What are the acute and chronic adverse effects of cannabis use, and how should they be managed?

Cannabis Side Effects: Acute and Chronic Adverse Effects

Cannabis causes a spectrum of dose-dependent adverse effects ranging from mild neuropsychiatric symptoms to serious cardiovascular events, with the most concerning long-term risks being cannabis use disorder (affecting ~10% of chronic users), persistent neurocognitive impairment (especially with adolescent-onset use), psychotic disorders in vulnerable individuals, and cardiovascular complications including myocardial infarction and stroke. 1, 2

Acute Adverse Effects

Common Short-Term Effects

• Neuropsychiatric symptoms include dizziness, confusion, anxiety, fatigue, dry mouth, and memory impairment occurring within minutes to hours of use 1, 2
• Cardiovascular effects manifest as dose-dependent tachycardia, elevated blood pressure, coronary vasoconstriction, and orthostatic hypotension 1, 2
• Severe acute reactions at high doses include paranoia, severe confusion, acute psychotic symptoms, and panic attacks 1, 2

Serious Acute Complications

• Cardiovascular emergencies such as arrhythmias, myocardial ischemia, and myocardial infarction can occur, particularly in patients with pre-existing coronary disease 1, 2
• Cannabis hyperemesis syndrome presents with cyclical vomiting episodes characteristically relieved by hot showers, typically after long-standing use (>4 times weekly for over a year) 1, 2
• Acute intoxication causes impaired coordination, motor vehicle crashes (doubling fatal collision risk), and in older adults may cause sedation, obtundation, and myocardial ischemia 2, 3

Route-Specific Risks

• Edible cannabis products account for only 0.32% of sales but 10.7% of emergency department visits due to delayed onset causing unintentional overdosing 1
• Vaping THC concentrates poses unique risks, exemplified by the 2019 outbreak of acute lung injury associated with vitamin E acetate 2

Chronic Adverse Effects

Cannabis Use Disorder and Dependence

• Approximately 10% of adults with chronic cannabis use develop cannabis use disorder, characterized by clinically significant impairment or distress 2
• Early onset of cannabis use, especially weekly or daily use, strongly predicts future dependence 2
• A randomized trial demonstrated that participants receiving a medical cannabis card had almost twice the incidence of developing cannabis use disorder within 12 weeks compared to controls 2

Withdrawal Syndrome

• Non-life-threatening withdrawal symptoms occur within 3 days after cessation in long-term daily users and may last up to 14 days 2
• Symptoms include sleep disturbances, appetite changes, abdominal pain, irritability, anxiety, nervousness, restlessness, and aggression 2, 4

Neurocognitive Impairment

• Persistent cognitive deficits develop with regular use, including executive function impairment (inhibitory control, decision-making), reduced processing speed, and verbal learning/memory deficits 2, 5
• Structural brain damage includes altered gray matter volume, cortical thickness changes, and disrupted prefrontal cortex connectivity affecting decision-making and impulse control 2, 5
• Adolescent-onset use causes the most severe and lasting neurological damage through glutamate excitotoxicity and disruption of critical neurotransmitter systems during vulnerable neurodevelopmental periods 2, 5

Psychiatric Complications

• Cannabis use is associated with increased risk for developing depressive disorders and may exacerbate existing psychiatric disorders in vulnerable individuals 2
• High doses of THC are associated with psychotic symptoms, with chronic use elevating risk for schizophrenia and psychotic disorders, particularly with early-onset use 2, 5
• Early cannabis use is associated with neuropsychological decline, elevated risk for psychotic disorders in adulthood, higher risk for depression, and suicidal ideation or behavior 2, 5

Cardiovascular Disease

• Long-term cannabis use is associated with adverse cardiovascular events including myocardial infarction, stroke, and arrhythmias 2
• Cannabis causes sympathetic stimulation through catecholamine reuptake blockade, coronary vasoconstriction, increased endothelin-1, decreased nitric oxide, and a prothrombotic state through increased platelet activation 2
• Combined use with tobacco produces greater cardiovascular effects than either substance alone 2

