ISSN 1359-9321 The Galton Institute NEWSLETTER Galtonia candicans Issue Number 69 December 2008 there has been much speculation that Contents there exist ‘genes for…’ many types of Cannabis and Psychosis: mental illness.2 However, as the evi- The Environment Trigger dence mounts which suggests gene- Cannabis and Psychosis 1 by environment interactions in human Benjamin Capps and David development – particularly in the effects Nutt of exposure to an environmental patho- Professor John Thoday 8 (Centre for Ethics in Medicine and gen on a person’s health is conditional Henry Wellcome L.I.N.E., upon her genotype3 – emphasis has IUSSP Seminar on University of Bristol) switched from discovering the Medelian Trade-offs in Female ‘units’ that cause phenotypes, to the Life Histories: 9 understanding of the complex relation- Introduction ship between genes and environment.4 Apparent IQ stability across There is growing evidence to suggest This paper addresses the ethical issues several decades 12 that there is a gene-environment interac- that arise from evidence that suggests tion between drug-taking and mental that some of the negative health effects health, that includes known environ- of cannabis use, in particular psychosis, mental pathogens and risk factors to may be predicted by genetic polymor- Milo Keynes specific substance-use disorders, and a phisms. We attempt to balance a heterogeneity in responses to these I am sad to have to announce that ‘genetic determinist’ view of disease Milo Keynes (our current Newsletter specific causes.5 One such drug is (e.g. a ‘gene for psychosis’) with the Editor) suffered a stroke on August cannabis, whose use is associated with concurrent evidence that the phenotypic 19th, 2008. After a difficult period psychosis: a disorder that is categorised expression of a gene, such as adult-onset he is now back in active rehabilita- as conditions in which a person’s ability tion and we all wish him a good and psychosis, may require an environmental to test reality is impaired.6 A relation- speedy recovery from here. trigger. Our primary aim is to offer ship between psychosis, in particular David Galton tentative suggestions as to how the ‘post- schizophrenia, and cannabis has been genomic era’ – a period in which society suggested for some time see6 but only is inundated with genetic data and novel Published by: recently have Caspi et al claimed applications of gene modification, evidence for a gene-environment The Galton Institute screening, and selection – may influence interaction in the effects of adolescent- 19 Northfields Prospect drug policies in the UK, specifically with onset cannabis use on adult psychosis.7 Northfields regard to cannabis use. In light of our They present data that suggest that LONDON SW18 1PE emergence from the Genomic Revolu- cannabis-induced psychosis has a genetic Telephone: 020-8874 7257 tion, it is appropriate that society component (a functional polymorphism considers the ethico-social implications General Secretary: of the catechol-0-methyltransferase of the ‘nature-nurture’ debate in this Mrs Betty Nixon (COMT) gene), thus strengthening the context.1 Newsletter Editor: view that gene-hunters can locate gene- to-disorder connections, even for David Galton (present issue) Cannabis and Psychosis multifactoral disorders, which minimally Web site: Genotype has long been associated represent a risk factor for asymptomatic www.galtoninstitute.org.uk with various mental health disorders, and carriers. Others have reported a similar GALTON INSTITUTE NEWSLETTER 1 DECEMBER 2008 link between COMT genotype and Neuropharmaceuticals are often autonomous decision to experience a psychotic symptoms, but as of yet the referred to as ‘drugs’, and tend to be certain mental state, despite the potential exact nature of the gene-environment either strictly controlled as medicines, or physical, psychological, legal and social and gene-gene relationship between when then fall outside this ‘legitimate’ costs, is a ‘voluntary’ action (as opposed psychosis and cannabis use remains use, classified as illicit, and therefore out to the burden of disease that compels unresolved, despite a growing number of of bounds for recreational use. When drug use on patients). However, many other human and animal studies.8 PSs are used outside the medical setting, drugs used in medicine have a hedonistic they are seen as being ‘misused’ on the value for recreational users (and evi- grounds that they can be categorically dence suggests that cannabis may also Importantly, Caspi et al argue that regarded as ‘harmful’ to the user or have a medicinal value for some pa- such a connection may only be apparent others around him, and intrinsically tients), and the therapeutic advantage is among individuals in a sample that has related to poverty, mental health and replaced by the attainment of ‘out of it’ been exposed to specific non-genetic illness, and criminality. There is experiences. Thus, the legal distinction risks: specifically adolescent-onset overwhelming evidence that widespread is one of