Long-term effects of cannabis

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Though the long-term effects of cannabis have been studied extensively, there remains much to be concluded. Many studies have investigated whether long-term use of cannabis can cause or contribute to the development of a variety of physical and mental illnesses. The vast majority of this research focuses on frequent or heavy cannabis users, those who use cannabis at least once a day. Recent research has investigated whether its long-term effects on adolescents might differ from those on adults.

Both advocates and opponents of the drug are able to call upon numerous scientific studies supporting their respective positions. For instance, studies have associated heavy cannabis use with the development of various mental disorders. However, discerning between correlation and causation is a challenge. It is unclear whether cannabis use causes mental illness, cannabis use exacerbates mental illness, or both mental illness and cannabis use are caused by an additional factor.

Positive effects of long-term cannabis use have also been noted.[1]

Contents

Reproductive and endocrine effects [edit]

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.[2][3] 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.[4][5] However, the relevance of these results to human cannabis use has not yet been determined.

Pregnancy [edit]

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.[6] 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.[7][8]

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 marijuana 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 marijuana-using mothers had better autonomic stability and reflexes.[9] Another similar study on Jamaican children found that children who had been exposed to marijuana 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.[10]

Some studies have found that children of tobacco and marijuana-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.[11][12] This may be due to the fact that the endocannabinoid system plays a large role in prenatal neural development.[13][14][15][16] However, the previously discussed studies on Jamaican children conflict with this assumption.

Cannabis dependency [edit]

Main article: Cannabis dependence

Despite cannabis being the most widely used illicit drug in the Western world,[17] controlled trials for "cannabis use disorder" have only been reported in literature in the last 15 years. Dr. Jack E. Henningfield of NIDA ranked the relative addictiveness of 6 substances (cannabis, caffeine, cocaine, alcohol, heroin and nicotine). Cannabis ranked least addictive, with caffeine the second least addictive and nicotine the most.[18]

Withdrawal [edit]

Main article: Cannabis withdrawal

Mental health [edit]

Several studies correlate cannabis use with the development of anxiety, psychosis, and depression.[19][20][21] 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.[22] However, others offer the opposite direction of causality, or consider cannabis to only form parts of the "causal constellation."[23][24] 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.[25] Indeed, as much as 60% of the mentally ill are suspected to be substance abusers, and many seem to prefer cannabis and alcohol.[26]

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."[27] In a 2007 review of available data, Zammit and colleagues found a dose-dependent correlation between cannabis use and psychotic illness.[28] They concluded that the heaviest cannabis users are 40% more likely than non-users to suffer a psychotic illness,[29] while the aforementioned 2005 study suggested a 60-80% increased risk.[22]

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."[30] 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.[31] 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 [edit]

Much of the evidence for short-lived cannabis psychosis is based on case reports in which heavy cannabis use has preceded the onset of a psychotic episode, which then remits upon abstinence.[32][33][34][35][36]

A DTI study[37] published in May 9, 2006 showed no brain structural change associated with adolescent cannabis use. They concluded that "cannabis use, in at least moderate amounts, during adolescence does not appear to be neurotoxic."[37]

Chronic Psychosis [edit]

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.[38]

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.[39]

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[40]) 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".[40] 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.[40] 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[41] 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".[7] 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.[42]

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.[43] Studies have shown that a risk does exist in some individuals with a predisposition to mental illness to develop symptoms of psychosis.[20] 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[44] — 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.[20]

Correlation versus causation [edit]

See also: Correlation does not imply 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.[24]

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.[45]

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".[46] 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."[47]

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.[48][49] 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.[50]

Cannabis use does not appear to be causally related to the incidence of schizophrenia,[43] 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.[51][52]

Depressive disorder – Unipolar [edit]

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.[7] 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 marijuana use and with more advanced stages of marijuana use. Relative to newer users, non-dependent marijuana users had 1.6 times greater risk of MDE. Cannabis dependence was associated with a 3.4 time greater risk of major depression.[53] 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.[54]

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 [marijuana] 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."[44]

Depressive disorder – Bipolar [edit]

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.[55]

Suicidality [edit]

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.[56] 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 had a cannabis use disorder.[57]

Cannabidiol in the treatment of schizophrenia [edit]

A recent study has shown that cannabidiol (a major constituent of cannabis) may be as effective as atypical antipsychotics in treating schizophrenia.[58] Further research has verified these results. Leweke et al., (2009) performed a double blind, 4 week, explorative study controlled clinical trial, to compare the effects of purified cannabidiol and the atypical antipsychotic amisulpride on improving the symptoms of schizophrenia in 42 patients with acute paranoid schizophrenia. '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'.[59] The authors conclude cannabidiol revealed substantial antipsychotic properties in acute paranoid schizophrenia (Leweke et al., 2009). This led the authors to suggest the endocannabinoid system plays an adaptive role in the development of paranoid schizophrenia and that this research provides evidence that this mechanism may be a valuable target for 'antipsychotic treatment strategies'.[59]

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 Δ9-THC only, and the third consisted of users who tested positive for both Δ9-THC and CBD. The Δ9-THC only subset scored significantly higher for unusual experiences, while users of both Δ9-THC and CBD had much lower introvertive anhedonia scores.[60]

