Jump to content

Long-term effects of cannabis

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by 141.70.81.136 (talk) at 02:25, 21 October 2012 (→Memory and intelligence: grammar). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Though the long-term effects of cannabis have been studied, there remains much to be concluded. Many studies[which?] have investigated whether long-term use of cannabis can cause or contribute to the development of illnesses such as heart disease, bipolar disorder, depression, mood swings or schizophrenia.

Both advocates and opponents of the drug are able to call upon numerous scientific studies supporting their respective positions. For instance, while cannabis has been implicated in the development of various mental disorders in some studies[which?], these studies differ widely as to whether cannabis use is the cause of the mental problems displayed in heavy users, whether the mental problems are exacerbated by cannabis use, or whether both the cannabis use and the mental problems are the effects of some other cause. Positive effects of long-term cannabis use have also been noted.[1]

Reproductive and endocrine effects

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.[2][3]

Research has demonstrated that human sperm contains receptors which are stimulated by substances like THC and other cannabis-related chemicals. Tests have implied that smoking of marijuana could impact the sperm's functions, though this impact is unknown.[4] There is some evidence that cannabis may compromise female fertility with a modest association reported between cannabis use and infertility in Mueller et al.'s[5] case controlled study of 150 women with primary anovulatory infertility. While Wenger et al.[6] indicate evidence that THC and anandamide increase the duration of pregnancy and increase the frequency of stillbirth in rats. In a report prepared for the Australian National Council on Drugs, Copeland, Gerber and Swift conclude that current understanding suggests cannabis-related substances are contraindicated in pregnancy, as are compounds that interact with endocannabinoid synthesis and metabolism.[7][8]

Higher rates of testicular cancer in western nations have been linked to use of cannabis. A study conducted by the Fred Hutchinson Cancer Research Center and funded by the National Institutes of Health, published in the journal Cancer March 15, 2009, linked long-term use of cannabis to an increased risk of 70 percent for testicular cancer with the scientists concluding that cannabis is harmful to the human endocrine and reproductive system (The risk of cancer is increased from 0.4% to roughly 0.6%).The study also demonstrated a link between an increase in cannabis use and incidences of testicular cancer in men since the 1950s.[9][10][11]

Pregnancy

A study of the development of 59 Jamaican children was conducted with the children being monitored from childbirth to age 5 years. 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. Testing was done at 1, 3, and 30 days of age with the Brazelton Neonatal Behavioral Assessment Scales, and at ages 4 and 5 years with the McCarthy Scales of Children's Abilities test. Data was also collected from the child's home environment and temperament, as well as standardized tests. The results over the entire research period showed no significant differences in development testing outcomes between using and non-using mothers. At 30 days of age, however, the children of marijuana-using mothers had higher scores on autonomic stability and reflexes.[12] The absence of any differences between the exposed and non-exposed groups in the early neonatal period suggest that the better scores of exposed neonates at 1 month are traceable to the cultural positioning and social and economic characteristics of mothers using marijuana that select for the use of marijuana but also promote neonatal development.

Some studies have found that children of tobacco and marijuana-smoking mothers more frequently suffer from permanent cognitive deficits, concentration disorders, hyperactivity, and impaired social interactions than non-exposed children of the same age and social background.[13][14] A recent study, with participation of scientists from Europe and the United States, has now identified that naturally occurring endocannabinoid molecules play a role in establishing how certain nerve cells connect to each other in the fetal brain.[15][16][17] Another study examining cannabinoid receptor proteins (CBRs) expressed in brain cells of mice determined that endogenous endocannabinoids assist in directing brain cell directional development while in the womb.[18] The researchers suggest that elevated blood THC levels due to cannabis consumption would affect brain development of human fetuses. In contrast, other studies in Jamaica have suggested that cannabis use by expectant mothers does not appear to cause birth defects or developmental delays in their newborn children.[12][19]

Cannabis dependency

Main article: Cannabis dependence

Despite cannabis being the most widely used illicit drug in the Western world,[20] controlled trials for cannabis use disorder have only been reported in literature in the last 15 years. Research has shown a substantial percentage of cannabis users develop cannabis-related problems, including dependency. Overall, the addiction potential for cannabis is significantly less than that for tobacco, alcohol, cocaine or heroin, but slightly higher than that for psilocybin, mescaline, or LSD.[21][22]

