Long-term effects of cannabis
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The long-term effects of cannabis have been the subject of ongoing debate. Because cannabis is illegal in most countries, clinical research presents a challenge; as such, there remains much to be concluded. In 2017, the U.S. National Academies of Sciences, Engineering, and Medicine issued a report summarizing much of the published literature on health effects of cannabis, into categories regarded as conclusive, substantial, moderate, limited and of no or insufficient evidence to support an association with a particular outcome.
Cannabis is the most widely used illicit drug in the Western world, and although in the United States 10 to 20% of consumers who use cannabis daily become dependent, it is different from addiction. Cannabis use disorder is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition requiring treatment. A 2012 review of cannabis use and dependency in the United States by Danovitch et al said that "42% of persons over age 12 have used cannabis at least once in their lifetime, 11.5% have used within the past year, and 1.8% have met diagnostic criteria for cannabis abuse or dependence within the past year. Among individuals who have ever used cannabis, conditional dependence (the proportion who go on to develop dependence) is 9%." Although no medication is known to be effective in combating dependency, combinations of psychotherapy such as cognitive behavioural therapy and motivational enhancement therapy have achieved some success.
Cannabis dependence develops in 9% of users, significantly less than that of heroin, cocaine, alcohol, and prescribed anxiolytics, but slightly higher than that for psilocybin, mescaline, or LSD. Dependence on cannabis tends to be less severe than that observed with cocaine, opiates, and alcohol. A 2018 review of the nature of dependency on marijuana states that the risk of dependence formation among regular marijuana consumers has declined since 2002.
Memory and intelligence
Acute cannabis intoxication has been shown to negatively affect attention, psychomotor task ability, and short-term memory. Studies of chronic cannabis users have demonstrated, although inconsistently, a long-lasting effect on the attention span, memory function, and cognitive abilities of moderate-dose long-term users. Once cannabis use is discontinued for several months, these effects disappear, unless the user started consuming during adolescence, it is speculated that this is due to neurotoxic effects of cannabis interfering with critical brain development.
Chronic use of cannabis during adolescence, a time when the brain is still developing, is correlated in the long term with lower IQ and cognitive deficits. It is not clear, though, if cannabis use causes the problems or if the causality is in the reverse. Recent studies have shown that IQ deficits existed in some subjects before chronic cannabis use, suggesting that lower IQ may instead be a risk factor for cannabis addiction.
A prospective cohort study that took place between 1972 and 2012 investigated the association between cannabis use and neuropsychological decline. Subjects were tested at various points in their life administering multiple[disambiguation needed] different neuropsychological tests. The authors concluded that:
- persistent cannabis users show neuropsychological decline from childhood to midlife.
- neuropsychological impact of cannabis use is global instead of restricted to specific cognitive domains
- its effects last for longer than a week
- the findings cannot be explained by comorbidity with dependence on other drugs.
- the findings cannot be explained by comorbidity with schizophrenia
- cannabis use is correlated with lower levels of education
- the negative effect on intelligence is greater than that attributable to the lack of education.
- ceasing consumption does not fully restore cognitive function on adolescents.
Cannabis contains over 100 different cannabinoid compounds, many of which have displayed psychoactive effects. The most distinguished cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD), with THC being the primary psychoactive agent. The effects of THC, and CBD are salient regarding psychosis and anxiety.
As of 2017 there is clear evidence that long term use of cannabis increases the risk of psychosis, regardless of confounding factors, and particularly for people who have genetic risk factors. However, even in those with no family history of psychosis, the administration of pure THC in clinical settings has been demonstrated to elicit transient psychotic symptoms.
Chronic psychosis and schizophrenia spectrum disorders
According to the National Academies of Sciences, Engineering and Medicine, there is substantial evidence of a statistical association between cannabis use and the development of schizophrenia or other chronic psychoses, with the highest risk potentially among the most frequent users. A possible connection between psychosis and cannabis is controversial because observational studies suggest a correlation but do not establish any causative effect of cannabis on long-term psychiatric health. Medical evidence strongly suggests that the long-term use of cannabis by people who begin use at an early age display a higher tendency towards mental health problems and other physical and development disorders, although a causal link could not be proven by the available data. The risks appear to be most acute in adolescent users. In one 2013 review, the authors concluded long-term cannabis use "increases the risk of psychosis in people with certain genetic or environmental vulnerabilities", but does not cause psychosis. Important predisposing factors were genetic liability, childhood trauma and urban upbringing. Another review that same year concluded that cannabis use may cause permanent psychological disorders in some users such as cognitive impairment, anxiety, paranoia, and increased risks of psychosis. Key predisposing variables included age of first exposure, frequency of use, the potency of the cannabis used, and individual susceptibility. Nevertheless, some researchers maintain there exists "a strong association between schizophrenia and cannabis use...", while cannabis use alone does not predict the transition to subsequent psychiatric illness. Many factors are involved, including genetics, environment, time period of initiation and duration of cannabis use, underlying psychiatric pathology that preceded drug use, and combined use of other psychoactive drugs.
