Long-term effects of cannabis
The long term effects of cannabis have been the subject of ongoing debate. Because cannabis is illegal in most countries, research presents a challenge; as such there remains much to be concluded. Studies have investigated both the detrimental and beneficial effects of long-term use of cannabis. The vast majority of this research focuses on those who use cannabis at least once a day. Recent research has investigated whether its long-term effects on adolescents differ from those on adults.
A 2013 literature review said that exposure to marijuana had biologically-based physical, mental, behavioral and social health consequences and was "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, and vasculature". The authors cautioned that "evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions". 
Data supporting negative effects of cannabis alone are weak.[medical citation needed] Discerning between correlation and causation is an important consideration. Studies exist showing both negative and positive effects, and much is conflicting.[medical citation needed] For instance, studies have associated heavy cannabis use with the development of various mental disorders, while other science points to both an ameliorative effect[medical citation needed] and no relationship whatsoever.[medical citation needed]
- 1 Memory and intelligence
- 2 Reproductive and endocrine effects
- 3 Mortality
- 4 Dependency
- 5 Mental health
- 6 Behavioral effects
- 7 Cancer
- 8 Gateway drug hypothesis
- 9 Respiratory effects
- 10 See also
- 11 References
Memory and intelligence
|This section may be confusing or unclear to readers. (December 2013)|
Most scientific research leans toward cognitive deficits during intoxication and a residual effect for heavy users. A 2013 literature review said that changes in "attention, psychomotor task ability, and short-term memory" were associated with very recent (12 to 24 hours) marijuana use, available date does not evidence any long-term central nervous system effects. "Any long-term effects of residual drug on the CNS could be influenced by the acute effects of the drug, the susceptibility of the user, or any pre-existing psychiatric disorder."
The strongest evidence regarding cannabis and memory focuses on its non-acute negative effects on short-term and working memory. Evidence also suggests that long-term effects exist, but these appear to be reversible except possibly in very heavy users.
Reproductive and endocrine effects
Cannabis consumption in pregnancy is associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring. A 2012 systematic review found although it was difficult to draw firm conclusions, there was some evidence that prenatal exposure to certain substances, especially marijuana and cocaine, was associated with "deficits in language, attention, areas of cognitive performance, and delinquent behavior in adolescence". A report prepared for the Australian National Council on Drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy as it may interact with the endocannabinoid system.
Fatal overdoses associated with cannabis use have not been reported as of 2010; there have not been good controlled broad-based population studies on its association with mortality. A 2010 literature review by Calabria et al found 19 studies between 1990 and 2008 assessing the risk of mortality associated with cannabis use: nine studies for cancer, four for suicide, four on motor vehicle accidents, and two on all causes. The way cannabis use is reported varied across the studies, so a limitation of the review was that it was difficult to compare cannabis usage (heavy to light) across the studies. Because of the low number of studies available, they found insufficient evidence for conclusions about mortality among all cannabis users for all causes. They said other studies "suggest that some adverse health outcomes may be elevated among heavy cannabis users, namely, fatal motor vehicle accidents, and possibly respiratory and brain cancers". One study the review examined found that the risk of cardiovascular mortality was not higher, while non-cardiovascular mortality was higher. Other factors correlated with cannabis use (for example, alcohol and tobacco use, or increased risk-taking behaviors) could be a factor in those findings. The review did not evaluate indirect effects of cannabis use on mortality, such as the "argument that cannabis use may be associated with other illicit drug use ..." The review was limited in that the largest studies did not follow regular cannabis users for a long enough time to detect deaths from cancer and heart disease, and the authors concluded that longer-term studies were needed.
Cannabis is the most widely used illicit drug in the Western world. Marijuana use disorder is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition requiring treatment.
Several studies correlate cannabis use with the development of anxiety, psychosis, and depression. Some researchers at least partially attribute the correlation between cannabis use and mental illness to self-medication.[medical citation needed] Indeed, as much as 60% of the mentally ill are suspected to be substance abusers, and many seem to prefer cannabis and alcohol.[medical citation needed] The suggested increase in psychotic episodes and the development of psychosis is relatively modest, and these occurrences are rare to begin with.[medical citation needed]
A 2007 review of available data by Moore, Zammit and colleagues found a dose-dependent correlation between cannabis use and psychotic illness. They concluded that the heaviest cannabis users are 40% more likely than non-users to suffer a psychotic illness.