Respiratory issues [edit]

Cannabis sativa from Vienna Dioscurides, 512 AD

Although cannabis smoke contains many of the same carcinogens as tobacco smoke,[61] some believe it to be less carcinogenic to humans.[62] Recent studies have shown that there are no links between cannabis smoking and cancer.[63][64] 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.[65][66] 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/bioavailability, 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".[67] Another study found vaporizers to be "a safe and effective cannabinoid delivery system."[68][69]

In a 20-year study of 5,000 young adults, researchers found that, unlike tobacco use, smoking a joint 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 use of marijuana actually increases both lung capacity and volume over the years, possibly because marijuana smokers often take deep breaths, which exercises lung tissue. The correlation only decreased after the equivalent of about ten years of smoking a joint every day. Only lung volume and capacity were examined, not throat irritation, coughing, or lung cancer.[70] Note that the prevalence of carcinogens in every day life, specifically automobile exhaust, charred food, and any other relatively volatile organic compounds, when combusted, creates significant amounts of a-pyrene along with other known carcinogens and mutagens including a wide array of polycyclic aromatic hydrocarbons. A 2012 report by the British Lung Foundation quoted evidence that the risk of developing lung cancer is nearly 20 times higher from smoking typical cannabis cigarettes than than from smoking tobacco cigarettes, due to the tendency not to use filters on cannabis cigarettes; and deeper, longer inhaling.[71] However, this report was called into question by Prof. David Nutt who proposed accusations of the report citing dubious sources, containing conflicting evidence and exclusively focusing on supporting evidence rather than submitting a balanced perspective of the debate.[72] In contrast to the British Lung Foundation report, a large 2006 study looked at 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 lung cancer link to marijuana, even in heavy smokers when adjusting for several confounders including cigarette smoking and alcohol use. The study even speculated a possible protective effect.[73]

Behavioral effects [edit]

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.[74] 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 marijuana 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.[75]

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.[76]

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."[77] 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.[78] A 2013 study confirmed this correlation and also found that marijuana users had better insulin resistance, lower insulin levels, and higher high-density lipoprotein ("good cholesterol") levels.[79]

Gateway drug hypothesis [edit]

Main article: Gateway drug theory#Cannabis

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.[80] A July 2006 study by Ellgren et al.[81] 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.[81] 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.[82] 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[83][84] challenges these findings. A 12 year study on 214 boys from ages 10–12 showed that adolescents who used marijuana 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[85] 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.

Memory and intelligence [edit]

Most scientific research leans toward cognitive deficits during intoxication and a residual effect for heavy users [86][87][88][89][90](despite some studies pointing to the contrary [91],[92]). However, there is hardly any consensus on whether or not there is any irreversible and long term damage to cognitive functioning from marijuana use.

In 1999, a naturalistic study by highly reputed scientists, conducted over a period of 15 years found no link between cognitive decline and marijuana usage [93].

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".[94] On his studies regarding cannabis use, lead researcher and Harvard professor Harrison Pope said he found marijuana 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”.[95]

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 marijuana 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.[96] 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".[96] However, Nadia Solowij has conducted several studies which make her conclude that there is, in fact, long term cognitive impairment with heavy marijuana use.[97]

A 2008 study suggested that long-term, heavy cannabis use (over five joints daily for more than ten years) are associated with structural abnormalities in the hippocampus and amygdala areas of the brain.[98] 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.[99] 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."[100] 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 [which plays a part in memory and navigation] of rat after administration of very high doses of THC was not shown."[101][102][103]

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. [104]

The strongest evidence regarding cannabis and memory focuses on its non-acute negative effects on short-term and working memory.[105] Evidence also suggests that long-term effects exist, but these appear to be reversible except possibly in very heavy users.[106]

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.[107]

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, marijuana is harmful to the brain.[108] 1,000 individuals from New Zealand were IQ-tested at ages 13 and 38, the age of onset of smoking marijuana. 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.[109][110][111] 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 [New Zealand subjects], suggesting that the causal effects estimated in [the New Zealand study] are likely to be overestimates, and that the true effect could be zero".[112]

A July 2012 report in Brain reveals neural-connectivity impairment in some brain regions following prolonged cannabis use initiated in adolescence or young adulthood.[113]

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.[114] 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.[115]

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.[116]

Cancer risk [edit]

Epidemiological studies have shown that smoking cannabis increases the risk of acquiring cervical cancer, prostate cancer, and adult-onset glioma among non-tobacco smokers. Lung cancer and colorectal cancer in contrast showed no increase in risk.[117] The marijuana-cancer link is complicated. For example, in contrast to the epidemiological study suggesting a glioma cancer link, a number of studies have suggested that the cannabinoids contained in marijuana could be used to treat these very same tumors.[118][119][120][121][122]

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.[123] 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.[124] In September 2012, a study published in the journal Cancer became the third to link marijuana use to the development of testicular cancer.[125]

Cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same carcinogens as tobacco smoke.[61] However, these carcinogens can be reduced or avoided by eating cannabis-infused foods and tinctures, or by using a vaporizer. Additionally, research has not found any correlation between cannabis use and lung cancer, likely because its antioxidant effect counteracts the carcinogens present.[117]

Positive effects [edit]

