CBD is a common non-intoxicating cannabinoid constituent of cannabis

Among US adults , daily cannabis use was significantly more common among those with past-month serious psychological distress , compared to those without past-month SPD Systematic reviews have found associations between frequent cannabis use and hyperemesis syndrome , especially among young individuals reporting cannabis use, though co-occurring mental health problems appear common . In a meta-analytic review, the risk for CUD was 33% in persons with daily and near-daily cannabis use compared to 12% in those with any lifetime use . Among the US general adult population , cannabis-use quantity , p<0.001) and frequency , p<0.001, but not age-of-onset, predicted CUD and other cannabis-related problems among those individuals with past-year use . In a comprehensive systematic review, daily cannabis use predicted an elevated risk of cannabis withdrawal syndrome in different populations of PWUC . In several multi-variate analyses-based studies, high-frequency cannabis use predicted multiple adverse consequences, including dependence and impaired driving . A US-based sample showed that frequency of cannabis use was associated with poorer mental/physical health and reduced health-related quality-of-life . In a secondary analysis of a randomized controlled trial assessing pharmacotherapy for CUD, larger reductions in drying cannabis use frequency after treatment were associated with greater improvements in quality-of-life .

Comprehensive reviews have concluded that the greatest psychosocial functioning deficits were observed among individuals reporting chronic/frequent cannabis use; these effects may arise regardless of whether the onset of use occurred in adolescence or adulthood . Among PWUC in the US’ general adult population who reported driving under the influence of cannabis , the predicted probabilities of cannabis-impaired driving were highest for those with more frequent use, with 57% predicted probability for those with daily use . Overall, frequent and intensive cannabis use strongly and consistently predicts long-term adverse outcomes from cannabis use after controlling for at least some of the other risk factors . However, there is a general need for better measures of the overall ‘magnitude’ of cannabis exposure that consider and integrate cannabis use frequency, amounts, and potency to better estimate associations with these adverse outcomes .Cannabis products have further diversified in their pharmacological characteristics, including composition or amounts of the major cannabinoids THC and cannabidiol . There is substantial evidence of a dose-response relationship between THC-amount/potency and acute adverse effects and some evidence for long-term effects . Reviews generally suggest more extensive white matter/brain alterations among PWUC consuming high- as opposed to lower-potency cannabis products . Exposure to cannabis products with higher THC potency is generally associated with acutely impaired cognition, memory problems, and increased symptoms and severity of CUD . Systematic reviews have confirmed a dose-response relationship between frequent use of high-potency cannabis and psychotic symptoms and disorders, although questions remain about causality.

High-potency cannabis use is associated with significantly higher anxiety or depression outcomes in youth, and adolescents using high potency cannabis are less likely than older individuals to titrate their cannabis dose, and so increase their risk of cannabis dependence or other harms . In a pharmacodynamic study of edible cannabis product use, low THC doses produced moderate subjective but not cognitive or psychomotor impairment effects. High doses produced more marked subjective effects and impairment . Among youth aged PWUC in the US, the risk of progressing from cannabis use initiation to CUD significantly increased for each percentage increase in the national average THC level of cannabis observed. Those initiating cannabis use at a national THC content average of 12.3% had a 2.6 times higher risk of CUD incidence than those initiating use at a 4.9% THC content average . In the Netherlands, an increase in THC potency levels of cannabis sold was significantly associated with rising admissions to cannabis treatment, and admissions dropped when the average THC content declined . Cannabis extracts/concentrates typically contain extremely high THC concentrations , and their inhalation can rapidly deliver an exceptionally high dose of THC into the body. Concentrate use is generally associated with higher THC exposure and blood-THC levels, stronger neuro-behavioral intoxication and impairments, higher levels of dependence, and depression and anxiety in cohort studies, although select acute impairments from concentrate use may be moderated by tolerance or THC-saturation effects among user-individuals . Samples of individuals using cannabis flower and concentrate products reported significant associations between cannabis potency used and multiple negative physical and mental health outcomes .

Among a large sample of adolescents, experimental cannabis use involving concentrates predicted subsequent progression to frequent use compared to other cannabis product types.It has demonstrated neuroprotective, anti-inflammatory, and anxiolytic effects in laboratory studies and attenuates some of the neurocognitive and behavioral effects of THC, with few and mostly mild adverse effects of itself . In clinical trials for CUD, CBD-based pharmacotherapies have somewhat reduced cannabis use frequency, craving and withdrawal symptoms . Consequently, the use of cannabis with high CBD-to-THC ratios has been suggested as a way to reduce adverse outcomes of cannabis use . A systematic review found that CBD attenuates some of THC’s acute psychoactive effects, such as intensity of psychosis/anxiety symptoms and emotional/reward processing. However, it does not consistently affect memory and cognitive functions or the level of intoxication produced by THC . Other studies have found inconsistent evidence on whether combined CBD and THC use attenuates memory impairment and hippocampal volume changes, suggesting that extremely high doses of CBD are required for attenuation . In a systematic review, only one of four studies found that CBD produced a significant reduction in THCinduced psychiatric symptoms . Studies of the effects of CBD vary in methodology, dosing, and routes of administration . Questions remain about CBD-related dose/effect relationships and whether its protective effects differ between individuals reporting frequent and infrequent cannabis use . Overall, CBD may attenuate some of THC’s acute deleterious effects, but this may largely be limited to exceptionally CBD-rich cannabis products, and it may not reliably protect against the cognitive and psychomotor impairments produced by THC.

