Potential for Harm
The use of marijuana for medical purposes remains highly controversial and is fraught with a lack of good quality evidence regarding the specifics of clinical effectiveness and the details of treatment. Additionally, while there is clearly the potential for therapeutic benefits from the use of cannabis based products, there is also the potential for harm. An overview of current understanding regarding potential problems with the use of cannabis products in certain populations and conditions is reviewed below.
The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship. Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.
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The Great Debate: Should Marijuana for Recreational Use be Legal?
The increasingly widespread legalization of recreational marijuana has raised debates regarding the impact of its use on society as a whole. Cultural acceptance for its use is debated against the adverse impact on social, medical and psychiatric parameters. The medical and psychiatric community has raised a number of concerns regarding a wide variety of negative health effects, both physical and psychiatric, based on growing scientific evidence. Based on these concerns, a recent publication, Smoke and Mirrors – The Recreational Marijuana Debate, presents a well-organized argument against the legalization of recreational use of marijuana.
Marijuana – Potential for Harm
While there is great hope for the therapeutic potential of cannabis, it is not for everyone and certain groups have been identified who should likely avoid use of cannabis. The following groups are believed to be potentially at increased risk of harm from use of cannabis:
- Children, adolescents, and young adults (<25 y/0)
- Women who are pregnant or breastfeeding
- Those with a personal or family history of psychotic disorders such as schizophrenia
- Those with a history of chronic lung disease, cardiovascular disease and/or kidney disease
Children, Adolescents, and Young Adults (<25 y/o)
While animal studies suggest use of cannabinoids alters brain development in adolescence, human studies are inconclusive. Generally speaking, human studies have evaluated two broad categories of evidence regarding cannabinoids. First, non-invasive brain imaging studies that measure structural and functional changes within the brain related to exposure to cannabinoids. Second, studies have evaluated changes in neurocognitive functioning in cannabis users.
Human brain imaging studies have identified structural differences in young cannabis users compared with non-users. The majority of the evidence finds changes in the medial temporal regions (learning and memory, emotional processing) and frontal regions (decision-making, executive functioning, response inhibition, emotion regulation). However, not all studies have supported these conclusions.
Studies evaluating neurocognitive functioning in adolescents also remain divided in their conclusions regarding the effects of cannabis on brain development. There is growing evidence that adolescent cannabis use is particularly associated with impaired attention processing, executive functioning, and memory but the actual degree to which adolescent cannabis use is directly related to these impairments is uncertain. It has not been definitively determined if this cognitive impairment is permanent or reversible with discontinuation of cannabis use.
Longitudinal research spanning nearly 3 decades has revealed mixed results. One important study measured intelligence in early adolescence (age 13 – prior to the participants’ use of cannabis) and monitored for changes in intelligence through age 38. Frequent cannabis use was associated with declines in IQ by age 38 as well as more frequent findings of cannabis addiction. In contrast, in a more recent longitudinal study of IQ, this relationship did not hold true. In particular, the second study evaluating identical twin pairs concluded that cannabis use does not directly cause declines in IQ.
It should be noted that the studies described here are primarily based on the use of recreational cannabis products which have relatively high levels of THC. Medical cannabis products, on the other hand, have varying levels and ratios of THC to CBD and their use may not result in the same findings. More research is needed to clarify the risks and dangers of cannabis use in adolescents and young adults. In the meantime, caution with weighing the potential benefits against the uncertain risks should be engaged prior to treatment with cannabis products in this age group.
Pregnancy and Breastfeeding
Animal studies demonstrate that tetrahydrocannabinol (THC) crosses the placenta and results in fetal THC plasma levels approximately 10% of maternal levels after acute THC exposure and repeated THC exposure can result in much higher fetal concentrations. Both animal and human studies suggest that prenatal or perinatal cannabis use can result in long-term neurological impairments. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice discourages the use of medical cannabis during preconception, pregnancy and breastfeeding due to concern for potential harm including impaired neurologic development. Unfortunately, use of marijuana among pregnant women increased by 69% between 2009 and 2016 and it is currently estimated that 22% of pregnant women smoke marijuana.
Evidence also suggests cannabis use during pregnancy may be linked to preterm delivery, low birth weight or growth problems, birth defects, newborn behavioral problems as well as long-term impaired cognitive and behavioral functioning. There is evidence that cannabis use is associated with greater risk of stillbirth, birth defects including anencephaly (severely impaired brain development) and heart defects. It has been reported that the likelihood of stillbirth or miscarriage is 12 times higher among women using marijuana during pregnancy.
