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: cannabis reduction: adjunct psychological therapy versus treatment as usual 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. outcome findings in words findings in numbers quality of evidence behavior frequency of cannabis use(group-based therapy)follow up: 1 yearpeople in the intervention groups scored a little lower compared to people receiving treatment as usual but there was no clear difference between the therapy groups and standard care. this finding is based on data of moderate quality.md 0.1 lower (2.44 lower to 2.24 higher)*moderate mental state average score (panss) - positive symptomsfollow up: 12 monthson average, people receiving cannabis reduction therapy scored lower than people treated with treatment as usual but there was no clear difference between groups. this finding is based on data of moderate quality.md 0.3 lower (2.55 lower to 1.95 higher)*moderate quality of life average score (who qol questionnaire)follow up: 1 yearson average, people receiving cannabis reduction therapy scored higher compared to people in the control group receiving treatment as usual. there was, however, no clear difference between the groups and these findings are based on data of moderate quality.md 0.9 higher (1.15 lower to 2.95 higher)*moderate no study reported any data on outcomes such as relapse, adverse effects, leaving the study early and information relating to satisfaction with treatment * at present the meaning of these scores in day-to-day care is unclear. 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, 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. 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. 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. depressive 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. 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. a 2017 review suggests that cannabis has been shown to improve the mood of depression-diagnosed patients. 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. 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. among cannabis users of all ages, there may be an increased risk of developing depression, with heavy users seemingly having a higher risk. 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. 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. 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. 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. 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. however, some participants that have been previously diagnosed with bipolar disorder, had a worsen occurrence with mania symptoms. 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. 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 main article: gateway drug theory § cannabis 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. 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 friendship associations 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. 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. 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. 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. injection initiation leads to further patterns of injection initiation which will eventually lead to addiction. 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". 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. 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, 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. 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. 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. cancer 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." lung 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