Tuesday, 15 September 2015

Marijuana: Does it Cause Cognitive Impairment During Driving?

Evidence has shown that cannabis is associated with an increased risk of motor vehicle accidents, especially when combined with alcohol. Presented here is one clinician’s guide for screening for cannabis in a chronic pain practice.

Twenty-three states and the District of Columbia currently have legalized medical marijuana and 10 states completely have decriminalized the substance. Our goal as healthcare providers is to improve our patients’ health and well-being, to replace maladaptive behaviors with more adaptive coping skills, and to educate patients about behaviors or activities that put them or others at risk for adverse outcomes.

I believe that the use of marijuana in chronic pain patients receiving opioid analgesics, or other controlled substances, puts them, and others, at significant increased risk for adverse outcomes, especially in settings that require complete attention, alertness, and mental acuity. These skills are required while driving and frequently necessary at the workplace. In addition, prescribing medications to patients who use marijuana may put you, the prescriber, and your medical practice at increased risk for lawsuits.

 
Flickr: FotoSleuthFollowFord Falcon crash
This feature will briefly review the evidence regarding the efficacy of marijuana, as well as safety concerns, with a focus on how marijuana can adversely affect a patient’s ability to operate an automobile.

Marijuana’s Efficacy

Clinical research has demonstrated that marijuana has efficacy in the management of intractable nausea, anorexia, and vomiting in cancer patients undergoing chemotherapy, HIV/AIDS patients, and cachexic patients, as well as in other debilitating medical disorders.1-3 There also are multiple studies documenting marijuana’s efficacy with some intractable pain disorders.

However, there is a difference between a therapeutic dose of medicinal marijuana in the form of Marinol and tetrahydrocannabinol (THC) from smoking marijuana—both in terms of known dosage, potency, and purity.2 The amount of THC absorbed in Marinol is known; in contrast, the dose of THC absorbed via smoking marijuana varies—and by all accounts, is much stronger than in the past.2

Reviews of the pharmacology of marijuana indicate that the percentage of THC contained in current marijuana cigarettes often is many times greater than its counterpart from the 1960s and 1970s.4 This finding is important because the effects of THC are dose-related. Ashton noted that most of the research on cannabis was performed in the 1970s using doses of 5 to 25 mg THC.4 In prior studies, subjects may have been given marijuana cigarettes with between 1.5% and 4% THC, whereas marijuana on the street today may contain between 10% and 30%, or more, of THC. Because of the higher concentration of THC in today’s marijuana, impairment levels are higher than those noted in past studies.

My bias has come from personal experience with patients, as well as scientific studies. A large body of data demonstrates that marijuana may cause significant mental status changes, including altered perception with occasional hallucinations and delusions, euphoria and dysphoria. We must consider the issue of risk to the individual smoking marijuana not only from immediate usage but also long-term effects, including the possibility of substance abuse.

Safety of Today’s Marijuana: Gateway Drug?

My clinical practice consists of a high-risk population, including current or former substance abusers. When I reviewed my patients’ early drug abuse history, which included childhood/adolescent experimentation, it strongly suggested that for the majority of patients in this population, marijuana was a gateway drug that either led to more regular marijuana abuse or, more commonly, to the use of more potent substances including opiates, heroin, and cocaine.

This opinion was confirmed by clinical evaluation as well as responses on follow-up questionnaires of these patients. Patients were also asked to respond to the following questions:
  • Did your early-life (preadolescent or adolescent) use of alcohol or marijuana serve as a gateway drug, making it more likely that you would use a more potent drug later in life?
  • Do you think early-life (preado-lescent or adolescent) use of alcohol or marijuana results in an increased use of more potent drugs later in life?
In both instances, the overwhelming responses (>75%) indicated their belief that alcohol or marijuana were gateway drugs.5
My own experience was confirmed in an observational study by Pesce et al.6 In that study, 21,746 urine specimens were obtained from chronic pain patients. The investigators noted that up to 13% of the patients tested positive for the acid form of THC. Moreover, there was a roughly 4-fold incidence (odds ratio, >3.7) in the use of cocaine and methamphetamine among marijuana users in this patient population.6

Taking this into consideration, I revisited this issue with many of my high-risk pain patients and the majority agreed that legalizing recreational marijuana for individuals over age 18 can be expected to result in major psychosocial problems as well as significant added risks in the workplace, in many activities requiring full attention and concentration (eg, riding bicycles and other athletic activities), as well as an increase in driving and work accidents.

