This is a set of notes and additional ideas and references that is intended to accompany the article "Cannabis & Psychosis" article from the June 2005 issue of Erowid Extracts. It is not intended to stand alone.

• THC : Some interesting research has been done to look at animal models for psychosis and endogenous systems that are implicated in psychotic disorders.
• Dosage : A major issue not covered by most of the surveys is actually how much people take. Smoking frequency cannot be equated to dosage without additional information. Some people smoke small amounts of weak cannabis at least once per day (one example is mixing a small amount of leaf or brick-cannabis with tobacco in a cigarette), while others smoke strong buds regularly. The issue of actual dosage needs to be looked at in 'natural' populations.
• Health Benefits: There are a number of health benefits that are now associated with cannabis use, including the more recently discovered issues related to Alzheimers and cardio vascular diseases. No risk can be taken in isolation and the possible small increased risk of psychotic disorders in some people cannot, by itself, decide whether cannabis use is "overall harmful" or not.
• Medicinal Interactions. Although no indication is given as to whether diagnosed psychotics were identified in most of the studies and their data considered separately, there is the possibility that people who are undergoing treatment for mental health problems may experience a negative interaction between their medication and the cannabis itself, increasing the frequency of psychotic symptoms.
  
  This is a fairly minor point, because diagnosed psychotics should only represent a small portion of the study sample. However, it needs to be taken into consideration when evaluating a study design that looks at symptoms and relapse rates for psychosis sufferers. Some anti-psychotics -- especially haloperidol-type drugs -- are considered to be very unpleasant to take if one uses cannabis (Marchese et al. 2003; Green et al. 2004). If there is a substantial increase in side effects caused by an interaction between medications and cannabis, it is important to separate those from the more general effect of cannabis on the population. In other words, these examples suggest that cannabis use 'worsens symptoms for psychosis sufferers' rather than causes psychosis.
• Self Reporting Bias : One point made by one of the reviewers of the article was that they had not seen any work on looking at whether the reporting bias associated with admitting to cannabis use could be correlated with willingness to report strange thoughts. Both could be caused by a "general public openness about personal foibles" personality trait. PL (erowid reviewer) writes:

  "That is, assume two populations: individuals open to public discussion, and closed more private individuals. The open dudes would say yes a lot more often to 'smoke dope' and 'have crazy idea' than the closed. To test this hypothesis, you could have to have other factors that are (presumably) unrelated by potentially embarrassing, 'made remark that unintentionally embarrasses an acquaintance' or 'fart at public events when sitting next to a stranger' and use that as a placeholder for 'openness to publicly disclose personal foible', and test for correlations, and see if that is stronger or weaker than correlations between cannabis and psychoses." [PL - personal communication]

"Despite widespread concern, we have found no strong evidence that use of cannabis in itself has important consequences for psychological or social health. This finding is not equivalent to the conclusion that use of cannabis is harmless in psychosocial terms; problems with the available evidence render it equally unable to support this proposition. Better evidence is needed in relation to cannabis, which is widely used, and in relation to other drugs that, although less widely used, might have important effects." macleod 2004

"The claim about cannabis and psychosis is widely understood in the popular media and public debate in Australia to imply that cannabis use has increased the number of cases of psychosis in the population (in the sense of causing cases of psychosis that would not otherwise have occurred)." degenhardt 2003 p45

"It may be particularly difficult to control psychotic symptoms in patients using cannabis. This is not true for cocaine, I had people with good control of psychosis smoking crack daily and taking a good antipsychotic dose. Most people tolerate cannabis well, but the cases vunerable to psychosis do not improve if the substance is not completely discontinued. I suppose is some sort of psychotic phenomena with low dopaminergic turnover. Just my 2 cents." PJ PN, MD, private communication.