medical indication (regulated cannabis use. They do not rule out other use of many drugs has massive eco- by the Medicines and Healthcare possible environmental risks and nomic and social costs; however, the link Products Regulatory Agency) and the pathogens; and they conclude: ‘Our to drug misuse is not always straightfor- socio-historical context of specific drugs. findings suggest that a rôle of some ward, and furthermore, it is often not Thus, understanding the circumstances susceptibility genes may be to influence helpful to describe different ‘drugs’ of drug (mis)use is part of a wider study response to these pathogenic environ- under a unified heading, since they often of the social construction and biochemi- ments’.9 This supports a (not uncontro- have very different pharmacological cal investigation of the effects of versial)10 view that ‘Cannabis use… is a effects, social acceptability, long and particular drugs.22 component cause, [but also] part of a short term psychological effects, medical complex constellation of factors leading uses, and legal status.14 There is evidence that cannabis has to psychosis’.11 Thus, it is proposed that medicinal benefits to offer, such as the risk of developing psychosis is The health-recreation distinction has controlling some forms of pain, alleviat- higher in those who are ‘genetically significant socio-political results. For ing nausea and vomiting due to chemo- vulnerable’ to the disease and are example, while medicines used as part of therapy, treating wasting due to AIDS, exposed at some time to cannabis, but therapy are considered as an acceptable and combating muscle spasms associated the aetiology and medical link is still medical intervention if properly pre- with multiple sclerosis. However, difficult to specify. This may include (or scribed (on the not unproblematic current research has not proved persua- an absence of) a family history of, or grounds of evidence-based medicine),15 sive to allow licensed use of cannabis, genetic predisposition to psychosis, and 23 recreational drug use is often dispropor- for example as an analgesic. A nega- a personal history of unusual tionately associated with social problems tive political view of cannabis as a ‘triggering’ (environmental) experiences. and crime,16 global instability,17 and the recreational drug remains a dominant ‘global burden of disease’.18 The political force, because of the sugges- comorbid effects of many drugs19 tions that its use increases the use of The Regulation of Neuropharma- therefore become a justification for other illicit drugs or that it is a ‘gateway’ ceuticals and Cannabis paternalistic government intervention.20 drug, encouraging uptake of other drug 24 Cannabis is a psychoactive substance However, this distinction is not as clear- use, though the evidence for this is 13 (PS), and is in the class of neuropharma- cut as some legal and social norms weak. The opposition to recognise ceuticals (pharmacological agents whose would indicate. Most drugs, whether cannabis as a medical treatment seems to primary mode of action is through used in medicine or for recreational be concerns as to potential side effects, altering the metabolism of neurotrans- purposes, have side effects. When used such as hallucinations, delusions and 25 mitters) many of which are widely used in therapy, these unwanted (and un- clinically significant schizophrenia, in medicine and for recreational pur- avoidable) effects are tolerated as a cost and that there are medical alternatives, 26 poses. It is primarily classified as a of curing, treating or elevating the for example, for pain management. hallucinogen; its active ingredient is primary condition. This is despite the delta-9-tetrahydrocannabinol; and it is large numbers of deaths caused by Cannabis Use in the Post-Genomic normally smoked or ingested. Cannabis adverse drug reactions, and the lack of Era is a widely used drug12 that is currently effectiveness for many patients of We now live in what some call the categorised in the UK as illicit though in particular prescribed drugs.21 This cost- ‘Post-genome era’. Data from the a lower class [C] than other drugs such analysis of health benefits is not evident human genome project, and potentially as heroin and cocaine [class A].13 in the recreational use of drugs, since the large amounts of raw epidemiological DECEMBER 2008 2 GALTON INSTITUTE NEWSLETTER data stemming from projects such as UK may become integral to perspectives of as a ‘gene for…’. Biobank, provide society with a unprece- drug (mis)use and the prediction, dented understanding of human inheri- prevention and treatment of non- So, should carriers of this variant be tance, difference and diseases; and this commutable diseases. This paper told of their risk of developing a psy- potentially gives rise to novel genetic focuses on cannabis-induced psychosis, chotic condition if they are exposed to ‘tests’ and escalating lists of diagnosable which, like many other diseases, has a cannabis? The first case may be if diseases and risk predispositions.