A study, published in the Cancer Prevention Research journal, showed that long-term cannabis users were, roughly, 62% 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 factors that might influence the results, smoking marijuana from once every two weeks to three 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 started using it at an older age appeared to have less risk of head and neck cancers than those who started it at a younger age. Compared to people who never used cannabis, those who began using it between the ages of 15 and 19 years were 47% less likely to develop head and neck cancer, while users who began at age 20 or older had a 61% reduced risk. The authors of the study also note that cannabinoids have been shown to have potential antitumor effects.[1]

Cannabis is a strong antioxidant and therefore defends cells from β-amyloid, the peptide that causes Alzheimer's disease.[126] Some studies have found that cannabis has no effect on ageing-related cognitive decline[127] while others suggest that it slows cognitive decline through its antioxidant effect.[128] The cannabinoids present in cannabis have been reliably shown to lessen cell damage and death from ischemia, likely due to their antioxidant properties.[129]

Cannabis is an effective treatment for a wide array of diseases. These effects can be attributed to cannabidiol, a cannabinoid present in cannabis, as well as tetrahydrocannabinol (THC), another cannabinoid and its primary psychoactive component.[130]

See also [edit]

References [edit]

  1. ^ a b "Could smoking pot cut risk of head, neck cancer?". Reuters. 2009-08-25. Retrieved 2012-12-07. 
  2. ^ Rossato, M.; Ion Popa, F.; Ferigo, M.; Clari, G.; Foresta, C. (2004). "Human Sperm Express Cannabinoid Receptor Cb1, the Activation of Which Inhibits Motility, Acrosome Reaction, and Mitochondrial Function". Journal of Clinical Endocrinology & Metabolism 90 (2): 984–991. doi:10.1210/jc.2004-1287. PMID 15562018.  edit
  3. ^ Schuel, H.; Burkman, L. J.; Lippes, J.; Crickard, K.; Mahony, M. C.; Giuffrida, A.; Picone, R. P.; Makriyannis, A. (2002). "Evidence that anandamide-signaling regulates human sperm functions required for fertilization". Molecular Reproduction and Development 63 (3): 376–387. doi:10.1002/mrd.90021. PMID 12237954.  edit
  4. ^ Kalant, H.K. and Roschlau, W.H.E. (1998). Principles of Medical Pharmacology (6 ed.). pp. 373–375. ISBN 0779699459. 
  5. ^ Hall, W.; Solowij, N. (1998). "Adverse effects of cannabis". The Lancet 352 (9140): 1611–1616. doi:10.1016/S0140-6736(98)05021-1. PMID 9843121.  edit
  6. ^ Mueller, B. A.; Daling, J. R.; Weiss, N. S.; Moore, D. E. (1990). "Recreational drug use and the risk of primary infertility". Epidemiology (Cambridge, Mass.) 1 (3): 195–200. doi:10.1097/00001648-199005000-00003. PMID 2081252.  edit
  7. ^ a b c 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. 
  8. ^ "Information and Resources • NCPIC". Ncpic.org.au. 2011-03-11. Retrieved 2011-04-20. 
  9. ^ Hayes, J. S.; Lampart, R.; Dreher, M. C.; Morgan, L. (1991). "Five-year follow-up of rural Jamaican children whose mothers used marijuana during pregnancy". The West Indian medical journal 40 (3): 120–123. PMID 1957518.  edit
  10. ^ Dreher, M. C.; Nugent, K.; Hudgins, R. (1994). "Prenatal marijuana exposure and neonatal outcomes in Jamaica: An ethnographic study". Pediatrics 93 (2): 254–260. PMID 8121737.  edit
  11. ^ Huizink, A. C.; Mulder, E. J. H. (2006). "Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring". Neuroscience & Biobehavioral Reviews 30 (1): 24–41. doi:10.1016/j.neubiorev.2005.04.005. PMID 16095697.  edit
  12. ^ Fried, P. A.; Watkinson, B.; Gray, R. (2003). "Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana". Neurotoxicology and teratology 25 (4): 427–436. doi:10.1016/S0892-0362(03)00029-1. PMID 12798960.  edit
  13. ^ 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. Lay summary – ScienceDaily (May 29, 2007). 
  14. ^ Berghuis, P.; Dobszay, M. B.; Wang, X.; Spano, S.; Ledda, F.; Sousa, K. M.; Schulte, G.; Ernfors, P. et al. (2005). "Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor". Proceedings of the National Academy of Sciences 102 (52): 19115–19120. doi:10.1073/pnas.0509494102. PMC 1323195. PMID 16357196.   edit