The temporal relationship between cannabis and psychosis was reviewed in 2014, and the authors proposed that "[b]ecause longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship" between cannabis and psychosis, but that "more work is needed to address the possibility of gene-environment correlation."
In 2016 a meta-analysis was published on associations studies covering a range of dosing habits, again showing that cannabis use is associated with a significantly increased risk of psychosis, and alleged that a dose–response relationship exists between the level of cannabis use and risk of psychosis. The risk was increased 4-fold with daily use, though the analysis was not adequate to establish a causal link. Another 2016 meta-analysis found that cannabis use only predicted transition to psychosis among those who met the criteria for abuse of or dependence on the drug.
Another 2016 review concluded that the existing evidence did not show that cannabis caused psychosis, but rather that early or heavy cannabis use were among many factors more likely to be found in those at risk of developing psychosis. An opposing view was expressed by Suzanne Gage and coauthors reviewing the literature available in 2016, who regarded the epidemiologic evidence on cannabis use and psychosis strong enough "to warrant a public health message that cannabis use can increase the risk of psychotic disorders," but also cautioning that additional studies are needed to determine the size of the effect. Such a public health message was subsequently issued in August 2019 by the Surgeon General of the United States. The review by Gage et al. also stated "If the association between cannabis and schizophrenia is causal and of the magnitude estimated across studies to date, this would equate to a schizophrenia lifetime risk of approximately 2% in regular cannabis users (though risk for broader psychotic outcomes will be greater). This implies that about 98% of regular cannabis users will not develop schizophrenia...[and that] risk could be much greater in those at a higher genetic risk, or in those who use particularly potent strains of cannabis.:11 Expressed in terms of odds ratio, another study found that "Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3.2, 95% CI 2.2–4.1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4.8, 2.5–6.3)." To calculate what the increased odds ratio means for schizophrenia specifically, a 2005 review placed the lifetime morbid risk of narrowly defined schizophrenia at 0.72%.  For some locations, this translates into a substantial population attributable risk, such that "assuming causality, if high-potency cannabis types were no longer available, then 12% of cases of first-episode psychosis could be prevented across Europe, rising to 30% in London and 50% in Amsterdam." 
A 2019 meta-analysis found that 34% of people with cannabis-induced psychosis transitioned to schizophrenia. This was found to be comparatively higher than hallucinogens (26%) and amphetamines (22%).
In spite of all of this supposed evidence of a causal relationship - or suggestion of a causal relationship - between cannabis and psychosis, the general population statistics shows no increase in psychosis incidence rates in any developed country over the last 50 years, in spite of a five-fold increase in cannabis use rates. To quote Macleod et all 2004: “Cannabis use appears to have increased substantially amongst young people over the past 30 years, from around 10% reporting ever use in 1969–70, to around 50% reporting ever use in 2001, in Britain and Sweden. If the relation between use and schizophrenia were truly causal and if the relative risk was around five-fold then the incidence of schizophrenia should have more than doubled since 1970. However population trends in schizophrenia incidence suggest that incidence has either been stable or slightly decreased over the relevant time period.”
Of note, cannabis with a high THC to CBD ratio produces a higher incidence of psychological effects. CBD may show antipsychotic and neuroprotective properties, acting as an antagonist to some of the effects of THC. Studies examining this effect have used high ratios of CBD to THC, and it is unclear to what extent these laboratory studies translate to the types of cannabis used by real life users. Research has suggested that CBD can safely reduce some symptoms of psychosis in general.
A 2014 review examined psychological therapy as add-on for people with schizophrenia who are using cannabis:
|Summary of adjunct therapy for cannabis users with psychosis|
|Results are limited and inconclusive because of the small number and size of randomized controlled trials available and quality of data reporting within these trials. More research is needed to explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment, for those that both use cannabis and have schizophrenia.|
Cannabis use may precipitate new-onset panic attacks and depersonalization/derealization symptoms simultaneously. The association between cannabis use and depersonalisation/derealisation disorder has been studied.
Some individuals experiencing depersonalisation/derealisation symptoms prior to any cannabis use have reported the effects of cannabis to calm these symptoms and make the depersonalisation/derealisation disorder more manageable with regular use.
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. A 2017 review suggests that cannabis has been shown to improve the mood of depression-diagnosed patients.
Teenage cannabis users show no difference from the general population in incidence of major depressive disorder (MDD), but an association exists between early exposure coupled with continued use into adult life and increased incidence of MDD in adulthood. Among cannabis users of all ages, there may be an increased risk of developing depression, with heavy users seemingly having a higher risk.
A February 2019 systematic review and meta-analysis found that cannabis consumption during adolescence was associated with an increased risk of developing depression and suicidal behavior later in life, while finding no effect on anxiety.
