals
Authors: Rachel A Rabin, Tony P George
Journal: The Lancet Psychiatry (2016)

There is no cure for schizophrenia. Accordingly, clinicians must do their best at managing the various symptoms that emerge during the course of the disease. Therefore, identification of putative risk factors that trigger relapse and contribute to poor prognosis is crucial. Because cannabis might contribute to the development of schizophrenia,1Moore TH Zammit S Lingford-Hughes A et al.Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review.Lancet. 2007; 370: 319-328Summary Full Text Full Text PDF PubMed Scopus (1632) Google Scholar the continued effect of the drug on the course of the disease is of great clinical interest and a focus on how to improve outcomes in this disorder is essential. In their observational study, Tabea Schoeler and colleagues2Schoeler 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 Psych. 2016; (published online Aug 22.)http://dx.doi.org/10.1016/S2215-0366(16)30230-9Google Scholar investigated the effects of different patterns of cannabis (eg, use, frequency, and potency) on risk of relapse in patients with first episode psychosis in South London, UK. Findings showed that cannabis' effects on outcome varied depending on the particular cannabis-using profile of the individual. More specifically, cannabis users who had continuous, high frequency and high potency exposure had the worst outcome, in terms of risk of relapse (OR 3·28, 95% CI 1·22–9·18), number of relapses (IRR 1·77, 95% CI 0·96–3·25), time to relapse (b −0·22, 95% CI −0·40 to −0·04), and more intense psychiatric care after the onset of psychosis compared with former users (OR 3·16, 95% CI 1·26–8·09). Further, high frequency, high potency users relapsed more quickly than did patients who consumed high potency cannabis at a lower frequency, hash-like cannabis users, and patients who were never (regular) cannabis users. This study offers several strengths over other studies that have assessed the association between cannabis and outcome in patients with psychotic disorders. First, this study was prospective, and assessed cannabis use trajectories during the first 2 years after the onset of psychosis. A major limitation of previous cross-sectional studies is their inability to differentiate between cause and effect. This caveat has led to the self-medication hypothesis,3Khantzian EJ The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence.Am J Psychiatry. 1985; 142: 1259-1264Crossref PubMed Scopus (1851) Google Scholar an over-popularised explanation for addictive behaviours that posits that cannabis is used by patients to help mitigate the negative effects of the disorder as well as side effects associated with antipsychotic treatment. Inconsistent with this idea, findings from Schoeler and colleagues showed that cannabis might contribute to symptomatology rather than alleviating it. This finding underscores the importance of employing the appropriate temporal and longitudinal paradigms when assessing the effects of cannabis on outcome in patients across the schizophrenia spectrum. Cannabis is a difficult substance to quantify. Accordingly, the researchers aimed to assess cannabis exposure not only as a measure of continuity and frequency, but also with respect to potency. Cannabis is a very complex plant that can be bred to yield hundreds of strains, each with a unique combination of cannabinoids. However, in most studies cannabis is conceptualised as a uniform drug. Cannabis varies substantially in the level of its two major cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Levels of CBD can range from almost zero to up to 40%.4Hardwick S King LA Home Office cannabis potency study 2008.http://www.dldocs.stir.ac.uk/documents/potency.pdfGoogle Scholar Notably, these two cannabinoids have opposing properties and thus can produce divergent effects. For example, THC is often associated with deleterious effects such as impaired cognition, anxiety, and psychotic-like symptoms, whereas CBD has been associated with antipsychotic and anxiolytic-like effects, and might even offer neuroprotection.5Morrison PD Zois V McKeown DA et al.The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning.Psychol Med. 2009; 39: 1607-1616Crossref PubMed Scopus (225) Google Scholar, 6Zuardi AW Crippa JA Hallak JE Moreira FA Guimaraes FS Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.Braz J Med Biol Res. 2006; 39: 421-429Crossref PubMed Scopus (282) Google Scholar, 7McPartland JM Duncan M Di Marzo V Pertwee RG Are cannabidiol and Delta(9)-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review.Br J Pharmacol. 2015; 172: 737-753Crossref PubMed Scopus (340) Google Scholar In view of these differences, the researchers aimed to decipher the type of cannabis their study sample consumed by asking participants to describe their preferred type of cannabis: skunk-like (high THC) or hash-like (high CBD). The investigators should be commended for confronting this issue; however, the manner in which it was addressed raises concern. Can patients with first episode psychosis accurately identify the type of cannabis they are using? Objective quantitative analysis might more reliably capture cannabis potency versus qualitative methods. Additionally, the assessment of potency as a binary variable might be too simplistic for such a complex plant in view of the fact that effects of cannabis depend not only on THC potency, but also on the ratio of THC to CBD.8Zuardi AW Hallak JE Crippa JA Interaction between cannabidiol (CBD) and (9)-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids.Psychopharmacology. 2012; 219: 247-249Crossref PubMed Scopus (57) Google Scholar The importance of studying the type of cannabis of users has recently been highlighted in the scientific literature.9Hagerty SL Williams SL Mittal VA Hutchison KE The cannabis conundrum: Thinking outside the THC box.J Clin Pharmacol. 2015; 55: 839-841Crossref PubMed Scopus (7) Google Scholar As cannabis research progresses, hopefully investigators will begin to regard cannabis as a conglomerate of cannabinoids rather than one homogeneous substance. Findings presented by Schoeler and colleagues2Schoeler 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 Psych. 2016; (published online Aug 22.)http://dx.doi.org/10.1016/S2215-0366(16)30230-9Google Scholar support the idea that clinicians should actively intervene and help patients to quit cannabis and remain abstinent. Nevertheless, the investigators suggest a possible harm reduction model in which interventions could focus on persuading cannabis users to reduce use or shift to less potent forms of cannabis, especially patients with psychosis who are otherwise unable to stop using cannabis. However, the proposal of such a framework might be problematic. In the same respect that not all cannabis is the same, not all users are the same. That is, skunk users might differ from hash users. Additionally, if high potency users switch to low potency cannabis, conceivably, they might use more cannabis in an attempt to chase the familiar high. Better characterisation of these different users is warranted to develop appropriate and tailored interventions. The investigators' results highlight the association between cannabis and subsequent relapse in patients with first episode psychosis, especially in those who are frequently exposed to high potency preparations. As a result of genetic modification and advanced methods of cultivation, high THC cannabis is becoming the norm, therefore addressing the increased risks implicated with these strains of cannabis should be of high priority. In the past 12 months, TPG has received industry sponsored grants from Pfizer, and served as a member of a Data Monitoring Committee for Novartis. RAR declares no competing interests. RAR and TPG both contributed to the writing of the Comment. Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational studyAdverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis. Full-Text PDF Open Access