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The long term effects of cannabis has been the subject of ongoing debate. Because cannabis is illegal in most countries, research presents a challenge. There remains much to be concluded. Studies have investigated both the detrimental and beneficial effects of long-term use of cannabis. The vast majority of this research focuses on those who use cannabis at least once a day. Recent research has investigated whether its long-term effects on adolescents differ from those on adults.

Data supporting negative effects of cannabis alone are weak. Discerning between correlation and causation is an important consideration. Studies exist showing both negative and positive effects, and much is conflicting. For instance, studies have associated heavy cannabis use with the development of various mental disorders, while other science points to both an ameliorative effect and no relationship whatsoever.

Memory and intelligence

Most scientific research leans toward cognitive deficits during intoxication and a residual effect for heavy users.

The strongest evidence regarding cannabis and memory focuses on its non-acute negative effects on short-term and working memory. Evidence also suggests that long-term effects exist, but these appear to be reversible except possibly in very heavy users.

Long-term effects found

A 1998 Journal of Neuroscience in vitro research, which was carried out on hippocampal cells excised from decapitated rats, using THC carried in ethyl alcohol to saturate the neurons, suggests that THC is toxic for cultured hippocampal neurons.

A 2001 study published in Neurology concluded that "very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence." This study consisted of 22 individuals, of which 7 were considered "heavy" users by smoking an average of 94 joints per week.

A 2008 study suggested that long-term, heavy cannabis use (over five joints daily for more than ten years) is associated with structural abnormalities in the hippocampus and amygdala areas of the brain. The hippocampus, thought to regulate emotion and memory, and the amygdala, involved with fear and aggression, tended to be smaller in heavy and long-term cannabis users than in controls. For heavy users participating in the study, volume was an average of 12% lower in the hippocampus and 7.1% lower in the amygdala. However, the sample size of the study was small, with only 31 participants total (15 heavy users and 16 non-users). The study concluded that "heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health;" however, there was a lack of prior brain testing. According to commentary provided by the National Cannabis Prevention and Information Centre (NCPIC), these brain regions are intricately involved in learning and memory processes and are considered core components of the emotional brain and the research found that in addition left hippocampal and amygdala volume was inversely associated with cumulative doses of cannabis over the previous 10 years, as well as subthreshold positive psychotic symptoms. In their commentary, NCPIC state: "While modest use may not lead to significant neurotoxicity, these results corroborate similar findings within the animal literature and indicate that heavy daily cannabis use over protracted periods exerts harmful effects on brain tissue and mental health." An earlier 1998 report by INSERM and CNRS, which was directed by Dr. Pierre-Bernard Roques, determined that, "former results suggesting anatomic changes in the brain of chronic cannabis users, measured by tomography, were not confirmed by the accurate modern neuro-imaging techniques (such as MRI) ... Moreover, morphological impairment of the hippocampus of rat after administration of very high doses of THC was not shown."

No effects found

In 1999, a naturalistic study, conducted over a period of 15 years found no link between cognitive decline and cannabis usage.

In a 2001 study looking at Neuropsychological performance in long-term cannabis users, researchers found "some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use". On his studies regarding cannabis use, lead researcher and Harvard professor Harrison Pope said he found cannabis is not dangerous over the long term, but there are short-term effects. From neuropsychological tests, Pope found that chronic cannabis users showed difficulties, with verbal memory in particular, for "at least a week or two" after they stopped smoking. Within 28 days, memory problems vanished and the subjects “were no longer distinguishable from the comparison group”.

A 2002 longitudinal study published in the Canadian Medical Association Journal concluded that "marijuana does not have a long-term negative impact on global intelligence," and that "current marijuana use had a negative effect on global IQ score only in subjects who smoked 5 or more joints per week." The study, which monitored subjects since birth, examined IQ scores before, during and after cessation of regular cannabis use. It found current light users and former users showed average IQ gains of 5.8 and 3.5 respectively, compared to an IQ gain of 2.6 for those who had never used cannabis. The study did show an average IQ decrease of 4.1 for heavy users who smoked 5 or more joints per week. However the study mentions that "The IQ deficit among heavy current users in the present study likely reflected residue of the drug in their bodies". However, Nadia Solowij has conducted several studies which make her conclude that there is, in fact, long term cognitive impairment with heavy cannabis use.

Researchers from the University of California, San Diego School of Medicine failed to show substantial, systemic neurological effects from long-term recreational use of cannabis. Their findings were published in the July 2003 issue of the Journal of the International Neuropsychological Society. The research team, headed by Dr Igor Grant, found that cannabis use did affect perception, but did not cause permanent brain damage. Researchers looked at data from 15 previously published controlled studies involving 704 long-term cannabis users and 484 nonusers. The results showed long-term cannabis use was only marginally harmful on the memory and learning. Other functions such as reaction time, attention, language, reasoning ability, perceptual and motor skills were unaffected. The observed effects on memory and learning, they said, showed long-term cannabis use caused "selective memory defects", but that the impact was very small.

A number of human studies that compared brain scans of marijuana users with those of non-users failed to show any significant structural atrophy: "The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI." "Computerized transaxial tomography (CTT) studies of 12 young men having histories of heavy cannabis smoking revealed no evidence of cerebral atrophy." "Only the subject with a history of alcoholism showed any abnormal cerebral function on clinical tests or any abnormality in the CT scan, compared with normal controls." "Computed tomographic scans were obtained from 19 men with long histories of heavy marijuana smoking and who were also observed to smoke large amounts of marijuana under research ward conditions. The ventricular system and subarachnoid spaces were normal in size and showed no indication of atrophic change." "These findings are consistent with recent literature suggesting that cannabis use is not associated with structural changes within the brain as a whole or the hippocampus in particular." "On the basis of available research, it was concluded that there is no evidence that marijuana produces gross structural cerebral changes and little evidence that it leads to functional impairment"

In adolescents

Long-term effects found

A July 2012 report in Brain reveals neural-connectivity impairment in some brain regions following prolonged cannabis use initiated in adolescence or young adulthood.

A 35-year study published August 2012 in Proceedings of the National Academy of Sciences and funded partly by NIDA and other NIH institutes provides objective evidence that, at least for adolescents, cannabis is harmful to the brain. 1,000 individuals from New Zealand were IQ-tested at ages 13 and 38, the age of onset of smoking cannabis. Users who started in adolescence showed an average decline of 8 IQ points, and quitting cannabis did not appear to reverse the loss. However, individuals who started cannabis use after the age of 18 did not show similar declines in memory, attention, focus, or IQ. Results of the study came into question when a new analysis was published January 2013 in Proceedings of the National Academy of Sciences. Researchers noted other differences among the study group including education, occupation and other socioeconomic factors that showed the same effect on IQ as cannabis use. From the abstract: "A simulation of the confounding model reproduces the reported associations from the , suggesting that the causal effects estimated in are likely to be overestimates, and that the true effect could be zero".

No effects found

A 2006 study using diffusion MRI did not find any structural brain changes associated with adolescent cannabis use. It concluded that "cannabis use, in at least moderate amounts, during adolescence does not appear to be neurotoxic."