Adolescent cannabis users show no difference from their peers in suicidal ideation or rate of suicide attempts, but those who continue to use cannabis into adult life exhibit an increased incidence of both, although multiple other contributory factors are also implicated.
In the general population a weak (indirect) association appears to exist between suicidal behaviour and cannabis consumption in both psychotic and non-psychotic users, although it remains unclear whether regular cannabis use increases the risk of suicide. Cannabis use is a risk factor in suicidality, but suicide attempts are characterized by many additional risk factors including mood disorders, alcohol use, stress, personal problems and poor support.
Gateway drug hypothesis
The gateway drug hypothesis asserts that the use of soft drugs such as cannabis, tobacco or alcohol may ultimately lead to the use of harder drugs. Whether the role of cannabis in other drug use is causative or simply the result of the same influencing factors of drug use in general is debated.
Large-scale longitudinal studies in the UK and New Zealand from 2015 and 2017 showed an association between cannabis use and an increased probability of later disorders in the use of other drugs.
A 2013 literature review said that exposure to cannabis 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".
In healthy (non-psychotic) individuals, long-term use may have significant effects in certain brain areas, such as a reduction of volume in the hippocampus. 
Heart and circulation
The acute effects of cannabis use in humans include a dose-dependent increase in heart rate, typically accompanied by a mild increase in blood pressure while lying down and postural hypotension - a drop in blood pressure when standing up. These effects may vary depending on the relative concentration of the many different cannabinoids that can affect the cardiovascular function, such as cannabigerol. Smoking cannabis decreases exercise tolerance. Cardiovascular effects may not lead to serious health issues for the majority of young, healthy users; on the contrary, heart attack, that is myocardial infarction, stroke, and other adverse cardiovascular events, have occurred in association with its use. Cannabis use by people with cardiovascular disease poses a health risk because it can lead to increased cardiac work, increased catecholamine levels, and impaired blood oxygen carrying capacity due to the production of carboxyhemoglobin.
A 2012 review examining the relation of cancer and cannabis found little direct evidence that cannabinoids found in cannabis, including THC, are carcinogenic. Cannabinoids are not mutagenic according to the Ames test. However, cannabis smoke has been found to be carcinogenic in rodents and mutagenic in the Ames test. Correlating cannabis use with the development of human cancers has been problematic due to difficulties in quantifying cannabis use, unmeasured confounders, and cannabinoids potential as cancer treatment.
According to a 2013 literature review, cannabis could be carcinogenic, but there are methodological limitations in studies making it difficult to establish a link between cannabis use and cancer risk. The authors say that bladder cancer does seem to be linked to habitual cannabis 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."
There have been a limited number of studies that have looked at the effects of smoking cannabis on the respiratory system. Chronic heavy cannabis smoking is associated with coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis. Regular cannabis use has not been shown to cause significant abnormalities in lung function.
Regular cannabis smokers show pathological changes in lung cells similar to those that precede the development of lung cancer in tobacco smokers. 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.
A 2013 review which specifically examined the effects of cannabis on the lung concluded "[f]indings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use, although evidence is mixed concerning possible carcinogenic risks of heavy, long-term use."
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 "[o]ur 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 "[o]ur results cannot preclude the possibility that cannabis may exhibit an association with lung cancer risk at extremely high dosage." The same authors supported further study, and called attention to evolving means of cannabis consumption: "Specifically, respiratory risks may differ with the use of water pipes and vaporizers or with consuming oral preparations."
Cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same carcinogens as tobacco smoke. A 2012 special report by the British Lung Foundation concluded that cannabis smoking was linked to many adverse effects, including bronchitis and lung cancer. 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. Cannabis smoke has been listed on the California Proposition 65 warning list as a carcinogen since 2009, but leaves and pure THC are not.
Head and neck
A 2011 review of studies in the United States found that although some supported the hypothesis that cannabis use increased the risk of getting head and neck cancer, when other factors are accounted for the majority did not. Gordon and colleagues (2013) said there was a risk of these cancers associated with cannabis use over a long period of time. A 2015 review found no association with lifetime cannabis use and the development of head and neck cancer.
A 2013 literature review by Gordon and colleagues concluded that inhaled cannabis is associated with lung disease, although Tashkin's 2013 review has found "no clear link to chronic obstructive pulmonary 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.
Smoking cannabis has been linked to adverse respiratory effects including: chronic coughing, wheezing, sputum production, and acute bronchitis. It has been suggested that the common practice of inhaling cannabis smoke deeply and holding breath could lead to pneumothorax. In a few case reports involving immunocompromised patients, pulmonary infections such as aspergillosis have been attributed to smoking cannabis contaminated with fungi. The transmission of tuberculosis has been linked to cannabis inhalation techniques, such as sharing water pipes and 'Hotboxing'.
