Legalize Cannabis for Recreational Use? Not so Fast!
Currently 24 states - most recently Ohio on November 7, 2023 -and the District of Columbia have legalized recreational marijuana use. Medical use of marijuana is now legal in 39 states and D.C..Legalization has fuels a dramatic increase in use, particularly notable among young adults. Statistics from the National Institutes of Health (NIH) show marijuana use by adults aged 19-30 years reached an all-time high in 2021 with 43% reporting use in the past year, an increase from 34% in 2016. Daily use rose to 11% in 2021, i.e., more than one in ten young adults uses marijuana daily.
As cannabis use skyrockets, not surprisingly, so do cannabis-related traffic injury emergency room visits - by 223% in a recently reported Canadian study. Similarly, hospitalizations attributable to cannabis increased 1.6 times after legalization and commercialization of cannabis in Canada, primarily for cannabis-induced psychosis.
Perhaps before jumping into widespread legalization of marijuana for recreational use, it would be wise to carefully explore the risks of cannabis which are often understated and overlooked. A risk/benefit analysis, comparing the pros and cons of legalization is in order. Unfortunately, much of the clinical research on the benefits and risks of marijuana use can be categorized as poor or insufficient quality. Limitations include reliance on retrospective or observational data, often only with short term follow up. Prospective, randomized comparative studies with longer term follow up are desperately needed to guide public policy with profound health and safety implications for society.
We’ll start by looking at what the available existing studies tell us about the potential benefits of the drug.
PROs/BENEFITS of Cannabis Use
Medical use of cannabis is well established for two rare seizure disorders - Lennox-Gastaut Syndrome (LGS) and Davet Syndrome. Oral cannabidiol (CBD) was effective in decreasing the number of seizures compared to placebo. The FDA has approved Epidiolex, a purified extract of cannabidiol containing no THC for these disorders.
HIV or cancer associated nausea, vomiting and loss of appetite The FDA has approved nabilone (brand name Cesamet ) - a synthetic cannabinoid - for use in patients with severe nausea and vomiting during cancer chemotherapy. Another synthetic cannabis-like drug, dronabinol (brand name Marinol) has been approved for loss of appetite in AIDS patients as well as chemotherapy-induced nausea and vomiting.
Chronic pain Studies evaluating cannabis in persons with pain show mixed results.. A large review of the best studies of medical cannabis for chronic neuropathic (nerve) pain concluded that the benefits of medical cannabis for the treatment of chronic pain may be outweighed by potential side effects. For example, a recent analysis found the risk for cannabis use disorder (CUD) was greatest in chronic pain patients over 65 years of age. A recent meta-analysis of 36 randomized clinical trials of cannabinoids for pain - the gold standard in clinical medical research - found most trials showed no benefit. Topical cannabinoids are legally sold in the U.S. but are not FDA regulated and cannot be claimed to prevent, diagnose or cure any disease. Significant concerns with these non-FDA regulated products are contamination with other potentially harmful substances and the actual content of THC or cannabinoid present.
PTSD/Anxiety Small, poor quality observational studies suggest cannabis may help with the symptoms of posttraumatic stress disorder (PTSD). However, veterans who use cannabis more than once weekly have more depression, anxiety and suicidal ideation. Though claims are made for marijuana for anxiety relief, use of cannabis more than once a month has been shown to increase social anxiety disorder.
With the exception of the clinical scenarios described earlier, the currently available evidence for benefits of medical marijuana fails to justify the exuberant claims sold to the public. We’ll turn now to the other side of the question - the hazards to individuals and society in general with more widespread use of the drug.
CONs/RISKS of Cannabis Use
Damage to the adolescent/young adult brain Through adolescence until about age 24 years, the brain is actively growing, remodeling, establishing critical neurologic pathways involved in information processing, decision making and impulse control. During this time the brain may be most vulnerable to environmental exposures including cannabis. In fact, cannabis and cannabinoids have been shown to impact adolescent and young adult neurodevelopment at multiple points with structural changes including altered gray matter development, particularly in the hippocampus and decreased white matter myelination (where cannabis receptors are located) demonstrated on magnetic resonance imaging (MRI). Regular young cannabis users perform poorly on tests of learning capacity, memory, delayed recall, and information processing. Alarmingly, regular adolescent/young adult cannabis users have a 37% increase in depression, 50% increase in suicidal ideation and a 3-4 fold increase in suicide attempts compared to nonusers. Cannabis use may increase the risk for schizophrenia by 4-5 times.
What are the consequences of the cognitive and structural brain changes seen in adolescent/young adult cannabis users with continued use into midlife? A recent landmark study (2022) evaluated more than 1000 persons followed from birth to age 45 with comprehensive assessments of IQ, memory, and an extensive battery of neuropsychological tests regularly performed. Interviews assessing substance use, including cannabis, were performed at regular intervals after age 18 to age 45. Brain MRI was performed at age 45. Long term cannabis users (using cannabis at least weekly at age 45 and at earlier assessments) were found to have a significant decline in IQ and performed worse on tests of learning, memory and processing speed than non users. Of these persons, one-third started using cannabis before age 18. Brain MRIs showed significantly smaller hippocampus volumes in long term users at age 45 compared to non users. The hippocampus is the portion of the brain which plays a key role in short and long term memory as well as spatial memory for navigation. Notably, the hippocampus is reduced in size in persons with schizophrenia and is one of the first regions of the brain to demonstrate damage in Alzheimer’s disease. The potential devastating implications of these findings demand urgent further investigation, specifically whether long-term cannabis users are at increased risk of dementia later in life.