Withdrawal

Main article: Cannabis withdrawal

At one time cannabis was considered a drug that had no withdrawal symptoms because users did not display symptoms similar to those withdrawing from alcohol or opiates. Contrary to this, experimental research supports reports of users who relate evidence of heavy cannabis use producing psychological and physical withdrawal symptoms.[23]

Mental health

Cannabis use has been assessed by several studies[24] to be correlated with the development of anxiety, psychosis, and depression.[25][26] Studies have also shown a large correlation between tobacco cigarette smoking and such brain disorders, but there is not much said about cause and effect. [citation needed] Some studies regarding cannabis assess that the causality is more likely to involve a path from cannabis use to psychotic symptoms rather than a path from psychotic symptoms to cannabis use,[27] while others assess the opposite direction of the causality, or hold cannabis to only form parts of the "causal constellation", while not inflicting mental health problems that would not have occurred in the absence of the cannabis use.[28][29] A common interpretation of the correlation and theorized direction of the causality is the self-medication hypothesis, which is based on partially or fully attributing the correlation between psychiatric diseases and cannabis to the extensive substance abuse among sufferers of certain mental disorders, before diagnosis in many cases, which increases the likeliness of cannabis use among the mentally ill and the undiagnosed, thus accounting for correlation and debunking some claims of causality with the opposite direction.[30] As much as 60% of the mentally ill are suspected to be substance abusers, and many seem to prefer cannabis and alcohol.[31] Dr Stanley Zammit of Bristol and Cardiff universities (in the Daily Express newspaper of 27 July 2007) reported, "Even if cannabis did increase the risk of psychosis, most people using the drug would not get ill" But he added: "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." A 2007 study of studies published in the Lancet concluded that cannabis users are 40% more likely to be sufferers of a psychotic illness than non-users.[32]

The BEACH[33] study (Bettering the Evaluation and Care of Health) conducted by the Australian General Practice Statistics and Classification Centre, based at the University of Sydney, found 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 GP, 48% had a psychological problem, including 19% with depression, 9% with psychosis and 6% had anxiety.[34] However, it was also noted that few cannabis users actually tell their doctors that they use it, which could potentially bias the results of the study. Much of the evidence for a short-lived cannabis psychosis is largely based on case reports where heavy cannabis use has preceded the onset of a psychotic episode, which then remits on abstinence.[35] Depictions of a toxic or acute cannabis psychosis have been reported in a number of countries such as New Zealand,[36] South Africa,[37] Sweden[38] and the UK.[39]

A DTI study[40] published in May 9, 2006 showed no brain structural change associated with adolescent cannabis use. It was concluded "cannabis use, in at least moderate amounts, during adolescence does not appear to be neurotoxic"[40]

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.[41]

The direction of causation was more directly examined in a study by Dr. Mikkel Arendt of Aarhus University in Risskov, Denmark, and colleagues, which found that individuals treated for psychotic episodes following cannabis use had the same likelihood of having a mother, sister or other "first-degree" relative with schizophrenia as did the individuals who had actually been treated for schizophrenia themselves. This suggests that the psychosis blamed on cannabis use is in fact the result of a genetic predisposition towards schizophrenia. "These people would have developed schizophrenia whether or not they used cannabis"[42]

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[43]) 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".[43] 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.[43] 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[44] 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 illnes 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".[45] 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.[46]

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.[47] Studies have shown that a risk does exist in some individuals with a predisposition to mental illness to develop symptoms of psychosis.[25] 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[48] — 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.[25]

Correlation versus causation

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.[29]

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.[49]

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".[50] 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."[51]

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.[52][53] 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.[54]

Cannabis use does not appear to be causally related to the incidence of schizophrenia,[47] 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.[55][56]

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.[57] 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 never 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.[58] 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.[59]

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."[48]

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.[60]

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.[61] 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.[62]

Cannabidiol in the treatment of schizophrenia

A recent study has shown that cannabidiol (a major constituent of cannabis) may be as effective as atypical antipsychotics in treating schizophrenia.[63] 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'.[64] 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'.[64]

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.[65]

Respiratory problems

Although cannabis smoke contains many of the same carcinogens as tobacco smoke,[66] some believe it to be less carcinogenic to humans.[67] Smoking is the most harmful method of drug consumption, as 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.[68][69] 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/bioavailibility, 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 semipermiable 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 posses. By comparison, vaporization of cannabis contributes to a relatively large amount of lung irritation due to the very high ratio of active THC/CBD in the 150C partially condensed vapor, which, in large quantities inhaled does contribute significantly to acute lung irritation from pulmonary admistration of any medication or aerosol. A study found that subjects were "only 40% as likely to report respiratory symptoms as users who do not vaporize, even across a range of net material combustion products inhaled. "[70] Another study found vaporizers to be "a safe and effective cannabinoid delivery system."[71][72]