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".[not in citation given]  The report continues that of the number of patients who mentioned cannabis use to their general practitioner, 48% had a psychological condition, including 19% with depression, 9% with psychosis and 6% with anxiety.[unreliable medical source?] The study states that few cannabis users tell their doctors of their use, which could potentially bias the results of the study.[medical citation needed][original research?]
Although there has been an association noted between cases of acute psychosis and long-term cannabis use, the precise nature of the relationship is controversial; evidence suggests that cannabis use may worsen psychotic symptoms and increase the risk of relapse.
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.[unreliable medical source?] Studies have shown that a risk does exist in some individuals with a predisposition to mental illness to develop symptoms of psychosis.[medical citation needed] 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.[medical citation needed]
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.[medical citation needed]
A 2008 Cochrane review said there was insufficient evidence "to say whether using cannabis causes an improvement or a deterioration of the mental health of people with schizophrenia".
A 2009 review said 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. Cannabis use does not appear to be causally related to the incidence of schizophrenia.[medical citation needed]
A 2011 paper said that after alcohol and nicotine, cannabis was the substance most abused by people with schizophrenia; whether the condition generally precedes, or postdates substance use is however uncertain, since evidence from studies is limited.[non-primary source needed]
As early as 2006, it was hypothesized based on animal and clinical evidence that cannabidiol (CBD), a cannabinoid present in cannabis, may be an effective atypical antipsychotic in treating schizophrenia and bipolar disorder.
Less attention has been given to the association between cannabis use and depression, though according to the Australian National Drug & Alcohol Research Centre, it is possible this is because cannabis users who have depression are less likely to access treatment than those with psychosis. Chen and colleagues (2002) re-analyzed the US National Comorbidity Survey (NCS) to examine the relationship between cannabis use and a major depressive episode and discovered that the risk of first major depressive episode (MDE) was moderately associated with the number of occasions of cannabis use and with more advanced stages of cannabis use. Relative to newer users, non-dependent cannabis users had 1.6 times greater risk of MDE. Cannabis dependence was associated with a 3.4 times greater risk of major depression.[non-primary source needed]
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 with bipolar disorder. 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.[medical citation needed]
A 2010 systematic review assessing the risk of cannabis-related mortality found four studies on suicide that met inclusion criteria on the literature review, and said that three studies found an increased risk of suicide associated with cannabis use and an increased risk of completed suicide. One study found early use of cannabis associated with a higher risk of attempted suicide. The authors concluded that evidence was "unclear as to whether regular cannabis use increases the risk of suicide"; limitations of the review were a) variables such as co-occurring depression or alcohol use were not controlled for in the studies on suicide; b) many studies on cannabis do not have long enough follow-up periods on regular users; c) studies "used diverse exposure and outcome measures that make comparison across studies problematic".
Cannabinoids are strong antioxidants and therefore defends cells from β-amyloid, the peptide that causes Alzheimer's disease.[medical citation needed] Some studies have found that cannabis has no effect on ageing-related cognitive decline[medical citation needed] while others suggest that it slows cognitive decline through its antioxidant effect. The cannabinoids present in cannabis lessen cell damage and death from ischemia, likely due to their antioxidant properties.
Government studies often point to statistical data accumulated by methods like the National Household Survey on Drug Abuse (NHSDA), the Monitoring the Future (MTF) study, and the Arrestee Drug Abuse Monitoring (ADAM) program, which claim lower school averages and higher dropout rates among users than non-users. However, these surveys are usually self-administered and may be anonymous, which greatly reduces their reliability. Additionally, while they establish a relationship between cannabis use and academic underperformance they do not determine whether the former causes the latter. The ADAM study is conducted anonymously, but only seeks information from a sample of people who have been arrested for drug-related offenses. Socially deviant behavior may be found more frequently in individuals of the criminal justice system compared to those in the general population, including non-users. In response, independent studies of college students have shown that there was no difference in grade point average, and achievement, between cannabis users and non-users. However, the users surveyed had slightly more difficulty deciding on career goals, and a smaller number were seeking advanced professional degrees.