  15. ^ Harkany, T.; Guzmán, M.; Galve-Roperh, I.; Berghuis, P.; Devi, L. A.; MacKie, K. (2007). "The emerging functions of endocannabinoid signaling during CNS development". Trends in Pharmacological Sciences 28 (2): 83–92. doi:10.1016/j.tips.2006.12.004. PMID 17222464.  edit
  16. ^ JR Minkel: Marijuana-Like Chemicals Guide Fetal Brain Cells, Scientific American, May 24, 2007
  17. ^ Anthony, J. C.; Warner, L. A.; Kessler, R. C. (1994). "Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: Basic findings from the National Comorbidity Survey". Experimental and Clinical Psychopharmacology 2 (3): 244. doi:10.1037/1064-1297.2.3.244.  edit
  18. ^ "Relative Addictiveness of Drugs". The New York Times. Tfy.drugsense.org. 1994-08-02. Retrieved 2013-01-07. 
  19. ^ 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. 
  20. ^ a b c Henquet, C.; Krabbendam, L.; Spauwen, J.; Kaplan, C.; Lieb, R.; Wittchen, H. -U.; Van Os, J. (2005). "Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people". BMJ 330 (7481): 11. doi:10.1136/bmj.38267.664086.63. PMC 539839. PMID 15574485.  edit
  21. ^ Patton, G. C.; Coffey, C.; Carlin, J. B.; Degenhardt, L.; Lynskey, M.; Hall, W. (2002). "Cannabis use and mental health in young people: Cohort study". BMJ 325 (7374): 1195–1198. doi:10.1136/bmj.325.7374.1195. PMC 135489. PMID 12446533.  edit
  22. ^ a b Fergusson, D. M.; Horwood, L. J.; Ridder, E. M. (2005). "Tests of causal linkages between cannabis use and psychotic symptoms". Addiction 100 (3): 354–366. doi:10.1111/j.1360-0443.2005.01001.x. PMID 15733249.  edit
  23. ^ Hall, W.; Degenhardt, L.; Teesson, M. (2004). "Cannabis use and psychotic disorders: An update". Drug and Alcohol Review 23 (4): 433–443. doi:10.1080/09595230412331324554. PMID 15763748.  edit
  24. ^ a b Arseneault, L.; Cannon, M.; Witton, J.; Murray, R. M. (2004). "Causal association between cannabis and psychosis: Examination of the evidence". The British journal of psychiatry : the journal of mental science 184 (2): 110–117. doi:10.1192/bjp.184.2.110. PMID 14754822.  edit
  25. ^ Earth Erowid (2005). "Cannabis & Psychosis - A guide to current research about cannabis and mental health". 
  26. ^ Drake, R. E.; Wallach, M. A. (1989). "Substance abuse among the chronic mentally ill". Hospital & community psychiatry 40 (10): 1041–1046. PMID 2807205.  edit
  27. ^ Morgan, Tom (27). "Smoking cannabis doubles the risk of mental illness". Daily Express. 
  28. ^ Moore, T. H.; Zammit, S.; Lingford-Hughes, A.; Barnes, T. R.; Jones, P. B.; Burke, M.; Lewis, G. (2007). "Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review". The Lancet 370 (9584): 319–328. doi:10.1016/S0140-6736(07)61162-3. PMID 17662880.  edit
  29. ^ "Cannabis 'raises psychosis risk'". BBC News (2007-07-27). Retrieved on 2007-11-03.
  30. ^ "The BEACH Project". Retrieved 17 October 2009. 
  31. ^ "Depression, psychosis strike dope smokers". The Australian. Australian Associated Press. 29 September 2009. Retrieved 17 October 2009. 
  32. ^ Chopra, G. S.; Smith, J. W. (1974). "Psychotic reactions following cannabis use in East Indians". Archives of general psychiatry 30 (1): 24–27. doi:10.1001/archpsyc.1974.01760070014002. PMID 4808733.  edit
  33. ^ Eva, J. (1992). Cannabis psychosis. Psychiatric Bulletin 16: 310–311
  34. ^ Solomons, K.; Neppe, V. M.; Kuyl, J. M. (1990). "Toxic cannabis psychosis is a valid entity". South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 78 (8): 476–481. PMID 2218786.  edit
  35. ^ Bernhardson, G.; Gunne, L. M. (1972). "Forty-six cases of psychosis in cannabis abusers". The International journal of the addictions 7 (1): 9–16. PMID 5043840.  edit
  36. ^ Carney, M.; Bacelle, L.; Robinson, B. (1984). "Psychosis after cannabis use". British Medical Journal 288 (6423): 1047. doi:10.1136/bmj.288.6423.1047. 
  37. ^ a b Delisi, L. E.; Bertisch, H. C.; Szulc, K. U.; Majcher, M.; Brown, K.; Bappal, A.; Ardekani, B. A. (2006). "A preliminary DTI study showing no brain structural change associated with adolescent cannabis use". Harm Reduction Journal 3: 17. doi:10.1186/1477-7517-3-17. PMC 1524733. PMID 16684342.  edit
  38. ^ Miettunen, J.; Tormanen, S.; Murray, G. K.; Jones, P. B.; Maki, P.; Ebeling, H.; Moilanen, I.; Taanila, A. et al. (2008). "Association of cannabis use with prodromal symptoms of psychosis in adolescence". The British Journal of Psychiatry 192 (6): 470–471. doi:10.1192/bjp.bp.107.045740. PMID 18515902.  edit
