There are marked differences in the knowledge on the medical uses of cannabis and cannabinoids in different diseases. For nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia in HIV/AIDS, spasticity in multiple sclerosis and spinal cord injury there is strong evidence for medical benefits. For many other indications, such as epilepsy, movement disorders and depression there is much less available data.
Clinical studies with single cannabinoids or, less often with whole plant preparations (smoked marijuana, encapsulated cannabis extract) have often been inspired by positive anecdotal experiences of patients employing crude cannabis products. The anti-emetic, the appetite enhancing, relaxing effects, analgesia, and therapeutic use in Tourette's syndrome were all discovered in this manner.
Incidental observations have also revealed therapeutically useful effects in a study with patients with Alzheimer's disease wherein the primary issue was an examination of the appetite- stimulating effects of THC. Not only appetite and body weight increased, but disturbed behaviour among the patients also decreased. The discovery of decreased intraocular pressure with THC administration in the beginning of the 1970s was also serendipitous. For this reason, more surveys have been conducted in the past decade questioning individuals that use cannabis therapeutically.
(Lousia Degenhardt & Wayne Hall):
There has been considerable debate about the reasons for the association observed between cannabis use and psychosis in both clinical and general population samples. Among the hypotheses proposed to explain the association are the following: 1) common factors explain the co-occurrence; 2) cannabis causes psychosis that would not have occurred in the absence of cannabis use; 3) cannabis precipitates psychosis among persons who were vulnerable to developing the disorders; 4) cannabis use worsens or prolongs psychosis among those who have already developed the disorder; and 5) that persons with psychosis are more likely to become regular or problematic cannabis users than persons without psychosis. (...)
The evidence suggests that common factors do not explain the conjoint occurence between cannabis use and psychosis, and it is unlikely that cannabis use causes psychosis among persons who would otherwise not have developed the disorder. The evidence is more consistent with the hypotheses that cannabis use may precipitate psychosis among vulnerable individuals, increase the risk of relapse among those who have already developed the disorder, and may be more likely to lead to dependence in persons with schizophrenia. (...)
If cannabis use would cause new psychoses, then the frequency of schizophrenia would increase as the frequency of cannabis use increased in the age group at risk. Because there has been a dramatic increase in the frequency of cannabis use in Australia this hypothesis predicts an increase in psychosis among more recent birth cohorts. A decrease in the age of first cannabis use over this period also predicts an increase of early onset cases of psychosis. Degenhardt and colleagues evaluated this hypothesis by modeling trends in the number of persons with psychosis in Australia, because the frequency of regular cannabis use has increased. The evidence suggested there was no significant increase in the incidence of schizophrenia over the past 30 years in Australia, suggesting that rising cannabis use was not causally related to the incidence of schizophrenia. (...)
A number of studies have examined whether the age of onset of psychosis differs according to cannabis use. In a study of cases admitted to psychiatric hospitals over a 1-year period, cannabis users were significantly younger than nonusers - mean age of 29 years versus 40 years, respectively. (...) Another study examined first-episode cases of psychosis according to "drug abuse" status defined as using illegal drugs more than once per week for at least 1 month. Psychosis cases with a history of drug abuse were much more likely to have used cannabis compared with those without such history (88% vs 13%). They were also four times more likely to report the first signs of schizophrenia before the age of 20. The onset of substance abuse preceded or was in the same month as schizophrenia onset in 60%. These data are consistent with cannabis use precipitating the illness in these individuals. (...) In summary there is now reasonable evidence that persons with a vulnerability to schizophrenia have a higher risk of developing psychosis following the use of cannabis.
There is some evidence that some persons with schizophrenia who use cannabis are more likely to suffer a relapse. This hypothesis does not predict an increased frequency of schizophrenia among regular cannabis users. Rather, it predicts that persons with psychosis who are regular cannabis users are more likely to relapse, possibly increasing the number of persons with chronic schizophrenia. (...) Linszen and colleagues reported a prospective study of outcome of 93 psychotic patients assessed monthly over 1 year. The 24 patients who were cannabis users (11 were weekly and 13 were daily users) relapsed to psychotic symptoms sooner, and had more frequent relapses in the year of follow-up compared with patients who had not used cannabis. (...) In summary there is strong suggestive evidence that regular cannabis use worsens the prognosis of persons with schizophrenia. (...)
The principal psychoactive ingredient of cannabis is delta-9-tetrahydrocannabinol (THC), which acts on a specific cannabinoid receptor (CB1) in the brain. Although historically the dopaminergic system of the brain has been considered to play an important role in the psychotic disorders, there is increasing evidence that the cannabinoid system may be involved in schizophrenia and related psychotic disorders. For example, mice without the CB1 receptor show behaviors consistent with some of the symptoms of schizophrenia. Elevated levels of anandamide, an endogenous cannabinoid, have also been found in the cerebrospinal fluid of persons with schizophrenia, and a recent case control study found that persons with schizophrenia had a greater density of CB1 receptors in the prefrontal cortex than control individuals. (...)