A longitudinal study of heavy cannabis users from ages 14 to 25 in a Christchurch, New Zealand birth cohort concluded, "The results of the present study suggest that increasing cannabis use in late adolescence and early adulthood is associated with a range of adverse outcomes in later life. High levels of cannabis use are related to poorer educational outcomes, lower income, greater welfare dependence and unemployment and lower relationship and life satisfaction. The findings add to a growing body of knowledge regarding the adverse consequences of heavy cannabis use." However, this study primarily established correlation rather than causality.
A study published in the American Journal of Epidemiology in 2011, concluded that the prevalence of obesity is lower in cannabis users than in nonusers. A 2013 study confirmed this correlation and also found that cannabis users had better insulin resistance, lower insulin levels, and higher high-density lipoprotein ("good cholesterol") levels.
A 2008 study published in the British Journal of Psychiatry showed significant differences in Oxford-Liverpool Inventory of Feelings and Experiences scores between three groups: The first consisted of non-cannabis users, the second of users who tested positive for THC only, and the third consisted of users who tested positive for both THC and CBD. The Δ9-THC only subset scored significantly higher for unusual experiences, while users of both THC and CBD had much lower introvertive anhedonia scores. This suggests that CBD prevents some of the negative behavioral effects of THC.
According to a 2013 literature review, marijuana could be carcinogenic, but there are methodological limitations in studies making it difficult to establish a link between marijuana use and cancer risk. The authors say that bladder cancer does seem to be linked to habitual marijuana use, and that there may be a risk for cancers of the head and neck among long-term (more than 20 years) users. Gordon and colleagues said, "there does appear to be an increased risk of cancer (particularly head and neck, lung, and bladder cancer) for those who use marijuana over a period of time, although what length of time that this risk increases is uncertain."
In 2012 WebMD said that a number of studies had suggested a link between cannabis use and an increased risk of testicular cancer, but that the overall risk remained small and that more research is needed to confirm the findings. According to Gordon and colleagues, "several recent studies suggest an association between marijuana use and testicular germ cell tumors".
Gordon and colleagues in a 2013 literature review said: "Unfortunately, methodological limitations in many of the reviewed studies, including selection bias, small sample size, limited generalizability, and lack of adjustment for tobacco smoking, may limit the ability to attribute cancer risk solely to marijuana use." Reviewing studies adjusted for age and tobacco use, they said there was a risk of lung cancer even after adjusting for tobacco use, but that the period of time over which the risk increases is uncertain.
Cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same carcinogens as tobacco smoke.[unreliable medical source?] A 2012 literature review by the British Lung Foundation suggested that the risk of developing lung cancer is nearly 20 times higher from smoking typical cannabis cigarettes than from smoking tobacco cigarettes, due to deeper, longer inhalation and the lack of filters. They identified cannabis smoke as a carcinogen and also said awareness of the danger was low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. They said there was an increased risk from each cannabis cigarette due to drawing in large puffs of smoke and holding them.
In 2013 the International Lung Cancer Consortium found no significant additional lung cancer risk in tobacco users who also smoked cannabis. Nor did they find an increased risk in cannabis smokers who did not use tobacco. They concluded that "Our pooled results showed no significant association between the intensity, duration, or cumulative consumption of cannabis smoke and the risk of lung cancer overall or in never smokers." They cautioned that "Our results cannot preclude the possibility that cannabis may exhibit an association with lung cancer risk at extremely high dosage."
Head and neck cancer
Gordon and colleagues (2013) said there was a risk of head and neck cancer associated with marijuana use over a long period of time.
Gateway drug hypothesis
The gateway drug hypothesis asserts that the use of cannabis may ultimately lead to the use of harder drugs. For the most part, it was commonly thought that cannabis gateways to other drugs because of social factors. For example, the criminalization of cannabis in many countries associates its users with organized crime promoting the illegal drug trade.