  39. ^ Fernandez-Espejo, E.; Viveros, M. P.; Núñez, L.; Ellenbroek, B. A.; Rodriguez De Fonseca, F. (2009). "Role of cannabis and endocannabinoids in the genesis of schizophrenia". Psychopharmacology 206 (4): 531–549. doi:10.1007/s00213-009-1612-6. PMID 19629449.  edit
  40. ^ a b c Hope, C., Skunk cannabis can make well users psychotic: study, The Telegraph, 28 July 2009
  41. ^ Andréasson, S.; Allebeck, P.; Rydberg, U. (1989). "Schizophrenia in users and nonusers of cannabis. A longitudinal study in Stockholm County". Acta psychiatrica Scandinavica 79 (5): 505–510. doi:10.1111/j.1600-0447.1989.tb10296.x. PMID 2787581.  edit
  42. ^ Zammit, S.; Allebeck, P.; Andreasson, S.; Lundberg, I.; Lewis, G. (2002). "Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: Historical cohort study". BMJ (Clinical research ed.) 325 (7374): 1199. PMC 135490. PMID 12446534.  edit
  43. ^ a b Degenhardt L, Hall W, Lynskey M (2001). Comorbidity between cannabis use and psychosis: Modelling some possible relationships. Technical Report No. 121. Sydney: National Drug and Alcohol Research Centre. Retrieved 19.18.2006. 
  44. ^ a b Denson, T. F.; Earleywine, M. (2006). "Decreased depression in marijuana users". Addictive Behaviors 31 (4): 738–742. doi:10.1016/j.addbeh.2005.05.052. PMID 15964704.  edit
  45. ^ Andréasson, S.; Allebeck, P.; Engström, A.; Rydberg, U. (1987). "Cannabis and schizophrenia. A longitudinal study of Swedish conscripts". Lancet 2 (8574): 1483–1486. doi:10.1016/S0140-6736(87)92620-1. PMID 2892048.  edit
  46. ^ Schiffman, J.; Nakamura, B.; Earleywine, M.; Labrie, J. (2005). "Symptoms of schizotypy precede cannabis use". Psychiatry Research 134 (1): 37–42. doi:10.1016/j.psychres.2005.01.004. PMID 15808288.  edit
  47. ^ Boydell, J.; Dean, K.; Dutta, R.; Giouroukou, E.; Fearon, P.; Murray, R. (2007). "A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: Implications for the concept of cannabis psychosis". Schizophrenia Research 93 (1–3): 203–210. doi:10.1016/j.schres.2007.03.014. PMID 17462864.  edit
  48. ^ Arseneault, L.; Cannon, M.; Poulton, R.; Murray, R.; Caspi, A.; Moffitt, T. E. (2002). "Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study". BMJ 325 (7374): 1212. doi:10.1136/bmj.325.7374.1212. PMC 135493. PMID 12446537.  edit
  49. ^ 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. 
  50. ^ 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. , New Scientist
  51. ^ Degenhardt, L.; Hall, W.; Lynskey, M. (2003). "Testing hypotheses about the relationship between cannabis use and psychosis". Drug and Alcohol Dependence 71 (1): 37–48. doi:10.1016/S0376-8716(03)00064-4. PMID 12821204.  edit
  52. ^ "Earlier onset of schizophrenia linked to pot". Webmd.com. 2011-02-07. Retrieved 2012-10-09. 
  53. ^ Chen, C. Y.; Wagner, F. A.; Anthony, J. C. (2002). "Marijuana use and the risk of Major Depressive Episode". Social Psychiatry and Psychiatric Epidemiology 37 (5): 199–206. doi:10.1007/s00127-002-0541-z. PMID 12107710.  edit
  54. ^ Grant, B. F. (1995). "Comorbidity between DSM-IV drug use disorders and major depression: Results of a national survey of adults". Journal of substance abuse 7 (4): 481–497. doi:10.1016/0899-3289(95)90017-9. PMID 8838629.  edit
  55. ^ "Bipolar Disorder Daily News Blog: Cannabis in bipolar". Pendulum.org. 2005-05-21. Retrieved 2011-04-20. 
  56. ^ Borges, G.; Walters, E. E.; Kessler, R. C. (2000). "Associations of substance use, abuse, and dependence with subsequent suicidal behavior". American journal of epidemiology 151 (8): 781–789. PMID 10965975.  edit
  57. ^ Beautrais, A. L.; Joyce, P. R.; Mulder, R. T. (1999). "Cannabis abuse and serious suicide attempts". Addiction (Abingdon, England) 94 (8): 1155–1164. doi:10.1046/j.1360-0443.1999.94811555.x. PMID 10615730.  edit
  58. ^ Zuardi, A.W; J.A.S. Crippa, J.E.C. Hallak, F.A. Moreira, F.S. Guimarães (2006). "Cannabidiol as an antipsychotic drug". Brazilian Journal of Medical and Biological Research 39 (4): 421–429. doi:10.1590/S0100-879X2006000400001. PMID 16612464. 
  59. ^ a b Leweke, F. M.; Koethe, D.; Pahlisch, F.; Schreiber, D.; Gerth, C. W.; Nolden, B. M.; Klosterkötter, J.; Hellmich, M. et al. (2009). "S39-02 Antipsychotic effects of cannabidiol". European Psychiatry 24: S207. doi:10.1016/S0924-9338(09)70440-7.  edit