Although I read several dozen papers while working on this article, for those interested in learning more about the current state of research into this question, the place to start is with some of the excellent literature reviews that have been done recently and then read the papers describing more recent research. Unfortunately, all of the following are targeted at people comfortable with reading scientific medical literature and can be a lot of work :

1. Castle and Murray "Marijuana and Madness" : Published in mid-2004, this book consists of thirteen well written and edited chapters, each one a literature review on a topic related to the issue of whether cannabis causes mental illness. Authors of the chapters include many of those who have worked in the field and published other peer-reviewed articles on the topic. The tone is cautious and measured and the overall message is that the research to date is both very concerning but incomplete. [Erowid Library]
2. Macleod J, et al. "Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies",The Lancet, 2004 may 15, 363. An excellent literature review of all the major longitudinal surveys that have reported assocations between cannabis use and 'psychosocial harm'. Although published in 2004, it addresses the same dataset that Fergusson et al 2005 analyze. Overall, the authors find problems that lead them to the conclusion that "available evidence does not strongly support an important causal relation between cannabis use by young people and psychosocial harm, but cannot exclude the possibility that such a relation exists." [ Abstract ]
3. Degenhardt L, Hall W, Lynskey M. "Testing hypotheses about the relationship between cannabis use and psychosis." Drug and Alcohol Dependence 2003 71:37-48. A systematic attempt to try to validate a causal relationship between cannabis and schizophrenia by looking at rates of mental illness in Australia and age of onset for schizophrenia. They found "Cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it." [ Abstract ]
4. Fergusson DM, et al. "Tests of causal linkages between cannabis use and psychotic symptoms". Addiction. 2005 100:345-366 This is the main paper that came out in March 2005 that caused a flood of news reports to report that cannabis use doubles the risk of 'psychosis'. [ Abstract]
5. Henquet C, et al. "Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people" BMJ Dec 1 2004. Longitudinal survey in Germany with 2437 people aged 14 to 24, surveyed on two occasions about four years appart. It showed a small (5.6%) increase in "psychotic symptoms" among those without a "predispotion" for psychosis and a 23.8% increase in the risk of psychosis among those who were designated as having a predisposition for psychosis in the first interview. They also found a dose-response relationship with heavier cannabis use associated with larger increases in rates of psychotic symptoms. [ Abstract ]
6. Ferdinand RF, et al. "Cannabis use predicts future psychotic symptoms, and vice versa". Addiction 2005. 100:612-618. An example of a paper that finds confusion in the long term longitudinal data about whether cannabis use leads to psychosis or psychosis leads to cannabis use. [ Abstract ]
7. Smit F, Bolier L, Cuijpers P. "Cannabis use and the risk of later schizophrenia: a review". Addiction 99:425-430. 2004. A literature review of the major longitudinal studies. They dismiss the self medication hypothesis, the possibility that other drugs confound cannabis as a direct cause, and state that "cannabis use appears to act as a risk factor in the onset of schizophrenia, especially in vulnerable people, but also in people without prior history." Not as solidly argued as Castle & Murray, nor Macleod, but another useful view of the available literature. [ Abstract ]

• The Link Between Marijuana and Schizophrenia - July 21 2010 - Time.com
  Comment: A surprisingly in depth look at this complex topic for Time Magazine.
• Cannabis: Too much, too young? - Mar 26 2005 - NewScientist.com
  Comment: An interesting article, definitely worth reading on the topic.
• BBC : Key Research
  Comment: Good summary article, too strongly supports positive causal hypothesis.
• How Science is Skewed to Fuel Fears of Marijuana March 20, 2005, The Ottawa Citizen
• What is 'mental illness', article from June 12 NYTimes that suggests mental illness is increasing

• Cannabis could reverse psychosis, Dec 1 2005, theage.com.au
  A story suggesting that THC and Canabidiol may have opposite effects on symptoms of psychosis, with THC increasing and canabidiol decreasing psychotic symptoms.
  

  Use of cannabis had been linked with an increased risk of developing psychosis because of the effects of THC (tetrahydrocannabinol), which also gives users a high, researcher Leonora Long said. "The interesting thing is that you have these two compounds in the cannabis plant that produce opposing effects," Ms Long said. "One is liable to produce psychotic symptoms, while the other may be protective against psychosis. "Cannabidiol may also help alleviate the symptoms of epilepsy and also pain associated with inflammatory disorders such as multiple sclerosis," she said.

• Where there's smoke...
  Guardian story that appears to be part of the campaign to push Cannabis back to Class B (from Class C) on the basis of the recent research showing a correlation between heavy cannabis use and mental illness.
  

  "I'm not an alarmist," she says, "nor a reactionary. In fact, I'd say I'm one of the most liberal people I know." ... "I would rather my daughter took heroin [than cannabis]."