A study of twins by researchers at Virginia Commonwealth University showed that cannabis use in adolescence strongly predicted later use of multiple drugs. The main causation was tied to shared environmental and genetic vulnerability, but there was some evidence for a causal role of cannabis. A July 2006 study by Ellgren et al. strictly tested lab rats for the biological mechanism of the gateway drug effect. The study administered 6 "teenage" (28 and 49 days old) rats delta-9-tetrahydrocannabinol, and 6 were the control. One week after the first part was completed, catheters were inserted in the jugular vein of all of the adult rats and they were able to self-administer themselves heroin by pushing a lever. The study found that initially both groups behaved the same and began to self-administer heroin frequently, but then stabilized at different levels. The rats that had previously been administered THC consumed about 1.5 times more heroin than those that had not. Because many THC receptors interact with the opioid system, the study surmised that adolescent cannabis use overstimulates and alters the pleasure and reward structures of the brain, thus increasing the already high risk of addiction for people who start to use heroin. However, the rats took up self-administration at the same rate regardless of adolescent THC exposure, and observed levels of "drug-seeking behavior" were also the same. Psychopharmacologist Ian Stolerman, from King's College London, finds the biological cannabis gateway drug effect "somewhat preliminary", and states "it's too early to say there's a consensus, but a small number of studies like this suggest that there is a physiological basis for this effect." Other drugs, he notes, such as cocaine and amphetamines are involved in another brain pathway called the dopaminergic system. Cells in that system also interact with THC receptors and could be modified by cannabis exposure. Cannabinoid receptors are 10 times more prevalent in the brain than opioid receptors. According to Dr. Hurd, one of the study leaders, two other drugs that also stimulate opioid cells, and could therefore also feasibly cause a gateway effect, are nicotine and alcohol.
However, a December 2006 study by the American Psychiatric Association challenges these findings. A 12 year study on 214 boys from ages 10–12 showed that adolescents who used cannabis prior to using other drugs, including alcohol and tobacco, were no more likely to develop a substance abuse disorder than other subjects in the study. "This evidence supports what's known as the common liability model… states the likelihood that someone will transition to the use of illegal drugs is determined not by the preceding use of a particular drug, but instead by the user's individual tendencies and environmental circumstances", investigators stated in a press release. They added, "The emphasis on the drugs themselves, rather than other, more important factors that shape a person's behavior, has been detrimental to drug policy and prevention programs."
Models used in a 2002 study by RAND cast doubt on the gateway effect and show "that the marijuana gateway effect is not the best explanation for the link between marijuana use and the use of harder drugs", as noted by Andrew Morral, associate director of RAND's Public Safety and Justice unit and lead author of the study.
According to a 2013 literature review by Gordon and colleagues, inhaled marijuana is associated with lung disease.
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.
A 2012 literature review by the British Lung Foundation found lack of research on the effect of cannabis smoke alone due to common mixing of cannabis and tobacco and frequent cigarette smoking by cannabis users; a low rate of addiction compared to tobacco; and an episodic nature of cannabis use compared to steady frequent smoking of tobacco.
- "Medical Marijuana Policy in the United States". Stanford.edu. 2012-05-15. Retrieved 2013-01-15.
- Gordon AJ, Conley JW, Gordon JM (December 2013). "Medical consequences of marijuana use: a review of current literature". Curr Psychiatry Rep (Review) 15 (12): 419. doi:10.1007/s11920-013-0419-7. PMID 24234874.
- [dated info]Iversen L (Feb 2005). "Long-term effects of exposure to cannabis" (PDF). Current Opinion in Pharmacology (Review) 5 (1): 69–72. doi:10.1016/j.coph.2004.08.010. PMID 15661628.
- [dated info]Riedel G, Davies SN (2005). "Cannabinoid function in learning, memory and plasticity". Handb Exp Pharmacol (Review). Handbook of Experimental Pharmacology 168 (168): 445–77. doi:10.1007/3-540-26573-2_15. ISBN 3-540-22565-X. PMID 16596784.
- [dated info] Grotenhermen F (August 2007). "The toxicology of cannabis and cannabis prohibition". Chem. Biodivers. (Review) 4 (8): 1744–69. doi:10.1002/cbdv.200790151. PMID 17712818.
- Fonseca BM, Correia-da-Silva G, Almada M, Costa MA, Teixeira NA (2013). "The Endocannabinoid System in the Postimplantation Period: A Role during Decidualization and Placentation". Int J Endocrinol (Review) 2013: 510540. doi:10.1155/2013/510540. PMC 3818851. PMID 24228028.
- Irner TB (2012). "Substance exposure in utero and developmental consequences in adolescence: a systematic review". Child Neuropsychol (Review) 18 (6): 521–49. doi:10.1080/09297049.2011.628309. PMID 22114955.
- Copeland J, Gerber S, Swift W (2006). "Evidence-based answers to cannabis questions: a review of the literature" (PDF). Canberra: Australian National Council on Drugs.