Reproductive and endocrine effects
A study released by the National Academies of Sciences, Engineering, and Medicine cited significant evidence for a statistical link between mothers who smoke cannabis during pregnancy and lower birth weights of their babies. Cannabis consumption in pregnancy is associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring. Although the majority of research has concentrated on the adverse effects of alcohol, there is now evidence that prenatal exposure to cannabis has serious effects on the developing brain and is 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.
No fatal overdoses associated with cannabis use have ever been reported. Due to the small number of studies that have been conducted, the evidence is insufficient to show a long-term elevated risk of mortality from any cause. Motor vehicle accidents, suicide, and possible respiratory and brain cancers are all of interest to many researchers, but no studies have been able to show a consistent increase in mortality from these causes.
- "Medical Marijuana Policy in the United States". Stanford.edu. 2012-05-15. Retrieved 2013-01-15.
- "The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research" Health and Medicine Division. The National Academies of Sciences, Engineering and Medicine, 2017. Retrieved February 9, 2020. http://www.nap.edu/24625[page needed]
- 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. S2CID 29063282.
- Borgelt LM, Franson KL, Nussbaum AM, Wang GS (February 2013). "The pharmacologic and clinical effects of medical cannabis". Pharmacotherapy (Review). 33 (2): 195–209. CiteSeerX 10.1.1.1017.1935. doi:10.1002/phar.1187. PMID 23386598.
- Danovitch I, Gorelick DA (June 2012). "State of the art treatments for cannabis dependence". Psychiatr. Clin. North Am. (Review). 35 (2): 309–26. doi:10.1016/j.psc.2012.03.003. PMC 3371269. PMID 22640758.
- Wilkie G, Sakr B, Rizack T (March 2016). "Medical Marijuana Use in Oncology: A Review". JAMA Oncology. 2 (5): 670–675. doi:10.1001/jamaoncol.2016.0155. PMID 26986677.
- Budney AJ, Roffman R, Stephens RS, Walker D (December 2007). "Marijuana dependence and its treatment". Addict Sci Clin Pract (Review). 4 (1): 4–16. doi:10.1151/ASCP07414. PMC 2797098. PMID 18292704.
- Davenport, Steven (October 2018). "Falling rates of marijuana dependence among heavy users". Drug and Alcohol Dependence. 191: 52–55. doi:10.1016/j.drugalcdep.2018.06.025. PMID 30077891.
- Walsh, Z; Gonzalez, R; Crosby, K; S Thiessen, M; Carroll, C; Bonn-Miller, MO (February 2017). "Medical cannabis and mental health: A guided systematic review". Clinical Psychology Review. 51: 15–29. doi:10.1016/j.cpr.2016.10.002. PMID 27816801.
- Andrade, C (May 2016). "Cannabis and neuropsychiatry, 1: benefits and risks". The Journal of Clinical Psychiatry. 77 (5): e551–4. doi:10.4088/JCP.16f10841. PMID 27249079.
- Sagie S, Eliasi Y, Livneh I, Bart Y, Monovich E (2013). "[Short-and long-term effects of cannabinoids on memory, cognition and mental illness]". Harefuah (Review) (in Hebrew). 152 (12): 737–41, 751. PMID 24483000.
- Meier, Madeline H.; Caspi, Avshalom; Ambler, Anthony; Harrington, Hona Lee; Houts, Renate; Keefe, Richard S. E.; McDonald, Kay; Wardf, Aimee; Poultonf, Richie; Moffitt, Terrie E. (2012). "Persistent cannabis users show neuropsychologicaldecline from childhood to midlife" (PDF). PNAS USA. 109 (40): 2657–2664. doi:10.1073/pnas.1206820109. PMC 3479587. PMID 22927402. Retrieved 22 May 2020.
- Schoeler, T; Bhattacharyya, S (2013). "The effect of cannabis use on memory function: an update". Substance Abuse and Rehabilitation. 4: 11–27. doi:10.2147/SAR.S25869. PMC 3931635. PMID 24648785.
- Jackson, Nicholas J.; Isen, Joshua D.; Khoddam, Rubin; Irons, Daniel; Tuvblad, Catherine; Iacono, William G.; McGue, Matt; Raine, Adrian; Baker, Laura A. (2 February 2016). "Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies". Proceedings of the National Academy of Sciences. 113 (5): E500–E508. doi:10.1073/pnas.1516648113. PMC 4747759. PMID 26787878.
- Zehra A, Burns J, Liu CK, Manza P, Wiers CE, Volkow ND, et al. (2018). "Cannabis Addiction and the Brain: a Review". J Neuroimmune Pharmacol. 13 (4): 438–452. doi:10.1007/s11481-018-9782-9. PMC 6223748. PMID 29556883.
- Ross, J. Megan; Ellingson, Jarrod M.; Rhee, Soo Hyun; Hewitt, John K.; Corley, Robin P.; Lessem, Jeffrey M.; Friedman, Naomi P. (January 2020). "Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design". Drug and Alcohol Dependence. 206: 107712. doi:10.1016/j.drugalcdep.2019.107712. PMC 7179798. PMID 31753729.