Their comments also reinforce my conviction that many children, adolescents, and young adults are likely to be exposed to recreational marijuana more readily than would have been the case when there were established legal sanctions against marijuana use.
Editor’s Note: In Colorado and Washington State, the legal age for purchasing marijuana is 21, similar to the legal drinking age.

Risks vs Benefits: THC and Driving

It is now clear that marijuana plays a significant role in motor vehicle accidents (MVA) across the United States. Studies of acute THC use have found a 50% increase in risk of MVAs.7 As many as 33% of drivers tested at the scene of accidents were positive for marijuana and another 12% tested positive for marijuana and cocaine, according to studies reviewed by Brookoff et al and Sanderstom et al.8,9

Hartman and Huestis studied the effects of cannabis on driving skills and the evidence pointed to a significant increased risk in MVA when participants presented with 2 to 5 ng/mL of THC in their systems.10 The results of this study also revealed a significant need to consider decreased reaction time and increased distractibility in both regular THC users and occasional users.

Ramaekers et al also reported an increased crash risk among THC users, likely due to impairment of cognitive and psychomotor skills, as well as actual driving performance.11 More recent studies revealed that THC exposure significantly decreased psychomotor function on simulated driving tests and critical task taking (CTT) instruments. CTT is used to detect any impairment present regardless of the causation (ie, fatigue, alcohol, or cannabis intake).

In the study, subjects were trained on driving simulation software before taking a performance test. Subjects were administered single doses of 0, 250 and 500 mg/kg THC by smoking. Performance tests were conducted at regular intervals between 15 minutes and 6 hours after smoking and included measures of CTT, motor impulsivity (Stop signal task) and cognitive function (Tower of London). CTT performance declined after cannabis use by occasional cannabis users and the detrimental effects of THC use were detected up to 3 to 4 hours following cannabis smoking.

“At concentrations between 5 and 10 ng/mL, approximately 75% to 90% of the observations were indicative of significant impairment in every performance test. At THC concentrations >30 ng/mL the proportion of observations indicative of significant impairment increased to a full 100% in every performance test. It is concluded that serum THC concentrations between 2 and 5 ng/mL establish the lower and upper range of a THC limit for impairment,” the authors wrote.12

Further investigation of the impact of THC on psychomotor function was tested with the use of functional magnetic resonance imaging (fMRI) to track task performance 45 minutes after smoking THC in the same subjects.13 The results revealed the effects of THC on brain functions and behavior were greater than the distribution phase of THC detected in CTT. During the investigated fMRI time-period, THC levels ranged between 2.9 and 23.7 ng/mL (median value 9.4 ng/mL), close to the technical threshold adopted by authorities for the zero tolerance policy.

These concentrations are considered to be low and, yet, have detrimental effects on driving-related tasks as established by Ramaekers et al.12
Ramaekers et al also found that when chronic cannabis smokers abstained from use, CTT results and divided attention performance improved. However, impairment was still found 3 weeks after abstinence. These rates of impairment should raise red flags to clinicians, as the combination of central nervous system (CNS) depressants, opioid analgesics, and/or alcohol with cannabis would significantly increase impairment rates even after cannabis abstinence.12

In an article that discusses the California Compassionate Use Act (CUA), there is a section describing the inherent dangers to public safety resulting from drugged-driving.14 It noted, “the CUA does not supersede legislation prohibiting persons from engaging in conduct endangering others. California law prohibits driving under the influence of alcohol and drugs, and as a matter of law, a person authorized to use alcohol or a drug does not normally constitute a defense to a violation...”15

The dilemma of THC-impaired driving is extremely important to consider in the treatment of patients younger than 21 years of age because they have the most elevated risk of MVA fatality.16 A 2009 article on driver safety procedure published by the California Department of Motor Vehicles stated that “the use of medicinal marijuana approved by a physician should be handled in the same manner as any other prescription medication that may affect safe driving.”17

THC and Mental Health

The effect of THC on preadolescents and adolescents is not just related to psychomotor function, but rather, on overall neurocognitive development and functioning. The American Psychological Association reported a significant decrease in brain function by youths who were heavy cannabis users when using a lower dose than is legalized currently.18 Lisdahl reported abnormalities in the brain’s gray matter—a region connected with intelligence—detected in 16- to 19-year-olds who used marijuana once weekly for at least 1 year. 