Conclusions: The available epidemiologic evidence supports the following conclusions: 1) that cannabis use and psychosis are associated in clinical and general population samples; 2) the association is unlikely to be due to common causes or other confounding factors; 3) the time trends in schizophrenia and cannabis use are not consistent with hypothesis that cannabis use causes new schizophrenia; 4) in contrast, it is likely that cannabis use precipitates disorders in vulnerable individuals and exacerbates symptoms of psychosis in those who continue to use cannabis; 5) persons with schizophrenia and other psychoses may be more likely to become regular users if they use cannabis; and 6) emerging evidence on the role of the cannabinoid system in psychotic symptoms is consistent with the epidemiologic evidence that cannabis use can precipitate and exacerbate psychosis.
Modified according to: Degenhardt L, Hall W. Cannabis and psychosis. Curr Psychiatry Rep 2002;4(3):191-196.
I would like to comment on the paper by Lousia Degenhardt & Wayne Hall and add that during the past ten years some papers on the existence of a genuine cannabis psychosis were published. This psychosis is called "cannabis induced psychotic disorder" in the DSM-IV Manual (Diagnostic and Statistical Manual of Mental Disorders). These papers describe the main characteristics of this form of psychosis and the differences to paranoid schizophrenia. According to this research we must consider cannabis psychosis as a new entity, with its own characteristics, different from acute cannabis intoxication. The frequency is assumed to be low (1-2% of cannabis users) but this form of psychosis may be the first step to the development of schizophrenia if the subject does not stop using the drug.
(Institute of Medicine):
Among the studies that have investigated the relationship between prenatal marijuana exposure and birth outcome, the results have been inconsistent. Except for adolescent mothers, there is little evidence that gestation is shorter in mothers who smoke marijuana. Several studies of women who smoked marijuana regularly during pregnancy show that they tend to give birth to lower weight babies. (...)
For most of these studies, much of the harms associated with marijuana use are consistent with those associated with tobacco use, and smoking is a significant factor so the contribution of cannabinoids cannot be confirmed. However, Jamaican women who use marijuana rarely smoke it, but instead prepare it as tea. In a study of neonates born to Jamaican women who either did or did not ingest marijuana during pregnancy, there was no difference in neurobehavioral assessments made at 3 days after birth and at one month. (...)
Since 1978, the Ottawa Prenatal Prospective Study has been measuring the cognitive functions of children born to mothers who smoked marijuana during pregnancy. (...) The children in the different marijuana exposure groups showed no lasting differences in global measures of intelligence such as language development, reading scores, and visual or perceptual tests. Moderate cognitive deficits were detectable among these children when they were four days old and again at four years, but these deficits were no longer apparent at five years. Prenatal marijuana exposure was not, however, without lasting impact. By comparison, at both ages 5-6 and 9-12, children in the same study who were prenatally exposed to tobacco smoke scored significantly lower on tests of language skills and cognitive functioning.
Joy JE, Watson SJ, Benson JA, eds. Marijuana and medicine: Assessing the science base. Institute of Medicine. Washington DC: National Academy Press, 1999.
The consequences of prenatal exposure to cannabis are subtle. The impact during the course of pregnancy and upon the neonate appear to be considerably moderated by other risk factors with evidence from a number of cohorts suggesting mild effects upon fetal growth and central nervous system functioning. During the toddler stage, there is little evidence for a prenatal cannabis effect either upon growth or behavior. However, beyond the age of three, there are suggestive findings indicating a putative association between prenatal marihuana exposure and aspects of cognitive behavior that fall under the rubric of executive function. Particularly, the facets of this construct which appear impacted are the domains of attention/impulsivity and problem solving situations requiring integration and manipulation of basic visuoperceptual skills. Although there is a convergence of evidence, the very limited number of studies which have followed children beyond the age of three emphasizes the need for further, well controlled investigations in this area.
Fried P. Pregnancy. In: Grotenhermen F, Russo E, eds. Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Haworth Press, Bing-hamton/New York 2001, in press.
(Lynn Zimmer & John Morgan):
Studies of newborns, infants, and children show no consistent physical, developmental, or cognitive deficits related to prenatal marijuana exposure. Marijuana has no reliable impact on birth size, length of gestation, neurological development, or the occurence of physical abnormalities. The administration of hundreds of tests to older children has revealed only minor differences between the offspring of marijuana users and nonusers, and some are positive rather than negative. (...) While it is sensible to advise women to abstain from all drugs during pregnancy, the weight of evidence suggests that marijuana does not directly harm the human fetus.
Zimmer L, Morgan JP. Marijuana Myths Marijuana Facts. A review of the scientific evidence. New York/San Francisco: The Lindesmith Center, 1997.
It is unlikely that cannabis causes embryonic or fetal malformations. There are inconsistent epidemiological data on its effect on birth weight. There is evidence of subtle disturbances of cerebral development resulting in cognitive impairment in offspring of cannabis users. Some scientists assume such disturbances exist, while others believe that cannabis exerts no relevant negative effects. Possibly subtle cognitive marijuana-related disorders might not be observed before preschool or school age.(...)
No influences on physical fetal development in children born to chronic cannabis users have been reported. Yet, as far as possible, cannabis should be avoided during pregnancy and in lactating women because of the controversial evidence for subtle disturbances of cognitive development.
Grotenhermen F. Review of unwanted actions of Cannabis and THC. In: Grotenhermen F, Russo E, eds. Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Haworth Press, Bing-hamton/New York 2001, in press.
Grotenhermen F. Practical hints. In: Grotenhermen F, Russo E, eds. Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Haworth Press, Bing-hamton/New York 2001, in press.