- Schier, Alexandre Rafael de Mello; Ribeiro, Natalia Pinho de Oliveira; e Silva, Adriana Cardoso de Oliveira; Hallak, Jaime Eduardo Cecilio; Crippa, José Alexandre S.; Nardi, Antonio E.; Zuardi, Antonio Waldo (June 2012). "Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug". Revista Brasileira de Psiquiatria. 34: S104–S117. doi:10.1590/s1516-44462012000500008. ISSN 1516-4446. PMID 22729452.
- Walsh, Zach; Gonzalez, Raul; Crosby, Kim; S. Thiessen, Michelle; Carroll, Chris; Bonn-Miller, Marcel O. (2017-02-01). "Medical cannabis and mental health: A guided systematic review". Clinical Psychology Review. 51: 15–29. doi:10.1016/j.cpr.2016.10.002. ISSN 0272-7358. PMID 27816801.
- Crippa, José Alexandre; Zuardi, Antonio Waldo; Martín-Santos, Rocio; Bhattacharyya, Sagnik; Atakan, Zerrin; McGuire, Philip; Fusar-Poli, Paolo (October 2009). "Cannabis and anxiety: a critical review of the evidence". Human Psychopharmacology: Clinical and Experimental. 24 (7): 515–523. doi:10.1002/hup.1048. ISSN 0885-6222. PMID 19693792.
- Steenkamp, MM; Blessing, EM; Galatzer-Levy, IR; Hollahan, LC; Anderson, WT (March 2017). "Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review". Depression and Anxiety. 34 (3): 207–216. doi:10.1002/da.22596. PMID 28245077. S2CID 205737272.
- D'Souza, Deepak Cyril; Perry, Edward; MacDougall, Lisa; Ammerman, Yola; Cooper, Thomas; Wu, Yu-te; Braley, Gabriel; Gueorguieva, Ralitza; Krystal, John Harrison (2 June 2004). "The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis". Neuropsychopharmacology. 29 (8): 1558–1572. doi:10.1038/sj.npp.1300496. PMID 15173844. S2CID 12508404.
- Morrison, Paul D; Nottage, Judith; Stone, James M; Bhattacharyya, Sagnik; Tunstall, Nigel; Brenneisen, Rudolf; Holt, David; Wilson, Daniel; Sumich, Alex; McGuire, Philip; Murray, Robin M; Kapur, Shitij; ffytche, Dominic H (March 2011). "Disruption of Frontal Theta Coherence by Δ9-Tetrahydrocannabinol is Associated with Positive Psychotic Symptoms". Neuropsychopharmacology. 36 (4): 827–836. doi:10.1038/npp.2010.222. PMC 3055738. PMID 21150914.
- Bhattacharyya, Sagnik; Crippa, José Alexandre; Allen, Paul; Martin-Santos, Rocio; Borgwardt, Stefan; Fusar-Poli, Paolo; Rubia, Katya; Kambeitz, Joseph; O’Carroll, Colin; Seal, Marc L.; Giampietro, Vincent; Brammer, Michael; Zuardi, Antonio Waldo; Atakan, Zerrin; McGuire, Philip K. (2 January 2012). "Induction of Psychosis byΔ9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing". Archives of General Psychiatry. 69 (1): 27–36. doi:10.1001/archgenpsychiatry.2011.161. PMID 22213786.
- Freeman, Daniel; Dunn, Graham; Murray, Robin M.; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M.; Harrison, Paul J.; Harmer, Catherine J.; Cowen, Philip; Morrison, Paul D. (2015). "How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia". Schizophrenia Bulletin. 41 (2): 391–399. doi:10.1093/schbul/sbu098. PMC 4332941. PMID 25031222.
- Parakh P, Basu D (2013). "Cannabis and psychosis: have we found the missing links?". Asian J Psychiatr (Review). 6 (4): 281–7. doi:10.1016/j.ajp.2013.03.012. PMID 23810133.
- Hoch E, Bonnetn U, Thomasius R, Ganzer F, Havemann-Reinecke U, Preuss UW (2015). "Risks associated with the non-medicinal use of cannabis". Dtsch Arztebl Int (Review). 112 (16): 271–8. doi:10.3238/arztebl.2015.0271. PMC 4442549. PMID 25939318.
- Niesink, RJ; van Laar, MW (2013). "Does Cannabidiol Protect Against Adverse Psychological Effects of THC?". Frontiers in Psychiatry (Review). 4: 130. doi:10.3389/fpsyt.2013.00130. PMC 3797438. PMID 24137134.
- Chadwick, B.; Miller, M. L.; Hurd, Y. L. (2013). "Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness". Frontiers in Psychiatry. 4: 129. doi:10.3389/fpsyt.2013.00129. PMC 3796318. PMID 24133461.