19 Based on her findings, Lisdahl asked policymakers to address ways to prevent access to marijuana and to treat the abuse of cannabis for youth and young adults. She asked that they consider the effects from psychoactive chemicals found in marijuana and its long-term impact on neurocognitive function, such as anxiety, depression, and psychosis.19
In reviewing the actions of cannabis in humans, Webb et al20noted that there are multiple psychological effects including:
  • Effect on mood, which in recreational users manifests primarily as euphoria, with a high that comes on within minutes of smoking and may last for 2 hours or more, depending on dose.
  • Dysphoric reactions, which also can occur and often are dose-
    related and more common in naïve and psychologically vulnerable users.
  • Effects on perception, including distortion of spatial perception and impairment in time perception.
  • Hallucinations, which may occur with high doses.
  • Impairment of both cognition and psychomotor performance. The effects are dose-related but can be demonstrated after relatively small doses (5-10 ng/mL THC in a marijuana cigarette). It is noted that this finding has been confirmed in multiple neurocognitive and psychomotor tests and that the effects are additive with those of other CNS depressants.
Drug and Human Performance Fact Sheets from the National Highway Traffic Safety Administration (NHTSA) indicate that “the short-term effects of marijuana use include problems with memory and learning, distorted perception, difficulty in thinking and problem-solving, and loss of coordination. Heavy users may have increased difficulty sustaining attention, shifting attention to meet the demands of changes in the environment, and then registering, processing, and using information.”21

Some of the most common secondary adverse effects of long-term medical marijuana use include respiratory distress, depression and anxiety, gastrointestinal complaints, and CNS disorders.22 In heavy marijuana smokers, opioid-receptor blockade enhances the subjective and cardiovascular effects of marijuana, suggesting that endogenous opioids dampen cannabinoid effects in this population. In conjunction with cardiovascular effects, clinicians face the challenges of altered perception, mental status changes and the occasional dysphoria, hallucinations, and delusions associated with marijuana use in patients who may already have emotional disorders.

Alcohol and TCH

Mixing cannabis and alcohol increases the risk to the user and the public. In a population based case-controlled study, Laumon et al reviewed the issue of cannabis intoxication and fatal road crashes in France between October 2001 and September 2003.23 The study included the 6,766 drivers considered at fault in their crash and the results indicated “at least 2.5% of fatal crashes were estimated as being attributable to cannabis, compared with 28.6% for alcohol.” Conclusions of the study are outlined in Table 1.

Studies that assessed the risk of marijuana and alcohol causing driving impairment indicated that while both alcohol and marijuana alone impaired driving performance, combined alcohol and marijuana use caused more severe impairment.24,25

Another study by the NHTSA evaluated the effects of alcohol and marijuana use in 16 recreational users in a 4-way crossover-designed study. While the effects of low doses of marijuana and alcohol were minimal, the combination of moderate doses of marijuana and alcohol- impaired driving performance in city traffic situations.26 The NHTSA concluded that marijuana and alcohol combined severely impeded driving performance. “Mixing alcohol and marijuana may dramatically produce effects greater than either drug on its own.”26

THC and Texting

In 2010, Henderson et al wrote an article on sex differences in the effects of marijuana on simulated driving performance.27 Although no difference between the sexes were found, the article supported the existing literature that marijuana does affect simulated driving performance, particularly on complex tasks such as divided attention.

The authors noted “it is anticipated that many teenagers and young adults driving under the influence of marijuana are doing so while conversing with friends in the car, listening to music, talking on the cell phone, and/or texting messaging to others or reading texts from others. These behaviors divide the driver’s attention and are particularly dangerous under the influence of marijuana.”27
If we consider the research on THC exposure, and with such knowledge continue to prescribe opiates and/or CNS depressants to patients with a history of cannabis use, are we truly upholding our oath of non-malfeasance?

Summary

It is essential that health care providers write prescriptions for opiates or other CNS depressants for patients in a responsible manner, and with the recognition that our patients often use multiple other prescription medications or over-the-counter (OTC) substances. We need to be aware of all concurrent prescribed medications and OTC substances our patients are receiving and take them into account when we consider whether it is safe for such individuals to return to work or driving. It is our ethical responsibility to protect our patients and the public a large. Allowing our patients or recreational users to use marijuana before working or driving increases the risks for adverse outcomes.

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