A 2012 study conducted by researchers at UC San Diego failed to show deleterious effects on the adolescent brain from cannabis use. Researchers looked at brain scans taken before-and-after of subjects aged 16–20 years who consumed alcohol and compared them to subjects of the same age who used cannabis instead. The 92 person study was conducted over an eighteen-month period. While teen alcohol use resulted in observable reduced white matter brain tissue health, cannabis use was not linked to any damage. The study only looked at brain scans and did not look at performance. Publication is scheduled for April 2013 in Alcoholism: Clinical and Experimental Research.

Reproductive and endocrine effects

Research has demonstrated that human sperm expresses cannabinoid receptor type 1 (which is activated by THC) and that its activation may impair sperm's function. It has been shown that administration of high doses of THC to animals lowers serum testosterone levels, impairs sperm production, motility, and viability, disrupts the ovulation cycle, and decreases output of gonadotropic hormones. However, the relevance of these results to human cannabis use has not yet been determined.

Pregnancy

A case controlled study of 150 women with primary anovulatory infertility suggested that cannabis may affect female fertility, reporting a modest association between cannabis use and infertility. A report prepared for the Australian National Council on Drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy, as are compounds that interact with endocannabinoid synthesis and metabolism.

In a 1991 study, the development of 59 Jamaican children was monitored from birth to age 5 using the Neonatal Behavioral Assessment Scale and the McCarthy Scales of Children's Abilities. One-half of the sample's mothers used cannabis during pregnancy; they were paired with non-using mothers who matched age, parity, and socioeconomic status. The results after five years showed no statistically significant developmental differences between using and non-using mothers. The only difference observed was at 30 days of age, when the children of cannabis-using mothers had better autonomic stability and reflexes. Another similar study on Jamaican children found that children who had been exposed to cannabis prenatally had no significant differences from non-exposed infants at three days of age, and were better in some cognitive tests at one month of age.

Some studies have found that children of tobacco and cannabis-smoking mothers more frequently suffer from lasting cognitive deficits, concentration disorders, hyperactivity, and impaired social interactions than non-exposed children of the same age and social background. This may be due to the fact that the endocannabinoid system plays a large role in prenatal neural development. However, the previously discussed studies on Jamaican children conflict with this assumption.

Cannabis dependency

Cannabis is the most widely used illicit drug in the Western world. Controlled trials for "cannabis use disorder" have only been reported in literature in the last 15 years. Dr. Jack E. Henningfield of the National Institute on Drug Abuse ranked cannabis as less addictive than caffeine, cocaine, alcohol, heroin and nicotine. However, a small portion of heavy users do develop cannabis dependence.

Mental health

Several studies correlate cannabis use with the development of anxiety, psychosis, and depression. For example, a 2005 study associated daily cannabis use with an increased risk of psychosis by a factor of 1.6-1.8, and suggested that cannabis causes psychosis in this relationship. However, others offer the opposite direction of causality, or consider cannabis to only form parts of the "causal constellation." This research denies that cannabis use inflicts mental health problems that would not have occurred in its absence. Many researchers at least partially attribute the correlation between cannabis use and mental illness to self-medication. Indeed, as much as 60% of the mentally ill are suspected to be substance abusers, and many seem to prefer cannabis and alcohol.

The suggested increase in psychotic episodes and the development of psychosis is relatively modest, and these occurrences are rare to begin with. Dr. Stanley Zammit of Bristol and Cardiff universities reported, "Even if cannabis did increase the risk of psychosis, most people using the drug would not get ill...Nevertheless, we would still advise people to avoid or limit their use of this drug, especially if they start to develop any mental health symptoms or if they have relatives with psychotic illnesses." In a 2007 review of available data, Zammit and colleagues found a dose-dependent correlation between cannabis use and psychotic illness. They concluded that the heaviest cannabis users are 40% more likely than non-users to suffer a psychotic illness, while the aforementioned 2005 study suggested a 60-80% increased risk.

The BEACH study (Bettering the Evaluation and Care of Health) conducted by the Australian General Practice Statistics and Classification Centre suggested that "cannabis smokers are more likely to suffer depression, anxiety and psychosis." The report continues that of the number of patients who mentioned cannabis use to their general practitioner, 48% had a psychological problem, including 19% with depression, 9% with psychosis and 6% with anxiety. However, the study also noted that few cannabis users actually tell their doctors of their use, which could potentially bias the results of the study.

Acute psychosis

Much of the evidence for cannabis-induced acute psychosis is based on case reports in which heavy cannabis use has preceded the onset of a psychotic episode, which then remits upon abstinence.

Chronic psychosis

A large, unselected population-based study, published in British Journal of Psychiatry (2008), examined cannabis use and prodromal symptoms of psychosis at age 15–16 years and concluded that cannabis use was associated with prodromal symptoms of psychosis in adolescence.

Cannabis use during adolescence increases the risk of developing schizophrenia in adulthood due to interference with brain development. In adults with a genetic risk cannabis abuse can cause psychosis or may worsen the progress of schizophrenia.

In a recent study at the Institute of Psychiatry at King's College London, scientists have confirmed a link between potent cannabis use ("skunk" cannabis, which accounts for 80 per cent of street seizures of the drug in the UK) and transient psychotic symptoms in healthy people. After testing 22 healthy males in their late 20s by injecting them with THC, with a control dummy injection administered to a percentage of the sample group, a link was found between the chemical and psychosis, "in which hallucinations leave sufferers unable to know what is real and what is imagined". Dr Paul Morrison, who led the team, concluded, "these findings confirm that THC can induce a transient acute psychological reaction in psychiatrically well individuals". In addition, it was found that the extent of the psychotic reaction was not related to "the degree of anxiety or cognitive impairment" in the sample group. Further research is needed into the chemical makeup of skunk cannabis as it is believed stronger strains have virtually no traces of CBD (cannabidiol), which appears to counteract the damaging effects of THC. However, there is likely to be wide variation in the THC and CBD levels (and ratios) since numerous (perhaps even hundreds) of different strains of cannabis have been marketed by dealers as "skunk", some of which are descended from the original 1980s Amsterdam variety.

The largest longitudinal study examining the link between cannabis and psychosis was undertaken by Andreasson and colleagues and followed 45,570 male Swedish Army conscripts for 15 years. After controlling for other factors such as parental mental illness or a pre-existing psychotic illness at conscription, the study found that the odds of developing schizophrenia later in life were "1.5 times higher for those who had used cannabis 1-10 times and 2.3 times more likely for those who had used cannabis 10 times or more". Further to criticism that the study did not control for the use of other potentially psychotogenic substances such as amphetamines, a follow-up study re-analysed the data and ruled out this argument, finding that cannabis use remained predictive of schizophrenia in a dose-dependent manner even after accounting for other substance use and premorbid social integration.