  60. ^ Morgan, Celia J. A.; Curran, H. Valerie (2008). "Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis". British Journal of Psychiatry 192 (4): 306–307. doi:10.1192/bjp.bp.107.046649. PMID 18378995.  edit
  61. ^ a b Tomar, Rajpal C.; Beaumont and Hsieh (August 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. 
  62. ^ Melamede, R. (2005). "Cannabis and tobacco smoke are not equally carcinogenic". Harm Reduction Journal 2: 21. doi:10.1186/1477-7517-2-21. PMC 1277837. PMID 16232311.  edit
  63. ^ Donald Tashkin, M.D.: Study Finds No Link Between Marijuana Use And Lung Cancer, ScienceDaily, May 26, 2006
  64. ^ Gideon A. Caplan, Brian A. Brigham (1990-09-01). "Marijuana smoking and carcinoma of the tongue. Is there an association?". Cancer 66 (5): 1005–6. doi:10.1002/1097-0142(19900901)66:5<1005::AID-CNCR2820660535>3.0.CO;2-H. PMID 2201429. 
  65. ^ Grotenhermen, F. (2001). "Harm Reduction Associated with Inhalation and Oral Administration of Cannabis and THC". Journal of Cannabis Therapeutics 1 (3–4): 133–152. doi:10.1300/J175v01n03_09.  edit
  66. ^ Tashkin, D. P. (2005). "Smoked marijuana as a cause of lung injury". Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS \and] Istituto di clinica tisiologica e malattie apparato respiratorio, Universita di Napoli, Secondo ateneo 63 (2): 93–100. PMID 16128224.  edit
  67. ^ Earleywine, M.; Barnwell, S. (2007). "Decreased respiratory symptoms in cannabis users who vaporize". Harm Reduction Journal 4: 11. doi:10.1186/1477-7517-4-11. PMC 1853086. PMID 17437626.  edit
  68. ^ Abrams, D. I.; Vizoso, H. P.; Shade, S. B.; Jay, C.; Kelly, M. E.; Benowitz, N. L. (2007). "Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study". Clinical Pharmacology & Therapeutics 82 (5): 572–578. doi:10.1038/sj.clpt.6100200. PMID 17429350.  edit
  69. ^ Hazekamp, A.; Ruhaak, R.; Zuurman, L.; Van Gerven, J.; Verpoorte, R. (2006). "Evaluation of a vaporizing device (Volcano®) for the pulmonary administration of tetrahydrocannabinol". Journal of Pharmaceutical Sciences 95 (6): 1308–1317. doi:10.1002/jps.20574. PMID 16637053.  edit
  70. ^ Pletcher, M. J. (2012). "Association Between Marijuana Exposure and Pulmonary Function over 20 Years". JAMA: the Journal of the American Medical Association 307 (2): 173–181. doi:10.1001/jama.2011.1961.  edit
  71. ^ The impact of cannabis on your lungs. The British Lung Foundation (June 2012), Retrieved 6 June 2012
  72. ^ Nutt, David (2012-06-11). "Smoke without fire? Scaremongering by the British Lung Foundation over cannabis vs tobacco". Wordpress. Retrieved 12 June 2012. 
  73. ^ Hashibe, M.; Morgenstern, H.; Cui, Y.; Tashkin, D. P.; Zhang, Z. -F.; Cozen, W.; Mack, T. M.; Greenland, S. (2006). "Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study". Cancer Epidemiology Biomarkers & Prevention 15 (10): 1829–1834. doi:10.1158/1055-9965.EPI-06-0330. PMID 17035389.  edit
  74. ^ Abadinsky, H. (2004). Drugs: An Introduction (5th ed.). pp. 62–77; 160–166. ISBN 0-534-52750-7. 
  75. ^ Brill, N. Q.; Christie, R. L. (1974). "Marihuana use and psychosocial adaptation". Archives of general psychiatry 31 (5): 713–719. doi:10.1001/archpsyc.1974.01760170099016. PMID 4441242.  edit
  76. ^ Mendelson, H.H.; Kuehnle, J.C.; Greenberg, I. and Mello, N.K. (1976). "The Effects of Marihuana Use on Human Operant Behavior: Individual Data…". Pharmacology of Marihuana 2. New York: Academic Press. pp. 643–653. 
  77. ^ Fergusson, D. M.; Boden, J. M. (2008). "Cannabis use and later life outcomes". Addiction 103 (6): 969–976; discussion 976–8. doi:10.1111/j.1360-0443.2008.02221.x. PMID 18482420.  edit
  78. ^ Le Strat, Y.; Le Foll, B. (2011). "Obesity and Cannabis Use: Results from 2 Representative National Surveys". American Journal of Epidemiology 174 (8): 929–933. doi:10.1093/aje/kwr200. PMID 21868374.  edit
  79. ^ Penner, E. A.; Buettner, H.; Mittleman, M. A. (2013). "The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults". The American Journal of Medicine. doi:10.1016/j.amjmed.2013.03.002.  edit
  80. ^ Agrawal, A.; Neale, M. C.; Prescott, C. A.; Kendler, K. S. (2004). "A twin study of early cannabis use and subsequent use and abuse/dependence of other illicit drugs". Psychological medicine 34 (7): 1227–1237. doi:10.1017/S0033291704002545. PMID 15697049.  edit