Much of the concern surrounding cannabis use during pregnancy is focused on long term cognitive functioning and behavioral impairment. There is moderate evidence from two large longitudinal studies that suggest prenatal cannabis use is linked to lower IQ scores and decreased cognitive functioning later in life. There is also limited evidence that cannabis use is associated with behavioral problems such as attention problems, aggression, hyperactivity, impulsivity, depression and delinquent behaviors.
Evidence regarding cannabis use while breastfeeding is extremely limited. THC can be detected in the breast milk of women using cannabis but research is mixed on whether cannabis use during breastfeeding is associated with poorer motor development in infants.
Cannabis Use in Persons with Psychotic Disorders
Use of cannabis by patients with established psychotic disorders is likely associated with increased relapse and decreased adherence to treatment but the association between cannabis use and psychotic symptoms or other psychopathology remain unclear.The association between cannabis use and psychotic symptoms appears to be bi-directional: changes in cannabis use predicts changes in psychotic symptoms and vice versa.
Studies evaluating cannabis use in patients with new onset psychosis show that lesser use of cannabis is associated with better psychological function and decreased anxiety compared with greater use. Additionally, patients with new-onset psychotic disease who are using cannabis at baseline but subsequently discontinue use have better psychological functioning and fewer negative symptoms than patients who continue cannabis use.
Recent research indicates that use of high-dose THC cannabis increases the risk of psychosis 3-fold compared to nonusers, and 5-fold among daily users. This is particularly problematic in patients using ultra-high-THC such as wax dabs.
Cannabis Use and Onset of Psychotic Disorder
A review of multiple studies concludes that cannabis use alone is likely not sufficient to cause psychosis but it could be a contributing factor that interacts with genetic and environmental factors in vulnerable individuals to trigger psychosis. The causal nature of the association is unclear and includes the “reverse causality“ hypothesis – that is, the distress caused by early symptoms of psychotic disease leads some people to use marijuana for relief of psychological symptoms.
Recent evidence suggests there may be a causal role for cannabis use, especially for persons already at increased risk for developing a psychotic disorder due to genetics, history of childhood mistreatment or abuse, or other reasons. It has been reported that age of onset of psychosis for cannabis users is 2.7 years younger than for non-users. Onset of schizophrenia usually occurs in late adolescence or early adulthood, a time at which a delay of a few years could allow many patients to achieve important developmental milestones of late adolescence and early adulthood that could reduce long-term disability resulting from the schizophrenia. However studies remain conflicting as to whether cannabis or THC contributes as a cause of schizophrenia. THC is clearly recognized to be the cause of psychotic effects and use of higher concentration TCH products has been shown to be more strongly associated with development of psychotic disease than use of lower concentration THC cannabis. But there is also growing evidence that CBD has anti-psychotic benefits.
The research on associations between cannabis use and psychotic disease is based nearly exclusively on use of recreational cannabis products, which have relatively high levels of THC and low levels of CBD. On the other hand, products obtained through the a medical cannabis program have varying ratios of THC to CBD so existing research conclusions may not apply to patients using medical cannabis products with greater CBD:THC ratios or less total cannabinoid content.
Chronic lung, cardiovascular, and/or kidney disease
Due to a lack of evidence regarding the safety of cannabis use in patients with chronic kidney disease, and chronic lung conditions, cannabis use in this population should be avoided or initiated with caution.
Regarding cardiovascular risk, increased rates of acute myocardial infarction (MI) and car
diovascular mortality have been reported, including double the rates of heart attacks (MIs). Chronic marijuana use has also been reported to increase the rate of stroke.
Clinical Evidence For Harm – Highlights
Based on the 2017 report from the National Academies of Sciences, Engineering, and Medicine, the following conclusions have been drawn:
- The evidence is unclear as to whether and how cannabis use is associated with heart attack, stroke, and diabetes.
- The evidence suggests that smoking cannabis does not increase the risk for certain cancers (i.e., lung, head, and neck) in adults.
- There is modest evidence that cannabis use is associated with one subtype of testicular cancer.
- There is minimal evidence that parental cannabis use during pregnancy is associated with greater cancer risk in offspring.
- There exists a lack of data on the effects of cannabis or cannabinoid-based therapeutics on the human immune system.