A 2005 meta analysis of available data which evaluated several hypotheses regarding the correlation of cannabis and psychosis found that there is no support for the hypothesis that cannabis can cause cases of psychosis which would not have occurred otherwise, however further study is needed to explore the correlation between cannabis and other types of psychosis patients. Studies have shown that a risk does exist in some individuals with a predisposition to mental illness to develop symptoms of psychosis. The risk was found to be directly related to high dosage and frequency of use, early age of introduction to the drug, and was especially pronounced for those with a predisposition for mental illness. These results have been questioned as being biased by failing to account for medicinal versus recreational usage — critics contend it could be a causal relationship, or it could be that people who are susceptible to mental problems tend to smoke cannabis, or it could be connected to the criminalization of cannabis. Another important question is whether the observed symptoms of mental illness are actually connected to development of a permanent mental disorder; cannabis may trigger latent conditions, or be part of a complex coordination of causes of mental illness, referred to in psychology as the diathesis-stress model. People with developed psychological disorders are known to self-medicate their symptoms with cannabis as well, although one study has claimed that those with a predisposition for psychosis did not show a statistically significant increase in likelihood of cannabis use four years later.

Correlation versus causation

Some studies conclude that there is a correlation of cannabis use and some symptoms of psychosis, but do not necessarily support the notion that cannabis use is a sufficient or necessary cause for psychosis. It might be a component cause, part of a complex constellation of factors leading to psychosis, or it might be a correlation without forward causality at all.

For example, a review of the evidence by Louise Arsenault, et al., in 2004 reports that on an individual level, cannabis use confers an overall twofold increase in the relative risk of later schizophrenia, assuming a causal relationship. This same research also states that "There is little dispute that cannabis intoxication can lead to acute transient psychotic episodes in some individuals". The study synthesizes the results of several studies into a statistical model. The study does not correct for the use of other illicit drugs, and relies on self-reporting of cannabis dosage. The study also does not determine if the cannabis use preceded or followed the mental health problem.

Similarly, the landmark study, in 1987, of 50,000 Swedish Army conscripts, mentioned above, found that those who admitted at age 18 to having taken cannabis on more than 50 occasions, were six times more likely to develop schizophrenia in the following 15 years. In fact, psychosis cases were restricted to patients requiring a hospital admission. These findings have not been replicated in another population based sample. As the study did not control for symptoms preexisting onset of cannabis use, the use of other illicit drugs, the study does not resolve the correlation versus causality question but has fueled a major debate within the scientific community. This study also used self reporting for cannabis dosage.

A 2005 study found that "the 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". A schizotypal personality disorder is a personality disorder different from schizophrenia, though there is some evidence that the former may predispose to the latter. A 2007 British study concluded, "We found few appreciable differences in symptomatology between schizophrenic patients who were or were not cannabis users. There were no differences in the proportion of people with a positive family history of schizophrenia between cannabis users and non-users. This argues against a distinct schizophrenia-like psychosis caused by cannabis."

Research based on the Dunedin Multidisciplinary Health and Development Study has found that those who begin regular use of cannabis in early adolescence (from age 15, median 25 days per year by age 18) and also fit a certain genetic profile (specifically, the Val/Val variant of the COMT gene) are five times more likely to develop psychotic illnesses than individuals with differing genotypes, or those who do not use cannabis. The study was noted for having controlled for preexisting symptoms, but is open to the criticism that it cannot control for late adolescent onset of psychotic illness. Also, the study was on a cohort population, so there is no way to correlate a change in the rate of adolescent use with a change in the rate of incidence of schizophrenia in the study population. These points undermine its value in resolving the correlation versus causality question.

A study that inversely correlated cerebrospinal anandamide (an endogenous cannabinoid) levels with severity of schizophrenia (i.e., that anandamide was released in order to suppress psychosis) suggests that cannabis use may be an effect of schizophrenia or its predisposition, as opposed to a cause.

Cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use is highly likely to precipitate psychotic disorders in persons who are vulnerable to developing psychosis; and cannabis use is also likely to worsen the course of the disorder among those who have already developed it.

Cannabidiol in the treatment of schizophrenia

As early as 2006, it was hypothesized based on a variety of animal and clinical evidence that cannabidiol (CBD), a cannabinoid present in cannabis, may be an effective atypical antipsychotic in treating schizophrenia and bipolar disorder. Further research supported these results. A double-blind controlled clinical trial conducted in 2009 compared the effects of cannabidiol with those of the atypical antipsychotic amisulpride in 42 patients with acute paranoid schizophrenia. The study concluded that "both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride." This led the authors to suggest the endocannabinoid system plays an adaptive role in the development of paranoid schizophrenia and may therefore be a valuable treatment target.

Depressive disorder – Unipolar

Less attention has been given to the association between cannabis use and depression, though it is possible this is because cannabis users who suffer from depression are less likely to access treatment than those suffering from psychosis. Chen and colleagues (2002) re-analyzed the US National Comorbidity Survey (NCS) to examine the relationship between cannabis use and a major depressive episode and discovered that the risk of first Major Depressive Episode was moderately associated with the number of occasions of cannabis use and with more advanced stages of cannabis use. Relative to newer users, non-dependent cannabis users had 1.6 times greater risk of MDE. Cannabis dependence was associated with a 3.4 time greater risk of major depression. Grant (1995), using data from the US Longitudinal Alcohol Epidemiologic Survey, showed that a diagnosis of cannabis abuse or dependence within the past year was associated with a 6.4 fold chance of also receiving a diagnosis for major depression in that time.

A 2002 USC study (using Center for Epidemiologic Studies Depression scale) of 4,400 internet users ("an effort to recruit the most depressed and marijuana-involved participants, including those who might prove unwilling to travel to the laboratory or discuss drug use on the phone or in person") found that " ... those who used once per week or less had less depressed mood, more positive affect, and fewer somatic complaints than non-users. Daily users reported less depressed mood and more positive affect than non-users. The three groups did not differ on interpersonal symptoms. Separate analyses for medical vs. recreational users demonstrated that medical users reported more depressed mood and more somatic complaints than recreational users, suggesting that medical conditions clearly contribute to depression scores and should be considered in studies of marijuana and depression. These data suggest that adults apparently do not increase their risk for depression by using marijuana."

According to the Mayo Clinic, there exists no conclusive evidence of a causal relationship between cannabis and depression.

Depressive disorder – Bipolar

A 2005 literature review of the use of cannabis in mental health patients found that the drug can have very different effects on different patients. Although "no controlled trials of THC have been done in bipolar disorder", there is anecdotal evidence that "for some people marijuana is beneficial" as a treatment for bipolar disorder. The reviewers suggested that randomized studies and standardized administration techniques would be required to create conclusive evidence.

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Suicidality

The question of suicide and cannabis use is considered by Borges, Walters, and Kessler who examined whether cannabis use heightens the risk of suicide or attempted suicide. Cross-sectional data from the US National Comorbidity Survey indicated that cannabis-dependent individuals were 2.4 times more likely to report a suicide attempt than non-cannabis-dependent individuals, after controlling for socio-demographic factors, psychiatric disorders and other drug use. Beautrais et al. (1999) examined 302 hospitalized cases of suicide attempts and found that 16% screened positive for cannabis abuse or dependence, compared with 2% of a random community sample. After controlling for depression and social disadvantage the study found this translated to a twofold suicide attempt risk for those who used cannabis.

Researchers from Cardiff University School of Medicine analyzed over 30 years' worth of death records on more than 50,000 Swedish military recruits and found cannabis was unlikely to increase a person's suicide risk later on. Dr. Stanley Zammit of the department of psychological medicine stated, "we can pretty much rule out a strong effect of cannabis on long-term risk of suicide whether it's through depression or whatever".