  81. ^ a b Ellgren, M.; Spano, S. M.; Hurd, Y. L. (2006). "Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats". Neuropsychopharmacology 32 (3): 607–615. doi:10.1038/sj.npp.1301127. PMID 16823391.  edit
  82. ^ Hopkin, M. (2006). "Rats taking cannabis get taste for heroin". News@nature. doi:10.1038/news060703-9.  edit
  83. ^ "Marijuana Use Per Se Not a 'Gateway' To Illicit Drug Use, Study Says". NORML. Retrieved 2011-04-20. 
  84. ^ Tarter, R. E.; Vanyukov, M.; Kirisci, L.; Reynolds, M.; Clark, D. B. (2006). "Predictors of Marijuana Use in Adolescents Before and After Licit Drug Use: Examination of the Gateway Hypothesis". American Journal of Psychiatry 163 (12): 2134–2140. doi:10.1176/appi.ajp.163.12.2134. PMID 17151165.  edit
  85. ^ RAND | News Release | RAND Study Casts Doubt on Claims That Marijuana Acts as "Gateway" to the Use of Cocaine and Heroin[dead link]
  86. ^ Heishman et al. 1989;
  87. ^ Foltin et al. 1993;
  88. ^ Kelly et al. 1993;
  89. ^ Haney et al. 1997
  90. ^ http://www.safeaccessnow.org/downloads/long%20term%20cannabis%20effects.pdf
  91. ^ Effects of Acute Smoked Marijuana on Complex Cognitive Performance, Carl L Hart Ph.D1, Wilfred van Gorp Ph.D2, Margaret Haney Ph.D1, Richard W Foltin Ph.D1 and Marian W Fischman Ph.D1
  92. ^ Does Marijuana Use Cause Long-term Cognitive Deficits? Erik W. Gunderson, MD; Suzanne K. Vosburg, PhD; Carl L. Hart, PhD
  93. ^ http://aje.oxfordjournals.org/content/149/9/794.full.pdf
  94. ^ Neuropsychological performance in long-t... [Arch Gen Psychiatry. 2001] - PubMed - NCBI
  95. ^ Lost in the Weeds: Legalizing Medical Marijuana in Massachusetts
  96. ^ a b Fried, P.; Watkinson, B.; James, D.; Gray, R. (2002). "Current and former marijuana use: Preliminary findings of a longitudinal study of effects on IQ in young adults". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 166 (7): 887–891. PMC 100921. PMID 11949984.  edit
  97. ^ http://www.abc.net.au/quantum/poison/marijuan/nadia.htm
  98. ^ "Heavy pot smoking linked to smaller brains". New Scientist (2659). 4 June 2008. Retrieved 17 October 2009. 
  99. ^ Yücel, M.; Solowij, N.; Respondek, C.; Whittle, S.; Fornito, A.; Pantelis, C.; Lubman, D. I. (2008). "Regional Brain Abnormalities Associated with Long-term Heavy Cannabis Use". Archives of General Psychiatry 65 (6): 694–701. doi:10.1001/archpsyc.65.6.694. PMID 18519827.  edit
  100. ^ Lubman, Dan (June 2008). "Long-term cannabis use and regional brain abnormalities". NCPIC e-Zine. Retrieved 17 October 2009. 
  101. ^ INSERM-CNRS. Released June 1998. Excerpts from the Roques report. Hemp Info. Retrieved 5 March 2007
  102. ^ Rapport Roques sur la dangerosité des drogues. (French). Retrieved on 5 March 2007
  103. ^ L'alcool aussi dangereux que l'héroïne. (French) Retrieved on 5 March 2007
  104. ^ Bolla, K. I.; Brown, K.; Eldreth, D.; Tate, K.; Cadet, J. L. (2002). "Dose-related neurocognitive effects of marijuana use". Neurology 59 (9): 1337–1343. doi:10.1212/01.WNL.0000031422.66442.49. PMID 12427880.  edit
  105. ^ 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. 
  106. ^ Grotenhermen, F. (2007). "The Toxicology of Cannabis and Cannabis Prohibition". Chemistry & Biodiversity 4 (8): 1744–1769. doi:10.1002/cbdv.200790151. PMID 17712818.  edit
  107. ^ Chan, G. C.; Hinds, T. R.; Impey, S.; Storm, D. R. (1998). "Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol". The Journal of neuroscience : the official journal of the Society for Neuroscience 18 (14): 5322–5332. PMID 9651215.  edit
  108. ^ Meier, M. H.; Caspi, A.; Ambler, A.; Harrington, H.; Houts, R.; Keefe, R. S. E.; McDonald, K.; Ward, A. et al. (2012). "PNAS Plus: Persistent cannabis users show neuropsychological decline from childhood to midlife". Proceedings of the National Academy of Sciences 109 (40): E2657. doi:10.1073/pnas.1206820109.  edit
  109. ^ Study: Adolescent marijuana use leaves lasting mental deficits. Medical Xpress. 2012-08-27. 
  110. ^ "Study: Pot use before 18 harms adult IQ, memory". USA Today. 27 August 2012. Retrieved 28 August 2012. 
  111. ^ "Persistent Cannabis Users Show Neuropsychological Decline from Childhood to Midlife". JournalistsResource.org. Retrieved 2012-08-29. 
