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Biological plausibility of sex difference?
- Adam Jacobs (25 November 2002)
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Gender differences may be biologically plausible
- Nadia Solowij (3 December 2002)
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Cannabis abuse and suicidality in a longitidinal study
- Wen-Hung Kuo (7 December 2002)
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A novel idea idea to help young people refuse cannabis
- Oliver J Rooke, Hinemoa Elder (11 December 2002)
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Cannabis reduces risk of depression in men?
- Judith E. Meuwly Correll, 1700 Freiburg (7 January 2003)
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Confidentiality and Perceived Image of Cannabis Use as Potential Biases
- Kathryn M Drysdale, Matthew Casemore, Caroline Smith and Iain J. Robbé (Clinical Senior Lecturer). (28 January 2003)
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Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ
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Patton et al found a significant association between cannabis use and subsequent depression and anxiety in women, but not in men. To their credit, they assessed the difference between the sexes with a formal interaction test, and the significance of that test gives confidence that the difference between men and women was genuine. This result begs the question: why are the results different in men and women? There are two possibilities here. First, the relationship is causal, and cannabis use causes mood disorders in women, but not in men. Second, the relationship is not causal, and common factors that predispose to both cannabis use and mood disorders exist in women but not in men. Any common factors that predispose to mood disorders and cannabis use would undoubtedly be extremely complex, and probably impossible to adjust for completely in a study of this sort. Patton et al's adjustment of their analysis for factors such as alcohol use and parental separation is a sensible strategy, but I would be surprised if it even comes close to capturing the full complexity of the situation. How, then, are we to know if the relationship between cannabis use and mood disorders is causal? One thing that might be helpful is to consider biological plausibility. I find it easy to believe that common factors could predispose to both cannabis use and mood disorders in one sex but not the other, as the reasons why people may choose to use cannabis depend on many cultural and environmental influences that could easily differ between the sexes. A challenge for researchers is to identify what those differences are. On the other hand, if the relationship is causal, we would need to hypothesise that the way that the components of cannabis interact with receptors in the brain differs between men and women. Is there any evidence that they do? If it could be shown that the density or activity of cannabinoid receptors are different in men and women, that would lend support to the hypothesis of a causal relationship. If it cannot, I would remain sceptical about any suggested causality. Competing interests: None declared |
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Nadia Solowij, Research Fellow Illawarra Institute for Mental Health, University of Wollongong, Australia
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Adam Jacobs queries whether there is any evidence that components of cannabis may interact differentially with the cannabinoid receptor between men and women. While there is no specific evidence for differential receptor interactions between the sexes, there is evidence that the genetic expression of the cannabinoid receptor in humans varies according to gender (1). Further, levels of anandamide and 2-AG, the endogenous cannabinoids that bind to the receptor, have been found to differ in several brain regions between male and female mice (2). Cannabinoids interact extensively with the sex hormones and chronic use may alter the menstrual cycle and decrease ovulation (3). Early onset cannabis use may alter neural developmental processes by suppressing the expression of prolactin, growth hormone and the sex hormones, and it is possible that such neural alteration could result in differential neurobiological susceptibilities in females. Estrogen and progesterone appear to modulate the expression and density of cannabinoid receptors in certain brain regions, thus altering responsiveness to cannabinoids (3). Cannabinoids have been shown to produce greater effects in female than male rats on various behavioural measures (4). It has been hypothesised that greater deposits of fatty tissues in females could predispose them to a greater degree of storage of cannabinoids and their metabolites but this has not been verified. In general, there is a paucity of studies examining gender differences in humans but the evidence from animal research suggests a biological plausibility for sex differences in response to cannabis and its long term effects. This could potentially support a causal hypothesis to explain greater susceptibility to depression and anxiety in female cannabis users that requires further extensive research. 