The term cannabis-associated respiratory disease can refer to neoplastic (tumor-forming) processes or structural damage in the lung. Note, Cannabinoids have been shown in vitro to have antineoplastin activity, however, inhaling vapors of any vegetative matter, heated to near its flash point, regularly, can be shown to cause malignancies, as carcinogens are found in high concentrations specifically in the particulate residues, but also the gaseous products of oxidative decomposition.

However, recent studies have shown that there are no links between the regular smoking of marijuana and cancer.[73][74] 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.[75] 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.[76] 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.[77]

Smoking cessation

Cannabis is the most widely used illegal drug in the Western world.[78] There is plenty of documented evidence to suggest a need for users to find ways to assist them to stop using cannabis and the demand for treatment for cannabis dependency is increasing internationally.[79][80][81][82] There are a number of ways to quit cannabis and increasing evidence-based treatments for cannabis users wishing to change the patterns of their use. This article deals with the different interventions to assist in the cessation of cannabis use.

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 study (MTF), and the Arrestee Drug Abuse Monitoring (ADAM) program, which claim lower school averages and higher dropout rates among users than non-users. However, the major contributor to a lack of credibility in these studies, is that in many cases, like with NHSDA and MTF, these surveys are usually self-administered and may be anonymous. The likeliness of over- or under-representing data definitely undermines the effectiveness of these instruments.[83] 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, but the users had a little more difficulty deciding on career goals, and a smaller number were seeking advanced professional degrees.[84] Laboratory studies of the relationship between motivation and marijuana outside of the classroom, where volunteers worked on operant tasks for a wage representing a working world model, also fail to distinguish a noticeable difference between users and non-users.[85]

A longitudinal study of the long-term effects of cannabis usage from ages 14 to 21 on life outcomes up to age 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."[86]

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.[87]

Gateway drug hypothesis

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.[88] A July 2006 study by Ellgren et al.[89] 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.[89] 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.[90] 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[91][92] 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[93] 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

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.[94] The study did however show an average IQ decrease of 4.1 for heavy users.[94]

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.[95] 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 percent lower in the hippocampus and 7.1 percent 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.[96] 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."[97] 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."[98][99][100]

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."[101]

The strongest evidence regarding cannabis and memory focuses on its non-acute negative effects on short-term and working memory.[102] Evidence also suggests that long-term effects exist, but these appear to be reversible except possibly in very heavy users.[103]

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.[104]

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.[105] 1,000 individuals from New Zealanders 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.[106][107][108]

A July 2012 report in Brain reveals neural-connectivity impairment in some brain regions following prolonged cannabis use initiated in adolescence or young adulthood.[109]

Cancer risk

Cannabis smoke contains thousands of organic and inorganic chemicals in the tar. This includes many of the same carcinogens as tobacco smoke.[110]

Positive effects

A study, published in the Cancer Prevention Research journal, showed that long-term cannabis users were, roughly, 62 percent 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 percent less likely to develop head and neck cancer, while users who began at age 20 or older had a 61 percent reduced risk. The authors of the study also note that cannabinoids have been shown to have potential antitumor effects.[1]