- There is insufficient research to determine definitive conclusions concerning the effects of cannabis smoke or cannabinoids on immune competence.
- There is limited evidence to suggest that regular exposure to cannabis smoke may have anti-inflammatory activity.
- There is insufficient evidence to support or refute a statistical association between cannabis or cannabinoid use and adverse effects on immune status in individuals with HIV.
Prenatal, Perinatal, and Neonatal Exposure
- Smoking cannabis during pregnancy is linked to lower birth weight in the offspring.
- The relationship between smoking cannabis during pregnancy and other pregnancy and childhood outcomes is unclear.
Problematic Cannabis Use (Cannabis Addiction/Cannabis Use Disorder)
- Greater frequency of cannabis use increases the likelihood of developing problematic cannabis use.
- Initiating cannabis use at a younger age increases the likelihood of developing problematic cannabis use. It is estimated that 19% of individuals initiating use of marijuana in their teens progress to developing cannabis addiction, now termed “Cannabis Use Disorder” (CUD).
Cannabis Use and Abuse of Other Substances
- Cannabis use is likely to increase the risk for developing other substance addiction (other than cannabis use disorder).
- It is estimated that 50% of individuals who use cannabis recreationally every day likely meet criteria for CUD.
Injury and Death
- Cannabis use prior to driving increases the risk of being involved in a motor vehicle accident.
- In states where cannabis use is legal, there is increased risk of unintentional, nonfatal cannabis overdose related injuries among children.
- It is unclear whether cannabis use is associated with all-cause mortality or with occupational injury.
- Cannabis use is likely to increase the risk of developing schizophrenia and other psychoses; the higher the use the greater the risk.
- In individuals with schizophrenia and other psychoses, a history of cannabis use may be linked to better performance on learning and memory tasks.
- Cannabis use does not appear to increase the likelihood of developing depression, anxiety, and posttraumatic stress disorder.
- For individuals diagnosed with bipolar disorders, near daily cannabis use may be linked to greater symptoms of bipolar disorder than non-users.
- Heavy cannabis users are more likely to report thoughts of suicide than non-users.
- Regular cannabis use is likely to increase the risk for developing social anxiety disorder.
- Recent cannabis use impairs the performance in cognitive domains of learning, memory, and attention. Recent use may be defined as cannabis use within 24 hours of evaluation.
- A limited number of studies suggest that there are impairments in cognitive domains of learning, memory, and attention in individuals who have stopped smoking cannabis.
- Cannabis use during adolescence is related to impairments in subsequent academic achievement and education, employment and income, social relationships and social roles.
- Smoking cannabis on a regular basis is associated with chronic cough and phlegm production.
- Quitting cannabis smoking is likely to reduce chronic cough and production of phlegm.
- It is unclear whether cannabis use is associated with COPD, asthma, or worsened lung function.
- While there can be adverse effects associated with the use of marijuana and cannabanoids, their use is generally considered safe. No acute fatal cases due to cannabinoid toxicity have been documented in humans. While the effective oral dosing range of plant-based cannabinoids in humans is 0.05 -25mg/kg/day, no deaths occurred in monkeys treated acutely with oral dosing of THC 9,000mg/kg.
- Myocardial infarction (heart attack) may be triggered by inhaled THC in individuals who are unable to tolerate cannabis side effects such as rapid heart rate or drop in blood pressure.
Inhaled cannabis is relatively contraindicated in:
- Patients who are 25 years of age or younger
- Patients who have a current, past, or strong family history of psychosis
- Patients who have a current or past cannabis use disorder (marijuana addiction)
- Patients who have a current substance use disorder (chemical or behavioral)
- Patients who have cardiovascular or respiratory disease
- Patients who are pregnant or planning to become pregnant]
- Inhaled cannabis should be used with caution in patients who smoke tobaccco
Cannabis products should be used with caution in:
- Patients who are at increased risk of cardiovascular disease
- Patients who have anxiety or mood disorders
- Patients who are taking opioids or benzodiazepines
- Do not operate dangerous equipment or perform potentially dangerous activities after cannabis use
- Do not use with alcohol, opioids, or sedating drugs, especially benzodiazepines (Valium, Xanax, Klonopin etc)
- Keep cannabis safely stored under lock and key
While “safe” time frames for driving after exposure to cannabis products are highly individualized and not well defined, cannabis users are advised not to drive for at least:
- Three to four (3 to 4) hours after smoking
- Six (6) hours after oral ingestion
- Eight (8) hours if they experience a subjective “high”
THC serum concentrations of 2–5 μg/L have been shown to impair driving, and concentrations of 7–10 μg/L can produce impairment equivalent to a blood alcohol concentration of 0.05%. Sweden and Australia have zero tolerance for illegal drugs in drivers. Of those drivers convicted for impaired driving in Sweden, 90% had blood levels of THC <5-μg/L and 61% had blood levels of THC <1 μg/L.