These limitations for attenuating effect, in particular, seem to be the case with the majority of cannabis products on the non-medical market that typically contain relatively low levels or dosages of CBD. Notably, CBD by itself may actually produce or exacerbate selected impairment deficits, as may be particularly important for driving impairments and possible MVC involvement . Importantly, there are currently no empirically defined standards or risk thresholds for cannabis potency serving to reliably reduce adverse health outcomes . A systematic review also suggests that many, especially un-regulated cannabis products contain toxic contaminants such as microbes , heavy metals, pesticides, and residual solvents. Their direct human impact has not been assessed but they may increase the risks of infections, carcinogenicity, and adverse reproductive effects, ebb flow with the magnitude and route of exposure likely to influence outcomes . Unregulated illegal cannabis products also come without reliable information on product potency or composition, so PWUC should prefer legal and regulated cannabis products where these are available, as these can be presumed to be safer in regards to production and content quality and allow them to better self-regulate their use and thus protect their health .Modes of cannabis administration have diversified in recent years, especially in jurisdictions where cannabis is legal for non-medical use. While there are indications for differential or moderating mode-of-use based effects on health outcomes, there is very little comparative evidence on the health outcomes of these different cannabis administration modes . The most popular cannabis use modes include smoking cannabis plant material , vaping/vaporizing electronically heated herbal or liquid/extract, and orally ingesting cannabis ‘edible’ and ‘drinkable’ products . Cannabis smoking produces a relatively rapid onset and peak of psychoactive effects.

Acute effects may last 2-6 hours but residual effects may last for 24 hours or multiple days . A meta-analysis demonstrated that smoking cannabis alone was associated with significantly increased risk of cough, sputum production, wheezing, and dyspnea . Cannabis continues to be commonly smoked in combination with tobacco in many settings, which makes it difficult to assess the respiratory health effects of cannabis smoking alone. Co-use of cannabis and tobacco does, however, increase risks of adverse respiratory health outcomes that may be exacerbated by intensive inhalation practices . Cannabis smoking can produce both bronchodilation and broncho constriction. Chronic cannabis smoking increases the risk of chronic bronchitis, airway inflammation, bullous lung disease and pneumothorax, but it remains uncertain if it increases the risk of chronic obstructive pulmonary disease or lung cancer . Of different use modes available, cannabis smoking also features the highest environmental smoke exposure and emission rate, resulting in possible toxin exposure and related adverse effects to others . Cannabis vaporizing/vaping has become an increasingly popular use method, especially among younger individuals, because of perceived possible health advantages . Vaping can involve different cannabis products, namely herbal/flower products, liquids as well as cannabis concentrates. The vaporization process heats but aerosolizes the cannabis product into a vapour, which then is inhaled and absorbed through the respiratory system . While cannabis smoking and vaporizing provide for generally similar cannabinoid delivery dynamics, vaporization is a more ‘efficient’ mode of administration for THC and produces higher peak THC-levels . A placebo-controlled cross-over trial on the effects of smoked and vaporized cannabis at different dose-levels among individuals with infrequent use found dose-response relationships for subjective and cardiovascular effects and for cognitive and psychomotor impairment, with vaporization producing greater pharmacodynamic effects and higher blood-cannabinoid concentrations . It is uncertain, however, whether this holds true for more frequent use patterns. In another pharmacokinetic study, no major differences were observed in cannabinoid blood concentrations between individuals who smoked and vaped occasionally, but individuals with frequent use achieved higher concentrations from smoking, possibly through reverse titration.A study assessing subjective effects from different use modes found the least positive and negative effects reported to be associated with vaporization . Since the combustion process is avoided, cannabis vaporization reduces the formation of pyrolytic toxic compounds, including carbon monoxide and carcinogens . Individuals using cannabis by vaporization have reported fewer respiratory problem symptoms than smokers, but long-term effects remain unclear . Consequently, vaporization – at least in some forms – has been suggested as a ‘safer’ inhalation mode than smoking for cannabis use at least for pulmonary health. Overall, this further depends on the type of cannabis product used; for example, the use of high-potency extracts is associated with higher levels of acute and long-term effects.Furthermore, many cannabis extract products have been found to contain contaminants, for example pesticides, residual solvents, heavy metals or bacteria and fungi . Further concerns are that cannabis vaping products include toxins from flavouring agents and can cause bronchiolitis.

A recent outbreak of acute lung injuries among young adults in the US, including some deaths, was linked to the vaping of counterfeit cannabis oil cartridges adulterated with vitaminE acetate, an inflammatory irritant . Cannabis ingestionhas become common because it eliminates the respiratory risks of inhalation use and produces more prolonged and potentially intense psychoactive effects than other modes of use . While studies suggest that individuals using cannabis ‘edibles’ initiate use at a younger age, consume overall larger quantities of cannabis and drive more often after use, consumption of edibles occurs less commonly than other use modes . Ingestion of cannabis products has been observed to be increasing especially among older adult users . ‘Edible’ products are available in different compositions, usually with lower THC doses. They exert slower, although variable, bio-absorption and related effect dynamics that delay the onset of psychoactive effects yet produce a substantially longer duration of impairment than cannabis inhalation use . ‘Edible’ use can lead to sleepiness, nausea, anxiety and hallucinations, with some individuals reporting they are unable to perform normal tasks . While their use allows to avoid inhalation-related adverse consequences, their particular pharmaco dynamics make cannabis edibles more difficult for dose titration and increase the risks of unexpected levels of intoxication, including overdose experiences, especially in individuals with infrequent or those inexperienced in cannabis use.Adolescents report more negative effects from ‘edibles’ use than from smoking or vaping cannabis products, suggesting the need for caution in their intake and use.