See also

References

  1. ^ a b Could smoking pot cut risk of head, neck cancer? Reuters. Retrieved 9-6-2012
  2. ^ H.K. Kalant & W.H.E. Roschlau (1998). Principles of Medical Pharmacology (6th ed.). pp. 373–375.
  3. ^ Hall W, Solowij N (1998). "Adverse effects of cannabis". Lancet. 352 (9140): 1611–6. doi:10.1016/S0140-6736(98)05021-1. PMID 9843121. {{cite journal}}: Unknown parameter |month= ignored (help)
  4. ^ Schuel H, Burkman LJ, Lippes J; et al. (2002). "Evidence that anandamide-signaling regulates human sperm functions required for fertilization". Molecular Reproduction and Development. 63 (3): 376–87. doi:10.1002/mrd.90021. PMID 12237954. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Mueller BA, Daling JR, Weiss NS, Moore DE (1990). "Recreational drug use and the risk of primary infertility". Epidemiology. 1 (3): 195–200. doi:10.1097/00001648-199005000-00003. PMID 2081252. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Wenger T, Tóth BE, Juanéda C, Leonardelli J, Tramu G (1999). "The effects of cannabinoids on the regulation of reproduction". Life Sciences. 65 (6–7): 695–701. doi:10.1016/S0024-3205(99)00292-1. PMID 10462070.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ 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. ^ Daling, Janet; Swartz, Stephen (2009-03-15). "Marijuana Use Linked To Increased Risk Of Testicular Cancer". Cancer. American Cancer Society.
  10. ^ Testicular Cancer Risk Linked To Marijuana Smoking Medical News Today 02-09-2009.
  11. ^ Cannabis linked to testicular cancer . The Independent 02-09-2009.
  12. ^ a b Hayes JS, Lampart R, Dreher MC, Morgan L (1991). "Five-year follow-up of rural Jamaican children whose mothers used marijuana during pregnancy". The West Indian Medical Journal. 40 (3): 120–3. PMID 1957518. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Huizink AC, Mulder EJ (2006). "Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring". Neuroscience and Biobehavioral Reviews. 30 (1): 24–41. doi:10.1016/j.neubiorev.2005.04.005. PMID 16095697.
  14. ^ Fried PA, 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): 427–36. doi:10.1016/S0892-0362(03)00029-1. PMID 12798960.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ 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); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Berghuis P, Dobszay MB, Wang X; et al. (2005). "Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor". Proceedings of the National Academy of Sciences of the United States of America. 102 (52): 19115–20. doi:10.1073/pnas.0509494102. PMC 1323195. PMID 16357196. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Harkany T, Guzmán M, Galve-Roperh I, Berghuis P, Devi LA, 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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ JR Minkel: Marijuana-Like Chemicals Guide Fetal Brain Cells, Scientific American, May 24, 2007
  19. ^ Dreher MC, Nugent K, Hudgins R (1994). "Prenatal marijuana exposure and neonatal outcomes in Jamaica: an ethnographic study". Pediatrics. 93 (2): 254–60. PMID 8121737. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Anthony, J.; Warner, L.; Kessler, R. (1994). "Comparative epidemiology of dependence on tobacco, alcohol, controlled substance and inhalants: Basic findings from the National Comorbidity Survey". Experimental and Clinical Psychopharmacology. 2 (3): 244–268. doi:10.1037/1064-1297.2.3.244.
  21. ^ "Relative Addictiveness of Various Substances". Druglibrary.org. Retrieved 2011-04-20.
  22. ^ The Most Addictive Drugs
  23. ^ Budney, A.J.M.; Moore, B.A.; Vandrey, R.G.; Hughes, J.R. (2003). "The time course and significance of cannabis withdrawal". Journal of Abnormal Psychology. 112 (3): 393–402. doi:10.1037/0021-843X.112.3.393. PMID 12943018.
  24. ^ 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. {{cite book}}: Unknown parameter |month= ignored (help)
  25. ^ a b c 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.
  26. ^ Patton, G. C., Coffey, C., Carlin, J. B., Degenhardt, L., Lynskey, M., and Hall, W. 2002. Cannabis use and mental health in young people: cohort study. BMJ 325(7374): 1195-1198. Retrieved 45 March 2007
  27. ^ Fergusson, David M.; Horwood, John L.; Ridder, Elizabeth M. "Research Report: Tests of causal linkages between cannabis use and psychotic symptoms. University of Otago Christchurch School of Medicine published in the Society for the Study of Addiction (2004-11-05). Retrieved on 2007-11-03.