Two states, Nevada and Ohio, have set blood limits of ≥2 μg/L for THC or ≥5 μg/L for THCCOOH (a primary metabolite of THC) and Colorado has set(?) a limit of 5.0 μg/L THC in blood.. The highest limits in Europe are 3 μg/L for THC in Portugal and 50 μg/L for THCCOOH in Poland. While existing laws focus on THC and THCCOOH concentrations, appropriate cutoffs might also be selected for 11-OH-THC due its shorter detection window. THC- glucuronide, cannabinol, and cannabidiol concentrations in blood may also indicate recent cannabis smoking.
Of note, cannabinoids may be detected in the blood of chronic daily cannabis smokers for greater than one month after sustained abstinence. This is consistent with the time course of persisting neurocognitive impairment reported in recent studies. There is a strong public safety need to reduce cannabis-impaired driving and reduce cannabis-related motor vehicle injuries and deaths.
National Academy of Sciences
- The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research
International Cannabinoid Research Society
You tube video marijuana education links:
- Introduction to Medical Cannabis (Module 1) – The Endocannabinoid System by Dr. Towpik
- Introduction to Medical Cannabis (Module 2) – Pharmacology & Phytocannabinoids by Dr. Towpik
- Introduction to Medical Cannabis (Module 3) – Chronic Pain, Palliation & Case Studies by Dr. Towpik
- Introduction to Medical Cannabis (Module 4) – CINV & Epilepsy by Dr. Teh
- Introduction to Medical Cannabis (Module 5) – Adverse Effects & Potential Drug Interactions
- Introduction to Medical Cannabis (Module 6) – Patient Care, Dosing & Titration by Dr. Teh
These lay-person websites appear to be good resources for exploring medical marijuana. However, as is the case generally regarding medical applications of marijuana and its constitnuents, there is a huge amount of information that is not based in good science and relies on anecdotal (word-of-mouth) evidences. Reader, beware:
Marijuana – Should Recreational Use be Legal?
Medical Marijuana – Potential Harms Associated with Cannabis Use
- Brief Review of Human Studies Regarding Increased Risk of Harm with Cannabis Use – State of Minnesota – 2016
Medical Marijuana – Driving
- Establishing legal limits for driving under the influence of marijuana – 2014
- Medical Marijuana and Driving – a Review – 2014
- Impact of Prolonged Cannabinoid Excretion in Chronic Daily Cannabis Smokers’ Blood on Per Se Drugged Driving Laws – 2013
Medical Marijuana – Sleep & Sleep Apnea
- Medical Cannabis and the Treatment of Obstructive Sleep Apnea – An American Academy of Sleep Medicine Position Statement – 2018
- Cannabis, Cannabinoids, and Sleep: a Review of the Literature. – PubMed – NCBI
- Misc Abstracts @ Obstructive Sleep Apnea – 2017
- Cannabinoid May Be First Drug for Sleep Apnea – 2018
- Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial – Effects of Dronabinol in Obstructive Sleep Apnea – 2018
Medical Marijuana – Misc
- A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
- Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
- Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
- Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
- Cannabis-conclusions – 2017 National Academy of Sciences
- Cannabis-chapter-highlights – 2017 National Academy of Sciences
- Cannabis-report-highlights – 2017 National Academy of Sciences
- Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Bene ts of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
- Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
- Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
- Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
- Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
- Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
- Systematic review of systematic reviews for medical cannabinoids – 2018
- Adverse effects of medical cannabinoids – a systematic review – 2008
- Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
- Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
- Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
- Clinical Pharmacodynamics of Cannabinoids – 2004
- Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
- Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
- Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
- Pharmacology of Cannabinoids
- Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
- The Cannabis sativa Versus Cannabis indica Debate – An Interview with Ethan Russo, MD – 2016
- Review of the neurological benefits of phytocannabinoids – 2018
- Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinic… 2017 – PubMed – NCBI
Emphasis on Education
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