A 2012 study found the passage of a medical marijuana law to be associated with "an almost 5 percent reduction in the total suicide rate, an 11 percent reduction in the suicide rate of 20- through 29-year-old males, and a 9 percent reduction in the suicide rate of 30- through 39-year-old males", leading researchers to ask whether cannabis may help prevent suicide.

Effects on cognitive decline

Cannabis is a strong antioxidant and therefore defends cells from β-amyloid, the peptide that causes Alzheimer's disease. Some studies have found that cannabis has no effect on ageing-related cognitive decline while others suggest that it slows cognitive decline through its antioxidant effect. The cannabinoids present in cannabis have been reliably shown to lessen cell damage and death from ischemia, likely due to their antioxidant properties.

Behavioral effects

Government studies often point to statistical data accumulated by methods like the National Household Survey on Drug Abuse (NHSDA), the Monitoring the Future (MTF) study, and the Arrestee Drug Abuse Monitoring (ADAM) program, which claim lower school averages and higher dropout rates among users than non-users. However, these surveys are usually self-administered and may be anonymous, which greatly reduces their reliability. Additionally, while they establish a relationship between cannabis use and academic underperformance they do not determine whether the former causes the latter. The ADAM study is conducted anonymously, but only seeks information from a sample of people who have been arrested for drug-related offenses. Socially deviant behavior may be found more frequently in individuals of the criminal justice system compared to those in the general population, including non-users. In response, independent studies of college students have shown that there was no difference in grade point average, and achievement, between cannabis users and non-users. However, the users surveyed had slightly more difficulty deciding on career goals, and a smaller number were seeking advanced professional degrees.

Psychology studies have been conducted to test differences in motivation between users and non-users. A study in which volunteers completed operant tasks for a wage representing a working world model found no difference between users and non-users.

A longitudinal study of heavy cannabis users from ages 14 to 25 in a Christchurch, New Zealand birth cohort concluded, "The results of the present study suggest that increasing cannabis use in late adolescence and early adulthood is associated with a range of adverse outcomes in later life. High levels of cannabis use are related to poorer educational outcomes, lower income, greater welfare dependence and unemployment and lower relationship and life satisfaction. The findings add to a growing body of knowledge regarding the adverse consequences of heavy cannabis use." However, this study primarily established correlation rather than causality.

A study published in the American Journal of Epidemiology in 2011, concluded that the prevalence of obesity is lower in cannabis users than in nonusers. A 2013 study confirmed this correlation and also found that cannabis users had better insulin resistance, lower insulin levels, and higher high-density lipoprotein ("good cholesterol") levels.

A 2008 study published in the British Journal of Psychiatry showed significant differences in Oxford-Liverpool Inventory of Feelings and Experiences scores between three groups: The first consisted of non-cannabis users, the second of users who tested positive for THC only, and the third consisted of users who tested positive for both THC and CBD. The Δ9-THC only subset scored significantly higher for unusual experiences, while users of both THC and CBD had much lower introvertive anhedonia scores. This suggests that CBD prevents some of the negative behavioral effects of THC.

Cancer risk

Glioma

It is well established that the cannabinoids present in cannabis are effective treatments for gliomas. Research also suggests that the constituents of cannabis retard the growth of many other forms of cancer, including adenocarcinoma of the lung, prostate cancer, acute lymphoblastic leukemia and lymphoma, and skin cancer.

Testicular cancer

Cannabis use has been associated with testicular cancer in Western nations. A 2009 study conducted by the Fred Hutchinson Cancer Research Center and funded by the National Institutes of Health suggested that current cannabis users are 70% more likely to develop testicular cancer. Drug use was self-reported and reporting bias is therefore a possibility. A later study found that men who had used cannabis had twice the risk of developing testicular nongerminomatous germ cell tumors. A study published in September 2012 became the third to link cannabis use to the development of testicular cancer.

Lung cancer

Cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same carcinogens as tobacco smoke. However, research involving the association of cannabis use and lung cancer has been inconclusive, producing no strong evidence of a correlation. A large 2006 study considered oral, laryngeal, pharyngeal, and esophageal cancer and concluded that "the association of these cancers with marijuana, even long-term or heavy use, is not strong and may be below practically detectable limits." It found no correlation between cannabis use and lung cancer, even in heavy smokers, after adjusting for several confounders including cigarette smoking and alcohol use. The study even speculated a possible protective effect.

However, it is often claimed, despite the objections of the medical community, that cannabis must cause lung cancer in proportion to the amount of carcinogens it contains. For example, a 2012 report by the British Lung Foundation suggested that the risk of developing lung cancer is nearly 20 times higher from smoking typical cannabis cigarettes than from smoking tobacco cigarettes, due to deeper, longer inhalation and the lack of filters. The disparity between cannabis' carcinogen content and its cancer risk is likely due to the antitumor effects of its cannabinoids.

A 2005 study by Robert Melamede published in the Harm Reduction Journal found cigarette and cannabis smoke are not equally carcinogenic. The difference was due to nicotine in cigarette smoke and cannabinoids in cannabis smoke, which "minimize some carcinogenic pathways whereas tobacco smoke enhances some". Further, "despite potentially higher levels of polycyclic aromatic hydrocarbons found in cannabis smoke compared to tobacco smoke (dependent on what part of the plant is smoked), the THC present in cannabis smoke should exert a protective effect against pro-carcinogens that require activation", whereas nicotine potentially increases the carcinogenic effects of tobacco smoke.

In the largest study of its kind, researchers found no cancer-cannabis connection. Donald Tashkin, a pulmonologist at University of California, Los Angeles who studied marijuana for 30 years, "hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use". Instead, the study found "no association at all, and even a suggestion of some protective effect". The study, which involved a large population sample (1200 people with lung, neck, or head cancer, and a matching group of 1040 without cancer), with some of the most chronic marijuana smokers having smoked over 22,000 "joints", found no correlation between marijuana smoking and increased lung cancer risk, with the same being true for head and neck cancers as well. The results indicated no correlation between long and short-term cannabis use and cancer, indicating a possible therapeutic effect. Extensive cellular studies and some studies in animal models suggest that THC or cannabidiol has antitumor properties, either by encouraging programmed cell death of genetically damaged cells that can become cancerous, or by restricting the development of the blood supply that feeds tumors, or both.

Tashkin's findings in 2006 were refined from his team's earlier studies published in a Dec. 17th 2000 edition of the peer-reviewed journal Cancer Epidemiology Biomarker and Prevention. Opponents of marijuana have incorrectly cited Tashkin's original findings as "proof" that marijuana leaves the users at higher risk for cancer of the lung, and cancerous tumors,. This seemed to contradict assumptions made after some studies, like those from Dale Gieringer et al., which found that 118 carcinogens were produced when marijuana underwent combustion, and two carcinogens {2-Methyl-2, 4(2H-1-benzopyran-5-ol) & 5-azulene-3,8-dione} formed when marijuana underwent vaporization. To help explain the seemingly chemical proof of carcinogenicity inherent in the process of combustion, Tashkin noted "one possible explanation for the new findings....is that THC, a chemical in marijuana smoke, may encourage aging cells to die earlier and therefore be less likely to undergo cancerous transformation."