1. Onaivi, E.S., Leonard, C.M., Ishiguro, H., Zhang, P.W., Lin, Z., Akinshola, B.E. and Uhl, G.R. (2002) Endocannabinoids and cannabinoid receptor genetics. Progress in Neurobiology, 66, 307-344.. 2. Di Marzo, V., Petrocellis, L., Bisogno, T., Berger, A. and Mechoulam, R. (2002) Biology of endocannabinoids. In Onaivi, E. (Ed.) Biology of Marijuana: From gene to behavior, (pp. 125-173). London: Taylor & Francis. 3. Murphy, L.L. (2002) Marijuana and endocrine function. In Onaivi, E. (Ed.) Biology of Marijuana: From gene to behavior, (pp. 333-343). London: Taylor & Francis. 4. Tseng, A.H. and Craft, R.M. (2001) Sex differences in antinociceptive and motoric effects of cannabinoids. European Journal of Pharmacology, 430, 41-47. Nadia Solowij, PhD
Competing interests: None declared |
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Wen-Hung Kuo, Fellow NDRI, New York, NY, USA
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I read the cannabis related papers in BMJ with great interest (1,2,3). It was concluded that cannabis use are longitudinally associated with schizophrenia, depression, and anxiety. Another study based in the U.S., published in 2001 (4) also concluded that cannabis preceded depressive symptoms. Using this same U.S. based dataset from Epidemiologic Catchment Area (ECA) study (5), I found that diagnosis of cannabis abuse was also associated with incidence of suicide ideation in the following 15 years period. While gender and racial background were not associated with suicide ideation, cannabis abusers were 3 times greater in developing suicide ideation than non-abusers (adjusted odds ratio=3.00, CI=1.46- 6.18). Even after adjusting for the baseline diagnoses of depressive episode and alcohol abuse, cannabis abuse remained a significant risk factor for incident suicide ideation (adjusted odds ratio=2.72, CI=1.52- 6.50). Interestingly, we had a similar finding to Patton et al. (3). After dividing by gender, we found that the association of cannabis abuse and later suicide ideation was only manifested in women (adjusted odds ratio=3.91, CI=1.84-8.28) but not in men (adjusted odds ratio=1.82, CI=0.71-4.66). This gender interaction was marginally significant (Wald ÷2 =2.9, 0.05<p<0.1). We did not find any longitudinal association between cannabis abuse and incidence of suicide attempts (adjusted odds ratio=1.73, CI=0.72-4.14, Wald ÷2 =1.52, df=1, p<0.22), which suggests that the adverse effects of cannabis might contribute more to thoughts instead of behaviors. References 1. Arseneault H, Cannon M, Poulton R, Murray R, Caspi A, and Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002; 325: 1212-3. 2. Zammit S, Allebeck P, Andreasson S, Lundberg I, and Lewis G. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 2002; 325: 1199-201. 3. Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, and Hall W. Cannabis use and mental health in young people: cohort study. BMJ 2002; 325: 1195-98. 4. Bovasso GB: Cannabis abuse as a risk factor for depressive symptoms. Am J Psychiatry 2001; 158(12): 2033-7 5. Kuo WH, Gallo JJ, Tien AY: Incidence of Suicide Attempts and Ideation in Adults: the 13-year follow-up of a community sample in Baltimore, Maryland. Psych Med 2001; 31: 1181-91 Competing interests: None declared |
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Oliver J Rooke, consultant child and aolescent psychiatrist Child and Family Unit, Starship hospital, Auckland, New Zealand, Hinemoa Elder
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Dear sir/madam In common with other adolescent psychiatrists, we cannot help but be struck by the close relationship between psychotic illness and the consumption of cannabis. All efforts at psycho-education, cognitive therapy, motivational work etc. seem to be sabotaged by the widely held belief that to refuse a joint is not ‘cool’. Those of us who can remember our own adolescence will understand why all the above techniques are doomed without some means to make refusal honourable and therefore not risk alienating the young person from their peer group. Two recent papers in this journal provide compelling evidence that cannabis plays a causal role in schizophrenia. Two points are of interest, firstly that the quantities found necessary to substantially increase the risk are very moderate by today's standards of consumption and secondly that the risk is much greater if the consumer is 15 rather than 18 (1),(2). The particular vulnerability during adolescence supports evidence on the pathogenesis of schizophrenia - that the disorder represents a failure to arrest the normal, physiological process of pruning of synapses that occurs during adolescence (3). These facts emphasise the urgency of intervention in young psychotic