- van Winkel, Ruud; Kuepper, Rebecca (28 March 2014). "Epidemiological, Neurobiological, and Genetic Clues to the Mechanisms Linking Cannabis Use to Risk for Nonaffective Psychosis". Annual Review of Clinical Psychology. 10 (1): 767–791. doi:10.1146/annurev-clinpsy-032813-153631. PMID 24471373.
- Marconi, A; Di Forti, M; Lewis, CM; Murray, RM; Vassos, E (15 February 2016). "Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis". Schizophrenia Bulletin. 42 (5): 1262–1269. doi:10.1093/schbul/sbw003. PMC 4988731. PMID 26884547.
- Kraan, T; Velthorst, E; Koenders, L; Zwaart, K; Ising, HK; van den Berg, D; de Haan, L; van der Gaag, M (March 2016). "Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis". Psychological Medicine. 46 (4): 673–81. doi:10.1017/S0033291715002329. PMID 26568030.
- Ksir C, Hart CL (2016). "Cannabis and Psychosis: a Critical Overview of the Relationship". Curr Psychiatry Rep (Review). 18 (2): 12. doi:10.1007/s11920-015-0657-y. PMID 26781550. S2CID 36538598.
our review of the evidence leads us to conclude that both early use of cannabis and heavy use of cannabis are more likely in individuals with a vulnerability to a variety of other problem behaviors, such as early or heavy use of cigarettes or alcohol, use of other illicit drugs, and poor school performance.
- Gage, Suzanne H.; Hickman, Matthew; Zammit, Stanley (April 2016). "Association Between Cannabis and Psychosis: Epidemiologic Evidence". Biological Psychiatry. 79 (7): 549–556. doi:10.1016/j.biopsych.2015.08.001. PMID 26386480. S2CID 1055335.
- "Surgeon General's Advisory: Marijuana Use & the Developing Brain". 29 August 2019.
- Di Forti, Marta; Quattrone, Diego; Freeman, Tom P; Tripoli, Giada; Gayer-Anderson, Charlotte; Quigley, Harriet; Rodriguez, Victoria; Jongsma, Hannah E; Ferraro, Laura; La Cascia, Caterina; La Barbera, Daniele; Tarricone, Ilaria; Berardi, Domenico; Szöke, Andrei; Arango, Celso; Tortelli, Andrea; Velthorst, Eva; Bernardo, Miguel; Del-Ben, Cristina Marta; Menezes, Paulo Rossi; Selten, Jean-Paul; Jones, Peter B; Kirkbride, James B; Rutten, Bart PF; de Haan, Lieuwe; Sham, Pak C; van Os, Jim; Lewis, Cathryn M; Lynskey, Michael; Morgan, Craig; Murray, Robin M; Amoretti, Silvia; Arrojo, Manuel; Baudin, Grégoire; Beards, Stephanie; Bernardo, Miquel; Bobes, Julio; Bonetto, Chiara; Cabrera, Bibiana; Carracedo, Angel; Charpeaud, Thomas; Costas, Javier; Cristofalo, Doriana; Cuadrado, Pedro; Díaz-Caneja, Covadonga M; Ferchiou, Aziz; Franke, Nathalie; Frijda, Flora; García Bernardo, Enrique; Garcia-Portilla, Paz; González, Emiliano; Hubbard, Kathryn; Jamain, Stéphane; Jiménez-López, Estela; Leboyer, Marion; López Montoya, Gonzalo; Lorente-Rovira, Esther; Marcelino Loureiro, Camila; Marrazzo, Giovanna; Martínez, Covadonga; Matteis, Mario; Messchaart, Elles; Moltó, Ma Dolores; Nacher, Juan; Olmeda, Ma Soledad; Parellada, Mara; González Peñas, Javier; Pignon, Baptiste; Rapado, Marta; Richard, Jean-Romain; Rodríguez Solano, José Juan; Roldán Díaz, Laura; Ruggeri, Mirella; Sáiz, Pilar A.; Sánchez, Emilio; Sanjuán, Julio; Sartorio, Crocettarachele; Schürhoff, Franck; Seminerio, Fabio; Shuhama, Rosana; Sideli, Lucia; Stilo, Simona A; Termorshuizen, Fabian; Tosato, Sarah; Tronche, Anne-Marie; van Dam, Daniella; van der Ven, Elsje (May 2019). "The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study". The Lancet Psychiatry. 6 (5): 427–436. doi:10.1016/S2215-0366(19)30048-3. PMID 30902669.
- Saha, Sukanta; Chant, David; Welham, Joy; McGrath, John (2005). "A Systematic Review of the Prevalence of Schizophrenia". PLOS Medicine. 2 (5): e141. doi:10.1371/journal.pmed.0020141. PMC 1140952. PMID 15916472.
- Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin. 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMC 7147575. PMID 31618428.