A 1997 study examining the records of 64,855 Kaiser patients (14,033 of whom identified themselves as current smokers), also found no positive correlation between cannabis use and cancer.

A Research Triangle Institute study concluded that THC, a dilative agent (bronchodilator), may help cleanse the lungs by dilating the bronchi, and could actively reduce the instance of tumors. Additionally, a study by Rosenblatt et al. found no association between marijuana use and the development of head and neck squamous cell carcinoma. However, an animal study conducted on mice in 2000 linked cannabis smoking to the growth of cancerous tumors through the impairment of anti-tumor defenses.

A study presented at the May 2013 American Association for Cancer Research annual meeting reported that regular inhalation of cannabis smoke causes no greater risk of lung cancer than does abstinence or occasional smoking. The analysis was based on six case-control studies conducted between 1999-2012, comprised of over 5,000 subjects (2,159 cases and 2,985 controls) from individuals in the UK, US, New Zealand and Canada. They concluded: "Our pooled results showed no significant association between the intensity, duration, or cumulative consumption of cannabis smoke and the risk of lung cancer overall or in never smokers."

Head and neck cancer

A study, published in the Cancer Prevention Research journal, showed that long-term cannabis users were up to 61% less likely to develop head and neck cancers than people who did not use cannabis. After factoring out the impact of smoking, drinking, and other potentially confounding factors, smoking cannabis 1-3 times every two weeks, on average, was associated with about half the risk of head and neck cancer, compared with less frequent use. Cannabis users who began their use at age 20 or older appeared to have slightly less risk of head and neck cancers than those who started at a younger age. The authors also noted that this agrees with cannabinoids' known antitumor effects, particularly in gliomas.

Gateway drug hypothesis

The gateway drug hypothesis asserts that the use of cannabis may ultimately lead to the use of harder drugs. For the most part, it was commonly thought that cannabis gateways to other drugs because of social factors. For example, the criminalization of cannabis in many countries associates its users with organized crime promoting the illegal drug trade.

A study of twins by researchers at Virginia Commonwealth University showed that cannabis use in adolescence strongly predicted later use of multiple drugs. The main causation was tied to shared environmental and genetic vulnerability, but there was some evidence for a causal role of cannabis. A July 2006 study by Ellgren et al. strictly tested lab rats for the biological mechanism of the gateway drug effect. The study administered 6 "teenage" (28 and 49 days old) rats delta-9-tetrahydrocannabinol, and 6 were the control. One week after the first part was completed, catheters were inserted in the jugular vein of all of the adult rats and they were able to self-administer themselves heroin by pushing a lever. The study found that initially both groups behaved the same and began to self-administer heroin frequently, but then stabilized at different levels. The rats that had previously been administered THC consumed about 1.5 times more heroin than those that had not. Because many THC receptors interact with the opioid system, the study surmised that adolescent cannabis use overstimulates and alters the pleasure and reward structures of the brain, thus increasing the already high risk of addiction for people who start to use heroin. However, the rats took up self-administration at the same rate regardless of adolescent THC exposure, and observed levels of "drug-seeking behavior" were also the same. Psychopharmacologist Ian Stolerman, from King's College London, finds the biological cannabis gateway drug effect "somewhat preliminary", and states "it's too early to say there's a consensus, but a small number of studies like this suggest that there is a physiological basis for this effect." Other drugs, he notes, such as cocaine and amphetamines are involved in another brain pathway called the dopaminergic system. Cells in that system also interact with THC receptors and could be modified by cannabis exposure. Cannabinoid receptors are 10 times more prevalent in the brain than opioid receptors. According to Dr. Hurd, one of the study leaders, two other drugs that also stimulate opioid cells, and could therefore also feasibly cause a gateway effect, are nicotine and alcohol.

However, a December 2006 study by the American Psychiatric Association challenges these findings. A 12 year study on 214 boys from ages 10–12 showed that adolescents who used cannabis prior to using other drugs, including alcohol and tobacco, were no more likely to develop a substance abuse disorder than other subjects in the study. "This evidence supports what's known as the common liability model… states the likelihood that someone will transition to the use of illegal drugs is determined not by the preceding use of a particular drug, but instead by the user's individual tendencies and environmental circumstances", investigators stated in a press release. They added, "The emphasis on the drugs themselves, rather than other, more important factors that shape a person's behavior, has been detrimental to drug policy and prevention programs."

Models used in a 2002 study by RAND cast doubt on the gateway effect and show "that the marijuana gateway effect is not the best explanation for the link between marijuana use and the use of harder drugs", as noted by Andrew Morral, associate director of RAND's Public Safety and Justice unit and lead author of the study.

Respiratory effects

Although cannabis smoke contains many of the same carcinogens as tobacco smoke, current scientific data supports the possibility that cannabis smoking may not induce cancer. Of the various methods of cannabis consumption, smoking is considered the most harmful; the inhalation of smoke from organic materials can cause various health problems (e.g., coughing and sputum). Isoprenes help to modulate and slow down reaction rates, contributing to the significantly differing qualities of partial combustion products from various sources. Compared to tobacco much less cannabis material in weight is burned, with the average hand rolled cigarette at about 1 gram, tobacco or cannabis. Commercial cigarettes have numerous additives, many of which modify combustion in such a way to create a very consistent aerosol at any given air flow rate, perhaps to maximize nicotine delivery/bio-availability, and thus reduce total amount of smoke consumed to nicotine crossing the blood brain barrier. A relative abundance of terpenes and other higher molecular weight, adhesive molecules results in a smoke with higher mean particle size, as well as a corresponding higher deposition rate of particulate matter. This means more is deposited on the bronchioles, and larger airways, which the lungs can clear easier, as less of the very fine, highly toxic amorphous particles reach the delicate alveoli. Cilia cannot "sweep" up the combustion products effectively. Subjective lung irritation not based upon the amount of matter crossing the semipermeable gas exchange surfaces deep in the lungs, rather the primary factor is amount of matter which adheres to motile cilium. This also contributes to a noted expectorant effect of any smoke to some extent, due to the defense system the mucus membranes in the lungs possess. The study concluded: "A significant interaction revealed that the impact of a vaporizer was larger as the amount of cannabis used increased. These data suggest that the safety of cannabis can increase with the use of a vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease respiratory symptoms by switching to a vaporizer". Another study found vaporizers to be "a safe and effective cannabinoid delivery system."

In a 20-year study of 5,000 young adults, researchers found that, unlike tobacco use, smoking cannabis once a week or a bit more doesn't harm the lungs, with less clear results regarding heavy users due to a lack of very heavy users in the study. In fact, the study found that occasional cannabis use actually increases both lung capacity and volume over the years, possibly because cannabis smokers often take deep breaths, which exercises lung tissue. The correlation only decreased after the equivalent of about ten years of smoking cannabis once a day. Only lung volume and capacity were examined, not throat irritation, coughing, or lung cancer.

A 1997 study found that regular cannabis use does not appear to cause chronic obstructive pulmonary disease, in contrast with tobacco.

