-Testing shows some differences between THC- vs CBD-dominant cannabis
by Kate Kneisel, Contributing Writer, MedPage Today 2020-12-18
Must be read prior to engaging in activity
Study Authors: Thomas R. Arkell, Frederick Vinckenbosch, et al.; Thomas Cole, Richard Saitz
Target Audience and Goal Statement: Neurologists, nurses, primary care physicians, psychiatrists, public health/policy experts
The goal of this study was to determine the extent and duration of driving impairment caused by vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
Question Addressed:
- What is the magnitude and duration of driving impairment following vaporization of cannabis containing varying concentrations of THC and CBD?
Study Synopsis and Perspective:
Cannabinoids have been detected in up to 15% of fatally injured drivers involved in motor vehicle accidents, making cannabis impairment second only to alcohol as a cause of increased risk of crashes, and the trend appears to be increasing, according to data from the National Highway Traffic Safety Administration.
Action Points
- This study found that impairment of driving performance following vaporized Δ9-tetrahydrocannabinol (THC)-dominant and THC/cannabidiol (CBD)-equivalent cannabis compared with placebo was significantly greater at 40-100 minutes but not 240-300 minutes after vaporization.
- Note that while there were no significant differences between CBD-dominant cannabis and placebo, the effect size for CBD-dominant cannabis may not have excluded clinically important impairment, and the doses tested may not represent common usage.
The expanding legalization of recreational use of cannabis in many states and its therapeutic use for various indications make it increasingly important to understand the effects, and determine how healthcare professionals should advise their patients regarding the risks.
As with alcohol, acute cannabis intoxication is known to interfere with driving, as measured by the standard deviation of lateral position (SDLP), which detects lane weaving, swerving, and overcorrecting that typically accompanies alcohol- and drug-induced driving impairment.
Data from a small randomized trial in the Netherlands found that driving performance was impaired when healthy young people inhaled vaporized cannabis with THC, but not cannabis that was CBD-dominant.
Jan Ramaekers, PhD, of Maastricht University, and colleagues reported that at 40-100 minutes after vaping, SDLP was increased by THC-dominant cannabis (+2.33 cm, 95% CI 0.80-3.86, P<0.001) and THC/CBD-equivalent cannabis (+2.83 cm, 95% CI 1.28-4.39, P<0.001), but not by CBD-dominant cannabis (-0.05 cm, 95% CI -1.49 to 1.39, P>0.99), compared with placebo.
« Cannabis-induced driving impairment varies with cannabis strains, » Ramaekers told MedPage Today. « Strains that are rich with THC cause driving impairment, but strains that contain CBD and no THC do not. This is important as CBD strains may be prescribed for the treatment of medical conditions. »
The study, published online in JAMA, involved 26 healthy occasional cannabis users, who tested THC-dominant cannabis (13.75 mg of THC), CBD-dominant cannabis (13.75 mg of CBD), THC/CBD-equivalent cannabis (13.75 mg of both), and placebo.
The crossover trial included four experimental sessions — CBD, THC, THC/CBD, and placebo — scheduled at least 1 week apart. Participants were 23 years old on average and of « normal weight, » reported using cannabis less than twice a week in the previous year but more than 10 times in their lives, and had been driving at least 2 years and had normal weight.
In each session, participants waited 40-100 minutes after vaping and then drove a specially instrumented car over a 100-km highway circuit while maintaining a constant speed of 95 km/hour (59 mph) and a steady lateral position in the right (slower) traffic lane. Participants were instructed to drive in the middle of the lane, allowing about 1 meter of road surface on either side of the vehicle. The vehicle used had a dual accelerator and brake pedals that a licensed driving instructor who was also in the car could operate.
« THC-dominant and THC/CBD-equivalent cannabis produced a short-term impairment during experimental on-road driving, as indexed by a significant increase in SDLP measured 40 to 100 minutes following vaporization, » the researchers wrote. « In agreement with previous studies involving smoked cannabis or oral THC (dronabinol), this impairment was modest in magnitude and similar to that seen in drivers with a 0.05% blood alcohol content (≈2.4-2.5 cm). »
At 240 to 300 minutes after vaping, SDLP did not differ significantly for any group compared with placebo (P=0.20), the researchers reported.
Writing in an accompanying editorial, Thomas Cole, MD, MPH, and Richard Saitz, MD, MPH, both of Boston University and associate editors of JAMA, said that clinicians should caution their patients that cannabis products containing equal parts CBD and THC are no less impairing than products containing THC alone.
