Long-term effects of cannabis

Source: Wikipedia, the free encyclopedia.
(Redirected from
Cannabis and psychosis
)
Part of a series on
Cannabis
Cannabis
Chemistry
Consumption
Economics
Effects
Forms
Law
Variants
  • Genus
  • Species
  • Strains
  • Acapulco Gold
  • Blue Dream
  • Charlotte's web
  • Kush
  • Malawi Gold
  • Sour Diesel
Related

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 and there is limited evidence from which to draw conclusions.[1] 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.[2]

Dependency

Main article: Cannabis use disorder

Cannabis is the most widely used illicit drug in the Western world.

cognitive behavioural therapy and motivational enhancement therapy have achieved some success.[9]

Cannabis dependence develops in 9% of users, significantly less than that of heroin, cocaine, alcohol, and prescribed

anxiolytics,[10] 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.[11] A 2018 academic review, published in partnership with Canopy Growth, discussed the limitations of current studies of therapeutic and non-therapeutic cannabis use, and further stated that the nature of dependence formation among regular marijuana consumers has declined since 2002.[12]

Cambridge University published a study in 2015 that showed the surprising fact that in England and Wales, the use of cannabis had decreased. Although there was a reported decrease in use, the need for addiction treatment was surging. The study looked more in depth on how the potency of the cannabis affected someone's dependence on the drug. They tested three different levels of potency and found that the most potent cannabis had the highest amount of dependence. Researchers believe that this is because of the high that the participants felt after using. The lower potency strains did not give users the same high, which made them not desire or in turn depend on that strain as much.[13]

Memory and intelligence

Acute cannabis intoxication has been shown to negatively affect attention, psychomotor task ability, and short-term memory.[14][15] 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.[16][17]

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.[18][6][19]

A

neuropsychological tests
. The authors concluded that:

  • persistent cannabis users show neuropsychological decline from childhood to midlife.[16]
  • 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.[16]
Cannabis

Cannabis intoxication was not only found to affect attention, psychomotor task ability, and short-term memory.[14][15] It was also found that intoxicated users were facing the difficulty of having false memories.[20]

The use of cannabis has been heavily shown to affect the working-memory network function. Using large amounts of cannabis at a time is associated with hyperactivity of the network during a working-memory task. Most of these findings are showing that people who use cannabis on a daily basis will need additional effort in order to perform certain tasks.[21][22][23]

Mental health

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.[24][12] The effects of THC and CBD are salient regarding psychosis and anxiety.[25]

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.[2] 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.[26] 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.[27] The risks appear to be most acute in adolescent users.[27] 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.[26] 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.[28] 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.[29]

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."[30]

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

trichomes

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.[33] 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.[34] Such a public health message was subsequently issued in August 2019 by the Surgeon General of the United States.[35] 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.[34]: 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)."[36] To calculate what the increased odds ratio[36] means for schizophrenia specifically, a 2005 review placed the lifetime morbid risk of narrowly defined schizophrenia at 0.72%.[37] 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."[36]

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%).[38]

However, a 2004 study noted that general population statistics show no increase in psychosis incidence rates in any developed country over the last 50 years, despite a five-fold increase in cannabis use rates. To quote Macleod et al. 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."[39]

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.[28][40] Research has suggested that CBD can safely reduce some symptoms of psychosis in general.[41]

A 2014 review examined psychological therapy as add-on for people with schizophrenia who are using cannabis:

Cannabis reduction: adjunct psychological therapy versus treatment as usual[42]
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.[42]

Transient psychosis

As of 2017 there was 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,[43] but see previous section. 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.[44][45][46][47]

Depersonalization/derealization symptoms

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. Depersonalization is defined as a dissociative symptom in which one feels like an outside observer with respect to one's thoughts, body, and sensations. While derealization is marked by feelings of unreality and detachment from one's surroundings, such that one's environment is experienced as remote or unfamiliar.[48]

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.[49]

Depressive disorder

Less attention has been given to the association between cannabis use and

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.[50] The findings on marijuana's relationship to depressive disorder are scattered, showing that cannabis use has benefits, but can also be detrimental to overall mental health. However, sufficient evidence exists showing reductions in cannabis use improve anxiety, depression, and sleep quality.[51] A 2017 review suggests that cannabis has been shown to improve the mood of depression-diagnosed patients.[12]
This is indicative of a longitudinal relationship between cannabis reduction and improvements in anxiety and depression.