- Macleod, John; Oakes, Rachel; Copello, Alex; Crome, Ilana; Egger, Matthias; Hickman, Mathew; Oppenkowski, Thomas; Stokes-Lampard, Helen; Smith, George Davey (May 2004). "Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies". The Lancet. 363 (9421): 1579–1588. doi:10.1016/S0140-6736(04)16200-4. PMID 15145631. S2CID 3044549.
- Scuderi, C; Filippis, DD; Iuvone, T; Blasio, A; Steardo, A; Esposito, G (May 2009). "Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders". Phytotherapy Research (Review). 23 (5): 597–602. doi:10.1002/ptr.2625. PMID 18844286.
- Waldo Zuardi, Antonio; Alexandre S. Crippa, Jose; E.C. Hallak, Jaime; Bhattacharyya, Sagnik; Atakan, Zerrin; Martin-Santos, Rocio; K. McGuire, Philip; Silveira Guimaraes, Francisco (12 September 2012). "A Critical Review of the Antipsychotic Effects of Cannabidiol: 30 Years of a Translational Investigation". Current Pharmaceutical Design. 18 (32): 5131–5140. doi:10.2174/138161212802884681. PMID 22716160.
- McLoughlin, Benjamin C; Pushpa-Rajah, Jonathan A; Gillies, Donna; Rathbone, John; Variend, Hannele; Kalakouti, Eliana; Kyprianou, Katerina (14 October 2014). "Cannabis and schizophrenia". Cochrane Database of Systematic Reviews (10): CD004837. doi:10.1002/14651858.CD004837.pub3. PMID 25314586. S2CID 8434704.
- Madden, Sean P.; Einhorn, Patrick M. (February 2018). "Cannabis-Induced Depersonalization-Derealization Disorder". American Journal of Psychiatry Residents' Journal. 13 (2): 3–6. doi:10.1176/appi.ajp-rj.2018.130202.
- Diagnostic and statistical manual of mental disorders : DSM-5. (Fifth edition. ed.). American Psychiatric Association. 2013. p. 304.
- Copeland, Jan (2006). Evidence-based Answers to Cannabis Questions: A Review of the Literature. Australian National Council on Drugs. ISBN 978-1-877018-12-1.[page needed]
- Chadwick, Benjamin; Miller, Michael L; Hurd, Yasmin L (2013). "Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness". Frontiers in Psychiatry (Review). 4: 129. doi:10.3389/fpsyt.2013.00129. PMC 3796318. PMID 24133461.
- Lev-Ran, S.; Roerecke, M.; Le Foll, B.; George, T. P.; McKenzie, K.; Rehm, J. (24 June 2013). "The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies". Psychological Medicine. 44 (4): 797–810. doi:10.1017/S0033291713001438. PMID 23795762.
- Gobbi, Gabriella; Atkin, Tobias; Zytynski, Tomasz; Wang, Shouao; Askari, Sorayya; Boruff, Jill; Ware, Mark; Marmorstein, Naomi; Cipriani, Andrea; Dendukuri, Nandini; Mayo, Nancy (1 April 2019). "Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood". JAMA Psychiatry. 76 (4): 426–434. doi:10.1001/jamapsychiatry.2018.4500. PMC 6450286. PMID 30758486.
- Gibbs, Melanie; Winsper, Catherine; Marwaha, Steven; Gilbert, Eleanor; Broome, Matthew; Singh, Swaran P. (January 2015). "Cannabis use and mania symptoms: A systematic review and meta-analysis" (PDF). Journal of Affective Disorders. 171: 39–47. doi:10.1016/j.jad.2014.09.016. PMID 25285897.
- Serafini G, Pompili M, Innamorati M, et al. (2012). "Can cannabis increase the suicide risk in psychosis? A critical review". Current Pharmaceutical Design (Review). 18 (32): 5165–87. doi:10.2174/138161212802884663. PMID 22716157.
- 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.
- Courtney, Kelly E.; Mejia, Margie Hernandez; Jacobus, Joanna (6 May 2017). "Longitudinal Studies on the Etiology of Cannabis Use Disorder: A Review". Current Addiction Reports. 4 (2): 43–52. doi:10.1007/s40429-017-0133-3. PMC 5644349. PMID 29057198.
- Badiani, Aldo; Boden, Joseph M.; De Pirro, Silvana; Fergusson, David M.; Horwood, L. John; Harold, Gordon T. (May 2015). "Tobacco smoking and cannabis use in a longitudinal birth cohort: Evidence of reciprocal causal relationships". Drug and Alcohol Dependence. 150: 69–76. doi:10.1016/j.drugalcdep.2015.02.015. hdl:10523/10359. PMID 25759089.
- Taylor, Michelle; Collin, Simon M; Munafò, Marcus R; MacLeod, John; Hickman, Matthew; Heron, Jon (August 2017). "Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: findings from a UK birth cohort". Journal of Epidemiology and Community Health. 71 (8): 764–770. doi:10.1136/jech-2016-208503. PMC 5537531. PMID 28592420.