  112. ^ http://www.pnas.org/content/early/2013/01/09/1215678110.short
  113. ^ Zalesky, A.; Solowij, N.; Yucel, M.; Lubman, D. I.; Takagi, M.; Harding, I. H.; Lorenzetti, V.; Wang, R. et al. (2012). "Effect of long-term cannabis use on axonal fibre connectivity". Brain 135 (7): 2245–2255. doi:10.1093/brain/aws136. PMID 22669080.   edit
  114. ^ "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. 
  115. ^ Deena Beasley (2003-06-27). "Study - Pot doesn't cause permanent brain damage". Reuters. Retrieved 2013-01-07. 
  116. ^ Teen Marijuana Use May Show No Effect On Brain Tissue, Unlike Alcohol, Study Finds
  117. ^ a b Hashibe, M.; Straif, K.; Tashkin, D. P.; Morgenstern, H.; Greenland, S.; Zhang, Z. F. (2005). "Epidemiologic review of marijuana use and cancer risk". Alcohol 35 (3): 265–275. doi:10.1016/j.alcohol.2005.04.008. PMID 16054989.  edit
  118. ^ Parolaro D, Massi P (2008). "Cannabinoids as potential new therapy for the treatment of gliomas". Neurotherapeutics 8 (1): 37–49. doi:10.1586/14737175.8.1.37. PMID 18088200. 
  119. ^ Calatozzolo, C.; Salmaggi, A.; Pollo, B.; Sciacca, F. L.; Lorenzetti, M.; Franzini, A.; Boiardi, A.; Broggi, G. et al. (2008). "Expression of cannabinoid receptors and neurotrophins in human gliomas". Neurological Sciences 28 (6): 304–310. doi:10.1007/s10072-007-0843-8. PMID 18175076.   edit
  120. ^ Massi, P.; Vaccani, A.; Ceruti, S.; Colombo, A.; Abbracchio, M. P.; Parolaro, D. (2003). "Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines". Journal of Pharmacology and Experimental Therapeutics 308 (3): 838–845. doi:10.1124/jpet.103.061002. PMID 14617682.  edit
  121. ^ Blazquez, C.; González-Feria, L.; Alvarez, L.; Haro, A.; Casanova, M. L.; Guzmán, M. (2004). "Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas". Cancer Research 64 (16): 5617–5623. doi:10.1158/0008-5472.CAN-03-3927. PMID 15313899.  edit
  122. ^ Sánchez, C.; Galve-Roperh, I.; Canova, C.; Brachet, P.; Guzmán, M. (1998). "Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells". FEBS letters 436 (1): 6–10. doi:10.1016/S0014-5793(98)01085-0. PMID 9771884.  edit
  123. ^ Daling, J. R.; Doody, D. R.; Sun, X.; Trabert, B. L.; Weiss, N. S.; Chen, C.; Biggs, M. L.; Starr, J. R. et al. (2009). "Association of marijuana use and the incidence of testicular germ cell tumors". Cancer 115 (6): 1215–1223. doi:10.1002/cncr.24159. PMC 2759698. PMID 19204904.  edit
  124. ^ Lacson, J. C. A.; Carroll, J. D.; Tuazon, E.; Castelao, E. J.; Bernstein, L.; Cortessis, V. K. (2012). "Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk". Cancer 118 (21): 5374–5383. doi:10.1002/cncr.27554. PMID 22965656.  edit
  125. ^ Smoking Marijuana Tied to Testicular Cancer Web MD 09-10-2012.
  126. ^ Iuvone, T.; Esposito, G.; Esposito, R.; Santamaria, R.; Di Rosa, M.; Izzo, A. A. (2004). "Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells". Journal of Neurochemistry 89 (1): 134–141. doi:10.1111/j.1471-4159.2003.02327.x. PMID 15030397.  edit
  127. ^ Lyketsos, C. G.; Garrett, E.; Liang, K. Y.; Anthony, J. C. (1999). "Cannabis use and cognitive decline in persons under 65 years of age". American journal of epidemiology 149 (9): 794–800. doi:10.1093/oxfordjournals.aje.a009894. PMID 10221315.  edit
  128. ^ Bilkei-Gorzo, A. (2012). "The endocannabinoid system in normal and pathological brain ageing". Philosophical Transactions of the Royal Society B: Biological Sciences 367 (1607): 3326–3341. doi:10.1098/rstb.2011.0388.  edit
  129. ^ Hayakawa, K.; Mishima, K.; Fujiwara, M. (2010). "Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke". Pharmaceuticals 3 (7): 2197. doi:10.3390/ph3072197.  edit
  130. ^ Campos, A. C.; Moreira, F. A.; Gomes, F. V.; Del Bel, E. A.; Guimaraes, F. S. (2012). "Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders". Philosophical Transactions of the Royal Society B: Biological Sciences 367 (1607): 3364–3378. doi:10.1098/rstb.2011.0389. PMC 3481531. PMID 23108553.  edit

External links [edit]

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General
Cannabis strains
with subset strains
Pure indica
Indica-dominant
Pure sativa
Sativa-dominant
Usage
General
Preparations
Consumption
Phytocannabinoids
Effects
Culture
Pro-Cannabis
organizations
Use demographics
Politics
General
Politicians
and parties
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