Anxiety and depression have been found to increase susceptibility to marijuana use.[52] This is due to a desire to alleviate the symptoms of these experiences through marijuana use. Chronic users who use for anxiolytic purposes will even develop dependencies on cannabis, making it difficult to cope with anxiety when the drug is absent.

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.[53] Among cannabis users of all ages, there may be an increased risk of developing depression, with heavy users seemingly having a higher risk.[54] Heavy marijuana use in adolescence has also been associated with deficits in cognition. A recent study assessing changes in neuropsychological functioning resulting from long-term cannabis use followed a group of adolescents (ages 12 –15 at baseline) over a 14-year period. Researchers found that more days of use were correlated with decreases in inhibitory control, and visuospatial ability. Contrary to existing cross-sectional studies showing marijuana use in adolescence is associated with poor cognitive functioning, there were no associations between long-term cannabis use and memory and processing speed.[55] While this study showed no correlations between memory and cannabis use, others have found that there is. It is important to know that studies looking at associations between cannabis use and poor neurocognitive functioning have found that extended abstinence from marijuana leads to improvements in cognitive deficits. Decreases in cognition resulting from marijuana use are indeed reversible.

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.[56] In a longitudinal study assessing the associations between long term use and mental health in a group of individuals participating in a drug-based treatment for depression, researchers found that, compared to non-users, patients using both medically and non-medically experienced less improvement in depressive symptoms and an increase in suicidal ideation. Additionally, those who used non-medically, were less likely to visit the psychiatrist.[57] Further research should investigate this finding to see whether non-medical marijuana use serves as a barrier to treatment seeking behavior.

Mania symptoms

Mania is a mental illness marked by periods of great excitement or euphoria, delusions, and overactivity.[58] This is common in cannabis users when they hit a point of their high that could lead to paranoia, anxiety, increased heart rate. Some strains of the drug can have these effects on the individuals that use them, but no effects are guaranteed when used. A case review reported that an adult user had marijuana-induced mania even though they had no previous psychiatric history.[59] However, some participants that have been previously diagnosed with bipolar disorder, had a worsen occurrence with mania symptoms.[60] This showed that anyone, diagnosed or psychiatrically stable, can develop mania symptoms when under the influence of cannabis.

Suicidal behavior

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.[53]

In the general population a weak (indirect) association appears to exist between suicidal behaviour and cannabis consumption in both psychotic and non-psychotic users,[61] although it remains unclear whether regular cannabis use increases the risk of suicide.[62] 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.[61]

Gateway drug hypothesis

Main article:
Gateway drug theory § Cannabis

The

harder drugs. The release of dopamine at CB1 receptors when cannabinoids enter the body can enforce drug seeking behavior. In addition to the gateway framework, there is also the peer clustering theory which says that friendships influence drug seeking behaviors. Friends who use can influence one another to take drugs that are more rewarding and have a higher potential for abuse.[63]

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.[64][65][66]

Over time, the marijuana gateway hypothesis has been studied more and more. In one published study, the use of marijuana was shown not a reliable gateway cause of illicit drug use.[67]

However, social factors and environment influence drug use and abuse, making the gateway effects of cannabis different for those in differing social circumstances. A study looking at associations between drug injection and cannabis use in street-involved youth found that cannabis use was associated with slower time to injection initiation.[68] Injection initiation leads to further patterns of injection initiation which will eventually lead to addiction.[68]

Physical health

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".[3]

Researchers are concerned that with the increase in legalization will lead towards an increase of use which will in turn call for new strategies as well as rehabilitation to minimize the harm that cannabis can do on someone's body.[69]

Brain

Studies conflict on whether long-term cannabis use causes persistent structural changes in humans. Twin studies have shown no significant difference between users and non-users in twin pairs,[70] but other studies have demonstrated that chronic use affects white matter and hippocampal volume in the brains of healthy (non-psychotic) patients, which is where large amounts of cannabinoid-1 receptors are present.[71][72]