Respiratory Effects

• Cannabis smoking affects lung function and is associated with chronic bronchitis and chronic obstructive pulmonary disease 2
• The link between cannabis smoking and lung cancer remains unclear, often confounded by concomitant tobacco use 2

Special Population Risks

Pregnancy

• Cannabis use during pregnancy may negatively affect fetal brain development and increase risk for premature birth 2, 5
• Pregnant individuals should avoid all cannabis use 2

Adolescents and Young Adults

• Cannabis use may have a deleterious effect on adolescent brain development, with the developing brain showing increased susceptibility to cannabis-induced excitotoxicity and structural damage 2, 5
• Early initiation causes neuropsychological and neurodevelopmental decline, elevated risk for psychotic disorders in adulthood, and higher risk for depression and suicidal behavior 2, 5

Older Adults

• Cannabis use has increased among adults aged 65 years or older, who may be at higher risk for behavioral health issues including anxiety and depression 2
• Cannabis-related emergency department visits among older adults have increased, with acute toxicity potentially causing sedation, obtundation, and myocardial ischemia or infarction 2

Potency and Dose-Response Considerations

• Cannabis THC concentration has nearly doubled from 9% in 2008 to 17% in 2017, with concentrates reaching up to 70% THC 1, 2
• Higher doses of THC are associated with more severe acute effects, including psychosis in vulnerable individuals 2
• Modern high-potency products significantly elevate all health risks 2

Drug Interactions

• Cannabis inhibits several cytochrome P450 enzymes (CYP3A4, CYP2C9, CYP2C19), creating broad potential for drug-drug interactions 2
• Very high-risk interactions exist with warfarin; high-risk interactions with buprenorphine and tacrolimus 2
• Limited clinical data exist on interactions with most medications, making it difficult to provide informed guidance on potential interactions with approved therapeutics 1

Hepatotoxicity Risk with CBD

• CBD presents risks for hepatotoxicity, with a meta-analysis showing nearly 6-fold increase in liver enzyme elevation and drug-induced liver injury 1
• No cases were reported with total CBD doses <300 mg/day 1
• Monitoring liver enzymes with CBD use is important, particularly in cancer patients who may have baseline hepatic compromise 1

Clinical Management Approach

Assessment

• Assess current cannabis use patterns including frequency, dose, THC concentration, route of administration, and duration of use 1
• Screen for cannabis use disorder using validated criteria 1
• Evaluate for cannabis-induced complications including psychotic symptoms, cardiovascular events, respiratory symptoms, and hyperemesis syndrome 1, 2

Patient Education

• Inform patients about dose-dependent risks, emphasizing that higher THC concentrations (>17%) substantially increase adverse effects 2
• Warn vulnerable populations (adolescents, pregnant individuals, those with psychiatric or cardiovascular disease) about heightened risks 2, 5
• Educate about cannabis use disorder risk (~10% of chronic users) and withdrawal symptoms 2

Harm Reduction

• For patients who continue use despite counseling, recommend lowest effective dose, avoidance of high-potency products (>17% THC), and avoidance of edibles due to delayed onset and overdose risk 1, 2
• Start low and go slow with any cannabis product to minimize adverse effects, particularly in older adults and cannabis-naïve individuals 1

Treatment of Cannabis Use Disorder

• Comprehensive insurance coverage of evidence-based treatments for cannabis use disorder should be supported 1
• Dose tapering is advisable to reduce risk of discontinuation syndrome, though abrupt cessation is generally safe 2

Critical Pitfalls to Avoid

• Do not assume cannabis is benign because it is legal in many jurisdictions or perceived as "natural" 1, 2
• Do not overlook cardiovascular risk in patients with coronary disease, as cannabis can precipitate myocardial ischemia and infarction 2
• Do not dismiss psychiatric symptoms as unrelated to cannabis use, particularly psychosis in young adults 2, 5
• Do not fail to assess for cannabis use disorder in chronic users, as ~10% meet diagnostic criteria 2
• Do not ignore the neurotoxic effects in adolescents, which may cause permanent neurocognitive impairment 2, 5