  28. ^ Hall, Wayne; Degenhardt, Lousia; Teesson, Maree. "Cannabis use and psychotic disorders: an update". Office of Public Policy and Ethics, Institute for Molecular Bioscience University of Queensland Australia, and National Drug and Alcohol Research Centre University of New South Wales Australia published in Drug and Alcohol Review (December 2004). Vol 23 Issue 4. Pg 433-443
  29. ^ a b L. Arseneault; et al. (2004). "Causal association between cannabis and psychosis: examination of the evidence". The British Journal of Psychiatry. 184 (2): 110–117. doi:10.1192/bjp.184.2.110. PMID 14754822. {{cite journal}}: Explicit use of et al. in: |author= (help)
  30. ^ Earth Erowid (2005). "Cannabis & Psychosis - A guide to current research about cannabis and mental health".
  31. ^ Drake RE, Wallach MA (1989). "Substance abuse among the chronic mentally ill". Hospital & Community Psychiatry. 40 (10): 1041–6. PMID 2807205. {{cite journal}}: Unknown parameter |month= ignored (help)
  32. ^ "Cannabis 'raises psychosis risk'". BBC News (2007-07-27). Retrieved on 2007-11-03.
  33. ^ "The BEACH Project". Retrieved 17 October 2009.
  34. ^ "Depression, psychosis strike dope smokers". The Australian. Australian Associated Press. 29 September 2009. Retrieved 17 October 2009.
  35. ^ 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.
  36. ^ Eva, J. (1992). Cannabis psychosis. Psychiatric Bulletin 16: 310–311
  37. ^ Solomons, K.; Neppe, V.M.; Kuyl, J.M. (1990). "Toxic cannabis psychosis is a valid entity". South African Medical Journal. 78 (8): 476–481. PMID 2218786.
  38. ^ Bernhardson, G.; Gunne, L.M. (1972). "Forty-six cases of psychosis in cannabis abusers". International Journal of the Addictions. 7 (1): 9–16. PMID 5043840.
  39. ^ Carney, M.; Bacelle, L.; Robinson, B. (1984). "Psychosis after cannabis use". British Medical Journal. 288: 1047.
  40. ^ a b LE DeLisi; et al. (2006). "A preliminary DTI study showing no brain structural change associated with adolescent cannabis use" (PDF). Harm Reduction Journal. 3 (17). biomedcentral.com. doi:10.1186/1477-7517-3-17. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: unflagged free DOI (link)
  41. ^ 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.
  42. ^ Harding, Anne (3 November 2008). "Pot-induced psychosis may signal schizophrenia". Reuters. Retrieved 17 October 2009.
  43. ^ a b c Hope, C., Skunk cannabis can make well users psychotic: study, The Telegraph, 28 July 2009
  44. ^ Andreasson, 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. PMID 2787581.
  45. ^ Copeland, J.; Gerber, Saul; Swift, Wendy (2006). Evidence-based answers to cannabis questions: a review of the literature. ANCD Research Paper. Canberra: Australian National Council on Drugs. ISBN 1-877018-12-0. {{cite book}}: More than one of |author= and |last1= specified (help)|}
  46. ^ Zammit, S.; et al. (2002). "Self-reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study". British Medical Journal. 325 (7374): 1199–1201. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |pmcid= ignored (|pmc= suggested) (help)
  47. ^ a b 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)
  48. ^ a b T.F. Denson, M. Earleywine (June 20, 2005). "Decreased depression in marijuana users". Addictive Behaviors. 31 (4): 738–42. doi:10.1016/j.addbeh.2005.05.052. PMID 15964704.
  49. ^ S. Andreasson; et al. (1987). "Cannabis and Schizophrenia: A Longitudinal Study of Swedish Conscripts". The Lancet. 2 (8574): 1483–1486. doi:10.1016/S0140-6736(87)92620-1. PMID 2892048. {{cite journal}}: Explicit use of et al. in: |author= (help)
  50. ^ 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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  51. ^ 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". Schizophr. Res. 93 (1–3): 203–10. doi:10.1016/j.schres.2007.03.014. PMID 17462864. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  52. ^ 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.
  53. ^ 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)
  54. ^ 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); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link), New Scientist
  55. ^ "Testing hypotheses about the relationship between cannabis use and psychosis". Drug and Alcohol Dependence. 71 (1). ScienceDirect.com: 37–48. 2003-07-20. doi:10.1016/S0376-8716(03)00064-4. Retrieved 2012-10-09. {{cite journal}}: Unknown parameter |authors= ignored (help)
  56. ^ "Earlier onset of schizophrenia linked to pot". Webmd.com. 2011-02-07. Retrieved 2012-10-09.