A 2012 literature review by the British Lung Foundation identified cannabis smoke as a carcinogen and also found awareness of the danger was low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. Other observations include increased risk from each cigarette due to drawing in large puffs of smoke and holding them; lack of research on the affect of cannabis smoke alone due to common mixing of cannabis and tobacco and frequent cigarette smoking by cannabis users; low rate of addiction compared to tobacco; and episodic nature of cannabis use compared to steady frequent smoking of tobacco. Professor David Nutt, a UK drug expert, points out that the study cited by the British Lung Foundation has been accused of both “false reasoning” and “incorrect methodology”. Further, he notes that studies have failed to connect cannabis with lung cancer, and accuses the BLF of "scaremongering over cannabis".

See also

• Medical cannabis
• Effects of cannabis
• Cannabinoid hyperemesis syndrome

References

1. "Marijuana Research". scientificamerican.com. 2004-11-22. Retrieved 2013-01-15.
2. Laura L. Boles Ponto (2006). "Challenges of marijuana research". Brain. 129 (5): 1081–3. doi:10.1093/brain/awl092. {{cite journal}}: Unknown parameter |month= ignored (help)
3. Alok Jha (2012-05-31). "Ecstasy and cannabis should be freely available for study, says David Nutt". The Guardian. Retrieved 2013-01-15. {{cite journal}}: Cite journal requires |journal= (help)
4. "Medical Marijuana Policy in the United States". Stanford.edu. 2012-05-15. Retrieved 2013-01-15.
5. "Research into marijuana's medical benefits limited; scientists cite challenge of studying an illegal drug". bostonglobe.com. 2012-10-19. Retrieved 2013-01-15.
6. Sabrina Richards (2013), "Is Cannabis Really That Bad?", the-scientist.com
7. ^ "Could smoking pot cut risk of head, neck cancer?". Reuters. 2009-08-25. Retrieved 2012-12-07.
8. Bipolar Disorder May Be Ameliorated By Pot Smoking, Research Finds
9. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19560900, please use {{cite journal}} with |pmid=19560900 instead.
10. Iversen L. (2005), "Long-term effects of exposure to cannabis" (PDF), Current Opinion in Pharmacology, 5 (1): 69–72, doi:10.1016/j.coph.2004.08.010, PMID 15661628 {{citation}}: Unknown parameter |month= ignored (help)
11. Riedel G, Davies SN (2005). "Cannabinoid function in learning, memory and plasticity". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 168 (168): 445–77. doi:10.1007/3-540-26573-2_15. ISBN 3-540-22565-X. PMID 16596784.
12. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17712818, please use {{cite journal}} with |pmid=17712818 instead.
13. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9651215, please use {{cite journal}} with |pmid=9651215 instead.
14. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12427880, please use {{cite journal}} with |pmid=12427880 instead.
15. "Heavy pot smoking linked to smaller brains". New Scientist (2659). 4 June 2008. Retrieved 17 October 2009.
16. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18519827, please use {{cite journal}} with |pmid=18519827 instead.
17. Lubman, Dan (2008). "Long-term cannabis use and regional brain abnormalities". NCPIC e-Zine. Retrieved 17 October 2009. {{cite journal}}: Unknown parameter |month= ignored (help)
18. INSERM-CNRS. Released June 1998. Excerpts from the Roques report. Hemp Info. Retrieved 5 March 2007
19. Rapport Roques sur la dangerosité des drogues. Template:Fr icon. Retrieved on 5 March 2007
20. L'alcool aussi dangereux que l'héroïne. Template:Fr icon Retrieved on 5 March 2007
21. Lyketsos CG, Garrett E, Liang KY, Anthony JC. (1999), "Cannabis Use and Cognitive Decline in Persons under 65 Years of Age" (PDF), Am. J. Epidemiol., 149 (9): 794–800, doi:10.1093/oxfordjournals.aje.a009894, PMID 10221315{{citation}}: CS1 maint: multiple names: authors list (link)
22. Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. (2001), "Neuropsychological performance in long-term cannabis users", Arch Gen Psychiatry, 58 (10): 909–15, doi:10.1001/archpsyc.58.10.909, PMID 11576028 {{citation}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
23. Lost in the Weeds: Legalizing Medical Marijuana in Massachusetts
24. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11949984, please use {{cite journal}} with |pmid=11949984 instead.
25. Interview with Dr Nadia Solowij
26. "Minimal long-term effects of marijuana use found in central nervous system by UCSD researchers". Health.ucsd.edu. 2003-06-27. Retrieved 2013-01-07.
27. Deena Beasley (2003-06-27). "Study - Pot doesn't cause permanent brain damage" (PDF). Reuters. Retrieved 2013-01-07.
28. Block, RI (2000 Feb 28). "Effects of frequent marijuana use on brain tissue volume and composition". NeuroReport. 11 (3): 491–6. PMID 10718301. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
29. Co, BT (1977 Mar 21). "Absence of cerebral atrophy in chronic cannabis users. Evaluation by computerized transaxial tomography". JAMA: the Journal of the American Medical Association. 237 (12): 1229–30. PMID 576460. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
30. Hannerz, J (1983 Feb). "Neurological and neuroradiological examination of chronic cannabis smokers". Annals of neurology. 13 (2): 207–10. doi:10.1002/ana.410130219. PMID 6830182. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
31. Kuehnle, J (1977 Mar 21). "Computed tomographic examination of heavy marijuana smokers". JAMA: the Journal of the American Medical Association. 237 (12): 1231–2. PMID 576461. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
32. Tzilos, GK (2005 Jan-Feb). "Lack of hippocampal volume change in long-term heavy cannabis users". The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 14 (1): 64–72. doi:10.1080/10550490590899862. PMID 15804878. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
33. Wert, RC (1986 Jun). "The chronic cerebral effects of cannabis use. I. Methodological issues and neurological findings". The International journal of the addictions. 21 (6): 605–28. PMID 3017872. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
34. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22669080, please use {{cite journal}} with |pmid=22669080 instead.
35. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1073/pnas.1206820109, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1073/pnas.1206820109 instead.
36. "Study: Adolescent marijuana use leaves lasting mental deficits". Medical Xpress. 2012-08-27. {{cite journal}}: Cite journal requires |journal= (help)
37. "Study: Pot use before 18 harms adult IQ, memory". USA Today. 27 August 2012. Retrieved 28 August 2012.
38. "Persistent Cannabis Users Show Neuropsychological Decline from Childhood to Midlife". JournalistsResource.org. Retrieved 2012-08-29.
39. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 23319626, please use {{cite journal}} with |pmid=23319626 instead.
40. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1186/1477-7517-3-17, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1186/1477-7517-3-17 instead.
41. Teen Marijuana Use May Show No Effect On Brain Tissue, Unlike Alcohol, Study Finds
42. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15562018, please use {{cite journal}} with |pmid=15562018 instead.
43. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12237954, please use {{cite journal}} with |pmid=12237954 instead.
44. Kalant, H.K. and Roschlau, W.H.E. (1998). Principles of Medical Pharmacology (6 ed.). pp. 373–375. ISBN 0779699459.{{cite book}}: CS1 maint: multiple names: authors list (link)
45. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9843121, please use {{cite journal}} with |pmid=9843121 instead.
46. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2081252, please use {{cite journal}} with |pmid=2081252 instead.
47. ^ Copeland, Jan; Gerber, Saul; Swift, Wendy (2006). Evidence-based answers to cannabis questions: a review of the literature. Canberra: Australian National Council on Drugs. ISBN 978-1-877018-12-1.
48. "Information and Resources • NCPIC". Ncpic.org.au. 2011-03-11. Retrieved 2011-04-20.
49. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 1957518 , please use {{cite journal}} with |pmid=1957518 instead.
50. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 8121737, please use {{cite journal}} with |pmid=8121737 instead.
51. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16095697, please use {{cite journal}} with |pmid=16095697 instead.
52. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12798960, please use {{cite journal}} with |pmid=12798960 instead.
53. Berghuis P, Rajnicek AM, Morozov YM; et al. (2007). "Hardwiring the brain: endocannabinoids shape neuronal connectivity". Science. 316 (5828): 1212–6. doi:10.1126/science.1137406. PMID 17525344. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
54. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16357196 , please use {{cite journal}} with |pmid=16357196 instead.
55. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17222464, please use {{cite journal}} with |pmid=17222464 instead.
56. JR Minkel: Marijuana-Like Chemicals Guide Fetal Brain Cells, Scientific American, May 24, 2007
57. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi: 10.1037/1064-1297.2.3.244, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi= 10.1037/1064-1297.2.3.244 instead.
58. "Relative Addictiveness of Drugs". The New York Times. Tfy.drugsense.org. 1994-08-02. Retrieved 2013-01-07.
59. McLaren, Jennifer; Lemon, Jim; Robins, Lisa; Mattick, Richard P. (2008). Cannabis and Mental Health: Put into Context. National Drug Strategy Monograph Series. Australian Government Department of Health and Ageing. Retrieved 17 October 2009.
60. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1136/bmj.38267.664086.63, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1136/bmj.38267.664086.63 instead.
61. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1136/bmj.325.7374.1195, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1136/bmj.325.7374.1195 instead.
62. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1111/j.1360-0443.2005.01001.x , please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1111/j.1360-0443.2005.01001.x instead.
63. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15763748, please use {{cite journal}} with |pmid=15763748 instead.
64. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 14754822, please use {{cite journal}} with |pmid=14754822 instead.
65. Earth Erowid (2005). "Cannabis & Psychosis - A guide to current research about cannabis and mental health".
66. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2807205, please use {{cite journal}} with |pmid=2807205 instead.
67. Morgan, Tom (27). "Smoking cannabis doubles the risk of mental illness". Daily Express. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
68. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17662880, please use {{cite journal}} with |pmid=17662880 instead.
69. "Cannabis 'raises psychosis risk'". BBC News (2007-07-27). Retrieved on 2007-11-03.
70. "The BEACH Project". Retrieved 17 October 2009.
71. "Depression, psychosis strike dope smokers". The Australian. Australian Associated Press. 29 September 2009. Retrieved 17 October 2009.
72. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 4808733 , please use {{cite journal}} with |pmid= 4808733 instead.
73. Eva, J. (1992). Cannabis psychosis. Psychiatric Bulletin 16: 310–311
74. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2218786 , please use {{cite journal}} with |pmid= 2218786 instead.
75. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 5043840 , please use {{cite journal}} with |pmid= 5043840 instead.
76. Carney, M.; Bacelle, L.; Robinson, B. (1984). "Psychosis after cannabis use". British Medical Journal. 288 (6423): 1047. doi:10.1136/bmj.288.6423.1047.
77. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1192/bjp.bp.107.045740, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1192/bjp.bp.107.045740 instead.
78. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19629449, please use {{cite journal}} with |pmid=19629449 instead.
79. ^ Hope, C., Skunk cannabis can make well users psychotic: study, The Telegraph, 28 July 2009
80. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2787581 , please use {{cite journal}} with |pmid= 2787581 instead.
81. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12446534, please use {{cite journal}} with |pmid=12446534 instead.
82. ^ Degenhardt L, Hall W, Lynskey M (2001). "Comorbidity between cannabis use and psychosis: Modelling some possible relationships. Technical Report No. 121" (PDF). Sydney: National Drug and Alcohol Research Centre. Retrieved 19.18.2006. {{cite journal}}: Check date values in: |accessdate= (help); Cite journal requires |journal= (help)CS1 maint: multiple names: authors list (link)
83. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15964704, please use {{cite journal}} with |pmid=15964704 instead.
84. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2892048, please use {{cite journal}} with |pmid=2892048 instead.
85. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15808288, please use {{cite journal}} with |pmid=15808288 instead.
86. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17462864, please use {{cite journal}} with |pmid=17462864 instead.
87. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1136/bmj.325.7374.1212, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1136/bmj.325.7374.1212 instead.
88. Avshalom Caspi, Terrie E. Moffitt, Mary Cannon, Joseph McClay, Robin Murray, HonaLee Harrington, Alan Taylor, Louise Arseneault, Ben Williams, Antony Braithwaite, Richie Poulton, and Ian W. Craig (18 January 2005). "Moderation of the Effect of Adolescent-Onset Cannabis Use on Adult Psychosis by a Functional Polymorphism in the catechol-O-Methyltransferase Gene: Longitudinal Evidence of a Gene X Environment Interaction" (PDF). Society of Biological Psychiatry. 57 (10): 1117–27. doi:10.1016/j.biopsych.2005.01.026. PMID 15866551.{{cite journal}}: CS1 maint: multiple names: authors list (link)
89. Giuffrida A, Leweke FM, Gerth CW; et al. (2004). "Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms". Neuropsychopharmacology. 29 (11): 2108–14. doi:10.1038/sj.npp.1300558. PMID 15354183. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link), New Scientist
90. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/S0376-8716(03)00064-4, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/S0376-8716(03)00064-4 instead.
91. "Earlier onset of schizophrenia linked to pot". Webmd.com. 2011-02-07. Retrieved 2012-10-09.
92. Zuardi, A.W (2006). "Cannabidiol as an antipsychotic drug" (PDF). Brazilian Journal of Medical and Biological Research. 39 (4): 421–429. doi:10.1590/S0100-879X2006000400001. PMID 16612464. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
93. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/S0924-9338(09)70440-7, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/S0924-9338(09)70440-7 instead.
94. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12107710, please use {{cite journal}} with |pmid=12107710 instead.
95. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 8838629 , please use {{cite journal}} with |pmid= 8838629 instead.
96. Marijuana and depression: What's the link? - MayoClinic.com
97. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 10965975 , please use {{cite journal}} with |pmid= 10965975 instead.
98. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 10615730 , please use {{cite journal}} with |pmid= 10615730 instead.
99. Marijuana use unlikely to boost suicide risk | Reuters
100. Cannabis and suicide: longitudinal study
101. Marijuana Can Help Prevent Suicide, Study Suggests - Los Angeles - News - The Informer
102. http://ftp.iza.org/dp6280.pdf
103. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1111/j.1471-4159.2003.02327.x, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1111/j.1471-4159.2003.02327.x instead.
104. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15030397, please use {{cite journal}} with |pmid=15030397 instead.
105. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 10221315, please use {{cite journal}} with |pmid=10221315 instead.
106. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1098/rstb.2011.0388, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1098/rstb.2011.0388 instead.
107. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.3390/ph3072197, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.3390/ph3072197 instead.
108. Abadinsky, H. (2004). Drugs: An Introduction (5th ed.). pp. 62–77, 160–166. ISBN 0-534-52750-7.
109. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 4441242, please use {{cite journal}} with |pmid=4441242 instead.
110. Mendelson JH, Kuehnle JC, Greenberg I, Mello NK. (1976). "Operant acquisition of marihuana in man". J Pharmacol Exp Ther. 198 (1): 42–53. PMID 933012. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
111. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18482420, please use {{cite journal}} with |pmid=18482420 instead.
112. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1093/aje/kwr200, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1093/aje/kwr200 instead.
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115. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1124/jpet.103.061002, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1124/jpet.103.061002 instead.
116. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18175076, please use {{cite journal}} with |pmid=18175076 instead.
117. Parolaro D, Massi P (2008). "Cannabinoids as potential new therapy for the treatment of gliomas" (PDF). Neurotherapeutics. 8 (1): 37–49. doi:10.1586/14737175.8.1.37. PMID 18088200.
118. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1158/0008-5472.CAN-03-3927, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1158/0008-5472.CAN-03-3927 instead.
119. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9771884 , please use {{cite journal}} with |pmid=9771884 instead.
120. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 1159836, please use {{cite journal}} with |pmid=1159836 instead.
121. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22557710, please use {{cite journal}} with |pmid=22557710 instead.
122. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12091357, please use {{cite journal}} with |pmid=12091357 instead.
123. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12511587, please use {{cite journal}} with |pmid=12511587 instead.
124. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1002/cncr.24159, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1002/cncr.24159 instead.
125. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1002/cncr.27554, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1002/cncr.27554 instead.
126. Smoking Marijuana Tied to Testicular Cancer Web MD 09-10-2012.
127. ^ Tomar, Rajpal C. (2009). "Evidence on the carcinogenicity of marijuana smoke" (PDF). Reproductive and Cancer Hazard Assessment Branch Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. Retrieved 2012-06-23. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
128. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.alcohol.2005.04.008, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1016/j.alcohol.2005.04.008 instead.
129. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17035389, please use {{cite journal}} with |pmid=17035389 instead.
130. Nutt, David (2012-06-11). "Smoke without fire? Scaremongering by the British Lung Foundation over cannabis vs tobacco". Retrieved 12 June 2012.
131. Szalavitz, Maia (2013-06-13). "Marijuana Doesn't Increase Risk of Lung Cancer, Mental Illness or Death". Time.com.
132. The impact of cannabis on your lungs. The British Lung Foundation (June 2012), Retrieved 6 June 2012
133. Robert Melamede (2005). "Cannabis and tobacco smoke are not equally carcinogenic". Harm Reduct J. 2: 21. doi:10.1186/1477-7517-2-21. PMC 1277837. PMID 16232311.{{cite journal}}: CS1 maint: unflagged free DOI (link)
134. ^ Kaufman, Marc (2006-05-26). "Study finds no marijuana-lung cancer link". Washington Post. Retrieved 2006-07-13.
135. ^ "Study Finds No Link Between Marijuana Use And Lung Cancer". Science Daily. 26 May 2006.
136. Fred Gardner (2006-07-06). "Marijuana Smoking Does Not Cause Lung Cancer". Anderson Valley Advertiser.
137. "Pot smoking not linked to lung cancer". 23 May 2006. ScienceNOW, Abstract
138. Researchers At UCLA's Jonsson Cancer Center Report Smoking Marijuana May Increase Risk Of Head And Neck Cancers, Sciencedaily.com, 1999-12-20, retrieved 2011-04-20
139. ^ Dr. Steven M. Dubinett (July 2006). "Study Finds Marijuana Ingredient Promotes Tumor Growth, Impairs Anti-Tumor Defenses". Journal of Immunology.
140. Sarafian TA, Kouyoumjian S, Tashkin D, Roth MD (2002). "Synergistic cytotoxicity of Delta(9)-tetrahydrocannabinol and butylated hydroxyanisole". Toxicol. Lett. 133 (2–3): 171–9. doi:10.1016/S0378-4274(02)00134-0. PMID 12119125. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
141. Gieringer D., St. Laurent J., and Goodrich S. (2008). "Cannabis Vaporizer Combines Efficient Delivery of THC with Effective Suppression of Pyrolytic Compounds". Journal of Cannabis Therapeutics. 4 (1): 7–27. doi:10.1300/J175v04n01_02. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
142. S. Sidney; Quesenberry Jr, CP; Friedman, GD; Tekawa, IS (1997). "Marijuana use and cancer incidence (California, United States)". Cancer Causes & Control. 8 (5): 722–728. doi:10.1023/A:1018427320658. PMID 9328194. {{cite journal}}: Unknown parameter |month= ignored (help)
143. Huff J, Chan P (2000). "Antitumor effects of THC". Environmental Health Perspectives. 108 (10): A442–3. doi:10.2307/3435034. PMC 1240145. PMID 11097557. {{cite journal}}: Unknown parameter |month= ignored (help)
144. K.A. Rosenblatt; et al. (1 June 2004). "Marijuana Use and Risk of Oral Squamous Cell Carcinoma". Cancer Research. 64 (11): 4049–54. doi:10.1158/0008-5472.CAN-03-3425. PMID 15173020. {{cite journal}}: Explicit use of et al. in: |author= (help)
145. OASIS
146. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19638490, please use {{cite journal}} with |pmid=19638490 instead.
147. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15697049, please use {{cite journal}} with |pmid=15697049 instead.
148. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16823391, please use {{cite journal}} with |pmid=16823391 instead.
149. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/news060703-9, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/news060703-9 instead.
150. "Marijuana Use Per Se Not a 'Gateway' To Illicit Drug Use, Study Says". NORML. Retrieved 2011-04-20.
151. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17151165, please use {{cite journal}} with |pmid=17151165 instead.
152. RAND Study Casts Doubt on Claims That Marijuana Acts as "Gateway" to the Use of Cocaine and Heroin
153. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16232311, please use {{cite journal}} with |pmid=16232311 instead.
154. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi: 10.1300/J175v01n03_09, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi= 10.1300/J175v01n03_09 instead.
155. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16128224, please use {{cite journal}} with |pmid=16128224 instead.
156. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17437626, please use {{cite journal}} with |pmid= 17437626 instead.
157. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17429350, please use {{cite journal}} with |pmid=17429350 instead.
158. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16637053, please use {{cite journal}} with |pmid=16637053 instead.
159. Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1001/jama.2011.1961, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1001/jama.2011.1961 instead.
160. Tashkin DP, Simmons MS, Sherrill DL, Coulson AH (1997). "Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1 with age". American Journal of Respiratory and Critical Care Medicine. 155 (1): 141–8. doi:10.1136/thx.2006.077081. PMID 9001303. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
161. The impact of cannabis on your lungs, British Lung Association, 2012, retrieved 2013-01-09 {{citation}}: Unknown parameter |month= ignored (help)
162. Le, Bryan (2012-06-08), Drug prof slams pot lung-danger claims, The Fix, retrieved 2013-01-09

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