• Schiffman J, Nakamura B, Earleywine M, LaBrie J. "Symptoms of schizotypy precede cannabis use". Psychiatry Res. 2005;134(1):37-42. [ abstract ]

  [T]he onset of schizotypal symptoms generally precedes the onset of cannabis use. The findings do not support a causal link between cannabis use and schizotypal traits.
  
  Although researchers recognize an association between cannabis use and psychosis, whether or not cannabis contributes to the development of psychosis remains less clear (Bowers et al., 2001). Numerous investigations have sought to establish cannabis use as a causal factor in the development of schizophrenia with mixed results (Allebeck et al., 1993; Hall and Solowij, 1997; Arseneault et al., 2002). In attempts to elucidate the role of cannabis use in the development of schizophrenia, investigators have used various procedures. For example, some have employed prospective longitudinal research methods (Arseneault et al., 2002; Phillips et al., 2002), while others have used cross-sectional or retrospective designs (Bersani et al., 2002). Some investigators have examined the specificity of cannabis versus other drugs as a precursor of schizophrenia (Andreasson et al., 1987; Zammit et al., 2002), and others have examined the premorbid functioning of patients with schizophrenia and a history of cannabis use (Andreasson et al., 1989).
  
  Finally, some investigators have examined the rates of types of symptoms (i.e., negative or positive) among cannabis-using and non- Despite these intensive efforts, results vary. Recently, Phillips et al. (2002) asserted that cannabis might not play an important role in the development of psychosis. Specifically, Phillips et al. (2002) found that cannabis use or dependence in the year before study recruitment did not heighten risk of developing psychosis over the following 12-month period.
  
  

The following is a chronological collection of quotes from news stories that have touched on this issue in the last year. There have been hundreds, but these give a bit of a sense of the frequency with which cannabis and mental health has gotten media coverage.

• Dec 1 2004:

  "Frequent cannabis use during adolescence and young adulthood raises the risk of psychotic symptoms later in life, research suggests. The risk was much higher in young people who were already genetically vulnerable to developing psychosis. It is thought cannabis disrupts the balance of the key mood chemical dopamine in the brain." [ Cannabis raises risk of psychosis - Dec 1 2004 http://news.bbc.co.uk/2/hi/health/4052963.stm ]

• Dec 1, 2004

  "Teenagers and young adults who frequently use cannabis are increasing their risk of suffering from psychotic symptoms such as bizarre behavior and delusions later in life, Dutch scientists said on Wednesday. Young people with a family history, or pre-existing susceptibility to mental instability, are particularly vulnerable to the negative effects of the drug. 'Cannabis does not act in the same fashion on psychosis risk for everybody. There is a group that is particularly susceptible,' Professor Jim van Os, of Maastricht University in the Netherlands, told a news conference." [ Marijuana may increase risk of psychosis : Drug makes some users more vulnerable to mental problems - Dec 1 2004 - http://www.msnbc.msn.com/id/6629828/ ]

• Jan 25 2005:

  "Mr Easton, who is rector of Falkirk High School, said: 'Cannabis may not be as bad as heroin or cocaine but it's far from harmless or safe - recent medical research has shown it can cause psychosis. But many young people are unaware of the potential side-effects and out with schools it's now the equivalent of what a fag behind the bike sheds was 35 years ago.' "[ Youth 'cannabis epidemic' warning - Jan 25 2005 BBC http://news.bbc.co.uk/2/hi/uk_news/scotland/4205677.stm ]

• Jan 29 2005:

  "The government says it will review all academic and clinical studies linking cannabis use to mental health problems. The Department of Health says it is now generally agreed among doctors that cannabis is an "important causal factor" in mental illness... It is Russian roulette," he said. "For some people it can ease pain, but for others it can be an absolute disaster." [ Cannabis mental health risk probe - Jan 29 2005 http://news.bbc.co.uk/2/hi/health/4218851.stm ]

• March 1 2005:

  "New research from the Christchurch School of Medicine and Health Sciences, Otago University, raises more doubts over cannabis being a therapeutic and harmless drug. Professor David Fergusson and colleagues at the School, who have been gathering data on a cohort of 1000 people for 25 years, have just published a research paper which suggests that heavy users of cannabis are more likely to suffer from psychotic symptoms." [ Published by school where Fergusson D works. Mar 1 2005 http://www.chmeds.ac.nz/newsevents/cannabis.htm ]

• Mar 1 2005:

  "Smoking cannabis almost doubles the risk of psychotic mental illness such as schizophrenia, new research revealed today. Based on data gathered over 25 years, researchers in New Zealand suggested that effects on the brain caused by cannabis probably explained higher rates of psychosis. It was not likely to be due to people with mental illness having a greater wish to smoke." [ 'Cannabis doubles the risk of psychosis' - Evening Standard - March 1, 2005 - http://www.thisislondon.co.uk/news/articles/16948799 ]

• March 1 2005:

  "Smoking cannabis virtually doubles the risk of developing mental illnesses such as schizophrenia, researchers say. The New Zealand scientists said their study suggested this was probably due to chemical changes in the brain which resulted from smoking the drug. The study, published in the journal Addiction, followed over 1,000 people born in 1977 for 25 years." [ Drug 'doubles mental health risk' - Mar 1 2005 - http://news.bbc.co.uk/2/hi/health/4305783.stm

• Mar 19 2005:

  "The Home Secretary has ordered a review of the decision to downgrade cannabis, as new studies suggest a strong link between the drug and mental illness. Cannabis was downgraded from class B to class C in January last year, based on a recommendation from the Advisory Council on the Misuse of Drugs." [ Clarke orders rethink on cannabis - Mar 19 2005 http://news.bbc.co.uk/2/hi/uk_news/4364625.stm ]

• March 26 2005 :

  "Over the past couple of years van Os and several others have been building the case that, for some teenagers, smoking cannabis leads to serious mental health problems in later life, including schizophrenia. Van Os claims that marijuana is responsible for up to 13 per cent of schizophrenia cases in the Netherlands. And with cannabis use among teenagers on the rise, the age at first use falling (see Graphic), and the strength of cannabis on the up, he says the figure can only increase." [ Cannabis: Too much, too young? - Mar 26 2005 - Graham Lawton http://www.newscientist.com/channel/health/mg18524921.300

• Apr 1 2005:

  "Cannabis-based medicines can cause paranoia and anxiety in some people, a study has suggested. Swiss researchers found two out of eight men given drugs containing THC, a chemical extracted from cannabis, developed psychotic effects." [ Cannabis medicine 'causes harm' - Apr 1 2005 http://news.bbc.co.uk/2/hi/health/4396911.stm ]

• Dec 1 2005:

  "Almost half of patients treated for a cannabis related mental disorder go on to develop a schizophrenic illness, a study has suggested. The Danish study, in the British Journal of Psychiatry, found a third of them developed paranoid schizophrenia."
  [ "Drug disorder schizophrenia link" - Dec 1 2005 http://news.bbc.co.uk/2/hi/health/4486548.stm ]

• Shan HH. Culture-Bound Psychiatric Disorders Associated with Qigong Practice In China Hong Kong J Psychiatry, 10(3):12-14. 2000.
  
  Qigong (Chikung) is a meditative and visualization technique for "moving energy" around the body. It is a commonly taught technique in martial arts and some meditative practices.
  

  In recent years, increasing numbers of culture-bound psychiatric disorders associated with Chinese Qigong practice have been reported in China. Such mental disorders associated with Chinese Qigong practice could be regarded as a kind of culture-bound syndrome and this diagnosis has been accepted by the Chinese Classification of Mental Disorders (CCMD-2) and a Chinese textbook of psychiatry.
  
  The syndrome has also been accepted by the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders.(5) This term is defined as an acute, time-limited episode characterised by dissociate, paranoid, and other psychotic or nonpsychotic symptoms that occur after participation in the Chinese folk health-enhancing practice of Qigong (exercise of vital energy).

• Vickers A, Zollman C. ABC of Complementary Medicine: Hypnosis and relaxation therapies. BMJ 319:1346-1349. 1999 20 Nov.
  

  Hypnosis or deep relaxation can sometimes exacerbate psychological problems---for example, by retraumatising those with post-traumatic disorders or by inducing "false memories" in psychologically vulnerable individuals. Concerns have also been raised that it can bring on a latent psychosis, although the evidence is inconclusive. Hypnosis should be undertaken only by appropriately trained, experienced, and regulated practitioners. It should be avoided in established or borderline psychosis and personality disorders, and hypnotherapists should be competent at recognising and referring patients in these states.

• Rethink UK Believes Cannabis Causes Mental Illness

• Definition of Schizophrenia Joseph F Smith Medical Library