  57. ^ Copeland, J., Gerber, S., Swift, W. (2004), evidence-based answers to cannabis questions a review of the literature. National Drug and Alcohol Research Centre University of New South Wales A report prepared for the Australian National Council on Drugs. Available at http://ncpic.org.au/ncpic/links/information
  58. ^ Chen, C.-Y., Wagner, F.A. and Anthony, J.C. (2002). Marijuana use and the risk of major depressive episode: epidemiological evidence from the United States National Comorbidity Survey. Social Psychiatry and Psychiatric Epidemiology 37(5): 199–206
  59. ^ 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.
  60. ^ "Bipolar Disorder Daily News Blog: Cannabis in bipolar". Pendulum.org. 2005-05-21. Retrieved 2011-04-20.
  61. ^ 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.
  62. ^ Beautrais, A.L.; Joyce, P.R.; Mulder, R.T. (1999). "Cannabis abuse and serious suicide attempts". Addiction. 94 (8): 1155–1164. doi:10.1046/j.1360-0443.1999.94811555.x. PMID 10615730.
  63. ^ 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. ISSN 0100-879X ISSN 0100-879X. PMID 16612464. {{cite journal}}: Check |issn= value (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  64. ^ a b 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.
  65. ^ Celia J. A. Morgan, PhD and H. Valerie Curran, PhD, DClinPsy Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis
  66. ^ Tomar, Rajpal C. (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 23 June 2012 {{citation}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: year (link)
  67. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  68. ^ Franjo Grotenhermen (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  69. ^ Tashkin DP (2005). "Smoked marijuana as a cause of lung injury". Monaldi Arch Chest Dis. 63 (2): 93–100. PMID 16128224. {{cite journal}}: Unknown parameter |month= ignored (help)
  70. ^ Earleywine M, Barnwell SS (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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  71. ^ Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL (2007). "Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study". Clinical Pharmacology and Therapeutics. 82 (5): 572–578. doi:10.1038/sj.clpt.6100200. PMID 17429350. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  72. ^ 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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  73. ^ Donald Tashkin, M.D.: Study Finds No Link Between Marijuana Use And Lung Cancer, ScienceDaily, May 26, 2006
  74. ^ Gideon A. Caplan MB, BS, Brian A. Brigham: Marijuana smoking and carcinoma of the tongue. Is there an association?, "Cancer", June 29, 2006
  75. ^ Pletcher, MD, MPH, Mark J. (March 26, 1985-August 19, 2006). "Association Between Marijuana Exposure and Pulmonary Function Over 20 Years". The Journal of the American Medical Association. 307 (2): 173–181. doi:10.1001/jama.2011.1961. Retrieved 11 January 2012. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  76. ^ Staff (June 2012) The impact of cannabis on your lungs The British Lung Foundation, Retrieved 6 June 2012
  77. ^ Nutt, David. "Prof". Wordpress. Retrieved 12 June 2012.
  78. ^ Anthony, J., Warner, L. & Kessler, R. (1994). Comparative epidemiology of dependence on tobacco, alcohol, controlled substance and inhalants: Basic findings from the National Comorbidity Survey. Experimental and Clinical Psychopharmacology 2, 244-268.
  79. ^ Substance Abuse and Mental Health Services Administration, Office of Applied Studies (2003)Emergency department trends from the drug abuse warning network, final estimates 1999-2002DAWN series: D-24, DHHS Publication No. (SMA) 03-3780. Rockville, Maryland: Substance Abuse and Mental Health Services Administration, Office of Applied Studies.
  80. ^ Shand, F. and Mattick, R. (2002) Results from the 4th National Clients of Treatment Service Agencies census: Changes in clients’ substance use and other characteristics. Australian and New Zealand Journal of Public Health, 26, 352-357.
  81. ^ Australian Institute of Health and Welfare (2005d) Alcohol and other drug treatment services in Australia 2003-04: Report on the national minimum data set. Drug Treatment Series 4. AIHW cat. no. HSE 100 Canberra, Australian Institute of Health and Welfare.
  82. ^ Copeland, J (2004). "Developments in the treatment of cannabis use disorder". Current Opinion in Psychiatry. 17: 2114–2121.
  83. ^ H. Abadinsky (2004). Drugs: An Introduction (5th ed.). pp. 62–77, 160–166. ISBN 0-534-52750-7.
  84. ^ Brill NQ, Christie RL (1974). "Marihuana use and psychosocial adaptation". Archives of General Psychiatry. 31 (5): 713–9. doi:10.1001/archpsyc.1974.01760170099016. PMID 4441242. {{cite journal}}: Unknown parameter |month= ignored (help)