people before they damage their brains still further. For some time we have used the analogy that our patients are allergic to cannabis to explain to them why they are so vulnerable to the drug whilst their friends appear not to be. One of our patients suggested that it might be easier to refuse it if he were given a medical alert bracelet stating that he was allergic to it. Other patients have since also accepted the offer and wear their bracelets with pride. The short follow up that we have available suggests that it may be a successful addition to the usual techniques. A search of medline and Embase and PsychInfo submitting the terms (bracelet or medical alert or medalert) and cannabis revealed no articles. We propose that colleagues may consider a medical alert bracelet a worthwhile investment for their clients and perhaps even a topic for research. 1/ Zammit S, Allbeck P, Andreasson S et al 2002: Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 325: 1199-1201 2/ Arseneault L, Cannon M, Poulton R et al 2002: Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 325: 1212-1213 3/ Siekmeier P, Hoffmfman R. 2002: Enhanced semantic priming in schizophrenia: a computer model based on excessive pruning of local connections in association cortex. Brit. J. Psych. 180:345-350 Competing interests: None declared |
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Judith E. Meuwly Correll, health promotion worker/philosopher Suchtpräventionsstelle Freiburg, 1700 Freiburg
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I have two questions to the authors of the study: - Do I read table 3 correctly: More than weekly consumption of cannabis actually seems to reduce the risk of depression in young men by half? If this is true, why is it not commented upon in the article? (If it is true, then I'm wondering if there could be a possible link to some findings in a study published in Nature (vol 418 p 530) by Beat Lutz from the Max Planck Institute of Psychiatry in Munich: they have found that the cannabinoids - which are obviously similar to THC - play an important role in getting rid of unwanted memories in mice.) Which would be the odds ratio for only women with no cannabis use in table 3? I noticed that in Table 2 the odds ratio for women in the absence of cannabis use is already 2.5. I am reading currently many studies done about cannabis and as a philosopher am intrigued about the way studies and numbers are commented upon and which are not. Thank you for your help. Judith Meuwly Correll Competing interests: None declared |
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Kathryn M Drysdale, Intercalated B Sc medical student University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Matthew Casemore, Caroline Smith and Iain J. Robbé (Clinical Senior Lecturer).
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Dear Sir, We read with interest the paper by Patton et al. (1) concerning cannabis use and depression and anxiety. We thought that generally this study was well conducted and it reports an increasingly important area given the high prevalence of cannabis use (1,2). However there are two particular issues that we felt the authors could have considered in more detail. The first issue concerns the collection of data in waves 1-6 and particularly wave 7. The authors argue that the use of telephone interviews is "unlikely to have caused a systemic bias" (1). However 71% of participants still lived at home and we would suggest that ensuring the confidentiality of the replies requested would be very difficult. We would have been more reassured about this bias due to a lack of confidentiality if examples of the questions asked in the telephone interviews had been included in the paper. The second issue is the finding from this study of a significant association between cannabis use during adolescence and depression in later life in young women, but not in young men. The authors postulate that predisposing characteristics and psychosocial mechanisms may account for the different results between the sexes. We wondered if differentials in the willingness of young men and women to report symptoms of depression or anxiety could also be involved. Furthermore, differences in attitudes to cannabis and other illicit drug use among young men and women might have affected the level of use reported. We consider that further qualitative research into the beliefs and attitudes of adolescents and young adults in the areas of cannabis use, and depression and anxiety would help with the understanding of these results. Also the research might identify other factors which may independently link cannabis use and depression or anxiety. References 1) Patton GC, Coffey C., Carlin JB, Degenhardt L, Lynskey M, Hall, W. Cannabis use and mental health in young people: cohort study. BMJ 2002; 325:1195-8. 2) Rey JM and Tennant CG. Cannabis and Mental Health. BMJ 2002; 325: 1183-4. Competing interests: None declared |
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