Gastrointestinal tract

Long term cannabis users are at risk for developing cannabinoid hyperemesis syndrome (CHS), characterized by recurrent bouts of intense vomiting. The mechanism behind CHS is poorly understood and is contrary to the antiemetic properties of cannabis and cannabinoids.[73]

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

cannabinoids that can affect the cardiovascular function, such as cannabigerol. Smoking cannabis decreases exercise tolerance.[74] 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.[75]

Cancer

A 2012 review examining the relation of cancer and cannabis found little direct evidence that

confounders, and cannabinoids' potential as cancer treatment.[76]

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.[3] 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.[3] 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."[3]

Lung

There have been a limited number of studies that have looked at the

effects of smoking cannabis on the respiratory system.[77] Chronic heavy cannabis smoking is associated with coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis.[78] Regular cannabis use has not been shown to cause significant abnormalities in lung function.[79]

Regular cannabis smokers show pathological changes in lung cells similar to those that precede the development of lung cancer in tobacco smokers.[80] 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."[3] 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.[3]

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."[79]

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."[81]

Cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same

California Proposition 65 warning list as a carcinogen since 2009, but leaves and pure THC are not.[84]

Head and neck

A 2015 review found no association between head and neck cancer and lifetime cannabis smoking.[85]

Respiratory effects

Cannabis sativa from Vienna Dioscurides, 512 AD

A 2013 literature review by Gordon and colleagues concluded that inhaled cannabis is associated with lung disease,[3] although Tashkin's 2013 review has found "no clear link to chronic obstructive pulmonary disease".[79]

Smoking cannabis has been linked to adverse respiratory effects including: chronic coughing, wheezing, sputum production, and acute bronchitis.[83] 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'.[86]

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.[87][88]

Reproductive and endocrine effects

Main article:
Cannabis and male fertilty

Male cannabis use has been associated with reduced fertility and decreased sperm counts.[89] Initial epigenetic studies have shown that male cannabis use causes widespread DNA methylation changes in sperm, resulting in lower rates of fertilization and higher rates of miscarriage.[90] Sperm DNA methylation alterations from cannabis extract exposure are evident in the offspring of rats.[91]

Main article: Cannabis in pregnancy

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.[2] Cannabis consumption in pregnancy is associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring.[92] 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".[93] 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.[50]

Mortality

No fatal overdoses associated with cannabis use have ever been reported.[62] 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.[62]