  85. ^ H.H. Mendelson, J.C. Kuehnle, I. Greenberg; N.K. Mello (1976). "The Effects of Marihuana Use on Human Operant Behavior: Individual Data…". Pharmacology of Marihuana. Vol. 2. New York: Academic Press. pp. 643–653.{{cite book}}: CS1 maint: multiple names: authors list (link)
  86. ^ Fergusson DM, Boden JM (2008). "Cannabis use and later life outcomes". Addiction. 103 (6): 969–76, discussion 977–8. doi:10.1111/j.1360-0443.2008.02221.x. PMID 18482420. {{cite journal}}: Unknown parameter |month= ignored (help)
  87. ^ Yann Le Strat, Bernard Le Foll (2011). "Obesity and cannabis use: results from 2 representative national surveys". American Journal of Epidemiology. doi:10.1093/aje/kwr200. Retrieved 2012-10-09.
  88. ^ Agrawal A, Neale MC, Prescott CA, Kendler KS (2004). "A twin study of early cannabis use and subsequent use and abuse/dependence of other illicit drugs". Psychological Medicine. 34 (7): 1227–37. doi:10.1017/S0033291704002545. PMID 15697049. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  89. ^ a b Ellgren M, Spano SM, Hurd YL (2007). "Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats". Neuropsychopharmacology. 32 (3): 607–15. doi:10.1038/sj.npp.1301127. PMID 16823391. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  90. ^ Hopkin, Michael (2006). "Rats taking cannabis get taste for heroin". News@nature. doi:10.1038/news060703-9.
  91. ^ "Marijuana Use Per Se Not a 'Gateway' To Illicit Drug Use, Study Says". NORML. Retrieved 2011-04-20.
  92. ^ Tarter RE, Vanyukov M, Kirisci L, Reynolds M, Clark DB (2006). "Predictors of marijuana use in adolescents before and after licit drug use: examination of the gateway hypothesis". The American Journal of Psychiatry. 163 (12): 2134–40. doi:10.1176/appi.ajp.163.12.2134. PMID 17151165. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  93. ^ RAND | News Release | RAND Study Casts Doubt on Claims That Marijuana Acts as "Gateway" to the Use of Cocaine and Heroin[dead link‍]
  94. ^ 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. 166 (7): 887–91. PMC 100921. PMID 11949984. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ "Heavy pot smoking linked to smaller brains". New Scientist (2659). 4 June 2008. Retrieved 17 October 2009.
  96. ^ Yücel M, Solowij N, Respondek C; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ 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)
  98. ^ INSERM-CNRS. Released June 1998. Excerpts from the Roques report. Hemp Info. Retrieved 5 March 2007
  99. ^ Rapport Roques sur la dangerosité des drogues. Template:Fr icon. Retrieved on 5 March 2007
  100. ^ L'alcool aussi dangereux que l'héroïne. Template:Fr icon Retrieved on 5 March 2007
  101. ^ Bolla KI, Brown K, Eldreth D, Tate K, Cadet JL (2002). "Dose-related neurocognitive effects of marijuana use". Neurology. 59 (9): 1337–43. PMID 12427880. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  102. ^ 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.
  103. ^ Grotenhermen F (2007). "The toxicology of cannabis and cannabis prohibition". Chemistry & Biodiversity. 4 (8): 1744–69. doi:10.1002/cbdv.200790151. PMID 17712818. {{cite journal}}: Unknown parameter |month= ignored (help)
  104. ^ Chan GC, Hinds TR, Impey S, Storm DR (1998). "Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol". The Journal of Neuroscience. 18 (14): 5322–32. PMID 9651215. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  105. ^ Meier MH; et al. (2012-07-30). "Persistent cannabis users show neuropsychological decline from childhood to midlife". PNAS. 109 (40). doi:10.1073/pnas.1206820109. {{cite journal}}: Explicit use of et al. in: |author= (help)
  106. ^ Study: Adolescent marijuana use leaves lasting mental deficits, Medical Xpress, 2012-08-27
  107. ^ "Study: Pot use before 18 harms adult IQ, memory". USA Today. 27 August 2012. Retrieved 28 August 2012.
  108. ^ "Persistent Cannabis Users Show Neuropsychological Decline from Childhood to Midlife". JournalistsResource.org. Retrieved 2012-08-29.
  109. ^ Zalesky A; et al. (Jul 2012). "Effect of long-term cannabis use on axonal fibre connectivity". Brain: 2245–55. doi:10.1093/brain/aws136. {{cite journal}}: Explicit use of et al. in: |author= (help)
  110. ^ Tomar, Rajpal C. (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 23 June 2012 {{citation}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: year (link)
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Long-term_effects_of_cannabis&oldid=518959207"