- Rocchetti, Matteo; Crescini, Alessandra; Borgwardt, Stefan; Caverzasi, Edgardo; Politi, Pierluigi; Atakan, Zerrin; Fusar-Poli, Paolo (November 2013). "Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users". Psychiatry and Clinical Neurosciences. 67 (7): 483–492. doi:10.1111/pcn.12085. PMID 24118193.
Aims - Despite growing research in the field of cannabis imaging, mostly in those with a psychotic illness, the possible neurotoxic effects of smoked cannabis on the healthy brain have yet to be fully understood. There appears to be a need to evaluate the existing imaging data on the neuroanatomical effects of cannabis use on non‐psychotic populations. Conclusions - Our results suggest that in the healthy brain, chronic and long‐term cannabis exposure may exert significant effects in brain areas enriched with cannabinoid receptors, such as the hippocampus, which could be related to a neurotoxic action.
- Sidney, Stephen (November 2002). "Cardiovascular Consequences of Marijuana Use". The Journal of Clinical Pharmacology. 42 (S1): 64S–70S. doi:10.1002/j.1552-4604.2002.tb06005.x. PMID 12412838.
- Jones, Reese T. (November 2002). "Cardiovascular System Effects of Marijuana". The Journal of Clinical Pharmacology. 42 (S1): 58S–63S. doi:10.1002/j.1552-4604.2002.tb06004.x. PMID 12412837.
- Bowles, Daniel W.; O’Bryant, Cindy L.; Camidge, D. Ross; Jimeno, Antonio (July 2012). "The intersection between cannabis and cancer in the United States". Critical Reviews in Oncology/Hematology. 83 (1): 1–10. doi:10.1016/j.critrevonc.2011.09.008. PMID 22019199.
- Stephen Maisto; Mark Galizio; Gerard Connors (2014). Drug Use and Abuse. Cengage Learning. p. 278. ISBN 978-1-305-17759-8.
- W. Hall; N. Solowij (1998-11-14). "Adverse effects of cannabis". Lancet. 352 (9140): 1611–16. doi:10.1016/S0140-6736(98)05021-1. PMID 9843121. S2CID 16313727.
- Tashkin, Donald P. (June 2013). "Effects of Marijuana Smoking on the Lung". Annals of the American Thoracic Society. 10 (3): 239–247. doi:10.1513/AnnalsATS.201212-127FR. PMID 23802821.
- Hall W, Degenhardt L (2009). "Adverse health effects of non-medical cannabis use". Lancet. 374 (9698): 1383–91. doi:10.1016/S0140-6736(09)61037-0. PMID 19837255. S2CID 31616272.
- Zhang R, Zuo-Feng Z, Morgenstern H, et al. (15 February 2015). "Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium". International Journal of Cancer. 136 (4): 894–903. doi:10.1002/ijc.29036. PMC 4262725. PMID 24947688.
- Hashibe M, Ford DE, Zhang ZF (November 2002). "Marijuana smoking and head and neck cancer". J Clin Pharmacol (Review). 42 (11 Suppl): 103S–107S. doi:10.1002/j.1552-4604.2002.tb06010.x. PMID 12412843.
- "The impact of cannabis on your lungs". British Lung Association. June 2012. Archived from the original on 2013-09-27. Retrieved 2013-01-09.
- "Archived copy" (PDF). Archived from the original (PDF) on 2014-10-31. Retrieved 2014-11-01.CS1 maint: archived copy as title (link)[non-primary source needed]
- de Carvalho, M.F.F.; Dourado, M.R.; Fernandes, I.B.; Araújo, C.T.P.; Mesquita, A.T.; Ramos-Jorge, M.L. (December 2015). "Head and neck cancer among marijuana users: A meta-analysis of matched case–control studies". Archives of Oral Biology. 60 (12): 1750–1755. doi:10.1016/j.archoralbio.2015.09.009. PMID 26433192.
- [non-primary source needed] [needs update] 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 DP (June 2005). "Smoked marijuana as a cause of lung injury". Monaldi Arch Chest Dis (Review). 63 (2): 93–100. doi:10.4081/monaldi.2005.645. PMID 16128224.
- Lutchmansingh, D; Pawar, L; Savici, D (2014). "Legalizing Cannabis: A physician's primer on the pulmonary effects of marijuana". Current Respiratory Care Reports. 3 (4): 200–205. doi:10.1007/s13665-014-0093-1. PMC 4226845. PMID 25401045.
- National Academies Of Sciences, Engineering; Health Medicine, Division; Board on Population Health Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review Research Agenda (2017). The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academy of Sciences. doi:10.17226/24625. ISBN 978-0-309-45304-2. PMID 28182367.
- 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: 1–11. doi:10.1155/2013/510540. PMC 3818851. PMID 24228028.
In fact, maternal marijuana use has been associated with foetal growth restrictions, spontaneous miscarriage, and cognitive deficits in infancy and adolescence.
- 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. S2CID 25014303.