Complications in pregnancy Cannabis is now the most commonly used federally illegal drug in pregnancy with a 7% incidence among pregnant women in 2017. Some more recent data suggests the incidence in some populations is now 25-30%. Typically pregnant women are using the drug to attempt to alleviate nausea, vomiting or stress and are unaware of the potentially devastating consequences. THC crosses the placenta and is found in breast milk 6 days after maternal use of cannabis. Prenatal maternal cannabis exposure is now linked to increased risk of small for gestational birth infants, preterm births, and increased need for neonatal intensive care admission. Serious adverse childhood outcomes of prenatal cannabis use include increased risk of autism spectrum disorders, attention deficit/hyperactivity disorders and psychotic-like experiences. Paternal cannabis use is also linked to low birth weight infants and spontaneous abortions as well as sudden infant death syndrome. Both the American Academy of Pediatrics and the American College of Obstetrics and Gynecology strongly recommend pregnant women discontinue cannabis use during pregnancy and while breastfeeding.
Cardiovascular Disease New data emerging from multiple studies indicates that cannabis use - recreational or medical - increases the risk of cardiovascular disease. Cannabis increases sympathetic nervous system tone and when vaped or smoked increases carbon monoxide levels five-fold. This may account for the association of cannabis use with serious cardiac rhythm abnormalities including atrial fibrillation and ventricular tachycardia. Just as concerning are observational studies associating cannabis use with increased risk of hypertension, stroke, myocardial infarction (heart attack), and heart failure. A recent report of hospitalized adults over 65 with at least 2 cardiovascular risk factors found marijuana users had a significantly increased risk of a heart or brain event while hospitalized compared to the group who didn’t use cannabis. The latest findings (November, 2023) of a study of 150,000 persons followed for 4 years noted a 34% increase in risk of heart failure in daily marijuana users compared to non-users. Daily marijuana use may increase a person’s risk of coronary artery disease by one-third compared to non-smokers. Cannabis use should probably be considered a cardiovascular risk factor like elevated cholesterol or family history of early cardiac death.
Cannabis Use Disorder (CUD) CUD is an addictive condition described by an inability to stop or decrease marijuana use despite social, physical, or psychological problems related to the drug. Persons with CUD demonstrate addictive behaviors including craving the drug and experience withdrawal symptoms when attempting to stop marijuana. They may develop tolerance - the need to use more drug to get the same high. They may avoid important activities with friends or family in favor of using marijuana. Persons with CUD are at increased risk of both psychotic and non-psychotic bipolar disorder and unipolar depression. The prevalence of CUD is reported as high as 21% among persons who use cannabis in states with legal recreational use. Recreational users are at higher risk for moderate or severe CUD. A likely factor is the increased amount of THC - the primary psychoactive component of cannabis - in currently available marijuana.
Driving Impairment Multiple studies have demonstrated significant effects on driving performance attributable to cannabis. Cannabis smoking increases lane weaving, impairs reaction time, and impairs cognitive function. Substantial driving impairment occurs with recent cannabis smoking and correlates with blood THC levels. Not surprisingly, legalization and commercialization of cannabis is associated with a huge increase in cannabis related MVAs - 223%! Legalization and the higher THC concentrations in today’s marijuana product are the primary culprits.
Cannabis Hyperemesis Syndrome (CHS) Chronic cannabis users - at least weekly and often since adolescence - are at risk for CHS. The symptoms of CHS are intense, persistent vomiting, often without warning up to several times per hour. Abdominal pain and dehydration may also occur. An episode may last up to 48 hours. Some people with CHS find some relief of the nausea by taking hot showers or baths which they may do several times daily. CHS is not a rare problem and accounts for about 6% of all emergency room visits for vomiting. The only cure is to completely stop using cannabis.
Drug Interactions Cannabis alters the metabolism of multiple widely-used prescription drugs, including antidepressants, anti-diabetic drugs, tacrolimus (anti rejection, immunosuppressive drug), B-blockers (used for heart disease, hypertension) anticoagulants, statins and many others. Most commonly the interaction slows clearance of the drug, increasing blood levels and risk of side effects. Cannabis users absolutely should inform their physicians about the quantity and frequency of use.
A Gateway Drug? Does using cannabis cause the user to progress to the use of “harder” illicit drugs such as cocaine, heroin, or other opioids? In the teeth of the fentanyl crisis, this is a critical question. A Department of Justice sponsored analysis in 2018 reviewed 23 studies addressing the question and concluded the results were “mixed” and couldn't answer the question. The analysis noted the reviewed studies were limited and often flawed but many did find statistically significant associations between cannabis use and later use of illicit drugs. However, no unequivocal evidence of causality was found. Studies in mice exposed to cannabinoids have demonstrated evidence of enhanced opioid intake later in life. The jury is still out. However, particularly with higher THC content of currently used cannabis, more research on this question is urgently needed.
While there are selected situations where medical use of marijuana clearly has important clinical benefit, an emerging body of better quality research demonstrates we’ve underestimated and understated the consequences of cannabis legalization. Cannabis use poses devastating risks in pregnancy and may well be a significant factor in increasing cardiovascular disease. Perhaps the most catastrophic consequence is on the mental and cognitive health of regular users throughout their lives with enormous implications for society at both ends of the age spectrum. Laws restricting adolescent use of alcohol or tobacco (including vaping) haven’t been very effective and are not likely to interdict cannabis use in the youth population. It’s time to pause the rush to legalization, provide evidence-based education to the public, remove unnecessary legal barriers to quality research, and provide the tools to the FDA to evaluate the content of over-the-counter CBD and regulate the THC content of available drug.