« Drivers who consumed THC were generally aware that their driving was impaired, although participants reported that consumption of THC/CBD was associated with less anxiety, reduced strength of drug effects, and greater confidence to drive than THC alone, » Cole and Saitz said. « These findings challenge the myth that CBD ameliorates the psychoactive/psychomotor effects of THC. »
« Moreover, given that alcohol is a major preventable cause of motor vehicle crash deaths and risk is additive with cannabis, patients should be advised to avoid any drinking, particularly with cannabis use, before driving, » the editorialists stated.
Study limitations, Ramaekers and co-authors said, mostly involved the small sample size, meaning that participants may not be representative of people who use medicinal CBD or regularly use recreational cannabis. In addition, only one dose of CBD, one dose of THC, and a single 1:1 ratio of CBD and THC were tested, a dose that corresponds with the lower end of the range of CBD concentrations (0.10-655.27 mg/mL) observed in a sample of extracts sold online, Cole and Saitz noted.
Source Reference: JAMA 2020; 324: 2177-2186
Editorial: JAMA 2020; 24: 2163-2164
Study Highlights and Explanation of Findings:
Nearly 10% of cannabis users in the U.S. report using it for medicinal purposes, primarily to manage chronic pain. Medical cannabis and CBD are used in many conditions. In addition to pain management, medical cannabis may be used as a sleep aid or to ameliorate symptoms in neurological disorders like Parkinson’s disease and spasticity resulting from multiple sclerosis, for example.
In the U.S., pharmaceutical-grade CBD has been approved by the FDA for three rare pediatric epilepsies: Dravet and Lennox-Gastaut syndromes and tuberous sclerosis complex. CBD doses used in pediatric epilepsy often are in the range of 10-20 mg/kg, considerably higher than what was tested in the trial by Ramaekers and co-authors.
« It’s a low dose compared to pharmaceutical grade CBD, » Ramaekers said. « In cannabis strains that are presently sold on the free market, the amount of CBD one would consume after a single cannabis cigarette, however, is relatively low; it’s comparable to what was dosed in the present study. We focused on THC and CBD consumption that would primarily reflect recreational use of cannabis. »
But the THC dose studied also may not be what’s in a cannabis cigarette. « Cannabis strains vary considerably in terms of percentage of THC, » he noted. His team used THC-dominant (THC 22% and CBD<1%) cannabis to deliver a dose of 13.75 mg THC. Analysis of confiscated cannabis in different forms showed that the highest THC concentration for cannabis was 37% (with an average of 13% in 2009 vs 3% in the 1980s).
A proposed policy framework for driving under the influence of cannabis cites evidence showing that blood levels of THC do not correlate well with the level of impairment. Furthermore, the cognitive and psychomotor impairments associated with acute, occasional use are not always seen with chronic heavy use, the researchers explained.
Indeed, a study of cannabis tolerance noted that downregulation of cannabinoid receptor type 1 (CB1) in long-term chronic cannabis users has been associated with a normalization of dopaminergic output from the ventral tegmental area to the mesolimbic circuit, and a reduction of impairment during acute cannabis exposure.
While Ramaekers noted that the findings dispel the popular notion that CBD counteracts THC’s psychoactive effects, there are conflicting data regarding the interaction of CBD and THC.
Unlike THC, CBD does not act through the CB1 and CB2 receptors; some research has suggested that when used concomitantly, CBD has the potential to reduce THC’s psychotropic effects and potentiate its therapeutic anticonvulsant, analgesic effects, possibly due to the negative allosteric effects of CB1 receptors or the positive modulation of the endocannabinoid system.
In contrast, other data has found that oral CBD has no effect on the psychotropic effects of smoked cannabis, suggesting that CBD and THC interactions might depend on pharmacokinetics and routes of administration, as well as on their actions on CB1 or CB2 receptors.
Although CBD-dominant cannabis was not linked with significant cognitive or psychomotor impairment, the findings do not support the conclusion that it’s safe to drive after consuming CBD, Cole and Saitz cautioned. « The authors acknowledged that the doses tested may not represent common usage and the effect size for CBD-dominant cannabis may not have excluded clinically important impairment. »
Finally, clinicians prescribing medical cannabis or treating patients who use it recreationally must consider its potential interactions with other medications.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
Primary Source
JAMA
Source Reference: Arkell TR, et al « Effect of cannabidiol and Δ9-tetrahydrocannabinol on driving performance: a randomized clinical trial » JAMA 2020; 324: 2177-2186.
Secondary Source
JAMA
Source Reference: Cole TB, Saitz R « Cannabis and impaired driving » JAMA 2020; 24: 2163-2164.
Additional Source
MedPage Today
Source Reference: George J « Does Cannabidiol Impair Driving? » 2020.