- Calabria B, Degenhardt L, Hall W, Lynskey M (May 2010). "Does cannabis use increase the risk of death? Systematic review of epidemiological evidence on adverse effects of cannabis use". Drug Alcohol Rev (Review) 29 (3): 318–30. doi:10.1111/j.1465-3362.2009.00149.x. PMID 20565525.
- 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.
- [dated info]Moore TH, Zammit S, Lingford-Hughes A, et al. (July 2007). "Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review". Lancet (Review) 370 (9584): 319–28. doi:10.1016/S0140-6736(07)61162-3. PMID 17662880. Lay summary – BBC News (2007-07-27).
- "Bettering the Evaluation and Care of Health (BEACH)". Family Research Medicine Center. Retrieved 17 October 2009.
- [unreliable medical source?] "Depression, psychosis strike dope smokers". The Australian. Australian Associated Press. 29 September 2009. Retrieved 17 October 2009.
- Barceloux, Donald G (20 March 2012). "Chapter 60: Marijuana (Cannabis sativa L.) and synthetic cannabinoids". Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. p. 901. ISBN 978-0-471-72760-6.
- 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.
- Rathbone J, Variend H, Mehta H (2008). "Cannabis and schizophrenia". In Rathbone, John. Cochrane Database Syst Rev (Review) (3): CD004837. doi:10.1002/14651858.CD004837.pub2. PMID 18646115. (subscription required (. ))
- Fernandez-Espejo E, Viveros MP, Núñez L, Ellenbroek BA, Rodriguez de Fonseca F (November 2009). "Role of cannabis and endocannabinoids in the genesis of schizophrenia". Psychopharmacology (Berl.) (Review) 206 (4): 531–49. doi:10.1007/s00213-009-1612-6. PMID 19629449.
- Lichlyter, Bonnie; Purdon, Scot; Tibbo, Philip (2011). "Predictors of psychosis severity in individuals with primary stimulant addictions". Addictive Behaviors 36 (1–2): 137–9. doi:10.1016/j.addbeh.2010.08.019. PMID 20850224.
- Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimarães FS (April 2006). "Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug". Braz. J. Med. Biol. Res. (Review) 39 (4): 421–9. doi:10.1590/S0100-879X2006000400001. PMID 16612464.
- 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.
- Bilkei-Gorzo A (December 2012). "The endocannabinoid system in normal and pathological brain ageing". Philos. Trans. R. Soc. Lond., B, Biol. Sci. (Review) 367 (1607): 3326–41. doi:10.1098/rstb.2011.0388. PMC 3481530. PMID 23108550.
- [unreliable source?] Kazuhide H, Mishima K, Fujiwara M (2010). "Therapeutic potential of non-psychotropic cannabidiol in ischemic stroke". Pharmaceuticals (Review) 3 (7): 2197–2212. doi:10.3390/ph3072197.
- Abadinsky, H. (2004). Drugs: An Introduction (5th ed.). pp. 62–77; 160–166. ISBN 0-534-52750-7.
- 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.
- 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.
- 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.
- 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.
- 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.
- Parolaro, D; Massi, P (2008). "Cannabinoids as potential new therapy for the treatment of gliomas". Expert review of neurotherapeutics 8 (1): 37–49. doi:10.1586/1473718.104.22.168. PMID 18088200.
- "Smoking Marijuana Tied to Testicular Cancer". WebMD. 9 September 2012. Retrieved November 2013.
- [unreliable medical source?]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.
- "The impact of cannabis on your lungs". British Lung Association. June 2012. Retrieved 2013-01-09.
- Zhang R, Zuo-Feng Z, Morgenstern H, et al (15). "Abstract 3633: Cannabis smoking and lung cancer risk: pooled analysis in the International Lung Cancer Consortium". Cancer Research 73 (8). Lay summary – Oncology report (2013-05-08).
- 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.
- 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.
- Hopkin, M. (2006). "Rats taking cannabis get taste for heroin". News@nature. doi:10.1038/news060703-9.
- "Marijuana Use Per Se Not a 'Gateway' To Illicit Drug Use, Study Says". NORML. Retrieved 2011-04-20.
- 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.
- RAND Study Casts Doubt on Claims That Marijuana Acts as "Gateway" to the Use of Cocaine and Heroin[dead link]
- 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.
- 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.