See also

References

  1. ^ "Challenges and Barriers in Conducting Cannabis Research". The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies of Sciences, Engineering, and Medicine/National Academies Press. 2017. Archived from the original on 2021-02-26. Retrieved 2021-04-11.
  2. ^
    PMID 28182367.{{cite book}}: CS1 maint: multiple names: authors list (link)[page needed
    ]
  3. ^
    S2CID 29063282. Archived
    from the original on 2019-08-07. Retrieved 2018-08-28.
  4. S2CID 8503107
    .
  5. ^ a b "Is marijuana addictive?". National Institute on Drug Abuse. Archived from the original on 2022-10-24. Retrieved 2022-10-24. Marijuana use can lead to the development of problem use, known as a marijuana use disorder, which takes the form of addiction in severe cases. ... Marijuana use disorder becomes addiction when the person cannot stop using the drug even though it interferes with many aspects of his or her life.
  6. ^
    PMID 29556883
    .
  7. S2CID 20302345
    .
  8. S2CID 6660057
    .
  9. PMID 22640758
    .
  10. PMID 26986677
    .
  11. PMID 18292704
    .
  12. ^
    PMID 27816801
    .
  13. PMID 26213314
    .
  14. ^
    PMID 27249079
    .
  15. ^
    PMID 24483000. Archived
    from the original on 2022-10-24. Retrieved 2022-10-24.
  16. ^
    PMID 22927402
    .
  17. PMID 24648785
    .
  18. PMID 26787878
    .
  19. PMID 31753729
    .
  20. PMID 32041881
    .
  21. PMID 24633558
    .
  22. PMID 24038570
    .
  23. PMID 25823635
    .
  24. PMID 22729452
    .
  25. S2CID 13544234
    .
  26. ^
    PMID 23810133
    .
  27. ^
    PMID 25939318
    .
  28. ^
    PMID 24137134
    .
  29. PMID 24133461
    .
  30. PMID 24471373
    .
  31. PMID 26884547
    .
  32. S2CID 619268
    .
  33. 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.
  34. ^
    S2CID 1055335. Archived
    (PDF) from the original on 2021-09-25. Retrieved 2021-09-08.
  35. ^ "U.S. Surgeon General's Advisory: Marijuana Use and the Developing Brain". United States Department of Health and Human Services. 29 August 2019. Archived from the original on 11 February 2020. Retrieved 12 February 2020.
  36. ^
    PMID 30902669
    .
  37. PMID 15916472
    .
  38. PMID 31618428
    .
  39. S2CID 3044549
    .
  40. S2CID 21836765. Archived
    from the original on 2021-04-11. Retrieved 2020-05-25.
  41. S2CID 13446596
    .
  42. ^
    S2CID 8434704. Archived
    (PDF) from the original on 2021-03-01. Retrieved 2020-12-13.
  43. S2CID 205737272
    .
  44. S2CID 12508404
    .
  45. PMID 21150914
    .
  46. PMID 22213786
    .
  47. PMID 25031222
    .
  48. doi:10.1176/appi.ajp-rj.2018.130202
    .
  49. ^ Diagnostic and statistical manual of mental disorders : DSM-5. (Fifth edition. ed.). American Psychiatric Association. 2013. p. 304.
  50. ^
    ISBN 978-1-877018-12-1.[page needed
    ]
  51. PMID 28847455
    .
  52. PMID 27427415
    .
  53. ^
    PMID 24133461
    .
  54. S2CID 36763290
    .
  55. PMID 31822320
    .
  56. PMID 30758486
    .
  57. PMID 30086434
    .
  58. ^ "Mania: What Is It, Causes, Triggers, Symptoms & Treatment". Cleveland Clinic. Archived from the original on 2022-10-24. Retrieved 2022-10-24.
  59. PMID 21749837
    .
  60. PMID 25285897. Archived
    (PDF) from the original on 2019-12-29. Retrieved 2019-08-16.
  61. ^
    PMID 22716157
    .
  62. ^
    PMID 20565525
    .
  63. PMID 28511099
    .
  64. PMID 29057198
    .
  65. PMID 25759089
    .
  66. PMID 28592420
    .
  67. S2CID 233599789
    .
  68. ^
    PMID 29430806
    .
  69. S2CID 9858298. Archived
    from the original on 2022-06-03. Retrieved 2021-08-23.
  70. ^ NIDA. "What are marijuana's long-term effects on the brain?". National Institute on Drug Abuse. Archived from the original on 21 October 2022. Retrieved 29 October 2022.
  71. PMID 27789118. Archived
    from the original on 2023-04-21. Retrieved 2022-10-24.
  72. S2CID 8245635
    . 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.
  73. PMID 20485701
    .
  74. S2CID 27401560
    .
  75. S2CID 12193532
    .
  76. PMID 22019199
    .
  77. ISBN 978-1-305-17759-8. Archived
    from the original on 2023-01-13. Retrieved 2016-03-14.
  78. S2CID 16313727
    .
  79. ^
    S2CID 20615545
    .
  80. S2CID 31616272
    .
  81. PMID 24947688
    .
  82. S2CID 20738940
    .
  83. ^ a b c The impact of cannabis on your lungs (PDF). British Lung Association. 2012. Archived (PDF) from the original on 2022-10-24. Retrieved 2022-10-24.
  84. ^ "The Proposition 65 List". California Office of Environmental Health Hazard Assessment. Archived (PDF) from the original on 2014-10-31. Retrieved 2022-10-24.
  85. PMID 26433192
    .
  86. PMID 25401045
    .
  87. doi:10.1300/J175v01n03_09
    .
  88. PMID 16128224
    .
  89. PMID 32994467
    .
  90. PMID 34557312
    .
  91. PMID 36085240
    .
  92. PMID 24228028
    . In fact, maternal marijuana use has been associated with foetal growth restrictions, spontaneous miscarriage, and cognitive deficits in infancy and adolescence.
  93. S2CID 25014303
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Long-term_effects_of_cannabis&oldid=1205878175#Mental_health"